PMID:  Molecules. 2023 Feb 22 ;28(5). Epub 2023 Feb 22. PMID: 36903290 Abstract Title:  Phytomediated Silver Nanoparticles (AgNPs) Embellish Antioxidant Defense System, Ameliorating HLB-Diseased 'Kinnow' Mandarin Plants. Abstract:  Citrus production is harmed worldwide by yellow dragon disease, also known as Huanglongbing (HLB), or citrus greening. As a result, it has negative effects and a significant impact on the agro-industrial sector. There is still no viable biocompatible treatment for Huanglongbing, despite enormous efforts to combat this disease and decrease its detrimental effects on citrus production. Nowadays, green-synthesized nanoparticles are gaining attention for their use in controlling various crop diseases. This research is the first scientific approach to examine the potential of phylogenic silver nanoparticles (AgNPs) to restore the health of Huanglongbing-diseased 'Kinnow' mandarin plants in a biocompatible manner. AgNPs were synthesized usingas a reducing, capping, and stabilizing agent and characterized using different characterization techniques, i.e., UV-visible spectroscopy with a maximum average peak at 418 nm, scanning electron microscopy (SEM) with a size of 74 nm, and energy-dispersive spectroscopy (EDX), which confirmed the presence of silver ions along with different elements, and Fourier transform infrared spectroscopy served to confirm different functional groups of elements. Exogenously, AgNPs at various concentrations, i.e., 25, 50, 75, and 100 mgL, were applied against Huanglongbing-diseased plants to evaluate the physiological, biochemical, and fruit parameters. The findings of the current study revealed that 75 mgLAgNPs were most effective in boosting the plants' physiological profiles, i.e., chl a, chl b, total chl, carotenoid content, MSI, and RWC up to 92.87%, 93.36%, 66.72%, 80.95%, 59.61%, and 79.55%, respectively; biochemical parameters, i.e., 75 mgLconcentration decreased the proline content by up to 40.98%, and increased the SSC, SOD, POD, CAT, TPC, and TFC content by 74.75%, 72.86%, 93.76%, 76.41%, 73.98%, and 92.85%, respectively; and fruit parameters, i.e., 75 mgLconcentration increased the average fruit weight, peel diameter, peel weight, juice weight, rag weight, juice pH, total soluble solids, and total sugarby up to 90.78%, 8.65%, 68.06%, 84.74%, 74.66%, 52.58%, 72.94%, and 69.69%, respectively. These findings enable us to develop the AgNP formulation as a potential citrus Huanglongbing disease management method.

read more

PMID:  Plant Physiol Biochem. 2020 Mar ;148:70-79. Epub 2020 Jan 12. PMID: 31945669 Abstract Title:  Quercus leaf extracts display curative effects against Candidatus Liberibacter asiaticus that restore leaf physiological parameters in HLB-affected citrus trees. Abstract:  Citrus greening, also called Huanglongbing (HLB), is one of the most destructive citrus diseases worldwide. It is caused by the fastidious gram-negative-proteobacteria bacterium Candidatus Liberibacter asiaticus (CLas) and vectored by the Asian citrus psyllid (ACP), Diaphorina citri. Currently, there is no cure for HLB, no compounds have been successful in controlling HLB, and no sustainable management practices have been established for the disease. Thus, searching for alternative citrus greening disease mitigation strategies is considered an urgent priority for a sustainable citrus industry. The aim of this study was to use compounds extracted from oak, Quercus hemisphaerica, and to assess the antibacterial effects of these against CLas-infected citrus plants. The application of aqueous oak leaf extracts showed substantial inhibitory effects against CLas in citrus plants and the activity of genes related to starch. Significant differences were also observed in plant phenotypic and physiological traits after treatments. Citrus plants treated with oak extracts displayed an increase in stomatal conductance, chlorophyll content and nutrient uptake concurrently with a reduction of CLas titer, when compared to citrus plants treated with just water. The information provided from this study suggests a new management treatment program to effectively deal with the HLB disease.

read more

PMID:  Georgian Med News. 2023 Jan(334):6-9. PMID: 36864786 Abstract Title:  URTICA DIOICA EXTRACT DOWNREGULATES THE GENE EXPRESSION OF 5-RII IN HACAT CELLS: POSSIBLE IMPLICATIONS AGAINST ANDROGENIC SKIN DISEASES. Abstract:  Urtica dioica (Ud) is a perennial plant of temperate climate regions and has been reported therapeutic activity against benign prostate hyperplasia, mainly due to its 5-alpha-reductase (5-R) inhibition feature, which has been singly shown only in prostatic tissues until now. Also considering its use in traditional medicine against some dermatological problems and hair loss, we performed an in-vitro study to reveal its 5-R inhibition activity in skin cells whether this plant may have a therapeutic potential against androgenic skin diseases. After the preparation of Ud leaf extract and determination of non-cytotoxic concentration, cultured HaCaT cells were treated with the plant extract. RNA isolations were carried out from both non-treated and treated cell groups. cDNA synthesis was performed using gene specific primers of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as reference gene and 5-R type II (5-RII) as study material. Gene expressions were determined by real time reverse transcription quantitative polymerase chain reaction analysis. Results were represented as 'Target/GAPDH Fold Change'. Results of gene expression analysis showed that plant extract caused statistically significant downregulation of 5-RII gene expression (p=0.0021) in treated cells, compared to untreated control cells, and ended up with 0.58730.0586 fold change. This study is the first one showing the suppression of 5-RII gene expression on skin cells with unmixed or solitary Ud extract. With the currently reported anti-androgenic activity in HaCaT cells, it can be suggested that Ud has a solid scientific base and may have a promising future in cosmetic dermatology, and new product development against androgenic skin diseases.

read more

PMID:  Phytomedicine. 2023 Mar ;111:154648. Epub 2023 Jan 6. PMID: 36681052 Abstract Title:  Urtica dioica agglutinin (UDA) as a potential candidate for inhibition of SARS-CoV-2 Omicron variants: In silico prediction and experimental validation. Abstract:  BACKGROUND: The high number of mutations and consequent structure modifications in a Receptor-Binding Domain (RBD) of the spike protein of the Omicron variant of SARS-CoV-2 increased concerns about evading neutralization by antibodies induced by previous infection or vaccination. Thus, developing novel drugs with potent inhibitory activity can be considered an alternative for treating this highly transmissible variant. Considering that Urtica dioica agglutinin (UDA) displays antiviral activity against SARS-CoV-2, the potency of this lectin to inhibit the Receptor Binding Domain of the Omicron variant (RBD) was examined in this study.PURPOSE: This study examines how UDA inhibits the Omicron variant of SARS-CoV-2 by blocking its RBD, using a combination of in silico and experimental methods.METHODS: To investigate the interaction between UDA and RBD, the CLUSPRO 2.0 web server was used to dock the RBD-UDA complex, and molecular dynamics simulations were performed by the Gromacs 2020.2 software to confirm the stability of the selected docked complex. Finally, the binding affinity (G) of the simulation was calculated using MM-PBSA. In addition, ELISA and Western blot tests were used to examine UDA's binding to RBD.RESULTS: Based on the docking results, UDA forms five hydrogen bonds with the RBDactive site, which contains mutated residues Tyr501, Arg498, Arg493, and His505. According to MD simulations, the UDA-RBDcomplex is stable over 100 ns, and its average binding energy during the simulation is -87.201 kJ/mol. Also, the ELISA test showed that UDA significantly binds to RBD, and by increasing the concentration of UDA protein, the attachment to RBDbecame stronger. In Western blotting, RBDwas able to attach to and detect UDA.CONCLUSION: This study indicates that UDA interaction with RBDprevents virus attachment to Angiotensin-converting enzyme 2 (ACE2) and, therefore, its entry into the host cell. Altogether, UDA exhibited a significant suppression effect on the Omicron variant and can be considered a new candidate to improve protection against severe infection of this variant.

read more

PMID:  Environ Anal Health Toxicol. 2022 Dec ;37(4):e2022036-0. Epub 2022 Nov 10. PMID: 36916049 Abstract Title:  Tissues toxicity attenuation by vitamin E on oxidative damage induced by diazinon. Abstract:  Organophosphorus insecticides such as diazinon (DZN) are used worldwide in industry, veterinary practice, and agriculture. They may induce oxidative stress in different tissues. The use of antioxidants can protect tissues against oxidative stress. The aim of this study was to investigate the prophylactic and therapeutic roles of vitamin E against DZN-induced oxidative damage and biochemical alterations in various tissues of male Wistar rats. Thirty rats were divided into five groups: Control group received only corn oil as DZN solvent, DZN group received 100 mg/kg of DZN, E group received 150 mg/kg of vitamin E, E-DZN group received vitamin E and then dosed with DZN and DZN-E group received DZN and then dosed with vitamin E. All injections were carried out intraperitoneally. Plasma and various tissues were prepared and evaluated. Results showed that acute administration of DZN caused a significant induction of oxidative damage in the tested tissues via increased malondialdehyde level and some plasma biochemical indices, depletion of glutathione (GSH), reduced cholinesterase activity and change in the activities of superoxide dismutase, catalase and glutathione-S transferase. Treatment of rats with vitamin E resulted in an elevation in the level of GSH, normalizing the antioxidant enzymes activities and decreasing lipid peroxidation, although all these tests did not return to the normal level in certain tissues. The findings of this study suggest that both prophylactic and therapeutic treatments of rats with vitamin E provide a protective role against DZN-induced oxidative stress and cholinergic hyperactivity through free radicals scavenging and membrane stabilizing.

read more

PMID:  Nutrients. 2023 Feb 27 ;15(5). Epub 2023 Feb 27. PMID: 36904186 Abstract Title:  Effect of Vitamin E Supplementation on Chronic Insomnia Disorder in Postmenopausal Women: A Prospective, Double-Blinded Randomized Controlled Trial. Abstract:  Chronic insomnia disorder is one of the most common problems in postmenopausal women, exacerbated by underdiagnosis and improper treatment. This double-blinded, randomized, placebo-controlled trial was conducted to evaluate the potential of vitamin E to treat chronic insomnia as an alternative to sedative drugs and hormonal therapy. The study enrolled 160 postmenopausal women with chronic insomnia disorder, divided randomly into two groups. The vitamin E group received 400 units of mixed tocopherol daily, while the placebo group received an identical oral capsule. The primary outcome of this study was sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI), a self-evaluated and standardized questionnaire. The secondary outcome was the percentage of participants using sedative drugs. There were no significant differences in baseline characteristics between the study groups. However, the median PSQI score at baseline was slightly higher in the vitamin E group compared with the placebo (13 (6, 20) vs. 11 (6, 20);-value 0.019). After one month of intervention, the PSQI score was significantly lower (indicating better sleep quality) in the vitamin E group compared with the placebo (6 (1, 18) vs. 9 (1, 19);-value 0.012). Moreover, the improvement score was significantly higher in the vitamin E group compared with the placebo (5 (-6, 14) vs. 1 (-5,13);-value

read more

PMID:  Diabetes Metab Syndr Obes. 2023 ;16:565-574. Epub 2023 Mar 1. PMID: 36883138 Abstract Title:  Vitamin E Supplement Protects Against Gestational Diabetes Mellitus in Mice Through nuclear factor-erythroid factor 2-related factor 2/heme oxygenase-1 Signaling Pathway. Abstract:  BACKGROUND: Gestational diabetes mellitus (GDM) is the most common pregnant disorder worldwide. In this study, we aimed to explore whether vitamin E (VE) treatment alone could protect against GDM in a mouse model.METHODS: 6-week-old C57BL/6J female mice were fed on high-fat diet for two weeks and continued with high-fat diet after pregnancy to induce GDM. The pregnant mice were orally administrated with 2.5, 25 or 250 mg/kg VE twice per day during pregnancy together with high-fat diet. Oral glucose tolerance test, insulin amounts, oxidative stress and inflammation were then measured.RESULTS: Only 250 mg/kg VE could improve glucose tolerance and insulin level in pregnant mice. VE (250 mg/kg) effectively inhibited GDM-induced hyperlipidemia, and secretion of inflammatory cytokines such as tumor necrosis factor-and interleukin-6. VE also significantly ameliorated maternal oxidative stress at the late stage of pregnancy, and also improved reproductive outcomes, including increasing the litter size and birth weight in GDM mice. Moreover, VE also activated GDM-reduced nuclear factor-erythroid factor 2-related factor 2 (Nrf2) / heme oxygenase-1 signaling pathway in the maternal liver tissues of GDM mice.CONCLUSION: Our data clearly demonstrated that 250 mg/kg VE twice a day during pregnancy could significantly ameliorate the symptoms of GDM by alleviating oxidative stress, inflammation, hyperglycemia, and hyperlipidemia through Nrf2/HO-1 signaling pathway in GDM mice. Thus, additional VE supplement might be beneficial to GDM.

