PMID:  Curr Med Chem. 2023 ;30(33):3775-3797. PMID: 36424777 Abstract Title:  The Radioprotective Potentials of Silymarin/Silibinin Against Radiotherapy- Induced Toxicities: A Systematic Review of Clinical and Experimental Studies. Abstract:  BACKGROUND: Although radiotherapy is one of the main cancer treatment modalities, exposing healthy organs/tissues to ionizing radiation during treatment can lead to different adverse effects. In this regard, it has been shown that the use of radioprotective agents may alleviate the ionizing radiation-induced toxicities.OBJECTIVE: The present study aims to review the radioprotective potentials of silymarin/silibinin in the prevention/reduction of ionizing radiation-induced adverse effects on healthy cells/tissues.METHODS: Based on PRISMA guidelines, a comprehensive and systematic search was performed for identifying relevant literature on the "potential protective role of silymarin/silibinin in the treatment of radiotherapy-induced toxicities" in the different electronic databases of Web of Science, PubMed, and Scopus up to April 2022. Four hundred and fifty-five articles were obtained and screened in accordance with the inclusion and exclusion criteria of the current study. Finally, 19 papers were included in this systematic review.RESULTS: The findings revealed that the ionizing radiation-treated groups had reduced survival rates and body weight in comparison with the control groups. It was also found that radiation can induce mild to severe adverse effects on the skin, digestive, hematologic, lymphatic, respiratory, reproductive, and urinary systems. Nevertheless, the administration of silymarin/silibinin could mitigate the ionizing radiation-induced adverse effects in most cases. This herbal agent exerts its radioprotective effects through anti-oxidant, anti-apoptosis, anti-inflammatory activities, and other mechanisms.CONCLUSION: The results of the current systematic review showed that co-treatment of silymarin/silibinin with radiotherapy alleviates the radiotherapy-induced adverse effects in healthy cells/tissues.

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PMID:  Arch Physiol Biochem. 2022 Nov 3:1-15. Epub 2022 Nov 3. PMID: 36328030 Abstract Title:  Silymarin inhibits the lipogenic pathway and reduces worsening of non-alcoholic fatty liver disease (NAFLD) in mice. Abstract:  CONTEXT: The role of silymarin in hepatic lipid dysfunction and its possible mechanisms of action were investigated.OBJECTIVE: To evaluate the effects of silymarin on hepatic and metabolic profiles in mice fed with 30% fructose for 8 weeks.METHODS: We evaluated the antioxidant profile of silymarin; mice consumed 30% fructose and were treated with silymarin (120mg/kg/day or 240mg/kg/day). We performed biochemical, redox status, and histopathological assays. RT-qPCR was performed to detect ACC-1, ACC-2, FAS, and CS expression, and western blotting to detect PGC-1levels.RESULTS: Silymarin contains high levels of phenolic compounds and flavonoids and exhibited significant antioxidant capacity, the fructose-fed groups showed increased levels of AST, ALT, SOD/CAT, TBARS, hepatic TG, and cholesterol, as well as hypertriglyceridaemia, hypercholesterolaemia, and increased ACC-1 and FAS. Silymarin treatment reduced these parameters and increased mRNA levels and activity of hepatic citrate synthase.CONCLUSIONS: These results suggest that silymarin reduces worsening of NAFLD.

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PMID:  Sci Rep. 2022 Sep 23 ;12(1):15872. Epub 2022 Sep 23. PMID: 36151457 Abstract Title:  Silymarin reduces retinal microvascular damage in streptozotocin-induced diabetic rats. Abstract:  Diabetic retinopathy is a severe microvascular problem in diabetes mellitus. Silymarin is a flavonoid compound, and according to previous studies, it is a bioactive compound with potent antioxidant and anti-inflammatory properties. This investigation aims to peruse the impact of silymarin against diabetic retinopathy in streptozotocin (STZ)-provoked rats. Thirty-two adult male Wistar rats were randomly allocated into the control group, STZ group, STZ+silymarin (50 mg/kg), and STZ+silymarin (100 mg/kg). STZ rats received silymarin every day until 2 months after diabetes induction. The serum and retinal tissues were collected 2 months after silymarin treatment to determine biochemical and molecular analyses. Silymarin markedly lowered the serum glucose concentration in diabetic rats. Silymarin reduced the increased levels of advanced glycosylated end products (AGEs), the receptors for AGEs (RAGE), and reactive oxygen species (ROS) in diabetic rats. Silymarin also attenuated the phosphorylation of p38 MAP kinase and nuclear factor (NF)-B p65 and diminished diabetes-induced overexpression of inflammatory cytokines, vascular endothelial growth factor (VEGF), adhesion molecules, and extracellular matrix proteins in STZ rats. Our data suggested that silymarin has protective effects against diabetic retinopathy, which might be related to the inhibition of the AGEs/RAGE axis and its antioxidant and anti-inflammatory activities.

