PMID:  Intern Med. 2023 May 17. Epub 2023 May 17. PMID: 37197963 Abstract Title:  Zinc Supplementation and an Improved Quality of Life in Patients with Autoimmune Hepatitis. Abstract:  Background and Aims Patients with autoimmune hepatitis (AIH) reportedly have an impaired quality of life (QOL), mainly due to depression, even during remission. In addition, hypozincaemia has been demonstrated in patients with chronic liver disease, including AIH, and is known to be related to depression. Corticosteroids are known to cause mental instability. We therefore investigated the longitudinal association between zinc supplementation and changes in the mental status among AIH patients treated with corticosteroids. Patients and Methods This study enrolled 26 patients with serological remission of AIH routinely treated at our facility after excluding 15 patients who either discontinued polaprezinc (150 mg/day) within 24 months or interrupted treatment. Two questionnaires, the Chronic Liver Disease Questionnaire (CLDQ) and SF-36, were adopted to evaluate the QOL before and after zinc supplementation. Results Serum zinc levels were significantly elevated after zinc supplementation (P

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PMID:  Crit Rev Food Sci Nutr. 2023 May 15:1-12. Epub 2023 May 15. PMID: 37183697 Abstract Title:  Effect of zinc supplementation in the management of type 2 diabetes: A grading of recommendations assessment, development, and evaluation-assessed, dose-response meta-analysis of randomized controlled trials. Abstract:  The question of whether zinc supplementation may improve cardio-metabolic health in patients with type 2 diabetes mellitus (T2DM) remains controversial and require further evaluation. This study aimed to summarize the effectiveness of oral zinc supplementation in improving cardio-metabolic risk markers in people with T2DM. We searched PubMed, Scopus, and Web of Science from inception to April 2023, for randomized controlled trials (RCTs). RCTs of type 2 diabetic adults (aged18years) comparing zinc supplementation with placebo were included. We excluded studies if not randomized, involved co-supplementation, and were conducted in children or pregnant women. Glycemic indices, lipid profiles, blood pressure, anthropometric measure, c-reactive protein (CRP), creatinine, and serum zinc were extracted. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methods. We used a random-effect model to perform the dose-response analysis. Effect sizes were presented as mean difference (MD) and 95% confidence interval (CI). 22 studies (=1442 participants) were included. The certainty of the evidence was rated as moderate to high. Zinc supplementation significantly reduced glycemic indices: including two-hour postprandial glucose (2hpp) (mean difference (MD): -34.34mg/dl; 95%CI: -51.61-17.07), fast blood sugar (FBS) (MD: -23.32mg/dl; 95% CI: -33.81-12.83), and hemoglobin A1c (HbA1c) (MD: -0.47; 95% CI: -0.71-0.23). Zinc had a favorable effect on lipid profiles low-density lipoprotein (LDL) (MD: -10.76mg/dl; CI: -17.79-3.73), triglyceride (TG) (MD: -18.23mg/dl; CI: -32.81-3.65), total cholesterol (TC) (MD: -12.74mg/dl; CI: -21.68-3.80), VLDL (MD: -5.39mg/dl; CI: -7.35-3.43) and high-density lipoprotein (HDL) (MD: 4.04mg/dl; CI: 0.967.12). Systolic blood pressure (SBP) (MD): -3.64mmHg; 95% CI: -6.77-0.52), weight (MD: 1.00kg; 95% CI: 0.341.66), CRP (MD: -3.37mg/l, 95% CI: -4.05-2.70), and serum zinc (MD: 15.38g/dl; 95% CI: 10.7420.02) changed to a statistically significant extent with zinc supplementation. There was also a linear association between additional 10mg/d zinc treatment with FBS, HbA1c, HDL, LDL, TG, TC, and serum zinc. A non-linear dose-response gradient was seen for FBS, HDL, and SBP (

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PMID:  J Int Med Res. 2023 May ;51(5):3000605231171489. PMID: 37165643 Abstract Title:  Efficacy of zinc supplementation for the treatment of dysmenorrhoea: a double-blind randomised controlled trial. Abstract:  OBJECTIVES: To determine the efficacy of zinc sulfate supplementation in managing dysmenorrhoea.METHODS: In total, 103 high school students were randomised into an experimental arm (52 students) and a control arm (51 students) and received 40-mg zinc sulfate or placebo, respectively, over three cycles. Primary outcome measures were the mean Visual Analogue Scale score, which measured pain over three cycles, and the frequency of nausea and vomiting. Secondary outcomes were the use of additional analgesics and the frequency of allergic reactions.RESULTS: Fifty participants were analysed in each group. Mean pain scores were not significantly different between the groups before administering zinc sulfate therapy. Following the intervention, the mean pain scores for the treatment (2.802.28) and placebo (3.482.85) groups were not significantly different in the first cycle; however, scores in the treatment group were significantly better in the second (2.561.97 vs 3.802.77) and third (1.951.72 vs 3.952.82) cycles. No significant differences were observed between the groups in the nausea and vomiting incidence and the requirement for additional analgesics.CONCLUSIONS: Zinc sulfate reduces dysmenorrhoea severity with minimal or no adverse effects, especially with more than one cycle of usage.Trial Registration Number: PACTR202105843292338. The trial is publicly available and was registered at www.pactr.org on 25 May 2021.

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PMID:  J Trace Elem Med Biol. 2023 Jul ;78:127188. Epub 2023 Apr 28. PMID: 37163819 Abstract Title:  L-carnitine and Zinc supplementation impedes intestinal damage in methotrexate-treated adjuvant-induced arthritis rats: Reinstating enterocyte proliferation and trace elements. Abstract:  BACKGROUND: Methotrexate (MTX), a folic acid analogue, is used as a first-line treatment for rheumatoid arthritis (RA) since it has more therapeutic mechanisms than any other drug. Being an undeniable drug for the treatment of arthritis, even low-dose MTX provokes intestinal toxicity as a primary adverse effect and does not revive an anti-inflammatory element. Thus, our study aims to elucidate the anti-arthritic and prophylactic activity of supplements L-carnitine (L) and zinc (Z) against MTX-mediated intestinal damage in arthritis rats.METHODS: The rats were assessed for arthritic parameters such as body weight, paw volume, x-ray scan, and serum trace elements level. To analyze the toxic effects of MTX in the rats, intestine pH, mucosal weight, digestive enzymes, myeloperoxidase, histopathological, and immunohistochemical analysis were performed.RESULTS: Our study demonstrated that the arthritic parameters have shown that MTX has an ameliorative effect on arthritic rats. Besides, our findings showed that low-dose MTX (2.5 mg/kg b.w.) given once a week for two weeks during arthritis treatment had toxic effects in the rat's intestine, as evidenced by changes in intestine pH and mucosal weight, decreased digestive enzymes, increased MPO, and degenerative changes in histopathological analysis. Concurrent therapy of LZ with MTX, on the other hand, restored the modifications in these parameters.CONCLUSION: MTX in combination with LZ effectively manages arthritis than monotherapy and significantly prevents MTX-induced intestinal damage in arthritis rats. Thus, LZ could be used as an improved therapeutic and safety for MTX-instigated intestinal damage during arthritis treatments. Therefore, our combination of L-carnitine and zinc with MTX would be promising prophylactic activity for arthritis patients.

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PMID:  Z Naturforsch C J Biosci. 2023 Jan 27 ;78(1-2):27-48. Epub 2022 Jul 13. PMID: 35844107 Abstract Title:  Sakuranetin and its therapeutic potentials - a comprehensive review. Abstract:  Sakuranetin (SKN), a naturally derived 7--methylated flavonoid, was first identified in the bark of the cherry tree (s spp.) as an aglycone of sakuranin and then purified from the bark of. It was later reported in many other plants including,,spp.,spp.,spp., andspp. In plants, it functions as a phytoalexin synthesized from its precursor naringenin and is the only known phenolic phytoalexin in rice, which is released in response to different abiotic and biotic stresses such as UV-irradiation, jasmonic acid, cupric chloride, L-methionine, and the phytotoxin coronatine. Till date, SKN has been widely reported for its diverse pharmacological benefits including antioxidant, anti-inflammatory, antimycobacterial, antiviral, antifungal, antileishmanial, antitrypanosomal, glucose uptake stimulation, neuroprotective, antimelanogenic, and antitumor properties. Its pharmacokinetics and toxicological properties have been poorly understood, thus warranting further evaluation together with exploring other pharmacological properties such as antidiabetic, neuroprotective, and antinociceptive effects. Besides,studies or clinical investigations can be done for proving its effects as antioxidant and anti-inflammatory, antimelanogenic, and antitumor agent. This review summarizes all the reported investigations with SKN for its health-beneficial roles and can be used as a guideline for future studies.

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PMID:  Fundam Clin Pharmacol. 2022 Aug ;36(4):663-673. Epub 2022 Feb 21. PMID: 35156229 Abstract Title:  Sakuranetin exerts anticonvulsant effect in bicuculline-induced seizures. Abstract:  Epilepsy is a chronic neurological disorder characterized by an abnormal, spontaneous, and synchronized neuronal hyperactivity. Therapeutic approaches for controlling epileptic seizures are associated with pharmacoresistance and side effects burden. Previous studies reported that different natural products may have neuroprotector effects. Sakuranetin (SAK) is a flavanone with antiparasitic, anti-inflammatory, antimutagenic, antiallergic, and antioxidant activity. In the present work, the effect of SAK on seizures in a model of status epilepticus induced by bicuculline (BIC) in mice was evaluated. Male Swiss mice received an intracerebroventricular injection (i.c.v.) of SAK (1, 10, or 20mg/kg-SAK1, SAK10, or SAK20). Firstly, animals were evaluated in the open field (OF; 20min), afterwards in the elevated plus maze (EPM) test (5min). Next, 30min prior the administration of BIC (1mg/kg), mice received an injection of SAK (1 or 10mg/kg, i.c.v.) and were observed in the OF (20min) for seizures assessment. After behavioral procedures, immunohistochemical analysis of c-Fos was performed. Our main results showed that the lowest doses of SAK (1 and 10mg/kg) increased the total distance traveled in the OF, moreover protected against seizures and death on the BIC-induced seizures model. Furthermore, SAK treatment reduced neuronal activity on the dentate gyrus of the BIC-treated animals. Taken together, our results suggest an anticonvulsant effect of SAK, which could be used for the development of anticonvulsants based on natural products from herbal source.