read more

PMID:  Investig Clin Urol. 2023 Mar ;64(2):189-196. PMID: 36882179 Abstract Title:  Anti-fibrotic effect of tocotrienols for bladder dysfunction due to partial bladder outlet obstruction. Abstract:  PURPOSE: To investigate potential beneficial effects of tocotrienols which have been suggested to inhibit hypoxia-inducible factor (HIF) pathway, on partial bladder outlet obstruction (PBOO)-induced bladder pathology.MATERIALS AND METHODS: PBOO was surgically created in juvenile male mice. Sham-operated mice were used as controls. Animals received daily oral administration of either tocotrienols (T) or soybean oil (SBO, vehicle) from day 0 to 13 post-surgery. Bladder function was examinedby void spot assay. At 2 weeks post-surgery, the bladders were subjected to physiological evaluation of detrusor contractilityusing bladder strips, histology by H&E staining and collagen imaging, and gene expression analyses by quantitative PCR.RESULTS: A significant increase in the number of small voids was observed after 1 week of PBOO compared to the control groups. At 2 weeks post-surgery, PBOO+SBO mice showed a further increase in the number of small voids, which was not observed in PBOO+Tgroup. PBOO-induced decrease in detrusor contractility was similar between two treatments. PBOO induced bladder hypertrophy to the same degree in both SBO and Ttreatment groups, however, fibrosis in the bladder was significantly less prominent in the Tgroup than the SBO group following PBOO (1.8- vs. 3.0-fold increase in collagen content compared to the control). Enhanced levels of HIF target genes in the bladders were observed in PBOO+SBO group, but not in PBOO+Tgroup compared to the control.CONCLUSIONS: Oral tocotrienol treatment reduced the progression of urinary frequency and bladder fibrosis by suppressing HIF pathways triggered by PBOO.

read more

PMID:  Nanomedicine (Lond). 2022 Dec ;17(30):2231-2243. Epub 2023 Feb 28. PMID: 36853835 Abstract Title:  Cholesterol enhances the negative impact of vaping additives on lung surfactant model systems. Abstract:  Vaping has given rise to e-cigarette or vaping product use-associated lung injury. Model lung surfactant films were used to assess the impact of vape additives (vitamin E, vitamin E acetate, tetrahydrocannabinol, cannabidiol). This work builds upon our previous findings, by incorporating cholesterol, to understand the interplay between the additives and the sterol in surfactant function.Compression-expansion cycles of lipid monofilm at the air-water interface and Brewster angle microscopy allowed elucidating the effects of vape additives.Vape additives at 5 mol% inhibited proper lipid packing and reduced film stability. Cholesterol enhanced the additive effects, resulting in significantly destabilized films and altered domains. The observed impact could signify dysfunctional lung surfactant and impaired lung function.

read more

PMID:  J Toxicol Environ Health A. 2023 Apr 18 ;86(8):246-262. Epub 2023 Mar 1. PMID: 36859793 Abstract Title:  Short-term exposure of female BALB/cJ mice to e-cigarette aerosol promotes neutrophil recruitment and enhances neutrophil-platelet aggregation in pulmonary microvasculature. Abstract:  Despite the perception that e-cigarettes are safer than conventional cigarettes, numerous findings demonstrated that e-cigarette aerosol (EC) exposure induced compromised immune functionality, vascular changes even after acute exposure, and lung injury. Notably, altered neutrophil functionality and platelet hemodynamics have been observed post-EC exposure. It was hypothesized that EC exposure initiates an inflammatory response resulting in altered neutrophil behavior and increased neutrophil-platelet interaction in the pulmonary microvasculature. Neutrophil and platelet responses were examined up to 48 hrs following whole-body, short-term EC exposure without flavorants or nicotine in a murine model, which most closely modeled secondhand exposure. This study is the first to investigate the impact of EC exposure through lung intravital imaging. Compared to room air-exposed mice, EC-exposed mice displayed significantly increased 1.71.9-fold number of neutrophils in the pulmonary microvasculature associated with no marked change in neutrophils within whole blood or bronchoalveolar lavage fluid (BALF). Neutrophil-platelet interactions were also significantly elevated 1.92.5-fold in exposed mice. Plasma concentration of myeloperoxidase was markedly reduced 1.5-fold 48hr following exposure cessation, suggesting suppressed neutrophil antimicrobial activity. Cytokine expression exhibited changes indicating vascular damage. Effects persisted for 48hr post-EC exposure. Data demonstrated that EC exposure repeated for 3 consecutive days in 2.5hr intervals in the absence of flavorants or nicotine resulted in modified pulmonary vasculature hemodynamics, altered immune functionality, and a pro-inflammatory state in female BALB/cJ mice.

read more

PMID:  Toxics. 2023 Feb 7 ;11(2). Epub 2023 Feb 7. PMID: 36851030 Abstract Title:  Toxicological Assessment of Particulate and Metal Hazards Associated with Vaping Frequency and Device Age. Abstract:  Electronic nicotine delivery systems (ENDS) aerosols are complex mixtures of chemicals, metals, and particles that may present inhalation hazards and adverse respiratory health risks. Despite being considered a safer alternative to tobacco cigarettes, metal exposure levels and respiratory effects associated with device aging and vaping frequency have not been fully characterized. In this study, we utilize an automated multi-channel ENDS aerosol generation system (EAGS) to generate aerosols from JUUL pod-type ENDS using tobacco-flavored e-liquid. Aerosol puff fractions (1-50) and (101-150) are monitored and sampled using various collection media. Extracted aerosols are prepared for metal and toxicological analysis using human primary small airway epithelial cells (SAEC). ENDS aerosol-mediated cellular responses, including reactive oxygen species (ROS), oxidative stress, cell viability, and DNA damage, are evaluated after 24 h and 7-day exposures. Our results show higher particle concentrations in later puff fractions (0.135 mg/m) than in initial puff fractions (0.00212 mg/m). Later puff fraction aerosols contain higher toxic metal concentrations, including chromium, copper, and lead, which elicit increased levels of ROS followed by significant declines in total glutathione and cell viability. Notably, a 30% increase in DNA damage was observed after 7 days because of later puff fraction exposures. This work is consistent with ENDS aerosols becoming more hazardous across the use of pre-filled pod devices, which may threaten respiratory health.

read more

PMID:  Am J Physiol Lung Cell Mol Physiol. 2023 Apr 1 ;324(4):L468-L479. Epub 2023 Feb 21. PMID: 36809074 Abstract Title:  E-cigarette aerosols of propylene glycol impair BK channel activity and parameters of mucociliary function. Abstract:  Propylene glycol (PG) is a common delivery vehicle for nicotine and flavorings in e-cigarette (e-cig) liquids and is largely considered safe for ingestion. However, little is known about its effects as an e-cig aerosol on the airway. Here, we investigated whether pure PG e-cig aerosols in realistic daily amounts impact parameters of mucociliary function and airway inflammation in a large animal model (sheep) in vivo and primary human bronchial epithelial cells (HBECs) in vitro. Five-day exposure of sheep to e-cig aerosols of 100% PG increased mucus concentrations (% mucus solids) of tracheal secretions. PG e-cig aerosols further increased the activity of matrix metalloproteinase-9 (MMP-9) in tracheal secretions. In vitro exposure of HBECs to e-cig aerosols of 100% PG decreased ciliary beating and increased mucus concentrations. PG e-cig aerosols further reduced the activity of large conductance, Ca-activated, and voltage-dependent K(BK) channels. We show here for the first time that PG can be metabolized to methylglyoxal (MGO) in airway epithelia. PG e-cig aerosols increased levels of MGO and MGO alone reduced BK activity. Patch-clamp experiments suggest that MGO can disrupt the interaction between the major pore-forming BK subunit human Slo1 (hSlo1) and the gamma regulatory subunit LRRC26. PG exposures also caused a significant increase in mRNA expression levels ofand interleukin 1 beta (). Taken together, these data show that PG e-cig aerosols cause mucus hyperconcentration in sheep in vivo and HBECs in vitro, likely by disrupting the function of BK channels important for airway hydration.

read more

PMID:  Nicotine Tob Res. 2023 May 22 ;25(6):1145-1154. PMID: 36780924 Abstract Title:  Vaping Dose, Device Type, and E-Liquid Flavor are Determinants of DNA Damage in Electronic Cigarette Users. Abstract:  INTRODUCTION: Despite the widespread use of electronic cigarettes, the long-term health consequences of vaping are largely unknown.AIMS AND METHODS: We investigated the DNA-damaging effects of vaping as compared to smoking in healthy adults, including "exclusive" vapers (never smokers), cigarette smokers only, and nonusers, matched for age, gender, and race (N = 72). Following biochemical verification of vaping or smoking status, we quantified DNA damage in oral epithelial cells of our study subjects, using a long-amplicon quantitative polymerase chain reaction assay.RESULTS: We detected significantly increased levels of DNA damage in both vapers and smokers as compared to nonusers (p = .005 and p = .020, respectively). While the mean levels of DNA damage did not differ significantly between vapers and smokers (p = .522), damage levels increased dose-dependently, from light users to heavy users, in both vapers and smokers as compared to nonusers. Among vapers, pod users followed by mod users, and those who used sweet-, mint or menthol-, and fruit-flavored e-liquids, respectively, showed the highest levels of DNA damage. The nicotine content of e-liquid was not a predictor of DNA damage in vapers.CONCLUSIONS: This is the first demonstration of a dose-dependent formation of DNA damage in vapers who had never smoked cigarettes. Our data support a role for product characteristics, specifically device type and e-liquid flavor, in the induction of DNA damage in vapers. Given the popularity of pod and mod devices and the preferability of sweet-, mint or menthol-, and fruit-flavored e-liquids by both adult- and youth vapers, our findings can have significant implications for public health and tobacco products regulation.IMPLICATIONS: We demonstrate a dose-dependent formation of DNA damage in oral cells from vapers who had never smoked tobacco cigarettes as well as exclusive cigarette smokers. Device type and e-liquid flavor determine the extent of DNA damage detected in vapers. Users of pod devices followed by mod users, and those who use sweet-, mint or menthol-, and fruit-flavored e-liquids, respectively, show the highest levels of DNA damage when compared to nonusers. Given the popularity of pod and mod devices and the preferability of these same flavors of e-liquid by both adult- and youth vapers, our findings can have significant implications for public health and tobacco products regulation.

read more

PMID:  Asia Pac J Clin Oncol. 2023 Mar 13. Epub 2023 Mar 13. PMID: 36915942 Abstract Title:  The therapeutic effects of berberine for gastrointestinal cancers. Abstract:  Cancer is one of the most serious human health issues. Drug therapy is the major common way to treat cancer. There is a growing interest in using natural compounds to overcome drug resistance, adverse reactions, and target specificity of certain types of drugs that may affect several targets with fewer side effects and be beneficial against various types of cancer. In this regard, the use of herbal medicines alone or in combination with the main anticancer drugs is commonly available. Berberine (BBR), a nature-driven phytochemical component, is a well-known nutraceutical due to its wide variety of pharmacological activities, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and hypolipidemic. In addition, BBR exerts anticancer activities. In present article, we summarized the information available on the therapeutic effects of BBR and its mechanisms on five types of the most prevalent gastrointestinal cancers, including esophageal, gastric, colorectal, hepatocarcinoma, and pancreatic cancers.