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PMID:  Iran J Med Sci. 2022 Jul ;47(4):367-378. PMID: 35919076 Abstract Title:  Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels. Abstract:  BACKGROUND: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis.METHODS: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac-adrenergic receptors (-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan's multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P0.05.RESULTS: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE.CONCLUSION: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions.

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PMID:  Clin Nutr ESPEN. 2023 Apr ;54:436-442. Epub 2023 Feb 24. PMID: 36963891 Abstract Title:  Effects of adherence to the Mediterranean diet on fatigue and activities of daily living in geriatric individuals with COPD. Abstract:  BACKGROUND & AIMS: Fatigue is a commonly diagnosed symptom in cancers and many other chronic debilitating diseases. The second most important complaint after dyspnea in patients with Chronic Obstructive Pulmonary Disease (COPD) is the feeling of fatigue. Fatigue can have significant consequences on health status as it can limit patients' activities of daily living, lead to worsening prognosis, and is an indicator of mortality. It remains unclear how fatigue affects the daily life of COPD patients and what physical, social, and emotional challenges it brings. Some studies are showing that adhering to the Mediterranean diet significantly improves fatigue. In this study, the relationship between fatigue and adherence to a Mediterranean diet in COPD patients was investigated.METHODS: The present study is a descriptive, cross-sectional, and correlational study. The study population included65-year-old patients with a diagnosis of COPD who were hospitalized in Chest Diseases Clinics ofzmir Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital and Chest Diseases Clinic of Sivas Cumhuriyet University Hospital. The Personal Information Form, Mediterranean Diet Adherence Screener (MEDAS), COPD and Asthma Fatigue Scale (CAFS), and KATZ Activities of Daily Living Scale (Katz ADL) were used as data collection tools.RESULTS: Of the total 526 participants, 58.7% were men, 52.1% were overweight, 54.3% were ex-smokers, and 65.8% were non-drinkers. In the variables related to the disease, the mean duration of having COPD was 16.41 (SD 5.26) years. According to the GOLD classification of the participants, the severity of the disease was determined as Stage III in 57.4% of them, and the severity of dyspnea was determined as "3" (moderate severity) in 54.5% of them according to the mMRC scale. According to the results of the analysis, the mean MEDAS score was 7.84 (SD: 2.76). According to the participants' levels of adherence to the MD, of them, 43.8% had high adherence to MD and 29% had low adherence to MD. The mean CAFS score indicating the level of disease-related fatigue was 69.17 (SD: 15.73), and the lowest and highest scores were 25 and 100 respectively. According to the independence in activities of daily living of the participants, 77.3% were semi-dependent and 6.4% were independent. The comparison of the level of the participant's adherence to the MD according to their mean CAFS scores demonstrated that those who had high adherence to the MD obtained significantly lower scores than the participants in the other groups (p 

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PMID:  Curr Mol Med. 2023 Mar 20. Epub 2023 Mar 20. PMID: 36959141 Abstract Title:  Neuroprotective Potential of Hesperidin as Therapeutic Agent in the Treatment of Brain Disorders: Preclinical Evidence-based Review. Abstract:  Neurodegenerative disorders (NDs) are progressive morbidities that represent a serious health issue in the aging world population. There is a contemporary upsurge in worldwide interest in the area of traditional remedies and phytomedicines are widely accepted by researchers due to their health-promoted effects and fewer side effects. Hesperidin, a flavanone glycoside present in the peels of citrus fruits, possesses various biological activities including anti-inflammatory and antioxidant actions. In various preclinical studies, hesperidin has provided significant protective actions in a variety of brain disorders such as Alzheimer's disease, epilepsy, Parkinson's disease, multiple sclerosis, depression, neuropathic pain, etc. as well as their underlying mechanisms. The findings indicate that the neuroprotective effects of hesperidin are mediated by modulating antioxidant defence activities and neural growth factors, diminishing apoptotic and neuro-inflammatory pathways. This review focuses on the potential role of hesperidin in managing and treating diverse brain disorders.