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PMID:  Cell Mol Biol (Noisy-le-grand). 2019 Jun 30 ;65(5):54-58. Epub 2019 Jun 30. PMID: 31304907 Abstract Title:  Protective effect of sakuranetin in brain cells of dementia model rats. Abstract:  Alzheimer's disease (AD) is a high-incidence neurodegenerative disease with complex and diverse pathogenesis. With aging of the population and continuous improvement of living standards, the incidence of AD is on the increase. Therefore, there is need to develop more effective AD drugs in order to improve the quality of life of the elderly. Sakuranetin (SAK) is a dihydroflavonoid compound extracted from plants. It has many physiological properties. In this study, the effect of SAK on spatial discrimination in a rat model of cognitive dysfunction exposed to D-galactose was investigated with respect to its effect on malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, and on the expressions of interleukin-6 (IL-6), tumor necrosis factor-(TNF-) and nuclear factor-B inhibitory factor-(IB) in hippocampus of rats. The results obtained suggest that SAK may exert protective effects on brain cells through anti-oxidation mechanism. Moreover, the improvement in learning and memory impairment by SAK may also be related to the inhibition of inflammatory mediators in brain tissue. These findings provide scientific evidence that can be exploited for more effective treatment of Alzheimer's disease.

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PMID:  Mediators Inflamm. 2019 ;2019:1356356. Epub 2019 Sep 3. PMID: 31565031 Abstract Title:  Inhibition of MAPK and STAT3-SOCS3 by Sakuranetin Attenuated Chronic Allergic Airway Inflammation in Mice. Abstract:  Asthma allergic disease is caused by airway chronic inflammation. Some intracellular signaling pathways, such as MAPK and STAT3-SOCS3, are involved in the control of airway inflammation in asthma. The flavonoid sakuranetin demonstrated an anti-inflammatory effect in different asthma models. Our aim was to clarify how sakuranetin treatment affects MAPK and STAT3-SOCS3 pathways in a murine experimental asthma model. Mice were submitted to an asthma ovalbumin-induction protocol and were treated with vehicle, sakuranetin, or dexamethasone. We assayed the inflammatory profile, mucus production, and serum antibody, STAT3-SOCS3, and MAPK levels in the lungs. Morphological alterations were also evaluated in the liver. LPS-stimulated RAW 264.7 cells were used to evaluate the effects of sakuranetin on nitric oxide (NO) and cytokine production., sakuranetin treatment reduced serum IgE levels, lung inflammation (eosinophils, neutrophils, and Th2/Th17 cytokines), and respiratory epithelial mucus production in ovalbumin-sensitized animals. Considering possible mechanisms, sakuranetin inhibits the activation of ERK1/2, JNK, p38, and STAT3 in the lungs. No alterations were found in the liver for treated animals. Sakuranetin did not modifycell viability in RAW 264.7 and reduced NO release and gene expression of IL-1and IL-6 induced by LPS in these cells. In conclusion, our data showed that the inhibitory effects of sakuranetin on eosinophilic lung inflammation can be due to the inhibition of Th2 and Th17 cytokines and the inhibition of MAPK and STAT3 pathways, reinforcing the idea that sakuranetin can be considered a relevant candidate for the treatment of inflammatory allergic airway disease.

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PMID:  J Pharm Pharmacol. 2023 May 11. Epub 2023 May 11. PMID: 37167529 Abstract Title:  Chrysin prevents inflammation-coinciding liver steatosis via AMPK signalling. Abstract:  OBJECTIVES: We aimed to elucidate the therapeutic potential of Chrysin (CN) against the high-fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD) and its mechanism.METHODS: To assess the hypothesis, NAFLD was induced in C57BL/6 mice by feeding a high-fat diet for up to two months, followed by CN administration (for three months). Liver injury/toxicity, lipid deposition, inflammation and fibrosis were detected via molecular and biochemical analysis, including blood chemistry, immunoimaging and immunoblotting. Moreover, we performed proteomic analysis to illuminate Chrysin's therapeutic effects further.KEY FINDINGS: CN treatment significantly reduced liver-fat accumulation and inflammation, ultimately improving obesity and liver injury in NAFLD mice. Proteomic analysis showed that CN modified the protein expression profiles in the liver, particularly improving the expression of proteins related to energy, metabolism and inflammation. Mechanistically, CN treatment increased AMP-activated protein and phosphorylated CoA (P-ACC). Concurrently, it reduced inflammation and inflammation activation by inhibiting NLRP3 expression.CONCLUSIONS: In summary, CN treatment reduced lipid metabolism by AMPK and inflammasome activation by NLRP3 inhibition, ultimately improving NAFLD progression. These findings suggest that CN could be a potential treatment candidate for the NFLAD condition.

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PMID:  Pharmaceutics. 2023 Apr 12 ;15(4). Epub 2023 Apr 12. PMID: 37111711 Abstract Title:  Chrysin Is Immunomodulatory and Anti-Inflammatory against Complete Freund's Adjuvant-Induced Arthritis in a Pre-Clinical Rodent Model. Abstract:  Chrysin (5,7-dihydroxyflavone) has many pharmacological properties including anti-inflammatory actions. The objective of this study was to evaluate the anti-arthritic activity of chrysin and to compare its effect with the non-steroidal anti-inflammatory agent, piroxicam, against complete Freund's adjuvant (CFA)-induced arthritis in a pre-clinical model in rats. Rheumatoid arthritis was induced by injecting CFA intra-dermally in the sub-plantar region of the left hind paw of rats. Chrysin (50 and 100 mg/kg) and piroxicam (10 mg/kg) were given to rats with established arthritis. The model of arthritis was characterized using an index of arthritis, with hematological, biological, molecular, and histopathological parameters. Treatment with chrysin significantly reduced the arthritis score, inflammatory cells, erythrocyte sedimentation rate, and rheumatoid factor. Chrysin also reduced the mRNA levels of tumor necrosis factor, nuclear factor kappa-B, and toll-like recepter-2 and increased anti-inflammatory cytokines interleukin-4 and -10, as well as the hemoglobin levels. Using histopathology and microscopy, chrysin reduced the severity of arthritis in joints, infiltration of inflammatory cells, subcutaneous inflammation, cartilage erosion, bone erosion, and pannus formation. Chrysin showed comparable effects to piroxicam, which is used for the treatment of rheumatoid arthritis. The results showed that chrysin possesses anti-inflammatory and immunomodulatory effects that make it a potential drug for the treatment of arthritis.

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PMID:  Inflammopharmacology. 2023 Aug ;31(4):1863-1878. Epub 2023 Apr 21. PMID: 37083920 Abstract Title:  Chrysin, a 5,7-dihydroxyflavone restrains inflammatory arthritis in rats via subsiding oxidative stress biomarkers and inflammatory cytokines. Abstract:  This study was intended to appraise the anti-inflammatory and anti-arthritic potential of Chrysin (CR), a natural dietary flavone found in several plant genera, including Passiflora and Propalis, and honey. The in vitro anti-arthritic potential was assessed by protein denaturation and membrane stabilization assays. The acute anti-inflammatory action was assessed by Carrageenan and Xylene induced oedema models in Wistar rats. For determining anti-arthritic potential, 0.1 ml Complete Freund's adjuvant was injected into the left hind paw of rats to induce adjuvant-induced arthritis, followed by initiation of treatment with individual CR at 25, 50, 100 mg/kg and in combination with methotrexate (MTX) by oral gavage for 21 days. The standard treatment group was given MTX (1 mg/kg). Treatment with MTX, chrysin and their combination exhibited a notable inhibition of paw oedema and pain, restoration of body weight and immune organ weight as evident by the histology of ankle joints. Treatment with chrysin alone and in combination significantly (p

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PMID:  J Pharm Pharmacol. 2023 Apr 15. Epub 2023 Apr 15. PMID: 37061805 Abstract Title:  Chrysin and its nanoliposome ameliorated non-alcoholic steatohepatitis via inhibiting TLR4 signalling pathway. Abstract:  OBJECTIVES: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease histologically characterized by liver steatosis, hepatocellular injury, inflammation and fibrosis, resulting in cirrhosis and hepatocellular carcinoma, but effective measures and obvious pathogenesis for NASH remain elusive. Chrysin (CH) has been reported to have anti-inflammatory effects but shows lower bioavailability.METHODS: In this study, a chrysin nanoliposome (CH-NL) was first prepared and characterized. Then, we used the methionine-choline-deficient (MCD) diet to induce a mouse model of NASH. Finally, the effects of CH and CH-NL on NASH were evaluated in the liver of NASH mice.KEY FINDINGS: The results showed that CH or CH-NL significantly reduced the accumulation of lipids in hepatocytes, alleviated liver injury, decreased the generation of radical oxygen species, and attenuated the accumulation of collagen fibre in the liver of NASH mice. In addition, CH and its nano-liposomes markedly inhibited the production of inflammatory cytokines and inflammatory cell infiltration in the liver of NASH mice. Further studies found that CH-NL and CH-NL downregulated the MCD diet-induced activation of Toll-like receptor 4 (TLR4) signalling pathway in the liver of mice.CONCLUSIONS: CH and its nanoliposome alleviated MCD diet-induced NASH in mice, which might be through inhibiting TLR4 signalling pathway.

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PMID:  Life Sci. 2023 Jun 1 ;322:121668. Epub 2023 Apr 5. PMID: 37023949 Abstract Title:  Phloretin and phlorizin mitigates inflammatory stress and alleviate adipose and hepatic insulin resistance by abrogating PPARS273-Cdk5 interaction in type 2 diabetic mice. Abstract:  AIMS: The rising prevalence of type 2 diabetes mellitus (T2DM) and accompanying insulin resistance is alarming globally. Natural and synthetic agonists of PPARare potentially attractive candidates for diabetics and are known to efficiently reverse adipose and hepatic insulin resistance, but related side effects and escalating costs are the causes of concern. Therefore, targeting PPARwith natural ligands is advantageous and promising approach for the better management of T2DM. The present research aimed to assess the antidiabetic potential of phenolics Phloretin (PTN) and Phlorizin (PZN) in type 2 diabetic mice.MAIN METHODS: In silico docking was performed to check the effect of PTN and PZN on PPARS273-Cdk5 interactions. The docking results were further validated in preclinical settings by utilizing a mice model of high fat diet-induced T2DM.KEY FINDINGS: Computational docking and further MD-simulation data revealed that PTN and PZN inhibited the activation of Cdk5, thereby blocking the phosphorylation of PPAR. Our in vivo results further demonstrated that PTN and PZN administration significantly improved the secretory functions of adipocytes by increasing adiponectin and reducing inflammatory cytokine levels, which ultimately reduced the hyperglycaemic index. Additionally, combined treatment of PTN and PZN decreased in vivo adipocyte expansion and increased Glut4 expression in adipose tissues. Furthermore, PTN and PZN treatment reduced hepatic insulin resistance by modulating lipid metabolism and inflammatory markers.SIGNIFICANCE: In summary, our findings strongly imply that PTN and PZN are candidates as nutraceuticals in the management of comorbidities related to diabetes and its complications.