read more

PMID:  Food Funct. 2023 Apr 3 ;14(7):3269-3278. Epub 2023 Apr 3. PMID: 36916513 Abstract Title:  Caffeine can alleviate non-alcoholic fatty liver disease by augmenting LDLR expressiontargeting EGFR. Abstract:  Increasing low-density lipoprotein receptor (LDLR) protein levels represents a key strategy for the prevention and treatment. Berberine can reportedly alleviate non-alcoholic fatty liver disease (NAFLD) by increasing the LDLR expression in an ERK1/2 signaling-dependent manner of NAFLD. Studies have shown that caffeine can inhibit fat deposition in the livers of mice; however, caffeine has not been reported to alleviate NAFLD by augmenting the LDLR expressiontargeting EGFR. Here, an MTT assay, western blotting, RT-qPCR, immunohistochemistry, and surface plasmon resonance (SPR) analysis were used to investigate the role of caffeine in low-density lipoprotein cholesterol (LDL-C) clearance bothand., we found that caffeine could activate the EGFR-ERK1/2 signaling pathway in HepG2 cells, leading to increased LDLR mRNA and protein expression, and this effect could be inhibited by cetuximab. The SPR assay results have indicated that caffeine may increase the LDLR expression by directly binding to the EGFR extracellular domain and activating the EGFR-ERK1/2 signaling pathway., caffeine markedly improved fatty liver and related blood indices in ApoE KO mice with high-fat-diet-induced NAFLD. Consistent with ourresults, we found that caffeine could also activate EGFR-ERK1/2 signaling and promote the LDLR expression in ApoE KO mice. In summary, caffeine can enhance the LDLR expression by directly binding to EGFR and activating the EGFR-ERK1/2 signaling pathway. EGFR signaling may represent a novel target for the prevention and treatment of NAFLD.

read more

PMID:  Am J Transl Res. 2023 ;15(2):729-744. Epub 2023 Feb 15. PMID: 36915782 Abstract Title:  Berberine inhibits the growth of osteosarcoma through modulating MMP/NM-23 and MAPK/JNK signal pathways. Abstract:  OBJECTIVE: To investigate the effects and mechanisms of berberine (BBR) on the migration, invasion, proliferation and apoptosis of osteosarcoma cells in vitro.METHODS: Proliferation of MG-63 and U2OS cells was measured by the CCK-8 assay. Cells migration was examined by wound-healing assay. The invasion and metastasis of cells were evaluated by transwell invasion assay. Cells apoptosis was determined by the flow cytometry. Caspase-3 activity in MG-63 and U2OS cells was measured, and Western blot was used to measure the levels of Bax, Bcl-2, MMP-2 and MMP-9 in cells. In addition, the osteosarcoma graft tumor model of mice was established. The tumorigenesis of MG-63 cells in nude mice was compared among three groups. Immunohistochemistry assay was used to measure the levels of MMP-2, MMP-9 and NM-23 in tumor tissue.RESULTS: It was showed that BBR inhibited the proliferation of MG-63 and U2OS cells in vitro in time- and concentration-dependent manners. Moreover, BBR reduced the cells migration and invasion, also down-regulated the expressions of MMP-2 and MMP-9. BBR also inhibited the cells apoptosis by down-regulating the expression of Bcl-2 and up-regulating the expression of Bax. In nude mice, BBR obviously inhibited the tumorigenesis of MG-63 cells. Compared with the negative group, BBR decreased the levels of MMP-2 and MMP-9 and increased the level of NM-23. The molecular mechanism was associated with activation of the MAPK/JNK signal transduction pathway.CONCLUSIONS: BBR significantly regulates the biological behaviors of osteosarcoma cells and inhibits the growth of osteosarcoma. The molecular mechanism may be associated with the modulation of MMP/NM-23 and MAPK/JNK signals. BBR may be a potential drug for the treatment of osteosarcoma.

read more

PMID:  Purinergic Signal. 2023 Mar 15. Epub 2023 Mar 15. PMID: 36918462 Abstract Title:  Caffeine plus haloperidol reduces fatigue in an experimental model of Parkinson's disease - a prospective to AR-DR heterodimer antagonism. Abstract:  Fatigue is a non-motor symptom of Parkinson's disease (PD). Adenosinereceptor (AR) and compromised dopamine neurotransmission are linked to fatigue. Studies demonstrate that AR antagonism potentiates dopamine transmission via dopamine receptor D(DR). However, the heterodimer form of AR-DR in the striatum prompted questions about the therapeutic targets for PD patients. This study investigates the effects of caffeine (AR non-selective antagonist) plus haloperidol (DR selective antagonist) treatment in the fatigue induced by the reserpine model of PD. Reserpinized mice showed impaired motor control in the open field test (p

read more

PMID:  Diabetol Metab Syndr. 2023 Mar 8 ;15(1):37. Epub 2023 Mar 8. PMID: 36890514 Abstract Title:  Caffeine ameliorates the metabolic syndrome in diet-induced obese mice through regulating the gut microbiota and serum metabolism. Abstract:  OBJECTIVE: Obesity is associated with gut microbiota disorders, which has been related to developing metabolic syndromes. The research aims to investigate the effects of caffeine treatment on insulin resistance, intestinal microbiota composition and serum metabolomic changes in high-fat diet (HFD)-induced obesity mice.METHODS: Eight-week-old male C57BL/6 J mice were fed a normal chow diet (NCD) or HFD with or without different concentrations of caffeine. After 12 weeks of treatment, body weight, insulin resistance, serum lipid profiles, gut microbiota and serum metabolomic profiles were assessed.RESULTS: Caffeine intervention improved the metabolic syndrome in HFD-fed mice, such as serum lipid disorders and insulin resistance. 16S rRNA Sequencing analysis revealed that caffeine increased the relative abundance of Dubosiella, Bifidobacterium and Desulfovibrio and decreased that of Bacteroides, Lactobacillus and Lactococcus to reverse HFD-fed obesity in mice. Additionally, Caffeine Supplementation also altered serum metabolomics, mainly focusing on lipid metabolism, bile acid metabolism and energy metabolism. Caffeine increased its metabolite 1,7-Dimethylxanthine, which was positively correlated with Dubosiella.CONCLUSIONS: Caffeine exerts a beneficial effect on insulin resistance in HFD-mice, and the underlying mechanism may be partly related to altered gut microbiota and bile acid metabolism.

read more

PMID:  Chem Biol Drug Des. 2023 Mar 11. Epub 2023 Mar 11. PMID: 36905314 Abstract Title:  Current understanding and future prospects on Berberine for anticancer therapy. Abstract:  Berberine (BBR) is a potential plant metabolite and has remarkable anticancer properties. Many kinds of research are being focused on the cytotoxic activity of berberine in in vitro and in vivo studies. A variety of molecular targets which lead to the anticancer effect of berberine ranges from p-53 activation, Cyclin B expression for arresting cell cycles; protein kinase B (AKT), MAP kinase and IKB kinase for antiproliferative activity; effect on beclin-1 involved in autophagy; reduced expression of MMP-9 and MMP-2 for the inhibition of invasion and metastasis etc. Berberine also interferes with transcription factor-1 (AP-1) activity responsible for the expression of oncogenes and neoplastic transformation of the cell. It also leads to the inhibition of various enzymes which are directly or indirectly involved in carcinogenesis like N acetyl transferase, Cyclo-oxygenase-2, Telomerase and Topoisomerase. In addition to these actions, Berberine plays a role in, the regulation of reactive oxygen species and inflammatory cytokines in preventing cancer formation. Berberine anticancer properties are demonstrated due to the interaction of berberine with micro-RNA. The summarized information presented in this review article may help and lead the researchers, scientists/industry persons to use berberine as a promising candidate against cancer.

read more

PMID:  Molecules. 2023 Feb 24 ;28(5). Epub 2023 Feb 24. PMID: 36903391 Abstract Title:  Berberine-Based Carbon Quantum Dots Improve Intestinal Barrier Injury and Alleviate Oxidative Stress in C57BL/6 Mice with 5-Fluorouracil-Induced Intestinal Mucositis by Enhancing Gut-Derived Short-Chain Fatty Acids Contents. Abstract:  This study aims to evaluate the effect of berberine-based carbon quantum dots (Ber-CDs) on improving 5-fluorouracil (5-FU)-induced intestinal mucositis in C57BL/6 mice, and explored the mechanisms behind this effect. Thirty-two C57BL/6 mice were divided into four groups: normal control (NC), 5-FU-induced intestinal mucositis model (5-FU), 5-FU + Ber-CDs intervention (Ber-CDs), and 5-FU + native berberine intervention (Con-CDs). The Ber-CDs improved body weight loss in 5-FU-induced mice with intestinal mucositis compared to the 5-FU group. The expressions of IL-1and NLRP3 in spleen and serum in Ber-CDs and Con-Ber groups were significantly lower than those in the 5-FU group, and the decrease was more significant in the Ber-CDs group. The expressions of IgA and IL-10 in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, but the up-regulation was more significant in the Ber-CDs group. Compared with the 5-FU group, the relative contents of Bifidobacterium, Lactobacillus and the three main SCFAs in the colon contents were significantly increased the Ber-CDs and Con-Ber groups. Compared with the Con-Ber group, the concentrations of the three main short-chain fatty acids in the Ber-CDs group were significantly increased. The expressions of Occludin and ZO-1 in intestinal mucosa in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, and the expressions of Occludin and ZO-1 in the Ber-CDs group were more higher than that in the Con-Ber group. In addition, compared with the 5-FU group, the damage of intestinal mucosa tissue in the Ber-CDs and Con-Ber groups were recovered. In conclusion, berberine can attenuate intestinal barrier injury and oxidative stress in mice to mitigate 5-fluorouracil-induced intestinal mucositis, moreover, the above effects of Ber-CDs were more significant than those of native berberine. These results suggest that Ber-CDs may be a highly effective substitute for natural berberine.

read more

PMID:  J Oral Biol Craniofac Res. 2023 ;13(2):155-163. Epub 2022 Dec 28. PMID: 36618007 Abstract Title:  Onco-immunity and therapeutic application of amygdalin: A review. Abstract:  BACKGROUND: Amygdalin is known as a chemical compound derived from various fruits. The glycosides existing in this plant have been historically utilized as an anticancer agent. This review presented an overview of amygdalin and its onco-immunity and other therapeutic medical applications.METHOD: A literature search for studies relating to amygdalin and cancer treatment was carried out using PubMed and Google Scholar. Combinations of the following terms were used in the search strategies: "amygdalin," "rhodanese," "cyanide," "cyanogenic," "hypothiocyanite," "mandelonitrile," "glucosides," "cancer," "apoptosis," and "cytotoxicity," combined with a cancer term such as "seed," "almond," or "apricot," "cancer + cell line, antiproliferation or inhibition," "BAX From the March 3, 1981 until the April 15, 2021, all of the English-language papers were evaluated based on the inclusion criteria. Publications included reviews, chapters from books, and original research papers.RESULTS: The FDA prohibits Amygdalin from medical usage as an anticancer treatment due to a lack of proof of cure in cancer cases. When this natural-based compound is used with conditional chemotherapeutic medicines causes synergistic effects. Besides, amygdalin is used to manage asthma, improve the immune system, induce apoptosis in human renal fibroblasts, and inhibit hyperglycemia.CONCLUSION: Various medical uses of amygdalin have been found such as managing asthma, improving the immune system, inducing apoptosis in human renal fibroblasts, and inhibiting hyperglycemia. More effective in vitro and review studies are required to elucidate the exact role of this herb in medical applications.

read more

PMID:  Molecules. 2022 Nov 5 ;27(21). Epub 2022 Nov 5. PMID: 36364419 Abstract Title:  Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells. Abstract:  BACKGROUND: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of nutrients including proteins, lipids, fibers, and phenolic compounds and contain the aromatic cyanogenic glycoside amygdalin that has been shown to exert a cytotoxic effect on cancer cells by affecting the cell cycle, inducing apoptosis, and regulating the immune function.METHODS: Here, we describe a previously unexplored proapoptotic mechanism of action of amygdalin in breast cancer (MCF7) cells that involves the modulation of intracellular proteolysis. For comparative purposes, the same investigations were also conducted upon cell treatment with two apricot kernel aqueous extracts fromL.RESULTS: We observed that both the 20S and 26S proteasome activities were downregulated in the MCF7 cells upon 24 h treatments. Simultaneously, the autophagy cascade resulted in being impaired due to cathepsin B and L inhibition that also contributed to a reduction in cancer cell migration. The inhibition of these proteolytic systems finally promoted the activation of apoptotic events in the MCF7 cells.CONCLUSION: Collectively, our data unveil a novel mechanism of the anticancer activity of amygdalin, prompting further investigations for potential application in cancer preventative strategies.