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PMID:  Biochem Pharmacol. 2023 Apr ;210:115467. Epub 2023 Feb 26. PMID: 36849063 Abstract Title:  Geraniol ameliorates acute liver failure induced by lipopolysaccharide/D-galactosamine via regulating macrophage polarization and NLRP3 inflammasome activation by PPAR-methylation Geraniol alleviates acute liver failure. Abstract:  Geraniol (Ger), a natural acyclic monoterpene alcohol, has been reported to exert protective effects through anti-inflammation in Acute liver failure (ALF). However, its specific roles and precise mechanisms underlying anti-inflammatory effects in ALF have not yet fully explored. We aimed to investigated the hepatoprotective effects and mechanisms of Ger against ALF induced by lipopolysaccharide (LPS)/D-galactosamine (GaIN). In this study, the liver tissue and serum of LPS/D-GaIN-induced mice were collected. The degree of liver tissue injury was evaluated by HE and TUNEL staining. Serum levels of liver injury markers (ALT and AST) and inflammatory factors were measured by ELISA assays. PCR and western blotting were conducted to determine the expression of inflammatory cytokines, NLRP3 inflammasome-related proteins, PPAR-pathway-related proteins, DNA Methyltransferases and M1/M2 polarization cytokines. Immunofluorescence staining was used to assess the localization and expression of macrophage markers (F4/80 and CD86), NLRP3 and PPAR-. In vitro experiments were performed in macrophages stimulated with LPS with or without IFN-. Purification of macrophages and cell apoptosis was analyzed using flow cytometry. We found that Ger effectively alleviated ALF in mice, specified by the attenuation of liver tissue pathological damage, inhibition of ALT, AST and inflammatory factor levels, and inactivation of NLRP3 inflammasome. Meanwhile, downregulation M1 macrophage polarization may involve in the protective effects of Ger. In vitro, Ger reduced the activation of NLRP3 inflammasome and apoptosis through regulating PPAR-methylation by inhibiting M1 macrophage polarization. In conclusion, Ger protects against ALF through suppressing NLRP3 inflammasome-mediated inflammation and LPS-induced macrophage M1 polarization via modulating PPAR-methylation.

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PMID:  Front Immunol. 2023 ;14:1138215. Epub 2023 Mar 7. PMID: 36960064 Abstract Title:  Pharmacological potential of(L.) Dunal and(Willd.) Miers on the experimental models of COVID-19, T cell differentiation, and neutrophil functions. Abstract:  Cytokine release syndrome (CRS) due to severe acute respiratory coronavirus-2 (SARS-CoV-2) infection leads to life-threatening pneumonia which has been associated with coronavirus disease (COVID-19) pathologies. Centuries-old Asian traditional medicines such as(L.) Dunal (WS) andWilld.) Miers (TC) possess potent immunomodulatory effects and were used by the AYUSH ministry, in India during the COVID-19 pandemic. In the present study, we investigated WS and TC's anti-viral and immunomodulatory efficacy at the human equivalent doses using suitableandmodels. While both WS and TC showed immuno-modulatory potential, WS showed robust protection against loss in body weight, viral load, and pulmonary pathology in the hamster model of SARS-CoV2.pretreatment of mice and human neutrophils with WS and TC had no adverse effect on PMA, calcium ionophore, and TRLM-induced ROS generation, phagocytosis, bactericidal activity, and NETs formation. Interestingly, WS significantly suppressed the pro-inflammatory cytokines-induced Th1, Th2, and Th17 differentiation. We also used hACE2 transgenic mice to further investigate the efficacy of WS against acute SARS-CoV2 infection. Prophylactic treatment of WS in the hACE2 mice model showed significant protection against body weight loss, inflammation, and the lung viral load. The results obtained indicate that WS promoted the immunosuppressive environment in the hamster and hACE2 transgenic mice models and limited the worsening of the disease by reducing inflammation, suggesting that WS might be useful against other acute viral infections. The present study thus provides pre-clinical efficacy data to demonstrate a robust protective effect of WS against COVID-19 through its broader immunomodulatory activity.