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PMID:  Life Sci. 2023 Jul 15 ;325:121739. Epub 2023 May 9. PMID: 37164308 Abstract Title:  Pinostrobin induces acute leukemia cell apoptosis via the regulation of miR-410-5p and SFRP5. Abstract:  AIMS: This study attempted to explore the mechanisms involved in pinostrobin (PN)-mediated acute leukemia cell apoptosis regulated by miR-410-5p.MATERIAL AND METHODS: NB4 and MOLT-4 cells were cultured and treated with PN at the IC50 concentration. Apoptosis was examined by Annexin V-FITC/PI staining. RT-qPCR was used to measure the expression of caspase-3, BAK, BCL-W, and MCL-1. The target protein of PN was identified using LC-MS/MS followed by bioinformatic analysis. TargetScan, DIANA, and miRDB were used for the prediction of miRNAs involved in the PN-induced apoptosis mechanism. miRNA mimic transfection, RT-qPCR, and western blot analysis were performed to evaluate the regulatory effect of miRNA on its target and the involvement of miRNA in apoptosis induction by PN. In addition, the synergistic effect of PN and daunorubicin (DNR) were investigated by using the MTT assay.KEY FINDINGS: The results showed that PN reduced cell viability and induced apoptosis in both leukemia cell lines. From the LC-MS/MS and bioinformatics analysis, SFRP5 and miR-410-5p were selected as a potential PN target protein and miRNA, respectively. After miRNA mimic transfection, miR-410-5p, which is an onco-miRNA, was decreased and led to increased apoptosis in both cell lines, indicating that this miRNA is involved in PN-mediated apoptosis mechanisms. Moreover, PN demonstrated a synergistic effect with DNR, suggesting that PN may be used in combination with conventional chemotherapy drugs.SIGNIFICANCE: PN regulates the expression of miR-410-5p and SFRP5 to promote apoptosis in acute leukemia cells. It could be developed as an alternative treatment for leukemia in the future.

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PMID:  Biomed Pharmacother. 2023 Jun ;162:114686. Epub 2023 Apr 10. PMID: 37044025 Abstract Title:  Pinostrobin alleviates testicular and spermatological damage induced by polystyrene microplastics in adult albino rats. Abstract:  BACKGROUND: Polystyrene microplastics (PS-MPs) have become major environmental pollutants that adversely effects multiple organs specifically testicles. Pinostrobin (PN) is an important flavonoid which, shows several pharmacological potentials.PURPOSE: The current study was designed to elucidate the mitigative effects of PN against PS-MPs induced testicular toxicities in rats.METHODS: 48 male albino rats were randomly distributed into 4 groups, control, PS-MPs group (0.01 mg/kg), PS-MPs + PN group (0.01 mg/kg of PS-MPs; 40 mg/kg of PN) and PN group (40 mg/kg).RESULTS: PS-MPs intoxication substantially lessened the activities of glutathione peroxidase (GPx), glutathione reductase (GSR), superoxide dismutase (SOD) along with catalase (CAT) while, raised the level of malondialdehyde (MDA) as well as reactive oxygen species (ROS). Additionally, PS-MPs reduced luteinizing hormone (LH), plasma testosterone, follicle-stimulating hormone (FSH) concentration, sperm motility, sperm count, expression of steroidogenic enzymes and Bcl-2 (anti-apoptotic protein) along with the count of spermatogenic cells. While, dead sperm count, sperm abnormalities (tail, neck and head), Bax and caspase-3 (apoptotic proteins) expression along with histopathological anomalies were elevated. Moreover, PS-MPs exposure increased the level of inflammatory markers. However, PN treatment considerably decreased oxidative stress (OS) by reducing ROS as well as increased sperm motility and alleviated all the damages induced by the PS-MPs.CONCLUSION: Therefore, it is concluded that PN may prove a potential therapeutic candidate to restore all the PS-MPs-induced testicular toxicities.

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PMID:  Curr Top Med Chem. 2023 May 12. Epub 2023 May 12. PMID: 37183471 Abstract Title:  Antiproliferative Activity and Mechanisms of Action of Plant-Derived Flavonoids on Breast Cancer. Abstract:  Breast cancer is one of the main global diseases with a high mortality rate that mainly affects the female population. Despite the important advances that have been made concerning the treatments for this disease, research on less invasive therapies that generate fewer side effects for patients continues to develop. Consequently, researchers have turned their attention to using natural compounds (such as flavonoids) involved in molecular processes implicated in this type of cancer and are studying how these processes can be exploited to develop possible chemotherapies. This review offers a general description of studies on the antiproliferative activity of flavonoids obtained from natural sources for breast cancer treatment and their mechanism of action related to their structural characteristics. Reports were retrieved from electronic databases, such as Web of Science and Scopus using the following keywords: breast cancer, antiproliferative, flavonoids, and structure-activity. Articles published between 2015-2022 related to the topics mentioned above were selected, focusing on the flavonoids apigenin, luteolin, quercetin, and naringenin, as they are the ones with the highest activity and relevance according to the literature found.

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PMID:  Foods. 2023 May 5 ;12(9). Epub 2023 May 5. PMID: 37174437 Abstract Title:  Protective Effect of Quercetin and Ginger () Extract against Dimethoate Potentiated Fluoride-Induced Nephrotoxicity in Rats. Abstract:  This study aimed to determine the potential of quercetin and(ZO) Roscoe extract to alleviate the renal damage induced by dimethoate (DM) and fluoride (F) alone and by their combined exposure in rats. A total of 54 adult Wistar rats were randomly allocated to nine groups (= 6). A sub-lethal dose of DM (1/10th of the median lethal dose) was administered by oral gavage alone and along with F(4.5 ppm, three-fold the permissible limit) in their drinking water continuously for 28 days. Chromatographical analysis revealed the presence of quercetin, curcumin, and other phytochemicals with strong antioxidant properties in ZO-rhizome extract. Severe changes were observed in the levels of the renal biomarkers and histoarchitecture after co-administration of the toxicants, indicating greater kidney damage. The administration of ZO extract (300 mg/kg) along with either or both toxicants led to a significant restoration of the biochemical markers and renal antioxidant profile and histology.

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PMID:  J Clin Exp Dent. 2023 Apr ;15(4):e304-e310. Epub 2023 Apr 1. PMID: 37152491 Abstract Title:  Comparative antibacterial effects of ginger and marjoram extract versus conventional irrigants on maturebiofilms: Anstudy. Abstract:  BACKGROUND: This study evaluated antibacterial effects of Ginger and Marjoram extract compared with Routine Intracanal Irrigants on MatureBiofilms.MATERIAL AND METHODS: Sixty-six extracted human teeth, were randomly assigned to four groups 5.25% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX), chloroform extract of marjoram (Origanum majorana), and oil extract of ginger (Zingiber officinale), and two positive and negative control groups (n=11). Samples were contaminated with, except the negative control group. Then the root canals were irrigated with solutions above, after which dental debris was collected from each tooth separately, followed by culturing on plates containing BHI agar. The bacterial counts were finally determined with a colony counting machine.RESULTS: No bacterial growth was detected in the NaOCl, CHX, and negative control groups. However, some bacterial growth was observed in the ginger and marjoram groups. All four solutions successfully eliminatedbiofilms compared to the positive control group. Significant difference in the median bacterial growth between the ginger and marjoram groups and the positive control group (

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PMID:  Integr Cancer Ther. 2023 ;22:15347354231172732. PMID: 37157810 Abstract Title:  6-Shogaol Inhibits the Cell Migration of Colon Cancer by Suppressing the EMT Process Through the IKK/NF-B/Snail Pathway. Abstract:  6-Shogaol from ginger has anti-inflammatory, anti-oxidation and anti-cancer effects.To study the effects and possible mechanisms of 6-Shogaol on inhibiting the migration of colon cancer cells Caco2 and HCT116 and prove the effects on proliferation and apoptosis.The cells were treated with 6-Shogaol at the concentrations of 20, 40, 60, 80, and 100M, the cytotoxicity was tested by Colony formation assays and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and the Western blot was used to evaluate IKK/NF-B/Snail pathway and EMT-related proteins. In addition, in order to eliminate the interference of proliferation inhibition on the experiment, Caco2 cells were treated with 6-Shogaol at the concentrations of 0, 40, and 80M, HCT116 cells were treated with 6-Shogaol at the concentrations of 0, 20, and 40M, apoptosis was measured by Annex V/PI staining, and migration was measured by Wound healing assays and Transwell test.6-Shogaol significantly inhibited the growth of cells. The maximum inhibitory concentration of half of them was 86.63M in Caco2 cells and 45.25M in HCT116 cells. At 80M and 40M concentrations, 6-Shogaol significantly promoted apoptosis of colon cancer Caco2 cells and HCT116 cells, and also significantly inhibited cell migration (

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PMID:  Mol Nutr Food Res. 2023 Jul ;67(13):e2200773. Epub 2023 May 14. PMID: 37118920 Abstract Title:  6-Shogaol from Dried Ginger Protects against Intestinal Ischemia/Reperfusion by Inhibiting Cell Apoptosis via the BDNF/TrkB/PI3K/AKT Pathway. Abstract:  SCOPE: Intestinal ischemia-reperfusion (II/R) injury is a common pathological process with high morbidity and mortality. Effective prevention and treatment therapies for II/R are clinically necessary. 6-Shogaol (6-SG), the main active ingredient in dried ginger, behaviors multiple biological activities, including anti-inflammation, antioxidation, and anti-apoptosis. This study aims to elucidate the protective effects and mechanism of 6-SG against II/R-induced injury.METHODS AND RESULTS: Sprague-Dawley rats are pre-treated orally with 6-SG and subjected to II/R injury by clamping superior mesenteric artery for 1 h and reperfusion for 2 h. Caco-2 cells are challenged by hypoxia/reoxygenation to mimic II/R in vitro. 6-SG pre-treatment protects against II/R injury by reducing intestinal morphological damage and intestinal barrier injury via inhibiting cell apoptosis. Network pharmacology and molecular docking analyses reveal that 6-SG has a high affinity with brain-derived neurotrophic factor (BDNF) formed homodimer or heterodimer with NT4 instead of the monomer, and thus the dimer configuration is stabilized, activating BDNF/TrkB/PI3K/AKT signaling pathway and inhibiting II/R-induced cell apoptosis. The outcome is further validated both in vivo and in vitro.CONCLUSION: 6-Shogaol protects against II/R injury by inhibiting cell apoptosis through the BDNF/TrkB/PI3K/AKT pathway. This study offers a new understanding of the protection mechanism of 6-SG against II/R-induced injury.