read more

PMID:  Front Pharmacol. 2022 ;13:1013692. Epub 2022 Sep 20. PMID: 36204233 Abstract Title:  Amygdalin as a chemoprotective agent in co-treatment with cisplatin. Abstract:  Amygdalin is a naturally occurring glycoside used in traditional Chinese medicine and is known to have anti-cancer properties. Even though the anti-cancer properties of amygdalin are well known, its effect on normal cells has not been thoroughly investigated. The aim of the present study was to investigate a possible chemo-protective role of amygdalin against the cytotoxic effects of chemotherapy for normal human cells. Specifically, it was tested in combination with a strong chemotherapeutic drug cisplatin. Human non-tumorigenic MCF12F epithelial cell line, human fibroblasts cells, human breast cancer MCF7 and MDA-MB-231 cells were treated with cisplatin in a dose- and time-depended manner in the absence or presence of amygdalin. When MCF12F cells and fibroblasts underwent pre-treatment with amygdalin followed by cisplatin treatment (24 h amygdalin + 24 h cisplatin), the cell viability was increased (22%,

read more

PMID:  Cancers (Basel). 2022 Jun 24 ;14(13). Epub 2022 Jun 24. PMID: 35804883 Abstract Title:  Amygdalin Exerts Antitumor Activity in Taxane-Resistant Prostate Cancer Cells. Abstract:  Despite recent advances in the treatment of metastatic prostate cancer (PCa), resistance development after taxane treatments is inevitable, necessitating effective options to combat drug resistance. Previous studies indicated antitumoral properties of the natural compound amygdalin. However, whether amygdalin acts on drug-resistant tumor cells remains questionable. An in vitro study was performed to investigate the influence of amygdalin (10 mg/mL) on the growth of a panel of therapy-nave and docetaxel- or cabazitaxel-resistant PCa cell lines (PC3, DU145, and LNCaP cells). Tumor growth, proliferation, clonal growth, and cell cycle progression were investigated. The cell cycle regulating proteins (phospho)cdk1, (phospho)cdk2, cyclin A, cyclin B, p21, and p27 and the mammalian target of rapamycin (mTOR) pathway proteins (phospho)Akt, (phospho)Raptor, and (phospho)Rictor as well as integrin1 and the cytoskeletal proteins vimentin, ezrin, talin, and cytokeratin 8/18 were assessed. Furthermore, chemotactic activity and adhesion to extracellular matrix components were analyzed. Amygdalin dose-dependently inhibited tumor growth and reduced tumor clones in all (parental and resistant) PCa cell lines, accompanied by a G0/G1 phase accumulation. Cell cycle regulating proteins were significantly altered by amygdalin. A moderate influence of amygdalin on tumor cell adhesion and chemotaxis was observed as well, paralleled by modifications of cytoskeletal proteins and the integrin1 expression level. Amygdalin may, therefore, block tumor growth and disseminative characteristics of taxane-resistant PCa cells. Further studies are warranted to determine amygdalin's value as an antitumor drug.

read more

PMID:  Am J Chin Med. 2022 ;50(5):1361-1386. Epub 2022 Jun 8. PMID: 35681261 Abstract Title:  Amygdalin Induced Mitochondria-Mediated Apoptosis of Lung Cancer Cells via Regulating NF[Formula: see text]B-1/NF[Formula: see text]B Signaling Cascadeand. Abstract:  Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Amygdalin, a natural compound commonly distributed in plants of the Rosaceae species, owns anticancer activity, less side effects, wide source, and relatively low price. Although the apoptosis is a central process activated by amygdalin in cancer cells, the underlying molecular mechanisms through which amygdalin induces the apoptosis of lung cancer cells remain poorly understood. In this research work, amygdalin could suppress the proliferation of lung cancer A549 and PC9 cells by CCK8 assay. Amygdalin significantly promoted the apoptosis of lung cancer A549 and PC9 cells stained with Annexin V-FITC/PI by flow cytometry assay. Furthermore, amygdalin dose-dependently decreased the mitochondrial membrane potential (MMP) with JC-1 dye by flow cytometry. To investigate the underlying molecular mechanisms through which amygdalin induced mitochondria-mediated apoptosis of cancer cells, the differentially-expressed genes with a fold change>2.0 and

read more

PMID:  Sci Rep. 2022 Apr 20 ;12(1):6494. Epub 2022 Apr 20. PMID: 35444229 Abstract Title:  Amygdalin potentiates the anti-cancer effect of Sorafenib on Ehrlich ascites carcinoma and ameliorates the associated liver damage. Abstract:  The burden of cancer diseases is increasing every year, therefore, the demands to figure out novel drugs that can retain antitumor properties have been raised. This study aimed to investigate the anti-tumor properties of amygdalin (Amy) against Ehrlich ascites carcinoma (EAC) bearing mice and its protective properties against liver damage. Amy and the standard anticancer drug Sorafenib (Sor) were given alone or in combination to Swiss albino female mice that had been injected with EAC cells. Biochemical parameters of liver function (AST, ALT, GGT, total protein, albumin), tumor volume, oxidative stress [malondialdehyde, (MDA)] and antioxidative [superoxide dismutase (SOD), and reduced glutathione (GSH)] markers were measured. The hepatic expression of the antioxidant-related gene [nuclear factor erythroid-2-related factor 2 (Nrf2)], the migration-related gene [matrix metalloprotease 9 (MMP9)], and the angiogenesis-related gene [vascular endothelial growth factor (VEGF)] were evaluated by qPCR. The results revealed that EAC-bearing mice treated with Amy and/or Sor showed a decrease in the tumor burden and hepatic damage as evidenced by (1) decreased tumor volume, number of viable tumor cells; (2) increased number of dead tumor cells; (3) restored the liver function parameters; (4) reduced hepatic MDA levels; (5) enhanced hepatic GSH and SOD levels; (6) upregulated expression of Nrf2; (7) downregulated expression of MMP9 and VEGF, and (8) improved hepatic structure. Among all treatments, mice co-treated with Amy (orally) and Sor (intraperitoneally) showed the best effect. With these results, we concluded that the Amy improved the antitumor effect of Sor and had a protective role on liver damage induced by EAC in mice.

read more

PMID:  Biochem Biophys Res Commun. 2022 Apr 30 ;602:105-112. Epub 2022 Mar 3. PMID: 35259588 Abstract Title:  Amygdalin protects against acetaminophen-induced acute liver failure by reducing inflammatory response and inhibiting hepatocyte death. Abstract:  Amygdalin is a natural compound from Bitter Apricot Seed which is reported to have anti-inflammatory activity. Acetaminophen (APAP) resulted in drug-induced liver injury is the main cause of acute liver failure (ALI) worldwide and only N-acetylcysteine is the accepted detoxification drug. However, there is no effective medicine to perfect the hepatocyte death and secondary inflammation injury. In this study, we aim to investigate the protective effect of Amygdalin in the APAP-induced acute liver failure mice model. We establish the ALI model via intraperitoneal APAP injection and mice were treated with Amygdalin with intraperitoneal injection. We detected liver enzyme and histological change to evaluate the liver injury. We measured oxidative damage markers and inflammatory cell infiltration of liver tissues. At last, we investigated the mechanism of Amygdalin on protecting hepatocytes. Results showed that Amygdalin reduced ALT/AST level and decreased necrotic area of liver tissue. In addition, Amygdalin reduced the count of MPO+(neutrophils) and F4/80+(macrophages) of the liver and inhibited IL-6, TNF-a, and IL-1b expression. Amygdalin reduced liver SOD and MDA levels and increased Nrf2/NQO1/HO1 protein expression. Moreover, Amygdalin reduced TUNEL+ and P-MLKL + staining cells in liver tissue. Mechanically, Amygdalin promoted phosphorylation of AKT and suppressed JNK/RIP3/MLKL signaling.

read more

PMID:  Chin J Integr Med. 2023 Apr ;29(4):316-324. Epub 2021 Nov 24. PMID: 34816365 Abstract Title:  Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-/Smad Signaling. Abstract:  OBJECTIVE: To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro.METHODS: Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (-SMA), CD31 and transforming growth factor(TGF-)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10mol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed.RESULTS: High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I,-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P

read more

PMID:  Rev Bras Parasitol Vet. 2021 ;30(4):e012021. Epub 2021 Nov 1. PMID: 34730610 Abstract Title:  Punica granatum and amygdalin extracts plus cobalamin combined with albendazole reduce larval burden and myositis in experimental trichinosis. Abstract:  Trichinellosis is a zoonosis results from eating raw or semi-cooked meat of infected animals. Medicinal plants have been used lately as alternatives and/or combined therapies to resolve some drawbacks of the current regimens. This work analyzed the effect of albendazole monotherapy on Trichinella spiralis experimental infection (group A), in comparison to P. granatum and amygdalin extracts +cobalamin (group B), plus its combination with albendazole (group C). The study revealed that the extracts alone or combined with albendazole had an inferior effect to albendazole monotherapy regarding number of adult worms (40.833.82, 18.671.86 and 16.832.32, respectively). However, their effect was more obvious in muscle phase combined with albendazole, achieving the lower number of larvae/mL tissue homogenate (22.333.27 in comparison to 39.672.58 achieved by albendazole monotherapy). The extracts exerted a significant immunomodulatory effect by reducing the local CD4+ expression in the intestine as well as in muscle phase (1.150.25 and 3.800.65 in comparison to 4.970.37 and 12.200.87 with albendazole monotherapy, respectively). So, these extracts improved the therapeutic efficacy of albendazole, specifically in muscle phase and counteracted the inflammatory reaction caused by albendazole monotherapy, thus extensively alleviating the resulting myositis.

read more

PMID:  Life Sci. 2021 Nov 15 ;285:119961. Epub 2021 Sep 15. PMID: 34536497 Abstract Title:  In-vitro and in-vivo investigation of amygdalin, metformin, and combination of both against doxorubicin on hepatocellular carcinoma. Abstract:  AIM: Hepatocellular carcinoma (HCC) is a potentially life-threatening cancer. In the current study, anti-HCC efficacy of amygdalin, or metformin alone or in combination in comparison to doxorubicin was studied.MAIN METHODS: Both in-vitro and in-vivo based models. HepG-2 and Huh-7 cell lines as established in-vitro model for HCC were treated with different concentrations of indicated drugs to evaluate the cytotoxicity and determine ICfor 24, 48 and 72 h. Moreover, the effect of different treatments on apoptosis and cell cycle using flow cytometric analysis were studied. Hepatocellular carcinoma induced in rats by diethyl-nitrosamine and carbon tetrachloride was established, to further investigate the efficacy of indicated drugs. Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were measured by spectrophotometer, alpha-fetoprotein, cytochrome-c, caspase-3 and malondialdehyde were measured by ELISA, and liver biopsies were also evaluated histopathologically.KEY FINDINGS: In-vitro results showed that the combination has a promising effect when compared to amygdalin or metformin alone as it is more cytotoxic and have higher ability for induction of apoptosis and arresting cell cycle. In-vivo doxorubicin has a good effect for treating HCC. Also, the combination showed a promising prognostic effect depending on the cytotoxic activity and tumor marker when compared to amygdalin or metformin alone.SIGNIFICANCE: Based on the current data, it was hypothesized that amygdalin and metformin especially when used in combination will be a promising approach with low side effects for enhancement of HCC.

read more

PMID:  Environ Sci Pollut Res Int. 2023 Jan ;30(3):7415-7426. Epub 2022 Aug 30. PMID: 36040692 Abstract Title:  Increased risk of primary ovarian insufficiency by high-fructose diet consumption: a 90-day study in female rats. Abstract:  There is ambiguous evidence that high-fructose diet can induce toxicity in different organ systems but its endocrine disrupting effects by abnormal changes in female reproductive organs is poorly evidenced. This study aimed to address the reproductive safety of high fructose diet through clinical, biochemical, hormonal, histopathological, and immunohistochemical analysis. For this purpose, 5-6 weeks mature female Wistar rats were divided in three groups and each five animals/group exposed to standard chow+water+HFCS-55, standard chow+water+sucrose 75%w/v and standard chow+water for 90 days. Remarkable increase in most lipid profile factors and total body weights of HFCS-55 fed rats and sucrose fed rats were detected in similar pattern compared to control. At the same time, a battery of differential signs and symptoms in HFCS-fed groups including squamous metaplasia in the uterine tissue and ovarian congestion, significant increase in FSH and LH levels, meaningful decreased serum testosterone and 17-estradiol levels, and strong androgen receptor expression in ovaries and uterine of HFCS group of animals were recorded compared to other two study groups. These thought-provoking signs and signals of fructose induced reproductive toxicity in this model emphasis the contribution of HFCS-55 to deteriorated ovarian and endometrial health and increased risk primary ovarian insufficiency (POI) in women.