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PMID:  Cureus. 2023 Mar ;15(3):e36168. Epub 2023 Mar 15. PMID: 36937128 Abstract Title:  A Study of Efficacy and Safety of Ashwagandha (Withania somnifera) Lotion on Facial Skin in Photoaged Healthy Adults. Abstract:  Background Facial skin has an essential cosmetic function in both men and women, and photoaged skin can affect the quality of life in healthy people. Ashwagandha () which is also called Indian ginseng has adaptogenic properties and is used in traditional Indian medicine to maintain balance, energize, and rejuvenate. Objective This randomized, double-blind, and placebo-controlled study assessed the efficacy and safety of topical application of lotion containing 8% standardized Ashwagandha root extract on improvement of skin parameters in the photoaged facial skin of healthy subjects. Methods Fifty-six healthy men and women aged between 18 and 60 years with Fitzpatrick phototype III-VI skin grade were randomized to receive the topical application (lotion on facial skin) of either Ashwagandha 8% (AG, n=28), or an identical placebo (PL, n=28) for 60 days. The primary outcome was the change from baseline on day 60 in the scores for global physician assessment scoring for the five dermatological signs (skin wrinkles, pores, hydration/moisture, skin brightness/tone, and pigmentation) on facial skin. Secondary outcomes were changes from baseline in the transepidermal water loss (TEWL), melanin index, hydration, and skin elasticity (R2 ratio). Another efficacy outcome was quality of life using the health-specific Short Form Health Survey-12 (SF-12). Safety was assessed using local reactions and adverse events. Three (1 AG, 2 PL) patients were lost to follow-up and per-protocol (PP) data included 53 patients (27 AG, 26 PL). For measurement data, repeated measures analysis of variance (ANOVA) was used to assess treatment effect at different time periods in the PP dataset (n=53). Two groups were compared for differences using a t-test for continuous data or a Mann-Whitney 'U' test for ordinal data. Adverse events were compared between two groups using the chi-square test. Results Greater reduction (p

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PMID:  Pharmacology. 2023 ;108(3):301-307. Epub 2023 Feb 8. PMID: 36754044 Abstract Title:  Alkaloids in Withania somnifera (L.) Dunal Root Extract Contribute to Its Anti-Inflammatory Activity. Abstract:  The anti-inflammatory properties of the medicinal plant Withania somnifera (L.) Dunal (WS) are generally related to withanolides; consistently, several strategies are under investigation to increase the concentration of these compounds in WS extracts. However, a potential toxicity of withanolides has been highlighted, thus questioning the safety of such preparations. At variance, the relative contribution of alkaloids is underrated, in spite of preliminary evidence underlining a possible pharmacological relevance. Starting from these considerations, the efficacy/safety profile of WS root extract (WSE) was compared with those of WS extracts which are enriched in alkaloids (WSA) and withanolides (WSW), respectively. MTT assay was used to evaluate cell viability. The anti-inflammatory activities of the different extracts were estimated throughout the assessment of the inhibition of lipopolysaccharide (LPS)-activated release of nitric oxide (NO) and the upregulation of iNOS and COX-2 protein in RAW 264.7 cells. Both WSA and WSW were able to reduce LPS-mediated effects in RAW 264.7 cells, suggesting that alkaloids and withanolides may contribute to the anti-inflammatory activity of WSE. A significant higher anti-inflammatory activity and a lower toxicity were observed when WSA was compared to WSW. The present results highlighted that the contribution of alkaloids to WS pharmacological effects should not be neglected. Particularly, these compounds may concur to reach a more advantageous efficacy/safety profile when WS is used for anti-inflammatory purposes.

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PMID:  Invest New Drugs. 2023 Feb ;41(1):134-141. Epub 2023 Jan 24. PMID: 36692618 Abstract Title:  Viscosalactone B, a natural LSD1 inhibitor, inhibits proliferation in vitro and in vivo against prostate cancer cells. Abstract:  Lysine-specific demethylase 1 (LSD1) has been a promising target to treat prostate cancer, and discovery of novel LSD1 inhibitors would have great clinical significance. In this work, viscosalactone B was first identified as a novel LSD1 inhibitor. Viscosalactone B isolated from Withania Somnifera displayed antiproliferative activity against PC3, DU145, C42B, PC3/MDVR, DU145/MDVR, and C42B/MDVR cells with ICvalues of 1.17, 0.72, 3.86, 2.06, 0.96 and 1.15 M, respectively. In comparison, it was a selective LSD1 inhibitor with an ICvalue of 970.27 nM and could induce a significant accumulation of LSD1 substrates H3K9me1, H3K9me2, and H3K4me1 in a concentration-dependent manner in DU145 cells. According to docking studies, it formed hydrogen bonds with the Thr11, Lys14, and Arg8 residues of LSD1. Importantly, while it displayed potent antitumor efficacy in vivo, it did not show obvious cytotoxicity on the major organs of nude mice. Therefore, viscosalactone B, as a novel LSD1 inhibitor, is a potential candidate that can be used for the treatment of prostate cancer in clinics.