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PMID:  J Physiol Pharmacol. 2022 Dec ;73(6). Epub 2023 Apr 17. PMID: 37087565 Abstract Title:  6-Shogaol protects against isoproterenol-induced cardiac injury in rats through attenutating oxidative stress, inflammation, apoptosis and activating nuclear respiratory factor-2/heme oxygenase-1 signaling pathway. Abstract:  The current study investigated the preventive effect of 6-Shogaol on isoproterenol hydrochloride (ISO)-induced myocardial cardiac injury. 6-Shogaol (50 mg/kg b.w.) was administered for 14 days at pretreatment and ISO-induction (85 mg/kg b.w.) for the last two days (13th and 14th days) by subcutaneous injection. Cardiac markers in serum like creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), cardiac troponins T (cTn T) and I (cTn I) increased in ISO-induced rats. Moreover, lipid peroxidative markers like thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH) were raised, and the activities/level of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) were diminished in ISO-treated heart tissue. In addition, inflammatory and nuclear respiratory factor (Nrf)-2 signalling molecules were upregulated in ISO-induced ischemic rats. 6-Shogaol pretreatment decreased the activities of cardiac and lipid peroxidative markers and enhanced the antioxidant status in ISO-induced cardiac injury rats. Further, 6-Shogaol pretreatment inhibited serum inflammatory markers: tumour necrosis factor-alpha (TNF-), interleukin-6 (IL-6), nuclear factor-kappaB (NF-B), Nrf-2 molecule and heme oxygenase (HO)-1 in ISO-induced cardial damage rats. We noticed the effect of 6-Shogaol inhibited pro-apoptotic genes like B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Fas, caspase-3, -8, -9, cytochrome C, and inflammatory genes and increased Bcl-2 expression in ISO-treated rats. The cardioprotective activity of 6-Shogaol in rats with ISO-induced myocardial damage may be due to its ability to reduce oxidative stress, inflammation, and apoptosis, perhaps via the Nrf-2/HO-1 signalling pathway.

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PMID:  Life Sci. 2023 Jul 1 ;324:121735. Epub 2023 May 2. PMID: 37142088 Abstract Title:  Carvacrol enhances anti-tumor activity and mitigates cardiotoxicity of sorafenib in thioacetamide-induced hepatocellular carcinoma model through inhibiting TRPM7. Abstract:  AIMS: Sorafenib (Sora) represents one of the few effective drugs for the treatment of advanced hepatocellular carcinoma (HCC), while resistance and cardiotoxicity limit its therapeutic efficacy. This study investigated the effect of transient receptor potential melastatin 7 (TRPM7) inhibitor, carvacrol (CARV), on overcoming Sora resistance and cardiotoxicity in thioacetamide (TAA) induced HCC in rats.MATERIALS AND METHODS: TAA (200 mg/kg/twice weekly, intraperitoneal) was administered for 16 weeks to induce HCC. Rats were treated with Sora (10 mg/Kg/day; orally) and CARV (15 mg/kg/day; orally) alone or in combination, for six weeks after HCC induction. Liver and heart functions, antioxidant capacity, and histopathology were performed. Apoptosis, proliferation, angiogenesis, metastasis, and drug resistance were assessed by quantitative real time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry.KEY FINDINGS: CARV/Sora combination significantly improved survival rate, and liver functions, reduced Alpha-Fetoprotein level, and attenuated HCC progression compared with Sora group. CARV coadministration almost obviated Sora-induced changes in cardiac and hepatic tissues. The CARV/Sora combination suppressed drug resistance and stemness by downregulating ATP-binding cassette subfamily G member 2, NOTCH1, Spalt like transcription factor 4, and CD133. CARV boosted Sora antiproliferative and apoptotic activities by decreasing cyclin D1 and B-cell leukemia/lymphoma 2 and increasing BCL2-Associated X and caspase-3.SIGNIFICANCE: CARV/Sora is a promising combination for tumor suppression and overcoming Sora resistance and cardiotoxicity in HCC by modulating TRPM7. To our best knowledge, this study represents the first study to investigate the efficiency of CARV/ Sora on the HCC rat model. Moreover, no previous studies have reported the effect of inhibiting TRPM7 on HCC.

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PMID:  Life Sci. 2023 Jul 1 ;324:121743. Epub 2023 Apr 27. PMID: 37120013 Abstract Title:  Anti-inflammatory activity of carvacrol protects the heart from lipopolysaccharide-induced cardiac dysfunction by inhibiting pyroptosis via NLRP3/Caspase1/Gasdermin D signaling axis. Abstract:  AIMS: Lipopolysaccharide (LPS) is a well-known agent to induce septic conditions. Sepsis-induced cardiomyopathy has an overwhelming death rate. Carvacrol (CVL), a monoterpene phenol, has anti-inflammatory and antioxidant properties. This research aimed to investigate the effect of CVL on LPS-induced dysfunction in the heart. In this study, we evaluated the effect of CVL in LPS-stimulated H9c2 cardiomyoblast cells and Balb/C mice.MAIN METHODS: LPS was used to induce septic conditions in H9c2 cardiomyoblast cells in vitro and in Balb/C mice. A survival study was conducted to assess the survival rate of mice after LPS and/or CVL treatment.KEY FINDINGS: In vitro studies indicated that CVL inhibits reactive oxygen species (ROS) generation and abates pyroptosis mediated by NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in H9c2 cells. In mice, CVL intervention improved the survival rate in septic conditions. The CVL administration markedly improved the echocardiographic parameters and alleviated the LPS-induced reduction in the ejection fraction (%) and fraction shortening (%). The CVL intervention restored the myocardial antioxidants and histopathological alterations and decreased the pro-inflammatory cytokine contents in the heart. Further findings disclosed that CVL reduced the protein levels of NLRP3, apoptosis-associated speck-like protein (ASC), caspase 1, interleukin (IL)-18, IL-1, and the pyroptosis-indicative protein, gasdermin-D (GSDMD) in the heart. The autophagy-indicative proteins, beclin 1 and p62 in the heart were also restored in the CVL-treated group.SIGNIFICANCE: Altogether, our findings demonstrated that CVL has a beneficial effect and can be a potential molecule against sepsis-induced myocardial dysfunction.

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PMID:  Front Pharmacol. 2023 ;14:1161448. Epub 2023 Apr 5. PMID: 37089925 Abstract Title:  Carvacrol prevents acrylamide-induced oxidative and inflammatory liver damage and dysfunction in rats. Abstract:  Acrylamide causes hepatotoxicity with the effect of oxidative stress and inflammatory processes. Carvacrol is a monoterpenic phenol with antioxidant and anti-inflammatory properties.To determine the effects of carvacrol on oxidative liver injury induced by acrylamide administration in rats.Rats were divided into three groups of six animals each: healthy group acrylamide group (ACR), and acrylamide + carvacrol group (TACR). First, carvacrol (50 mg/kg) was administered intraperitoneally to the CACR group. One hour later, acrylamide (20 mg/kg) was given orally to the ACR and CACR groups. This procedure was performed for 30 days, after which the animals were sacrificed. The malondialdehyde (MDA) and total glutathione (tGSH) levels, total oxidant (TOS) and total antioxidant status (TAS), tumor necrosis factor-alpha (TNF-), interleukin-1beta (IL-1), and nuclear factor kappa b (NF-B) were measured in the excised liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined in blood serum samples. Liver tissues were also examined histopathologically.In the ACR group, malondialdehyde, TOS, ALT, AST levels, and NF-B, IL-1, and TNF-levels were found to be high, and tGSH and total antioxidant status levels were low. In addition, diffuse degenerative changes and necrosis in hepatocytes, and moderate inflammation in the portal region were detected in the liver tissues of the ACR group. While carvacrol prevented the biochemical changes induced by acrylamide, it also alleviated the damage in the histological structure.Carvacrol may be used for liver damage caused by acrylamide.

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PMID:  Int J Mol Sci. 2023 Mar 23 ;24(7). Epub 2023 Mar 23. PMID: 37047044 Abstract Title:  Anti-Cholinesterase and Anti--Amylase Activities and Neuroprotective Effects of Carvacrol and-Cymene and Their Effects on Hydrogen Peroxide Induced Stress in SH-SY5Y Cells. Abstract:  Several researchers have demonstrated the health and pharmacological properties of carvacrol and-cymene, monoterpenes of aromatic plants. This study investigated these compounds' possible anti-cholinesterase, anti--amylase, and neuroprotective effects. We evaluated the anti-acetylcholinesterase and anti--amylase activities at different concentrations of the compounds. The maximum non-toxic dose of carvacrol and-cymene against SH-SY5Y neuroblastoma cells was determined using an MTT assay. The neuroprotective effects of the compounds were evaluated on HO-induced stress in SH-SY5Y cells, studying the expression of caspase-3 using Western blotting assays. Carvacrol showed inhibitory activities against acetylcholinesterase (IC50 = 3.8g/mL) and butyrylcholinesterase (IC= 32.7g/mL). Instead, the anti--amylase activity of carvacrol resulted in an ICvalue of 171.2g/mL After a pre-treatment with the maximum non-toxic dose of carvacrol and-cymene, the expression of caspase-3 was reduced compared to cells treated with HOalone. Carvacrol and-cymene showed in vitro anti-enzymatic properties, and may act as neuroprotective agents against oxidative stress. Further studies are necessary to elucidate their possible use as coadjutants in preventing and treating AD in diabetic patients.

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PMID:  Taiwan J Obstet Gynecol. 2023 Mar ;62(2):256-263. PMID: 36965892 Abstract Title:  The effect of carvacrol on the proinflammatory cytokines, histology, and fertility outcome of cisplatin-related ovarian change in a rat model. Abstract:  OBJECTIVE: In women, agents used in chemotherapy treatment have side effects such as accelerating follicular depletion and early menopause. Thus, cytotoxic treatments may cause various effects ranging from partial damage to the ovary to premature ovarian failure (POI) and infertility. This study aimed to investigate the protective effect of carvacrol on cisplatin (CIS)-induced reproductive toxicity in female rats.MATERIALS AND METHODS: The animals were divided to four groups; a healthy group (HG), administered only cisplatin 2.5 mg/kg (CIS); cisplatin 2.5 mg/kg + carvacrol mg/kg (CC-50), and cisplatin 2.5 mg/kg + carvacrol 100 mg/kg (CC-100). In this study, the CC-50 and CC-100 groups were injected with carvacrol at 50 and 100 mg/kg intraperitoneally (IP). The CIS and HG groupswere administered normal saline as a solvent in the same way. One hour afterwardthe CC-50 and CC-100 groups were injected with cisplatin at 2.5 mg/kg IP. This procedure was continued once a day for 14 days. At the end of this period, six rats from each group were euthanized with high-dose anaesthesia. Biochemical (oxidant-antioxidant and proinflammatory cytokines) and histopathological examinations were performed on the right ovarian tissue removed from the dead rats. The remaining (n = 6 in each group) animals were kept in the laboratory with mature male rats for two months for breeding. Rats that didn't give birth within two months were considered infertile. A one-way ANOVA test was used for the biochemical analysis, the a Kruskal Wallis test was used for the histopathological analysis.RESULTS: It has been observed that cisplatine causes oxidative stress and inflammatory damage in the ovarian tissue of animals and ultimately causes infertility due to this oxidative stress. While carvacrol significantly suppressed cisplatin-related oxidative stress in ovarian tissue at the 50 and 100 mg/kg doses, it could suppress proinflammatory cytokine increase only at thecytokine increase only at the 100 mg/kg dose. In addition, carvacrol significantly reduced the development of cisplatin-related infertility (from 0 to 83.3%) at a dose of 100 mg/kg.CONCLUSION: These findings suggest that carvacrol at high doses can reduce the harmful effects of cisplatin on the ovary and improve ovarian reserve in rats.