read more

PMID:  Int J Mol Sci. 2023 Feb 24 ;24(5). Epub 2023 Feb 24. PMID: 36901891 Abstract Title:  Effects of Maternal High-Fructose Diet on Long Non-Coding RNAs and Anxiety-like Behaviors in Offspring. Abstract:  Increased fructose intake is an international issue. A maternal high-fructose diet during gestation and lactation could affect nervous system development in offspring. Long non-coding RNA (lncRNA) plays an important role in brain biology. However, the mechanism whereby maternal high-fructose diets influence offspring brain development by affecting lncRNAs is still unclear. Here, we administered 13% and 40% fructose water to establish a maternal high-fructose diet model during gestation and lactation. To determine lncRNAs and their target genes, full-length RNA sequencing was performed using the Oxford Nanopore Technologies platform, and 882 lncRNAs were identified. Moreover, the 13% fructose group and the 40% fructose group had differentially expressed lncRNA genes compared with the control group. Enrichment analyses and co-expression analyses were performed to investigate the changes in biological function. Furthermore, enrichment analyses, behavioral science experiments, and molecular biology experiments all indicated that the fructose group offspring showed anxiety-like behaviors. In summary, this study provides insight into the molecular mechanisms underlying maternal high-fructose diet-induced lncRNA expression and co-expression of lncRNA and mRNA.

read more

PMID:  Int J Environ Res Public Health. 2023 Feb 17 ;20(4). Epub 2023 Feb 17. PMID: 36834291 Abstract Title:  High-Fructose Diet-Induced Hyperuricemia Accompanying Metabolic Syndrome-Mechanisms and Dietary Therapy Proposals. Abstract:  Fructose is often used as a food ingredient due to its low production costs and sweetening power. In recent years, it has been noticed that people on a Western diet high in fructose have high levels of uric acid in their blood. It was recognized that the specific metabolism of fructose in the body might cause increased production of uric acid, which then may affect the intensification of lipogenesis and the development of metabolic syndrome (MetS), insulin resistance, gout, cardiovascular diseases, leptin resistance, or non-alcoholic fatty liver disease. So far, to treat hyperuricemia, it has been recommended to use a low-purine diet characterized by limiting protein-containing products. However, this recommendation often leads to an increased intake of carbohydrate-rich foods that may contain fructose. Increased fructose consumption may enhance the secretion of uric acid again and, consequently, does not have therapeutic effects. Therefore, instead of a low-purine diet, using healthy diets, such as DASH or the Mediterranean diet, which can benefit metabolic parameters, could be a better proposal. This article provides an overview of this approach, focusing on MetS and hyperuricemia among high-fructose dieters.

read more

PMID:  Med Sci Sports Exerc. 2023 May 1 ;55(5):803-812. Epub 2022 Dec 9. PMID: 36729699 Abstract Title:  Exercise Training Prevents High Fructose-Induced Hypertension and Renal Damages in Male Dahl Salt-Sensitive Rats. Abstract:  INTRODUCTION: High-fructose diet (HFr) causes metabolic syndrome, and HFr-induced hypertension and renal damage are exaggerated in Dahl salt-sensitive (DS) rats. Exercise training (Ex) has antihypertensive and renal protective effects in rats fed HFr; however, there has been little discussion about the DS rats, which exhibit metabolic disturbances. This study thus examined the effects of Ex on DS rats fed HFr.METHODS: Male DS rats were divided into three groups. The control group was fed a control diet, and both the HFr group and the HFr-Ex group were fed an HFr (60% fructose). The HFr-Ex group also underwent treadmill running (20 mmin -1 , 60 mind -1 , 5 dwk -1 ). After 12 wk, renal function, histology, and renin-angiotensin system were examined.RESULTS: HFr increased blood pressure, urinary albumin, and creatinine clearance, and Ex inhibited these increases. HFr induced glomerular sclerosis, podocyte injury, afferent arteriole thickening, and renal interstitial fibrosis, and Ex ameliorated them. HFr reduced plasma renin activity, and Ex further reduced the activity. HFr also increased the expression of angiotensinogen, renin, angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor, and Ex restored the ACE expression to the control levels. HFr decreased the expression of ACE2, angiotensin II type 2 receptor, and Mas receptor, and Ex restored the ACE2 and Mas receptor expressions to the control levels and further decreased the angiotensin II type 2 receptor expression. HFr increased the ACE activity and decreased the ACE2 activity, and Ex restored these activities to the control levels.CONCLUSIONS: Ex prevents HFr-induced hypertension and renal damages in DS rats. The changes in renal renin-angiotensin system may be involved in the mechanism of the antihypertensive and renal protective effects of Ex.

read more

PMID:  Food Funct. 2023 Feb 6 ;14(3):1710-1725. Epub 2023 Feb 6. PMID: 36722874 Abstract Title:  Ferulic acid supplementation alleviates hyperuricemia in high-fructose/fat diet-fed ratspromoting uric acid excretion and mediating the gut microbiota. Abstract:  The prevalence of hyperuricemia (HUA) has been rising, and it is typically accompanied by renal injury and intestinal flora disorder, leading to a non-negligible health crisis. Ferulic acid (FA), as a familiar polyphenol, has been proven to exert anti-hyperuricemic propertiesinhibiting uric acid (UA) synthesis; however, the detailed underlying mechanisms remain unclear. The aim of this study was to explore the regulatory effect of FA on UA excretion as a potential strategy for reducing UA levels, and the comorbidities of HUA. FA treatment downregulated the expression of urate absorption transporter genes and repressed the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-B) pathway in UA-stimulated HK-2 cells. To examine these effects, FA or allopurinol (positive control) was given to rats with HUA induced by a high-fructose/fat diet (HFFD) for 20 weeks. FA markedly decreased the serum UA, blood urea nitrogen, and creatinine levels. The expression of urate absorption transporters was downregulated, whereas the expression of secretion transporters was upregulated in the kidneys and intestines of FA-treated HUA rats. Additionally, FA mitigated renal oxidative stress, and suppressed the activation of the TLR4/NF-B pathway and the downstream inflammatory response-related markers in the kidneys. Moreover, FA remodeled the composition of the gut microbiota, characterized by an increase in beneficial bacteria (,and) and a decrease in pathogenic bacteria (,). In conclusion, our study validated FA as an effective nutrient to ameliorate HFFD-induced HUA, suggesting its potential to mitigate the HUA-associated renal impairment and intestinal microbiota disturbance.

read more

PMID:  J Agric Food Chem. 2023 Jan 25 ;71(3):1562-1576. Epub 2023 Jan 11. PMID: 36630317 Abstract Title:  Sesamolin Attenuates Kidney Injury, Intestinal Barrier Dysfunction, and Gut Microbiota Imbalance in High-Fat and High-Fructose Diet-Fed Mice. Abstract:  This study investigated the effects of sesamolin on kidney injury, intestinal barrier dysfunction, and gut microbiota imbalance in high-fat and high-fructose (HF-HF) diet-fed mice and explored the underlying correlations among them. The results indicated that sesamolin suppressed metabolic disorders and increased renal function parameters. Histological evaluation showed that sesamolin mitigated renal epithelial cell degeneration and brush border damage. Meanwhile, sesamolin inhibited the endotoxin-mediated induction of the Toll-like receptor 4-related IKK/NF-B p65 pathway activation. Additionally, sesamolin mitigated intestinal barrier dysfunction and improved the composition of gut microbiota. The correlation results further indicated that changes in the dominant phyla, including,,, and, were more highly correlated with a reduction in endotoxemia and metabolic disorders, as well as decreases in intestinal proinflammatory response and related renal risk biomarkers. The results of this study suggest that sesamolin attenuates kidney injuries, which might be associated with its effects on the reduction of endotoxemia and related metabolic disorders through the restoration of the intestinal barrier and the modulation of gut microbiota. Thus, sesamolin may be a potential dietary supplement for protection against obesity-associated kidney injury.

read more

PMID:  J Nutr Biochem. 2023 May ;115:109278. Epub 2023 Feb 3. PMID: 36739097 Abstract Title:  Sesamol promotes browning of white adipocytes through liver-adipose crosstalk signal of hepatic fibroblast growth factor 21. Abstract:  Sesamol (SEM), a lignan from sesame oil, exhibited potential benefits on obesity treatment by promoting browning of adipocytes, and the current study is aimed to explore the molecular mechanisms of SEM from the aspect of systemic liver-adipose crosstalk that mediated by hepatic fibroblast growth factor 21 (FGF21). Our in vivo data showed that SEM induced energy expenditure and white adipose tissue (WAT) browning by increasing the expression level of uncoupling protein-1 in high fat diet induced obese C57BL/6J mice. Elevated levels of circulating FGF21 associated with the increased expression of hepatic FGF21 were observed after SEM intervention. Simultaneously, the increased adipose fibroblast growth factor tyrosine kinase receptor 1/beta-klotho indicated that FGF21 sensitivity was enhanced by SEM in WAT. Furthermore, our in vitro results from HepG2 and 3T3-L1 cell lines confirmed the effects and revealed the mechanism of SEM on the white adipocytes browning. We found that with the specific inhibitors of PPAR, the SEM-mediated hepatic FGF21 expression was decreased, and with the specific inhibitors of PPAR, the browning effect of adipocytes by SEM combining with FGF21 was significantly suppressed. Taken together, the mechanism of SEM for inducing the WAT browning might be the modulation of SEM on liver-adipose crosstalk mediated by FGF21, and the PPARs family might be the targets of SEM. The novel findings from the present study provided evidence that SEM could be a potent obesity-treating compound.

read more

PMID:  Metab Brain Dis. 2023 Jun ;38(5):1503-1511. Epub 2023 Feb 27. PMID: 36847969 Abstract Title:  Effects of sesamin on A-induced oxidative stress and LTP impairment in a rat model of Alzheimer's disease. Abstract:  The present study examined the protective effect of sesamin (Ses) on-amyloid (A)-induced long-term potentiation (LTP) impairment at the PP-DG synapses in male rats. Wistar rats were randomly assigned to seven groups: control, sham, A; ICV Amicroinjection, Ses, A+Ses; first, ICV Ainjections and then receiving Ses, Ses+A: four weeks of pretreatment with Ses and then Ainjection, and Ses+A+Ses: pre (four weeks) and post (four weeks) treatment with Ses. Ses-treated groups received 30 mg/kg of Ses once a day by oral gavage for four weeks. After the treatment period, the animals were positioned in a stereotaxic device for surgery and field potential recording. The population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were evaluated in the DG region. Serum oxidative stress biomarkers (total oxidant status (TOS) and total antioxidant capacity (TAC)) were measured. Aimpaired LTP induction at the PP-DG synapses evidenced by a decrease in EPSP slope and PS amplitude of LTP. In Arats, Ses increased EPSP slope and PS amplitude of LTP in the DG granular cells. Also, an increase in TOS and a reduction in TAC caused by Awere significantly corrected by Ses. Ses could prevent A-induced LTP impairment at the PP-DG synapses in male rats, which can be due to its preventive effects on oxidative stress.