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PMID:  J Cell Mol Med. 2023 May ;27(9):1250-1260. Epub 2023 Mar 27. PMID: 36967712 Abstract Title:  Hispolon induces apoptosis in oral squamous cell carcinoma cells through JNK/HO-1 pathway activation. Abstract:  Oral squamous cell carcinoma (OSCC) has a high recurrence rate and poor prognosis. Hispolon, a polyphenolic compound with antiviral, antioxidant, and anticancer activities, is a potential chemotherapy agent. However, few studies have investigated the anti-cancer mechanism of hispolon in oral cancer. This present study used the cell viability assay, clonogenic assay, fluorescent nuclear staining, and flow cytometry assay to analyse the apoptosis-inducing effects of hispolon in OSCC cells. After hispolon treatment, the apoptotic initiators, cleaved caspase-3, -8, and-9, were upregulated, whereas the cellular inhibitor of apoptosis protein-1 (cIAP1) was downregulated. Furthermore, a proteome profile analysis using a human apoptosis array revealed the overexpression of heme oxygenase-1 (HO-1) by hispolon, which was determined to be involved in caspase-dependent apoptosis. Moreover, cotreatment with hispolon and mitogen-activated protein kinase (MAPK) inhibitors revealed that hispolon induces apoptosis in OSCC cells through activation of the c-Jun N-terminal kinase (JNK) pathway and not the extracellular signal-regulated kinase (ERK) or p38 pathway. These findings indicate that hispolon may exert an anticancer effect on oral cancer cells by upregulating HO-1 and inducing caspase-dependent apoptosis by activating the JNK pathway.

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PMID:  Int J Mol Sci. 2022 Nov 21 ;23(22). Epub 2022 Nov 21. PMID: 36430965 Abstract Title:  Hispolon Cyclodextrin Complexes and Their Inclusion in Liposomes for Enhanced Delivery in Melanoma Cell Lines. Abstract:  Hispolon, a phenolic pigment isolated from the mushroom species Phellinus linteus, has been investigated for anti-inflammatory, antioxidant, and anticancer properties; however, low solubility and poor bioavailability have limited its potential clinical translation. In this study, the inclusion complex of hispolon with Sulfobutylether--cyclodextrin (SBECD) was characterized, and the Hispolon-SBECD Complex (HSC) was included within the sterically stabilized liposomes (SL) to further investigate its anticancer activity against melanoma cell lines. The HSC-trapped-Liposome (HSC-SL) formulation was investigated for its sustained drug delivery and enhanced cytotoxicity. The inclusion complex in the solid=state was confirmed by a Jobs plot analysis, molecular modeling, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Proton nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy (SEM). The HSC-SL showed no appreciable deviation in size (

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PMID:  Arch Biochem Biophys. 2022 Sep 30 ;727:109303. Epub 2022 May 31. PMID: 35660410 Abstract Title:  Hispolon alleviates oxidative damage by stimulating the Nrf2 signaling pathway in PC12 cells. Abstract:  Natural products derived from the daily diet are garnering increasing attention for neurodegenerative disease (ND) treatment. Hispolon (His), a small molecule from Phellinus linteus, has been reported to have various pharmacological activities. Here, we evaluated its protective effect on a neuron-like rat pheochromocytoma cell line (PC12). Results showed that His could restore cell death induced by oxidative damage. Nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) plays a significant role in maintaining cellular redox homeostasis. After treatment with His, some Nrf2-governed antioxidant genes were upregulated in a dose-dependent manner. However, the protective effect of His on PC12 cells was easily terminated by Nrf2 knockdown, demonstrating that Nrf2 is a critical component in this cytoprotective process. Taken together, our study showed that His was not only an effective activator of Nrf2 but also a promising candidate for ND treatment.