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PMID:  Environ Toxicol. 2023 Jul ;38(7):1535-1547. Epub 2023 Mar 22. PMID: 36947485 Abstract Title:  Carvacrol protects against-Cyhalothrin-induced hepatotoxicity and nephrotoxicity by modulating oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress, and autophagy. Abstract:  -Cyhalothrin, a type II synthetic pyrethroid, has been widely used in households, agriculture, public health, and gardening to control insect pests. Despite its widespread usage, it is known to induce a variety of adverse effects, including hepatotoxicity and nephrotoxicity. The goal of this study was to investigate the protective effect of carvacrol, which has antioxidant, anti-inflammatory, anti-apoptotic, and some other properties, on-Cyhalothrin-induced hepatotoxicity and nephrotoxicity 35 male Sprague-Dawley rats were randomly divided into five groups for this purpose: I-Control group: II-CRV group (50mg/kg carvacrol), III-LCT group (6.23mg/kg LCT), IV-LCT+CRV 25 group (6.23mg/kg LCT+25mg/kg carvacrol), and V-LCT+CRV 50 group (6.23mg/kg LCT+50mg/kg carvacrol). Using biochemical, real-time PCR, and western blotting methods, the collected tissues were analyzed. While-Cyhalothrin treatment increased MDA levels, which are indicated of lipid peroxidation, but reduced SOD, CAT, GPx activities, and GSH levels. After receiving carvacrol therapy, the degree of oxidative stress reduced as the values of these parameters approached those of the control group. Increased inflammation, apoptosis, endoplasmic reticulum stress, and autophagy with-Cyhalothrin administration reduced with carvacrol co-administration, and liver and kidney tissues were protected from damage, depending on the degree of oxidative stress. After considering all of these data, it was discovered that-Cyhalothrin-induced oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress, and autophagy in the liver and kidneys; however, carvacrol protected the tissues from damage. Our findings indicate that carvacrol may be a promising protective agent in-Cyhalothrin-induced hepatotoxicity and nephrotoxicity.

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PMID:  Biotech Histochem. 2023 Nov ;98(5):336-345. Epub 2023 Mar 13. PMID: 36912062 Abstract Title:  Carvacrol protects rat liver exposed to formaldehyde by regulating oxidative stress, and asprosin and subfatin hormones. Abstract:  Toxic doses of formaldehyde (FA) can cause oxidative damage and impair energy metabolism. Asprosin (ASP) and subfatin (SUB) are adipokines produced by adipose tissue that help regulate energy metabolism. We investigated the effects of carvacrol (CAR), an antioxidant with hepatoprotective properties, on ASP and SUB in rats exposed to FA using immunohistochemistry and biochemistry. We used 42 male Wistar albino rats divided into six groups of seven: group 1, untreated control; group 2, FA (10 ppm FA by inhalation 8 h/day, 5 days/week); group 3, CAR-20 (20 mg/kg); group 4, CAR-40; group 5, FA (10 ppm FA by inhalation 8 h/day, 5 days/week) + CAR-20 (20 mg/kg); group 6, FA (10 ppm FA by inhalation 8 h/day, 5 days/week) + CAR-40 (40 mg/kg). Levels of ASP and SUB, and total oxidant status (TOS) and total antioxidant status (TAS) in blood and liver tissue were measured using ELISA. ASP and SUB immunoreactivity was assessed using immunohistochemistry. The number of apoptotic cells was determined using the TUNEL method. The number of apoptotic cells in group 2 was increased compared to group 1. TOS in group 2 was increased compared to group 1. The numbers of apoptotic cells and TOS in group 3 were decreased compared to group 1. TOS was decreased in group 6 compared to group 2, but TOS was increased compared to group 1. We found ASP and SUB immunoreactivity in the liver. All alterations were reversed by addition of CAR. It appears that FA disrupts energy metabolism and CAR ameliorates the destructive effects of FA when used at appropriate doses, although CAR might be harmful at high doses.

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PMID:  Chem Biol Interact. 2023 Jun 1 ;378:110482. Epub 2023 Apr 10. PMID: 37044286 Abstract Title:  Galangin as an inflammatory response modulator: An updated overview and therapeutic potential. Abstract:  Numerous chronic diseases, such as cancer, diabetes, rheumatoid arthritis, cardiovascular disease, and gastrointestinal disorders, all have an inflammation-based etiology. In cellular and animal models of inflammation, flavonols were used to show potent anti-inflammatory activity. The flavonols enhanced the synthesis of the anti-inflammatory cytokines transforming growth factor and interleukin-10 (IL-10) and reduced the synthesis of the prostaglandins IL-6, tumor necrosis factor-alpha (TNF-), and prostaglandin E2 (PGE2), IL-1. Galangin (GAL), a natural flavonol, has a strong ability to control apoptosis and inflammation. GAL was discovered to suppress extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B)p65 phosphorylation, which results in anti-inflammatory actions. Arthritis, inflammatory bronchitis, stroke, and cognitive dysfunction have all been treated with GAL. The current review aimed to demonstrate the anti-inflammatory properties of GAL and their protective effects in treating various chronic illnesses, including those of the heart, brain, skin, lungs, liver, and inflammatory bowel diseases.

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PMID:  Eur J Pharmacol. 2023 Apr 15 ;945:175621. Epub 2023 Feb 26. PMID: 36849103 Abstract Title:  Galangin alleviated myocardial ischemia-reperfusion injury by enhancing autophagic flux and inhibiting inflammation. Abstract:  UNLABELLED: Autophagy is critically involved in myocardial ischemia-reperfusion (I/R). Autophagy inhibition exacerbates myocardial I/R injury. Few effective agents target autophagy to prevent myocardial I/R injury. Effective drugs that promote autophagy in myocardial I/R warrant further investigation. Galangin (Gal) enhances autophagy and alleviates I/R injury. Here we conducted both in vivo and in vitro experiments to observe the changes in autophagy after galangin treatment and investigated the cardioprotective effects of galangin on myocardial I/R.METHODS: After 45-min occlusion of the left anterior descending coronary artery, myocardial I/R was induced by slipknot release. One day before surgery and immediately after surgery, the mice were injected intraperitoneally with the same volume of saline or Gal. The effects of Gal were evaluated using echocardiography, 2,3,5-triphenyltetrazolium chloride staining (TTC staining), western blotting, and transmission electron microscopy. Primary cardiomyocytes and bone marrow-derived macrophages were extracted in vitro to measure the cardioprotective effects of Gal.RESULTS: Compared with the saline-treated group, Gal significantly improved cardiac function and limited infarct enlargement after myocardial I/R. In vivo and in vitro studies demonstrated that Gal treatment promoted autophagy during myocardial I/R. The anti-inflammatory effects of Gal were validated in bone marrow-derived macrophages. These results strongly suggest that Gal treatment can attenuate myocardial I/R injury.CONCLUSION: Our data demonstrated that Gal could improve left ventricular ejection fraction and reduce infarct size after myocardial I/R by promoting autophagy and inhibiting inflammation.

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PMID:  Life Sci. 2023 Jul 15 ;325:121754. Epub 2023 May 7. PMID: 37156395 Abstract Title:  Physical exercise alleviates oxidative stress in brown adipose tissue and causes changes in body composition and nutritional behavior in rats with polycystic ovary syndrome. Abstract:  AIM: Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder in women. We investigate the effect of physical exercise on body composition, nutritional parameters, and oxidative stress in rats with PCOS.METHODS: Female rats were into three groups: Control, PCOS, and PCOS + Exercise. PCOS was induced by letrozole (1 mg/kg via p.o.) for 21 days consecutively. Physical exercise was swimming, for 21 consecutive days, 1 h/day with 5 % load. In all groups, we assessed the nutritional and murinometric parameters, body composition, thermography, and oxidative stress in brown adipose tissue (BAT) and peri-ovarian adipose tissue (POAT).KEY FINDINGS: In PCOS we observed an increase (P 

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In the wake of the recent Select Subcommittee on the Weaponization of the Federal Government, internal documents produced by Mark Zuckerberg of Facebook, tell a horrid story of the White House (through the office of the Surgeon General Vivek H. Murthy) directing tech platforms to censor and label as 'misinformation' true stories of vaccine injury and side effects -- the very definition of a disinformation campaign.

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PMID:  Phytomedicine. 2023 Jul 25 ;116:154864. Epub 2023 May 9. PMID: 37182278 Abstract Title:  Lycium barbarum (Wolfberry) glycopeptide prevents stress-induced anxiety disorders by regulating oxidative stress and ferroptosis in the medial prefrontal cortex. Abstract:  BACKGROUND: Lycium barbarum (Wolfberry) extract has been shown to be effective in neuroprotection against aging or neural injury. Knowledge of its potential roles and biological mechanisms in relieving mental disorders, however, remains limited.PURPOSE: To investigate the potency of Lycium barbarum glycopeptide (LbGp) in alleviating anxiety disorders and the related biological mechanisms.METHODS: LbGp was administrated to mice subjected to 14 days of chronic restrain stress (CRS) via the intragastric route. The anxiolytic effect was evaluated by a battery of behavioral assays. The morphology of neurons and glial cells was evaluated, and cortical neuronal calcium transients were recorded in vivo. The molecular mechanism of LbGp was also investigated.RESULTS: LbGp effectively relieved anxiety-like and depressive behaviors under CRS. Mechanistic studies further showed that LbGp treatment relieved oxidative stress and lipid peroxidation in the medial prefrontal cortex (mPFC). In particular, the ferroptosis pathway was inhibited by LbGp, revealing a previously unrecognized mechanism of the anxiolytic role of wolfberry extract.CONCLUSION: In summary, our results supported the future development of LbGp to prevent or ameliorate stress-induced anxiety disorders. Our work provides a promising strategy for early intervention for pateitents with mental disorders by applying natural plant extracts.