read more

PMID:  Br J Pharmacol. 2023 Mar 13. Epub 2023 Mar 13. PMID: 36914615 Abstract Title:  Honokiol, an inducer of sirtuin-3, protects against non-steroidal anti-inflammatory drug-induced gastric mucosal mitochondrial pathology, apoptosis and inflammatory tissue injury. Abstract:  BACKGROUND AND PURPOSE: Mitochondrial oxidative stress, inflammation and apoptosis primarily underlie gastric mucosal injury caused by the widely used non-steroidal anti-inflammatory drugs (NSAIDs). Alternative gastroprotective strategies are therefore needed. Sirtuin-3 pivotally maintains mitochondrial structural integrity and metabolism while preventing oxidative stress; however, its relevance to gastric injury was never explored. Here, we have investigated whether and how sirtuin-3 stimulation by the phytochemical, honokiol, could rescue NSAID-induced gastric injury.EXPERIMENTAL APPROACH: Gastric injury in rats induced by indomethacin was used to assess the effects of honokiol. Next-generation sequencing-based transcriptomics followed by functional validation identified the gastroprotective function of sirtuin-3. Flow cytometry, immunoblotting, qRT-PCR and immunohistochemistry were used measure effects on oxidative stress, mitochondrial dynamics, electron transport chain function, and markers of inflammation and apoptosis. Sirtuin-3 deacetylase activity was also estimated and gastric luminal pH was measured.KEY RESULTS: Indomethacin down-regulated sirtuin-3 to induce oxidative stress, mitochondrial hyperacetylation, 8-oxoguanine DNA glycosylase 1 depletion, mitochondrial DNA damage, respiratory chain defect and mitochondrial fragmentation leading to severe mucosal injury. Indomethacin dose-dependently inhibited sirtuin-3 deacetylase activity. Honokiol prevented mitochondrial oxidative damage and inflammatory tissue injury by attenuating indomethacin-induced depletion of both sirtuin-3 and its transcriptional regulators PGC1and ERR. Honokiol also accelerated gastric wound healing but did not alter gastric acid secretion, unlike lansoprazole.CONCLUSIONS AND IMPLICATIONS: Sirtuin-3 stimulation by honokiol prevented and reversed NSAID-induced gastric injury through maintaining mitochondrial integrity. Honokiol did not affect gastric acid secretion. Sirtuin-3 stimulation by honokiol may be utilized as a mitochondria-based, acid-independent novel gastroprotective strategy against NSAIDs.

read more

PMID:  Biomed Pharmacother. 2023 May ;161:114473. Epub 2023 Mar 6. PMID: 36889111 Abstract Title:  Magnolol improves Alzheimer's disease-like pathologies and cognitive decline by promoting autophagy through activation of the AMPK/mTOR/ULK1 pathway. Abstract:  Alzheimer's disease (AD) is the most common neurodegenerative disease. Amyloid-(A) plaque deposition and apoptosis are main pathological features of AD. Autophagy plays an important role in clearing abnormal protein accumulation and inhibiting apoptosis; however, autophagy defects often occur from the early stages of AD. The serine/threonine AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/unc-51-like kinase 1/2 (ULK1/2) pathway serves as an energy sensor and is involved in autophagy activation. Furthermore, magnolol is an autophagy regulator, and has potential for AD therapy. We propose that magnolol can ameliorate AD pathologies and inhibit apoptosis by regulating autophagy through the AMPK/mTOR/ULK1 pathway. We examined cognitive function and AD-related pathologies in AD transgenic mice and the protective mechanism of magnolol by western blotting, flow cytometry, and a tandem mRFP-GFP-LC3 adenovirus assay in Aoligomer (AO)-induced N2a and BV2 cell models. In our study, magnolol decreased amyloid pathology and ameliorated cognitive impairment in APP/PS1 mice. Moreover, magnolol inhibited apoptosis by downregulating cleaved-caspase-9 and Bax and upregulating Bcl-2 in APP/PS1 mice and AO-induced cell models. Magnolol promoted autophagy by degrading p62/SQSTM1, and upregulating LC3II and Beclin-1 expression. Magnolol activated the AMPK/mTOR/ULK1 pathway by increasing phosphorylation of AMPK and ULK1 and decreasing mTOR phosphorylation in in vivo and in vitro AD models. AMPK inhibitor weakened the effects of magnolol in promoting autophagy and inhibiting apoptosis, and ULK1 knockdown weakened the effect of magnolol on AO-induced apoptosis. These results indicate that magnolol inhibits apoptosis and improves AD-related pathologies by promoting autophagy through activation of the AMPK/mTOR/ULK1 pathway.

read more

PMID:  Medicina (Kaunas). 2023 Feb 1 ;59(2). Epub 2023 Feb 1. PMID: 36837487 Abstract Title:  Evaluating the Magnolol Anticancer Potential in MKN-45 Gastric Cancer Cells. Abstract:  Combination therapy improves the effect of chemotherapy on tumor cells. Magnolol, used in treating gastrointestinal disorders, has been shown to have anti-cancer properties. We investigated the synergistic effect of cisplatin and magnolol on the viability and maintenance of MKN-45 gastric cancer cells.The toxicity of magnolol and/or cisplatin was determined using the MTT technique. The trypan blue method was used to test magnolol and/or cisplatin's effect on MKN-45 cell growth. Crystal violet staining was used to assess the treated cells' tendency for colony formation. The expression of genes linked to apoptosis, cell cycle arrest, and cell migration was examined using the qPCR method.According to MTT data, using magnolol and/or cisplatin significantly reduced cell viability. The ability of the treated cells to proliferate and form colonies was also reduced considerably. Magnolol and/or cisplatin treatment resulted in a considerable elevation inexpression. However, the level ofexpression was dramatically reduced.andexpression levels were significantly increased in the treated cells, whileexpression was significantly reduced.These findings show that magnolol has a remarkable anti-tumor effect on MKN-45 cells. In combination with cisplatin, magnolol may be utilized to overcome cisplatin resistance in gastric cancer cells.

read more

PMID:  Exp Cell Res. 2023 Mar 1 ;424(1):113488. Epub 2023 Feb 1. PMID: 36736226 Abstract Title:  Magnolol induces cytotoxic autophagy in glioma by inhibiting PI3K/AKT/mTOR signaling. Abstract:  Glioma is difficult-to-treat because of its infiltrative nature and the presence of the blood-brain barrier. Temozolomide is the only FDA-approved drug for its management. Therefore, finding a novel chemotherapeutic agent for glioma is of utmost importance. Magnolol, a neolignan, has been known for its apoptotic role in glioma. In this work, we have explored a novel anti-glioma mechanism of Magnolol associated with its role in autophagy modulation. We found increased expression levels of Beclin-1, Atg5-Atg12, and LC3-II and lower p62 expression in Magnolol-treated glioma cells. PI3K/AKT/mTOR pathway proteins were also downregulated in Magnolol-treated glioma cells. Next, we treated the glioma cells with Insulin, a stimulator of PI3K/AKT/mTOR signaling, to confirm that Magnolol induced autophagy by inhibiting this pathway. Insulin reversed the effect on Magnolol-mediated autophagy induction. We also established the same in in vivo glioma model where Magnolol showed an anti-glioma effect by inducing autophagy. To confirm the cytotoxic effect of Magnolol-induced autophagy, we used Chloroquine, a late-stage autophagy inhibitor. Chloroquine efficiently reversed the anti-glioma effects of Magnolol both in vitro and in vivo. Our study revealed the cytotoxic effect of Magnolol-induced autophagy in glioma, which was not previously reported. Additionally, Magnolol showed no toxicity in non-cancerous cell lines as well as rat organs. Thus, we concluded that Magnolol is an excellent candidate for developing new therapeutic strategies for glioma management.

read more

PMID:  Metabolites. 2023 Jan 4 ;13(1). Epub 2023 Jan 4. PMID: 36677009 Abstract Title:  Magnolol as a Protective Antioxidant Alleviates Rotenone-Induced Oxidative Stress and Liver Damage through MAPK/mTOR/Nrf2 in Broilers. Abstract:  This study aimed to investigate the protective effects and molecular mechanism of magnolol supplementation on rotenone-induced oxidative stress in broilers. Two hundred and eighty-eight old male AA broilers were randomly divided into four groups: the CON group: basic diet with sunflower oil injection; the ROT group: basic diet with 24 mg/kg BW rotenone; the MAG + ROT group: basic diet with 300 mg/kg magnolol and rotenone injection; and the MAG group: basic diet with 300 mg/kg magnolol and sunflower oil injection. At 2127 days of age, the broilers in each group were intraperitoneally injected with rotenone (24 mg/kg BW) or the same volume of sunflower oil. The results showed that magnolol reversed the decrease in ADG post-injection and FBW via rotenone induction. Compared to the ROT group, MAG + ROT group enhanced the average daily gain post injection (p

read more

PMID:  Phytomedicine. 2023 Feb ;110:154597. Epub 2022 Dec 12. PMID: 36603340 Abstract Title:  Magnolol regulates miR-200c-3p to inhibit epithelial-mesenchymal transition and retinoblastoma progression by modulating the ZEB1/E-cadherin axis in vitro and in vivo. Abstract:  BACKGROUND: Retinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3-4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear.PURPOSE: The study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro.METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin,-catenin,-smooth muscle actin (-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo.RESULTS: Magnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma.CONCLUSION: Magnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and ca...

PMID:  Molecules. 2022 Sep 29 ;27(19). Epub 2022 Sep 29. PMID: 36234977 Abstract Title:  Magnolol as a Potential Anticancer Agent: A Proposed Mechanistic Insight. Abstract:  Cancer is a serious disease with high mortality and morbidity worldwide. Natural products have served as a major source for developing new anticancer drugs during recent decades. Magnolol, a representative natural phenolic lignan isolated from, has attracted considerable attention for its anticancer properties in recent years. Accumulating preclinical studies have demonstrated the tremendous therapeutic potential of magnolol via a wide range of pharmacological mechanisms against cancer. In this review, we summarized the latest advances in preclinical studies investigating anticancer properties of magnolol and described the important signaling pathways explaining its underlying mechanisms. Magnolol was capable of inhibiting cancer growth and metastasis against various cancer types. Magnolol exerted anticancer effects through inhibiting proliferation, inducing cell cycle arrest, provoking apoptosis, restraining migration and invasion, and suppressing angiogenesis. Multiple signaling pathways were also involved in the pharmacological actions of magnolol against cancer, such as PI3K/Akt/mTOR signaling, MAPK signaling and NF-B signaling. Based on this existing evidence summarized in the review, we have conclusively confirmed magnolol had a multi-target anticancer effect against heterogeneous cancer disease. It is promising to develop magnolol as a drug candidate for cancer therapy in the future.

read more

PMID:  Antioxidants (Basel). 2022 Dec 29 ;12(1). Epub 2022 Dec 29. PMID: 36670934 Abstract Title:  Bromelain Ameliorates Atherosclerosis by Activating the TFEB-Mediated Autophagy and Antioxidant Pathways. Abstract:  Bromelain, a cysteine protease found in pineapple, has beneficial effects in the treatment of inflammatory diseases; however, its effects in cardiovascular pathophysiology are not fully understood. We investigated the effect of bromelain on atherosclerosis and its regulatory mechanisms in hyperlipidemia and atheroprone apolipoprotein E-null () mice. Bromelain was orally administered to 16-week-old malemice for four weeks. Daily bromelain administration decreased hyperlipidemia and aortic inflammation, leading to atherosclerosis retardation inmice. Moreover, hepatic lipid accumulation was decreased by the promotion of cholesteryl ester hydrolysis and autophagy through the AMP-activated protein kinase (AMPK)/transcription factor EB (TFEB)-mediated upregulation of autophagy- and antioxidant-related proteins. Moreover, bromelain decreased oxidative stress by increasing the antioxidant capacity and protein expression of antioxidant proteins while downregulating the protein expression of NADPH oxidases and decreasing the production of reactive oxygen species. Therefore, AMPK/TFEB signaling may be crucial in bromelain-mediated anti-hyperlipidemia, antioxidant, and anti-inflammatory effects, effecting the amelioration of atherosclerosis.

read more

PMID:  Biomed Pharmacother. 2023 May ;161:114461. Epub 2023 Mar 6. PMID: 36889109 Abstract Title:  Diosmin mitigates dexamethasone-induced osteoporosis in vivo: Role of Runx2, RANKL/OPG, and oxidative stress. Abstract:  Secondary osteoporosis is commonly caused by long-term intake of glucocorticoids (GCs), such as dexamethasone (DEX). Diosmin, a natural substance with potent antioxidant and anti-inflammatory properties, is clinically used for treating some vascular disorders. The current work targeted exploring the protective properties of diosmin to counteract DEX-induced osteoporosis in vivo. Rats were administered DEX (7 mg/kg) once weekly for 5 weeks, and in the second week, vehicle or diosmin (50 or 100 mg/kg/day) for the next four weeks. Femur bone tissues were collected and processed for histological and biochemical examinations. The study findings showed that diosmin alleviated the histological bone impairments caused by DEX. In addition, diosmin upregulated the expression of Runt-related transcription factor 2 (Runx2) and phosphorylated protein kinase B (p-AKT) and the mRNA transcripts of Wingless (Wnt) and osteocalcin. Furthermore, diosmin counteracted the rise in the mRNA levels of receptor activator of nuclear factor-kB ligand (RANKL) and the reduction in osteoprotegerin (OPG), both were induced by DEX. Diosmin restored the oxidant/antioxidant equilibrium and exerted significant antiapoptotic activity. The aforementioned effects were more pronounced at the dose level of 100 mg/kg. Collectively, diosmin has proven to protect rats against DEX-induced osteoporosis by augmenting osteoblast and bone development while hindering osteoclast and bone resorption. Our findings could be used as a stand for recommending supplementation of diosmin for patients chronically using GCs.

read more

PMID:  J Biol Chem. 2023 Apr ;299(4):103059. Epub 2023 Feb 24. PMID: 36841479 Abstract Title:  Selective PPARmodulator diosmin improves insulin sensitivity and promotes browning of white fat. Abstract:  Peroxisome proliferator-activated receptor(PPAR) is a master regulator of adipocyte differentiation, glucolipid metabolism, and inflammation. Thiazolidinediones are PPARfull agonists with potent insulin-sensitizing effects, whereas their oral usage is restricted because of unwanted side effects, including obesity and cardiovascular risks. Here, via virtual screening, microscale thermophoresis analysis, and molecular confirmation, we demonstrate that diosmin, a natural compound of wide and long-term clinical use, is a selective PPARmodulator that binds to PPARand blocks PPARphosphorylation with weak transcriptional activity. Local diosmin administration in subcutaneous fat (inguinal white adipose tissue [iWAT]) improved insulin sensitivity and attenuated obesity via enhancing browning of white fat and energy expenditure. Besides, diosmin ameliorated inflammation in WAT and liver and reduced hepatic steatosis. Of note, we determined that iWAT local administration of diosmin did not exhibit obvious side effects. Taken together, the present study demonstrated that iWAT local delivery of diosmin protected mice from diet-induced insulin resistance, obesity, and fatty liver by blocking PPARphosphorylation, without apparent side effects, making it a potential therapeutic agent for the treatment of metabolic diseases.

read more

PMID:  Biol Trace Elem Res. 2023 Mar 6. Epub 2023 Mar 6. PMID: 36877398 Abstract Title:  Appraisal of the Pre-Emptive Effect of Lactoferrin Against Chromium-Induced Testicular Toxicity in Male Rats. Abstract:  Lactoferrin (LCF), a potent naturally occurring antioxidant, is a crucial component in preventing potassium dichromate (PDC) toxicity. The goal of the current work was to study the potential efficacy of LCF in preventing PDC(CrVI)-induced testicular toxicity and oxidative injury in rats. Six groups of male rats of Wistar stain were randomly categorized into: group 1, which served as the control; group 2 and 3 received LCF (200 and 300 mg/kg orally, respectively); group 4 received PDC (2 mg/kg i.p.); group 5 and 6 pretreated with LCF, followed by PDC as in group 4 with 90 min apart for 28 days. PDC-intoxicated rats showed a significantly altered spermogram with abnormal sperm morphology. PDC significantly upregulated serum FSH and downregulated testosterone levels. Additionally, PDC decreased the levels of testicular key antioxidant biomarkers (catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH)) with elevated lipid peroxidation marker (TBARS) and testicular chromium content. Moreover, it upregulated testicular proinflammatory cytokines, IL-1, IL-6, IL-10, and TNF-, induced histopathological changes in testes with significant immunohistochemical expression of FasL and moderate expression of Nrf2. Pretreatment with LCF significantly mitigated PDC-induced testicular toxicity by enhancing spermogram, improving hormonal levels, restoring testicular oxidant/antioxidant balance, and decreasing testicular IL-1, IL6, IL-10, and TNFlevels, and amending both FasL and Nrf2 immunohistochemical-expression. Additionally, LCF improved testicular histopathological picture and spermatogenesis. Our results highlight the importance of LCF as a superior protective modulator of PDC-induced testicular injury.

read more

PMID:  J Transl Med. 2023 Feb 28 ;21(1):156. Epub 2023 Feb 28. PMID: 36855062 Abstract Title:  Lactoferrin suppresses the progression of colon cancer under hyperglycemia by targeting WTAP/mA/NT5DC3/HKDC1 axis. Abstract:  BACKGROUND: Although the relationship between type 2 diabetes (T2D) and the increased risk of colorectal carcinogenesis is widely defined in clinical studies, the therapeutic methods and molecular mechanism of T2D-induced colon cancer and how does hyperglycemia affect the progression is still unknown. Here, we studied the function of lactoferrin (LF) in suppressing the progression of colon cancer in T2D mice, and uncovered the related molecular mechanisms in DNA 5mC and RNA m6A levels.METHODS: We examined the effects of LF (50% iron saturation) on the migration and invasion of colon tumor cells under high concentration of glucose. Then, transcriptomics and DNA methylation profilings of colon tumor cells was co-analyzed to screen out the special gene (NT5DC3), and the expression level of NT5DC3 in 75 clinical blood samples was detected by q-PCR and western blot, to investigate whether NT5DC3 was a biomarker to distinguish T2D patients and T2D-induced colon cancer patients from healthy volunteers. Futhermore, in T2D mouse with xenografted colon tumor models, the inhibitory effects of LF and NT5DC3 protein on colon tumors were investigated. In addition, epigenetic alterations were measured to examine the 5mC/mA modification sites of NT5DC3 regulated by LF. Utilizing siRNA fragments of eight mA-related genes, the special gene (WTAP) regulating mA of NT5DC was proved, and the effect of LF on WTAP/NT5DC3/HKDC1 axis was finally evaluated.RESULTS: A special gene NT5DC3 was screened out through co-analysis of transcriptomics and DNA methylation profiling, and HKDC1 might be a downstream sensor of NT5DC3. Mechanistically, LF-dependent cellular DNA 5mC and RNA mA profiling remodeling transcriptionally regulate NT5DC3 expression. WTAP plays a key role in regulating NT5DC3 mA modification and subsequently controls NT5DC3 downstream target HKDC1 expression. Moreover, co-treatment of lactoferrin and NT5DC3 protein restrains the growth of colon tumors by altering the aberrant epigenetic markers. Strikingly, clinical blood samples analysis demonstrates NT5DC3 protein expression is required to direct the distinction of T2D or T2D-induced colon cancer with healthy humans.CONCLUSIONS: Together, this study reveals that lactoferrin acts as a major factor to repress the progression of colon cancer under hyperglycemia, thus, significantly expanding the landscape of natural dietary mediated tumor suppression.

read more

PMID:  Pharmaceutics. 2023 Feb 7 ;15(2). Epub 2023 Feb 7. PMID: 36839884 Abstract Title:  Molecular Mechanisms of Inhibitory Effects of Bovine Lactoferrin on Invasion of Oral Squamous Cell Carcinoma. Abstract:  Lactoferrin (LF), an iron-binding glycoprotein, has been reported to have anticancer properties. However, the molecular mechanisms behind its anticancer effects on oral squamous cell carcinoma (OSCC) have not yet been elucidated. Therefore, we aimed to clarify the effects of LF on invasion of OSCC, and its underlying molecular mechanism. OSCC cell lines, HSC2 and HOC313, were treated with bovine LF (bLF). The effects of bLF on cell invasion were examined by a chamber migration assay, wound healing assay, and Boyden chamber method with a basement-membrane-analogue. Expression levels of MMP-1, MMP-3, and AP-1 were examined using RT-PCR, qRT-PCR, and western blotting. Roles of LRP1, a receptor of bLF, on cell invasion were analyzed using siLRP1 knockdown cells. Furthermore, to clarify the importance of LRP1 in invasion, the effects of bLF on tPA-induced invasion of OSCC cells were examined. The invasion assays showed that bLF suppressed invasion of the OSCC cells. Moreover, bLF down-regulated AP-1, and resulted in reductions of MMP-1 and MMP-3. With SiLRP1 knockdown, OSCC cells failed to induce their invasion, and bLF was not able to exert its effects on invasion. Furthermore, bLF remarkably inhibited tPA-induced cell invasion. These findings suggest the importance of LRP1 in bLF-suppressed invasion of OSCC cells via the reduction of AP-1 and MMP production.

read more

PMID:  Life Sci. 2023 Apr 15 ;319:121528. Epub 2023 Feb 23. PMID: 36828132 Abstract Title:  Lactoferrin alleviates cyclophosphamide induced-nephropathy through suppressing the orchestration between Wnt4/-catenin and ERK1/2/NF-B signaling and modulating klotho and Nrf2/HO-1 pathway. Abstract:  AIMS: Cyclophosphamide is an alkylating agent with vast arrays of therapeutic activity. Currently, its medical use is limited due to its numerous adverse events, including nephrotoxicity. This study aimed to follow the molecular mechanisms behind the potential renoprotective action of lactoferrin (LF) against cyclophosphamide (CP)-induced renal injury.MATERIALS AND METHODS: For fulfillment of our aim, Spragw-Dwaly rats were orally administrated LF (300 mg/kg) for seven consecutive days, followed by a single intraperitoneal injection of CP (150 mg/kg).KEY FINDINGS: Treatment of CP-injured rats with LF significantly reduced the elevated creatinine and blood urea nitrogen (BUN), markedly upregulated Nrf2/HO-1 signaling with consequent increase in renal total antioxidant capacity (TAC) and decrease in renal malondialdehyde (MDA) level. Furthermore, LF treatment significantly reduced the elevated renal p-ERK1/2 expression, tumor necrosis factor-(TNF), interleukin-6 (IL-6), nuclear factor-kappa B (NF-B) levels in CP-treated animals. Interestingly, LF treatment downregulated Wnt4/-catenin signaling and increased both renal klotho gene expression and serum klotho level. Furthermore, LF treatment reduced apoptosis in kidney tissue via suppressing GSK-3expression and modulating caspase-3 and Bcl2 levels. Histopathological examination of kidney tissue confirmed the protective effect of LF against CP-induced renal injury.SIGNIFICANCE: The present findings document the renoprotective effect of LF against CP-induced nephropathy, which may be mediated via suppressing ERK1/2/ NF-B and Wnt4/-catenin trajectories and enhancing klotho expression and Nrf2/HO-1 signaling.

read more

PMID:  J Nutr. 2022 Nov ;152(11):2451-2460. Epub 2022 Sep 2. PMID: 36774111 Abstract Title:  Lactoferrin Attenuates Intestinal Barrier Dysfunction and Inflammation by Modulating the MAPK Pathway and Gut Microbes in Mice. Abstract:  BACKGROUND: Deoxynivalenol (DON) is a major mycotoxin present in staple foods (particularly in cereal products) that induces intestinal inflammation and disrupts intestinal integrity. Lactoferrin (LF) is a multifunctional protein that contributes to maintaining intestinal homeostasis and improving host health. However, the protective effects of LF on DON-induced intestinal dysfunction remain unclear.OBJECTIVES: This study aimed to investigate the effects of LF on DON-induced intestinal dysfunction in mice, and its underlying protective mechanism.METHODS: Male BALB/c mice (5 wk old) with similar body weights were divided into 4 groups (n = 6/group) and treated as follows for 5 wk: Veh [peroral vehicle daily, commercial (C) diet]; LF (peroral 10 mg LF/d, C diet); DON (Veh, C diet containing 12 mg DON/kg); and LF + DON (peroral 10 mg LF/d, DON diet). Intestinal morphology, tight junction proteins, cytokines, and microbial community were determined. Data were analyzed by 2-factor ANOVA or Kruskal-Wallis test.RESULTS: The DON group exhibited lower final body weight (-12%), jejunal villus height (VH; -41%), and jejunal occludin expression (-36%), and higher plasma IL-1concentration (+85%) and jejunal Il1b mRNA expression (+98%) compared with the Veh group (P

read more

PMID:  Nutr Metab Cardiovasc Dis. 2023 Feb ;33(2):359-368. Epub 2022 Nov 3. PMID: 36577637 Abstract Title:  Habitual intakes of sugar-sweetened beverages associated with gut microbiota-related metabolites and metabolic health outcomes in young Chinese adults. Abstract:  BACKGROUND AND AIMS: Reducing consumption of sugar-sweetened beverages (SSBs) is a global public health priority because of their limited nutritional value and associations with increased risk of obesity and metabolic diseases. Gut microbiota-related metabolites emerged as quintessential effectors that may mediate impacts of dietary exposures on the modulation of host commensal microbiome and physiological status.METHODS AND RESULTS: This study assessed the associations among SSBs, circulating microbial metabolites, and gut microbiota-host co-metabolites, as well as metabolic health outcomes in young Chinese adults (n = 86), from the Carbohydrate Alternatives and Metabolic Phenotypes study in Shaanxi Province. Five principal component analysis-derived beverage drinking patterns were determined on self-reported SSB intakes, which were to a varying degree associated with 143 plasma levels of gut microbiota-related metabolites profiled by untargeted metabolomics. Moreover, carbonated beverages, fruit juice, energy drinks, and bubble tea exhibited positive associations with obesity-related markers and blood lipids, which were further validated in an independent cohort of 16,851 participants from the Regional Ethnic Cohort Study in Northwest China in Shaanxi Province. In contrast, presweetened coffee was negatively associated with the obesity-related traits. A total of 79 metabolites were associated with both SSBs and metabolic markers, particularly obesity markers. Pathway enrichment analysis identified the branched-chain amino acid catabolism and aminoacyl-tRNA biosynthesis as linking SSB intake with metabolic health outcomes.CONCLUSION: Our findings demonstrate the associations between habitual intakes of SSBs and several metabolic markers relevant to noncommunicable diseases, and highlight the critical involvement of gut microbiota-related metabolites in mediating such associations.