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PMID:  Front Med (Lausanne). 2023 ;10:1092294. Epub 2023 Apr 25. PMID: 37181372 Abstract Title:  The effect of exercise intervention on improving sleep in menopausal women: a systematic review and meta-analysis. Abstract:  BACKGROUND: Sleep disturbance is common in menopausal women and negatively affects their quality of life and could cause increased risks of other menopause-related diseases.OBJECTIVE: This systematic review aims to synthesize evidence regarding the effects of exercise interventions on improving sleep in menopausal women.METHODS: A comprehensive search in seven electronic databases for randomized controlled trials (RCTs) was performed on June 3, 2022. The systematic review included seventeen trials, ten of which provided data for the meta-analysis. The effects on outcomes were presented as mean differences (MDs) or standard mean differences (SMDs) and their 95% confidence intervals (CI). Cochrane risk-of-bias tool was used in quality assessment.RESULTS: The results suggest that exercise intervention significantly reduces insomnia severity (SMD = -0.91, 95% CI = -1.45 to -0.36,= 3.27,= 0.001) and alleviates sleep problems (MD = -0.09, 95% CI = -0.17 to -0.01,= 2.20,= 0.03). For sleep quality, the results showed that insignificant differences were found between the exercise intervention and the control groups (MD = -0.93, 95% CI = -2.73 to 0.87, Z = 1.01,= 0.31). The results of the subgroup analysis indicated that more apparent effects of exercise intervention were found among women with sleep disorders than among women without sleep disorders. Which exercise intervention duration was more beneficial to sleep outcomes could not be judged. Overall, there was a moderate risk of bias in the primary studies.CONCLUSION: According to this meta-analysis, exercise interventions can be recommended for menopausal women to improve their sleep. High-quality RCTs applying different types of exercise (e.g., walking, yoga, meditative exercise and so on) with different intervention durations as well as subjective and objective sleep assessment are warranted.SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022342277, identifier: CRD42022342277.

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PMID:  Neurobiol Pain. 2023 ;13:100126. Epub 2023 Mar 21. PMID: 37179769 Abstract Title:  Influence of routine exercise on the peripheral immune system to prevent and alleviate pain. Abstract:  Routine physical activity reduces the onset of pain and exercise is a first line treatment for individuals who develop chronic pain. In both preclinical and clinical research regular exercise (routine exercise sessions) produces pain relief through multiple mechanisms such as alterations in the central and peripheral nervous system. More recently, it has been appreciated that exercise can also alter the peripheral immune system to prevent or reduce pain. In animal models, exercise can alter the immune system at the site of injury or pain model induction, in the dorsal root ganglia, and systemically throughout the body to produce analgesia. Most notably exercise shows the ability to dampen the presence of pro-inflammatory immune cells and cytokines at these locations. Exercise decreases M1 macrophages and the cytokines IL-6, IL-1, and TFN, while increasing M2 macrophages and the cytokines IL-10, IL-4, and IL-1ra. In clinical research, a single bout of exercise produces an acute inflammatory response, however repeated training can lead to an anti-inflammatory immune profile leading to symptom relief. Despite the clinical and immune benefits of routine exercise, the direct effect of exercise on immune function in clinical pain populations remains unexplored. This review will discuss in more detail the preclinical and clinical research which demonstrates the numerous ways through which multiple types of exercise alter the peripheral immune system. This review closes with the clinical implications of these findings along with suggestions for future research directions.

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PMID:  Int J Mol Sci. 2023 Apr 25 ;24(9). Epub 2023 Apr 25. PMID: 37175535 Abstract Title:  Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of IntegrinV/5 in Parkinson's Disease. Abstract:  Parkinson's disease with cognitive impairment (PD-CI) results in several clinical outcomes for which specific treatment is lacking. Although the pathogenesis of PD-CI has not yet been fully elucidated, it is related to neuronal plasticity decline in the hippocampus region. The dopaminergic projections from the substantia nigra to the hippocampus are critical in regulating hippocampal plasticity. Recently, aerobic exercise has been recognized as an effective therapeutic strategy for enhancing plasticity through the secretion of various muscle factors. The exact role of FNDC5-an upregulated, newly identified myokine produced after exercise-in mediating hippocampal plasticity and regional dopaminergic projections in PD-CI remains unclear. In this study, the effect of treadmill exercise on hippocampal synaptic plasticity was evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced chronic PD models. The results showed that treadmill exercise substantially alleviated the motor dysfunction, cognition disorder, and dopaminergic neuron degeneration induced by MPTP. Here, we discovered that the quadriceps, serum, and brain FNDC5 levels were lower in PD mice and that intervention with treadmill exercise restored FNDC5 levels. Moreover, treadmill exercise enhanced the synaptic plasticity of hippocampal pyramidal neurons via increased dopamine levels and BDNF in the PD mice. The direct protective effect of FNDC5 is achieved by promoting the secretion of BDNF in the hippocampal neurons via binding the integrinV5 receptor, thereby improving synaptic plasticity. Regarding the indirect protection effect, FNDC5 promotes the dopaminergic connection from the substantia nigra to the hippocampus by mediating the interaction between the integrinV5 of the hippocampal neurons and the CD90 molecules on the membrane of dopaminergic terminals. Our findings demonstrated that treadmill exercise could effectively alleviate cognitive disorders via the activation of the FNDC5-BDNF pathway and enhance the dopaminergic synaptic connection from SNpc to the hippocampus in the MPTP-induced chronic PD model.

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PMID:  Metabolism. 2023 Jul ;144:155584. Epub 2023 May 5. PMID: 37150437 Abstract Title:  Exercise alleviates neovascular age-related macular degeneration by inhibiting AIM2 inflammasome in myeloid cells. Abstract:  The neovascular form of age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Vascular endothelial growth factor (VEGF) plays a crucial role in choroidal neovascularization (CNV), and anti-VEGF therapy is recommended as first-line therapy for nvAMD. However, many patients do not radically benefit from this therapy. Epidemiological data suggest that physical exercise is beneficial for many human diseases, including nvAMD. Yet, its protective mechanism and therapeutic potential remain unknown. Here, using clinical samples and mouse models, we found that exercise reduced CNV and enhanced anti-angiogenic therapy efficacy by inhibiting AIM2 inflammasome activation. Furthermore, transfusion of serum from exercised mice transferred the protective effects to sedentary mice. Proteomic data revealed that exercise promoted the release of adiponectin, an anti-inflammatory adipokine from adipose tissue into the circulation, which reduced ROS-mediated DNA damage and suppressed AIM2 inflammasome activation in myeloid cells of CNV eyes through AMPK-p47phox pathway. Simultaneous targeting AIM2 inflammasome product IL-1and VEGF produced a synergistic effect for treating choroidal neovascularization. Collectively, this study highlights the therapeutic potential of an exercise-AMD axis and uncovers the AIM2 inflammasome and its product IL-1as potential targets for treating nvAMD patients and enhancing the efficacy of anti-VEGF monotherapy.

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PMID:  Eur J Nutr. 2023 May 17. Epub 2023 May 17. PMID: 37195485 Abstract Title:  Associations of serum vitamin C concentrations with risk of all-cause and cause-specific mortality among individuals with and without type 2 diabetes. Abstract:  PURPOSE: Compared with people without diabetes, people with type 2 diabetes (T2D) are at higher risk of both subnormal vitamin C status and increased oxidative stress. We aimed to investigate the associations of serum vitamin C concentrations with all-cause and cause-specific mortality among adults with and without T2D.METHODS: The current analysis included 20,045 adults (2691 people with T2D and 17,354 without T2D) from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2003-2006. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline analyses were used to examine the dose-response relationship.RESULTS: After a median follow-up of 17.3 years, 5211 deaths were documented. Individuals with T2D had a lower level of serum vitamin C concentrations compared with those without T2D (the median value: 40.1 vs. 44.9 mol/L). Furthermore, the dose-response relationship between serum vitamin C and mortality showed different patterns between participants with and without T2D. In individuals without T2D, there was a nonlinear association of serum vitamin C concentrations with all-cause, cancer, and CVD mortality, with the lowest risk around a serum vitamin C concentration of 48.0 mol/L (all P

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PMID:  PeerJ. 2023 ;11:e15356. Epub 2023 May 11. PMID: 37193034 Abstract Title:  The effect of FMT and vitamin C on immunity-related genes in antibiotic-induced dysbiosis in mice. Abstract:  Antibiotics are double-edged swords. Although antibiotics are used to inhibit pathogenic bacteria, they also run the risk of destroying some of the healthy bacteria in our bodies. We examined the effect of penicillin on the organism through a microarray dataset, after which 12 genes related to immuno-inflammatory pathways were selected by reading the literature and validated using neomycin and ampicillin. The expression of genes was measured using qRT-PCR. Several genes were significantly overexpressed in antibiotic-treated mice, including CD74 and SAA2 in intestinal tissues that remained extremely expressed after natural recovery. Moreover, transplantation of fecal microbiota from healthy mice to antibiotic-treated mice was made, where GZMB, CD3G, H2-AA, PSMB9, CD74, and SAA1 were greatly expressed; however, SAA2 was downregulated and normal expression was restored, and in liver tissue, SAA1, SAA2, SAA3 were extremely expressed. After the addition of vitamin C, which has positive effects in several aspects, to the fecal microbiota transplantation, in the intestinal tissues, the genes that were highly expressed after the fecal microbiota transplantation effectively reduced their expression, and the unaffected genes remained normally expressed, but the CD74 gene remained highly expressed. In liver tissues, normally expressed genes were not affected, but the expression of SAA1 was reduced and the expression of SAA3 was increased. In other words, fecal microbiota transplantation did not necessarily bring about a positive effect of gene expression restoration, but the addition of vitamin C effectively reduced the effects of fecal microbiota transplantation and regulated the balance of the immune system.

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PMID:  Mech Ageing Dev. 2023 Jun ;212:111823. Epub 2023 May 14. PMID: 37192676 Abstract Title:  Fecal microbiota transplantation holds the secret to youth. Abstract:  Aging shows itself not just at the cellular level, with shortened telomeres and cell cycle arrest, but also at the organ and organismal level, with diminished brainpower, dry eyes, intestinal inflammation, muscular atrophy, wrinkles, etc. When the gut microbiota, often called the "virtual organ of the host," fails to function normally, it can lead to a cascade of health problems including, but not limited to, inflammatory bowel disease, obesity, metabolic liver disease, type II diabetes, cardiovascular disease, cancer, and even neurological disorders. An effective strategy for restoring healthy gut bacteria is fecal microbiota transplantation (FMT). It can reverse the effects of aging on the digestive system, the brain, and the vision by transplanting the functional bacteria found in the excrement of healthy individuals into the gut tracts of patients. This paves the way for future research into using the microbiome as a therapeutic target for disorders associated with aging.