read more

PMID:  Sleep Health. 2023 Apr ;9(2):159-176. Epub 2022 Nov 22. PMID: 36424247 Abstract Title:  Association between short sleep duration and intake of sugar and sugar-sweetened beverages: A systematic review and meta-analysis of observational studies. Abstract:  BACKGROUND: Findings of previous investigations that evaluated the relationship between sleep duration and sugar or sugar-sweetened beverages (SSBs) intake have been inconsistent. We aimed to summarize extant research that assessed the relation between short sleep duration and sugar and SSB intake.METHODS: A comprehensive search of PubMed, ISI Web of Sciences, Scopus, Science Direct, Embase, and Google Scholar was conducted. All observational studies that reported sleep duration as the exposure and intake of sugar or sugary drinks as the outcome were included. The quality of included studies was evaluated using the Newcastle-Ottawa Scale. The body of evidence was assessed using the GRADE approach. Random and fixed effects models were used to estimate pooled OR and 95% confidence intervals.RESULTS: Twenty-two studies in children and twelve in adults were included in the systematic review. Only 10 studies in children and 3 investigations in adults provided odds ratios (95% confidence intervals) for this association and could be included in the meta-analysis. All studies had a cross-sectional design and found a negative association between sleep duration and sugar in children, but not in adults. SSB intake was lower in those with sufficient sleep in all populations. Compared with those with sufficient sleep, children with short sleep duration had 16% (significant) higher odds of consuming sugar (OR: 1.16; 95% CI: 1.10, 1.21), 21% higher odds of soda intake (OR: 1.21; 95% CI: 1.16, 1.26), and 92% higher odds of consuming energy drink intake (OR: 1.92; 95% CI: 1.66, 2.22). However, sleep duration was not significantly associated with soft drink intake in children (OR: 1.17; 95% CI: 0.93, 1.48). In adults, the odds of drinking soda in those with short sleep duration was 1.2 times more than in those with sufficient sleep (OR: 1.20; 95% CI: 1.12, 1.28). Also, low vs. optimal sleep duration in adults was associated with a 58% increased intake of energy drinks (OR: 1.58; 95% CI: 1.31, 1.90). Of note, these findings in the adult population resulted from only 2 included investigations, due to the limited number of studies.CONCLUSION: The evidence reviewed supports a significant association between shorter sleep duration and higher SSBs intake in both children and adults, while such association with higher total sugar intake was significant in children but not in adults. Further research with more accurate measurements, sex-specific, and prospective designs should be carried out to clarify the causality and underlying mechanisms....

PMID:  J Ethnopharmacol. 2023 Jun 28 ;310:116376. Epub 2023 Mar 12. PMID: 36918050 Abstract Title:  Loquat fruit peel extract regulates lipid metabolism and liver oxidative stress in mice: In vivo and in silico approaches. Abstract:  ETHNOPHARMACOLOGICAL RELEVANCE: In Moroccan traditional medicine, fresh or dried loquat (Eriobotrya japonica (Thunb.) Lindl.) fruit peels infused in water and taken for 45 days are used as natural remedies against hypercholesterolemia, hyperglycemia and cardiovascular diseases. This is the first experimental study approving the folk medicinal use of loquat fruit peels originated from eastern Morocco.AIM OF THE STUDY: The study aims to investigate the effect of loquat fruit peel extract on lipid metabolism and liver oxidative status in mice as well as to predict the possible mechanisms.MATERIALS AND METHODS: The study was carried out using high fat/fructose diet-induced hyperlipidemic mice model treated with the loquat peel extract for 45 days at two doses (100 and 200 mg/kg/day) in comparison to fenofibrate drug. The plasma, tissue, fecal and biliary lipids and blood glucose were analyzed using enzymatic methods. The liver oxidative status was evaluated and the polyphenol profiling was conducted using the HPLC-DAD method. Possible mechanisms involved in the observed pharmacological effects were predicted by in silico method.RESULTS: The extract at a dose of 200 mg/kg possessed higher effect than at 100 mg/kg. It significantly reduced plasma total cholesterol (TC), triglycerides (TG), LDL-cholesterol, atherogenic index, LDL-C/HDL-C ratio and plasma glucose (-36%, -45%, -45%, -82%, -87%, 58%, respectively), while the HDL-cholesterol was increased (+172%). Moreover, the extract reduced TC and TG in the liver and adipose tissue by increasing their excretion in bile and fecal matter. It prevented the liver oxidative stress and decreased body weight and organ relative mass. The extract appears to be nontoxic (LD > 5000 mg/kg) and contains five polyphenols including ferulic acid (32.74  0.71 mg/g), caffeic acid (21.48  0.32 mg/g), 5-O-Caffeoylquinic acid (112.15  1.86 mg/g), chlorogenic acid (42.05  0.92 mg/g) and quercetin (32.69  0.68 mg/g). These phenolics and/or their circulating metabolites presented differential interaction capacities with the potential enzymes and transcription factors implicated in lipid homeostasis such as HMG-CoA reductase, lipoprotein lipase, fatty acid synthase, Cyp7a1, ABCG, PPARs, RXR, FXR and RAR.CONCLUSION: Our findings justify the traditional use of loquat fruit peels and suggest that their aqueous extract could be used as substrate to produce phytotherapeutic drugs or dietary supplements to prevent hyperlipidemia, hyperglycemia and related cardiovascular diseases.

...

PMID:  PeerJ. 2023 ;11:e14809. Epub 2023 Jan 30. PMID: 36743956 Abstract Title:  Exploring the mechanisms by which camel lactoferrin can killserovarand. Abstract:  There is a continuously increasing pressure associated with the appearance ofSerovar() and() that have developed pathogenic multiple antibiotic resistance and the cost of cure and control of these enterobacteriaceae infections increases annually. The current report for first time demonstrated the distinguished antimicrobial action of camel lactoferrin (cLf) obtained from the milk of different clans of camel in Saudi Arabia againstandThese cLf subtypes showed comparable antimicrobial potential when tested against the two bacterial strains but were superior to either bovine (bLf) or human lactoferrin (hLf). The synergism between lactoferrins and antibiotics concerning their antibacterial efficacies against the two bacterial strains was evident. Exploring mechanisms by which camel lactoferrin can killandrevealed that cLf affects bacterial protein profile. Besides, it interacts with bacterial lipopolysaccharides (LPS) and numerous membrane proteins ofand, with each bacterial strain possessing distinctive binding membrane proteins for lactoferrin. Furthermore, as evidenced by electron microscopy analysis, cLf induces extracellular and intracellular morphological changes in the test bacterial strains when used alone or in combination treatment with antibiotics. Lactoferrin and antibiotics combination strongly disrupts the integrity of the bacterial cells and their membranes. Therefore, cLf can killandby four different mechanisms, such as iron chelation, affecting some bacterial proteins, binding to bacterial LPS and membrane proteins, and impairing the integrity of the bacterial cells and their membranes.

read more

PMID:  Pharm Nanotechnol. 2023 Mar 16. Epub 2023 Mar 16. PMID: 36927427 Abstract Title:  Protective Effect of Curcumin and Nanocurcumin on Sperm Parameters and Oxidant-Antioxidants System of Rat Testis in Aluminium Phosphide Subacute Poisoning. Abstract:  OBJECTIVE: Aluminum phosphide (AlP) as an effective pesticide may contribute to oxidative stress and adversely influence sperm parameters. This study aimed to investigate the protective role of curcumin and nanocurcumin on oxidative damage in the testis of rats with AlP toxicity.METHODS: A total of 42 adult male Wistar rats were equally randomized into the following study groups (n=7): Control, Control+Curcumin, Control+Nanocurcumin, AlP, AlP+Curcumin, and AlP+Nanocurcumin. The testis tissue was used to investigate the levels of testicular malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and reduced glutathione (GSH) as well as the Catalase (CAT) and superoxide dismutase (SOD) enzyme activity. Epididymal sperm was used to perform sperm analysis.RESULTS: AlP administration led to a significant increase in MDA, and TOS levels and also markedly decreased the SOD activity and the levels of TAC and GSH in testis tissue (p

read more

PMID:  Toxicol Rep. 2023 ;10:376-381. Epub 2023 Mar 4. PMID: 36926661 Abstract Title:  Hepatoprotective potential offollowing prenatal aluminum exposure in Wistar rat pups. Abstract:  Over time, the use of plant-derived agents in the management of various human health conditions has gained a lot of attention. The study assessed the hepatoprotective potential of ethyl acetate fractionleaves (EFTI) during prenatal aluminum chloride exposure. Pregnant rats were divided into 5 groups (n = 4); Group I rats were administered 2 ml kgof distilled water (negative control), Group II rats received only 200 mg kgaluminum chloride (positive control), Group III rats were administered 200 mg kgaluminum chloride and 400 mg kgEFTI, Group IV rats were administered 200 mg kgaluminum chloride and 800 mg kgEFTI, Group V rats were administered 200 mg kgaluminum chloride and 300 mg kgVit E (comparative control). On postnatal day 1, the pups were euthanized, and liver tissues were harvested for the biochemical study (tissue levels of malondialdehyde, caspase-3, tumor necrosis factor-alpha, aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferases) and the liver histological examination. The administration of EFTI was marked with significant improvement in the tissue levels of malondialdehyde, caspase-3, tumor necrosis factor-alpha, aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferases. There was a marked improvement in histopathological changes associated with prenatal aluminum chloride exposure. In conclusion, the administration of EFTI was protective during prenatal aluminum chloride exposure of the liver in Wistar rats, and is mediated by the anti-lipid peroxidative, antiapoptotic, and anti-inflammatory activity of EFTI.

read more

PMID:  Molecules. 2023 Jan 2 ;28(1). Epub 2023 Jan 2. PMID: 36615587 Abstract Title:  Inhibition of Advanced Glycation End-Products byandExtracts and Effects on Human Hepatocyte and Fibroblast Viability. Abstract:  andare widely used by herbalists to cure diabetes mellitus. The aim of this study is to investigate the inhibitory potential of aqueous and various organic solvent fractions from both plants and some isolated compounds against advanced glycation end-products (AGEs). For this purpose, an in vitro BSA-fructose glycation model was used to evaluate the inhibition of AGE formation. Furthermore, the effects of the fractions on mouse fibroblast (NIH-3T3) and human hepatocyte (HepG2) survival were evaluated. The leaf, stem, and root fractions of both plants exhibited significant inhibition of AGEs formation. The ICvalues appeared to be less than 250g/mL; however, all fractions presented no adverse effects on NIH-3T3 up to 500g/mL. Otherwise, our phytochemical investigation afforded the isolation of a secoiridoid from thegenus named secoiridoid glucoside sweroside (), along with three known quinovic acid glycosides: quinovic acid-3---d-glucopyranoside (), quinovic acid-3---d-6-deoxy-glucopyranoside, 28---d-glucopyranosyl ester (), and quinovic acid 3---l-rhamnopyranosyl-(41)--d-glucopyranoside (). In particular,-are compounds which have not previously been described inroots. However, the isolated compounds did not exhibit AGE inhibitory activity. Further investigation on these potent antiglycation fractions may allow for the isolation of new antidiabetic drug candidates.

read more