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PMID:  Aging Dis. 2023 Jun 1 ;14(3):964-1678. Epub 2023 Jun 1. PMID: 37191418 Abstract Title:  Gut Microbiota is an Impact Factor based on the Brain-Gut Axis to Alzheimer's Disease: A Systematic Review. Abstract:  Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis of AD has been explained using cholinergic,-amyloid toxicity, tau protein hyperphosphorylation, and oxidative stress theories. However, an effective treatment method has not been developed. In recent years, with the discovery of the brain-gut axis (BGA) and breakthroughs made in Parkinson's disease, depression, autism, and other diseases, BGA has become a hotspot in AD research. Several studies have shown that gut microbiota can affect the brain and behavior of patients with AD, especially their cognitive function. Animal models, fecal microbiota transplantation, and probiotic intervention also provide evidence regarding the correlation between gut microbiota and AD. This article discusses the relationship and related mechanisms between gut microbiota and AD based on BGA to provide possible strategies for preventing or alleviating AD symptoms by regulating gut microbiota.

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PMID:  Biomedicines. 2023 Mar 27 ;11(4). Epub 2023 Mar 27. PMID: 37189634 Abstract Title:  Fecal Microbiota Transplantation in Inflammatory Bowel Disease. Abstract:  Inflammatory bowel diseases represent a complex array of diseases of incompletely known etiology that led to gastrointestinal tract chronic inflammation. In inflammatory bowel disease, a promising method of treatment is represented by fecal microbiota transplantation (FMT), FMT has shown its increasing effectiveness and safety in recent years for recurrent CDI; moreover, it showed real clinical benefits in treating SARS-CoV-2 and CDI co-infection. Crohn's disease and ulcerative colitis are characterized by immune dysregulation, resulting in digestive tract damage caused by immune responses. Most current therapeutic strategies are associated with high costs and many adverse effects by directly targeting the immune response, so modifying the microbial environment by FMT offers an alternative approach that could indirectly influence the host's immune system in a safe way. Studies outline the endoscopic and clinical improvements in UC and CD in FMT patients versus control groups. This review outlines the multiple benefits of FMT in the case of IBD by improving patients unbalanced gut, therefore improving endoscopic and clinical symptomatology. We aim to emphasize the clinical importance and benefits of FMT in order to prevent flares or complications of IBD and to highlight that further validation is needed for establishing a clinical protocol for FMT in IBD.

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PMID:  Epidemiol Mikrobiol Imunol. 2023 ;72(1):40-53. PMID: 37185024 Abstract Title:  The gut microbiota, its relationship to the immune system, and possibilities of its modulation. Abstract:  Research of the gut microbiota allows a better understanding of its composition and function and reveals the links between changes in the composition of bacteria and various intestinal but also systemic diseases. The gut microbiota performs several of important functions in the host body and influences many physiological processes. Gut bacteria synthesize many compounds needed for the proper function of the body (e.g., vitamins, short-chain fatty acids, and amino acids). They help maintain the integrity of the intestinal barrier and protect against pathogens. The gut microbiota plays a crucial role in the development and function of the immune system. Significant changes in the composition of the intestinal microbiota led to a dysbiotic state and the loss of its beneficial functions for humans. The review article summarizes the basic knowledge about the composition and function of the bacterial gut microbiota in healthy people, its role in the development of the immune system, and the mechanisms involved in maintaining homeostasis. It also presents current knowledge about the possibility of targeted modulation of the bacterial gut microbiota and faecal transplantation.

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PMID:  J Autoimmun. 2023 May 11:103058. Epub 2023 May 11. PMID: 37179170 Abstract Title:  Fecal microbiota transplantation in the treatment of systemic lupus erythematosus: What we learnt from the explorative clinical trial. Abstract:  Systemic lupus erythematosus (SLE) is an autoimmune disease with the characterized presence of autoantibodies and resulting in multiple organ damage, which is incurable and can be lethal. The current treatments are limited and less progress has been made in drug discovery for the last few decades. Researches imply that gut dysbiosis exists in both patients and murine models with SLE, taking part in the pathogenesis of SLE through multiple mechanisms such as microbiota translocation and molecular mimicry. Intestinal interventions on the gut microbiome by fecal transplantations to reconstitute the gut-immunity homeostasis serve as a novel therapeutic option for SLE patients. Fecal microbiota transplantation (FMT), which is usually used in intestinal diseases, has been firstly demonstrated to be safe and efficient in recovering gut microbiota structure of SLE patients and reducing lupus activity in our recent clinical trial, which is the first trial testing FMT therapy in SLE treatment. In this paper, we reviewed the results of the single-arm clinical trial and made recommendations on FMT practice in SLE treatment including therapeutic indications, screening items and dosage regimen, trying to provide references for future study and clinical practice. We also came up with the unanswered questions that need to be solved by the ongoing randomized controlled trial as well as the future expectations for the intestinal intervention strategies of SLE patients.

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PMID:  Cell Host Microbe. 2023 May 10 ;31(5):695-711. PMID: 37167952 Abstract Title:  Beneficial effects of fecal microbiota transplantation in recurrent Clostridioides difficile infection. Abstract:  Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI). However, the mechanisms underpinning its clinical efficacy are incompletely understood. Herein, we provide an overview of rCDI pathogenesis followed by a discussion of potential mechanisms of action focusing on the current understanding of trans-kingdom microbial, metabolic, immunological, and epigenetic mechanisms. We then outline the current research gaps and offer methodological recommendations for future studies to elevate the quality of research and advance knowledge translation. By combining interventional trials with multiomics technology and host and environmental factors, analyzing longitudinally collected biospecimens will generate results that can be validated with animal and other models. Collectively, this will confirm causality and improve translation, ultimately to develop targeted therapies to replace FMT.

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PMID:  Front Physiol. 2023 ;14:1166685. Epub 2023 Apr 21. PMID: 37153213 Abstract Title:  The role and mechanism of the gut microbiota in the development and treatment of diabetic kidney disease. Abstract:  Diabetic kidney disease (DKD) is a common complication in patients with diabetes mellitus (DM). Increasing evidence suggested that the gut microbiota participates in the progression of DKD, which is involved in insulin resistance, renin-angiotensin system (RAS) activation, oxidative stress, inflammation and immunity. Gut microbiota-targeted therapies including dietary fiber, supplementation with probiotics or prebiotics, fecal microbiota transplantation and diabetic agents that modulate the gut microbiota, such as metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors. In this review, we summarize the most important findings about the role of the gut microbiota in the pathogenesis of DKD and the application of gut microbiota-targeted therapies.

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n/a PMID:  In Vitro Cell Dev Biol Anim. 2023 Apr ;59(4):264-276. Epub 2023 May 12. PMID: 37173557 Abstract Title:  Resveratrol inhibits LPS-induced apoptosis in bovine mammary epithelial cells: the role of PGC1-SIRT3 axis. Abstract:  Resveratrol (Res) is a bioactive dietary component and alleviates apoptosis in multiple cell types. However, its effect and mechanism on lipopolysaccharide (LPS)-induced bovine mammary epithelial cells (BMEC) apoptosis, which commonly happens in dairy cows with mastitis, is unknown. We hypothesized that Res would inhibit LPS-induced apoptosis in BMEC through SIRT3, a NAD+-dependent deacetylase activated by Res. To test the dose-response effect on apoptosis, 0-50 M Res were incubated with BMEC for 12 h, followed by 250 g/mL LPS treatment for 12 h. To investigate the role of SIRT3 in Res-mediated alleviation of apoptosis, BMEC were pretreated with 50 M Res for 12 h, then incubated with si-SIRT3 for 12 h and were finally treated with 250 g/mL LPS for 12 h. Res dose-dependently promoted the cell viability and protein levels of Bcl-2 (Linear P<0.001) but decreased protein levels of Bax, Caspase-3 and Bax/Bcl-2 (Linear P<0.001). TUNEL assays indicated that cellular fluorescence intensity declined with the rising doses of Res. Res also dose-dependently upregulated SIRT3 expression, but LPS had the opposite effect. SIRT3 silencing abolished these results with Res incubation. Mechanically, Res enhanced the nuclear translocation of PGC1, the transcriptional cofactor for SIRT3. Further molecular docking analysis revealed that Res could directly bind to PGC1by forming a hydrogen bond with Tyr-722. Overall, our data suggested that Res relieved LPS-induced BMEC apoptosis through the PGC1-SIRT3 axis, providing a basis for further in vivo investigations of applying Res to relieve mastitis in dairy cows.

PMID:  J Pharmacol Sci. 2023 Jun ;152(2):112-122. Epub 2023 Apr 11. PMID: 37169475 Abstract Title:  Resveratrol, a SIRT1 activator, attenuates aging-associated alterations in skeletal muscle and heart in mice. Abstract:  Aging is associated with impairment of multiple organs, including skeletal muscle and heart. In this study, we investigated whether resveratrol, an activator of an NAD-dependent protein deacetylase Sirtuin-1 (SIRT1), attenuates age-related sarcopenia and cardiomyocyte hypertrophy in mice. Treatment of mice with resveratrol (0.4 g/kg diet) from 28 weeks of age for 32 weeks prevented aging-associated shortening of rotarod riding time. In the tibialis anterior (TA) muscle, histogram analysis showed that the atrophic muscle was increased in 60-week-old (wo) mice compared with 20-wo mice, which was attenuated by resveratrol. In the heart, resveratrol attenuated an aging-associated increase in the cardiomyocyte diameter. Acetylated proteins were increased and autophagic activity was reduced in the TA muscle of 60-wo mice compared with those of 20-wo mice. Resveratrol treatment reduced levels of acetylated proteins and restored autophagic activity in the TA muscle. Aging-related reduction in myocardial autophagy was also suppressed by resveratrol. Skeletal muscle-specific SIRT1 knockout mice showed increases in acetylated proteins and atrophic muscle fibers and reduced autophagic activity in the TA muscle. These results suggest that activation of SIRT1 by treatment with resveratrol suppresses sarcopenia and cardiomyocyte hypertrophy by restoration of autophagy in mice.

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PMID:  Breast Cancer. 2023 May 11. Epub 2023 May 11. PMID: 37166625 Abstract Title:  Resveratrol exhibits diverse anti-cancer activities through epigenetic regulation of E-cadherin and p21 in triple-negative breast cancer cells. Abstract:  BACKGROUND: Triple-negative breast cancer (TNBC) has an aggressive phenotype and poor outcome, however no specific targeted therapy has been established for TNBC lacking germline BRCA1/2 pathogenic variants. To develop a novel therapeutic strategy, we explored the potential of resveratrol (RSV) for TNBC treatment.METHODS: We investigated the effects of RSV on malignant phenotypes of TNBC cells as well as on apoptosis induced by ABT263, a specific inhibitor of BCL-2 and BCL-xL, using morphological observation, migration assay,-galactosidase staining, and Hoechst staining. To elucidate the underlying mechanisms of RSV-mediated effects, expression levels and histone acetylation levels of cadherin 1 (CDH1, E-cadherin) and cyclin dependent kinase inhibitor 1A (CDKN1A, p21) were determined by RT-qPCR, western blotting, and chromatin immunoprecipitation. Furthermore, knockdown analysis was conducted to evaluate the involvement of E-cadherin and/or p21 in RSV potentiation on cytotoxic activity of ABT263.RESULTS: RSV treatment induced epithelial-like cellular morphology and suppressed the migration capacity in MDA-MB-231 and BT-549-Luc TNBC cells.-galactosidase-positive cells were increased after RSV treatment, indicating the induction of cellular senescence, in MDA-MB-231 cells but not in BT-549-Luc cells. RSV increased the expression and histone acetylation of CDH1 and CDKN1A in both cells. Interestingly, pre-treatment with RSV enhanced the induction of apoptosis in the ABT263-treated MDA-MB-231 and BT-549-Luc cells, and knockdown of CDKN1A decreased ABT263-induced apoptosis in RSV-treated MDA-MB-231 cells.CONCLUSIONS: RSV represses the metastatic capacity and enhances the cytotoxic activity of ABT263 in TNBC cells. Our results suggested that RSV can potentially be used as a repressor of metastasis or a sensitizer to ABT263 for TNBC treatment via up-regulation of CDH1 and CDKN1A through epigenetic mechanisms.

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PMID:  Neurotherapeutics. 2023 May 9. Epub 2023 May 9. PMID: 37160530 Abstract Title:  Nanoparticles Enhance Solubility and Neuroprotective Effects of Resveratrol in Demyelinating Disease. Abstract:  Resveratrol is a natural polyphenol which may be useful for treating neurodegenerative diseases such as multiple sclerosis (MS). To date, current immunomodulatory treatments for MS aim to reduce inflammation with limited effects on the neurodegenerative component of this disease. The purpose of the current study is to develop a novel nanoparticle formulation of resveratrol to increase its solubility, and to assess its ability to prevent optic nerve and spinal cord degeneration in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Resveratrol nanoparticles (RNs) were made using a thin rehydration technique. EAE mice received a daily oral administration of vehicle, RNs or unconjugated resveratrol for one month. They were assessed daily for clinical signs of paralysis and weekly for their visual acuity with optokinetic responses (OKR). After one month, their spinal cords and optic nerves were stained for inflammation and demyelination and retinal ganglion cells immunostained for Brn3a. RNs were stable for three months. The administration of RNs did not have any effect on clinical manifestation of EAE and did not preserve OKR scores but reduced the intensity of the disease. It did not reduce inflammation and demyelination in the spinal cord and the optic nerve. However, RNs were able to decrease RGC loss compared to the vehicle. Results demonstrate that resveratrol is neuroprotective by reducing RGC loss. Interestingly, neuroprotective effects and decreased disease severity occurred without reduction of inflammation or demyelination, suggesting this therapy may fill an unmet need to limit the neurodegenerative component of MS.

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This fall, in a series of ground-breaking water memory experiments to be conducted legendary CymaScope instrument is set to reveal insights into the mechanisms of homeopathy, as well shedding light on what the real purpose of the King's Chamber may be. 

To learn how you can contribute to this important research mission, join the upcoming AUREA event on June 9-11th, and please read on...

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PMID:  Physiol Res. 2023 Apr 30 ;72(2):187-198. PMID: 37159853 Abstract Title:  The effects of resveratrol and melatonin on cardiac dysfunction in diabetic elderly female rats. Abstract:  We aimed to investigate the effects of melatonin and resveratrol on diabetes-related papillary muscle dysfunction and structural heart disorders. The protective effect of resveratrol and melatonin supplementation on cardiac functions was investigated in a diabetic elderly female rat model. 16-month-old rats (n=48) were allocated into 8 groups. Group1: Control, Group2: Resveratrol Control, Group3: Melatonin Control, Group4: Resveratrol and Melatonin Control, Group5: Diabetes, Group6: Diabetes Resveratrol, Group7: Diabetes Melatonin, Group8: Diabetes Resveratrol and Melatonin. Streptozotocin was injected intraperitoneally to the rats for experimental diabetes induction. Thereafter, resveratrol (intraperitoneal) and melatonin (subcutaneous) were administered for 4 weeks. Resveratrol and melatonin had a protective effect on the contractile parameters and structural properties of the papillary muscle, which was impaired by diabetes. it has been presented that diabetes impairs the contractile function of the papillary muscle for each stimulus frequency tested and the responses obtained as a result of Ca+2 uptake and release mechanisms from the Sarcoplasmic reticulum, and it has been observed that these effects are improved with resveratrol and melatonin injection. The decrease in myocardial papillary muscle strength in the diabetic elderly female rat can be reversed with the combination of resveratrol, melatonin and resveratrol+melatonin. Melatonin+resveratrol supplementation is no different from melatonin and/or resveratrol supplementation. Resveratrol and melatonin supplementation may have a protective effect on cardiac functions in a diabetic elderly female rat model.

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PMID:  Int Immunopharmacol. 2023 May ;118:110111. Epub 2023 Apr 5. PMID: 37028275 Abstract Title:  Sodium tanshinone IIA sulfonate attenuates sepsis-associated brain injury via inhibiting NOD-like receptor 3/caspase-1/gasdermin D-mediated pyroptosis. Abstract:  BACKGROUND: Sodium tanshinone IIA sulfonate (STS) has been reported to protect organ function in sepsis. However, the attenuation of sepsis-associated brain injury and its underlying mechanisms by STS has not been established.METHODS: C57BL/6 mice were used to establish the cecal ligation perforation (CLP) model, and STS was injected intraperitoneally 30 min before the surgery. The BV2 cells were stimulated by lipopolysaccharide after being pre-treated with STS for 4 h. The STS protective effects against brain injury and in vivo anti-neuroinflammatory effects were investigated using the 48-hour survival rate and body weight changes, brain water content, histopathological staining, immunohistochemistry, ELISA, RT-qPCR, and transmission electron microscopy. The pro-inflammatory cytokines of BV2 cells were detected by ELISA and RT-qPCR. At last, the levels of NOD-like receptor 3 (NLRP3) inflammasome activation and pyroptosis in brain tissues of the CLP model and BV2 cells were detected using western blotting.RESULTS: STS increased the survival rate, decreased brain water content, and improved brain pathological damage in the CLP models. STS increased the expressions of tight junction proteins ZO-1 and Claudin5 while reducing the expressions of tumor necrosis factor(TNF-), interleukin-1(IL-1), and interleukin-18 (IL-18) in the brain tissues of the CLP models. Meanwhile, STS inhibited microglial activation and M1-type polarization in vitro and in vivo. The NLRP3/caspase-1/ gasdermin D (GSDMD)-mediated pyroptosis was activated in the brain tissues of the CLP models and lipopolysaccharide (LPS)-treated BV2 cells, which was significantly inhibited by STS.CONCLUSIONS: The activation of NLRP3/caspase-1/GSDMD-mediated pyroptosis and subsequent secretion of proinflammatory cytokines may be the underlying mechanisms of STS against sepsis-associated brain injury and neuroinflammatory response.

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PMID:  Cell Death Discov. 2023 May 19 ;9(1):172. Epub 2023 May 19. PMID: 37202382 Abstract Title:  Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth. Abstract:  Glioblastomas are a highly aggressive cancer type which respond poorly to current pharmaceutical treatments, thus novel therapeutic approaches need to be investigated. One such approach involves the use of the bioactive natural product Tanshinone IIA (T2A) derived from the Chinese herb Danshen, where mechanistic insight for this anti-cancer agent is needed to validate its use. Here, we employ a tractable model system, Dictyostelium discoideum, to provide this insight. T2A potently inhibits cellular proliferation of Dictyostelium, suggesting molecular targets in this model. We show that T2A rapidly reduces phosphoinositide 3 kinase (PI3K) and protein kinase B (PKB) activity, but surprisingly, the downstream complex mechanistic target of rapamycin complex 1 (mTORC1) is only inhibited following chronic treatment. Investigating regulators of mTORC1, including PKB, tuberous sclerosis complex (TSC), and AMP-activated protein kinase (AMPK), suggests these enzymes were not responsible for this effect, implicating an additional molecular mechanism of T2A. We identify this mechanism as the increased expression of sestrin, a negative regulator of mTORC1. We further show that combinatory treatment using a PI3K inhibitor and T2A gives rise to a synergistic inhibition of cell proliferation. We then translate our findings to human and mouse-derived glioblastoma cell lines, where both a PI3K inhibitor (Paxalisib) and T2A reduces glioblastoma proliferation in monolayer cultures and in spheroid expansion, with combinatory treatment significantly enhancing this effect. Thus, we propose a new approach for cancer treatment, including glioblastomas, through combinatory treatment with PI3K inhibitors and T2A.

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PMID:  Int Wound J. 2023 May 18. Epub 2023 May 18. PMID: 37203309 Abstract Title:  Fucoidan promotes angiogenesis and accelerates wound healing through AKT/Nrf2/HIF-1signalling pathway. Abstract:  After skin injury, wound repair involves a complex process in which angiogenesis plays a crucial role. Previous research has indicated that fucoidan may aid in wound healing; we therefore hypothesised that fucoidan may speed up the process by promoting angiogenesis. In this study, we investigated the potential molecular mechanism underlying fucoidan's ability to accelerate wound healing by promoting angiogenesis. Using a full-cut wound model, we observed that fucoidan significantly intensified wound closure and promoted granulation formation and collagen deposition. Immunofluorescence staining revealed that fucoidan also promoted wound angiogenesis, specifically by accelerating the migration of new blood vessels to the middle area of the wound. Furthermore, fucoidan demonstrated the ability to enhance the proliferation of human umbilical vein endothelial cells (HUVECs) damaged by hydrogen peroxide (HO) and to improve the formation of endothelial tubes. Mechanistic studies revealed that fucoidan upregulated the protein levels of the AKT/Nrf2/HIF-1signalling pathway, which plays a crucial role in angiogenesis. This was further confirmed using the inhibitor LY294002, which reversed the promotion of endothelial tube formation by fucoidan. Overall, our findings suggest that fucoidan can promote angiogenesis via the AKT/Nrf2/HIF-1signalling pathway and accelerate wound healing.

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Being targeted by my own government for exercising protected speech, and especially for telling the truth about the mRNA jabs in an attempt to warn the public before their roll-out has not been easy.

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Unredacted Facebook emails released by Rep. Jim Jordan today expose White House demands to quash narratives, and remove memes and posts contradicting the governments COVID-19 messaging.

Originally published on www.childrenshealthdefense.org by John-Michael Dumais

Unredacted Facebook emails released by Rep. Jim Jordan today expose White House demands to quash narratives, and remove memes and posts contradicting the government's COVID-19 messaging.

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