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PMID:  Molecules. 2021 Jul 26 ;26(15). Epub 2021 Jul 26. PMID: 34361649 Abstract Title:  Hispolon Induces Apoptosis, Suppresses Migration and Invasion of Glioblastoma Cells and Inhibits GBM Xenograft Tumor Growth In Vivo. Abstract:  Hispolon, a polyphenol compound isolated from, has been reported to exhibit antioxidant, antiproliferative, and antitumor activities. This study aimed to explore the antitumor effects of hispolon on glioblastoma multiforme (GBM) cells in vitro and in vivo. The results revealed that hispolon significantly inhibited GBM cell proliferation and induced apoptosis through caspase-9 and caspase-3 activation and PARP cleavage. Hispolon also induced cell cycle G2/M phase arrest in GBM cells, as supported by flow cytometry analysis and confirmed by a decrease in cyclin B1, cdc2, and cdc25c protein expressions in a dose- and time-dependent manner. Furthermore, hispolon suppressed the migration and invasion of GBM cells by modulating epithelial-mesenchymal transition (EMT) markers via wound healing, transwell assays, and real-time PCR. Moreover, hispolon significantly reduced tumor growth in DBTRG xenograft mice and activated caspase-3 in hispolon-treated tumors. Thus, our findings revealed that hispolon is a potential candidate for the treatment of GBM.

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n/a PMID:  Immunol Lett. 2021 Mar ;231:35-42. Epub 2021 Jan 8. PMID: 33428992 Abstract Title:  Hispolon inhibits RANKL induced osteoclast differentiation in vitro. Abstract:  Hispolon (HISP) is a bioactive compound isolated from Phellinu linteus. It has various pharmacological activities, including antioxidant, anti-inflammatory, and anti-cancer. However, its anti-osteoclastogenic activity has not yet been reported. Hence, in the current study, we have explored the anti-osteoclastogenic activity of HISP and elucidated the molecular mechanisms. HISP inhibited the RANKL induced differentiation of RAW 264.7 cells into osteoclasts in a dose-dependent manner. Mechanistic studies showed that HISP inhibited RANKL-mediated activation of NF-B and MAPK signaling pathways in osteoclast precursors RAW 264.7 cells. In addition, Hispolon also downregulated the expression of master transcriptional factors essential for osteoclast differentiation, such as NFATc1 and c-FOS. In conclusion, these findings establish molecular mechanisms behind the anti-osteoclastogenic activity of HISP.

PMID:  Int J Med Mushrooms. 2019 ;21(4):381-392. PMID: 31002633 Abstract Title:  Methyl-Hispolon from Phellinus lonicerinus (Agaricomycetes) Affects Estrogen Signals in MCF-7 Breast Cancer Cells and Premature Aging in Rats. Abstract:  We studied Phellinus lonicerinus to determine the cytotoxic effect and the dual estrogenic activities of methyl-hispolon and their relation to estrogen signals in vivo and in vitro. The Glide scores of methyl-hispolon-estrogen receptor(ER) and methyl-hispolon-ERdocked complexes were -7.29 kcal/mol and -6.68 kcal/mol in docking simulations. Methyl-hispolon had a significant antiproliferative effect for estrogen-sensitive ER(+) MCF-7 cells in the absence of estrogen, and it exhibited dual estrogen activities. Methyl-hispolon increased the serum E2 in rats with premature ovarian failure and fulfilled the estrogenic function in the uterus and ovary. Methyl-hispolon significantly inhibited the expression of Ras, API, ER, C-myc, and cyclinDl, as well as their gene transcription in RL95-2 cells. The phosphorylation of ERK1/2 was inhibited by methyl-hispolon. Thus, methyl-hispolon has potential use in treating estrogen deficiency-related diseases, with good antitumor effects and estrogenic activity.

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PMID:  Nutrients. 2023 Feb 2 ;15(3). Epub 2023 Feb 2. PMID: 36771459 Abstract Title:  Malvidin-3--Glucoside Ameliorates Cadmium-Mediated Cell Dysfunction in the Estradiol Generation of Human Granulosa Cells. Abstract:  Cadmium (Cd) is a frequent environmental pollutant associated with biological toxicity that can harm female reproduction. Anthocyanins have been reported to reduce the toxicity of Cd. In the present study, the protective effects and underlying mechanisms of malvidin-3--glucoside (M3G) against the toxicity of Cd on female reproduction in KGN cells (human ovarian granulosa-like tumor cells) were investigated. After treating cells with 10mol/L cadmium chloride, the results showed that M3G lessened Cd-induced KGN cell cytotoxicity better than malvidin and malvidin-3,5--diglucoside. Additionally, M3G significantly decreased the Cd-induced generation of reactive oxygen species, inhibited the Cd-induced arrest of the G2/M phase of the cell cycle, and increased estradiol (E2) production. According to transcriptomic results, M3G reduced the abnormal expression of genes that responded to estrogen. Additionally, M3G promoted the endogenous synthesis and secretion of E2 by controlling the expression of CYP17A1 and HSD17B7. The current findings indicated that M3G is of great potential to prevent Cd-induced female reproductive impairment as a dietary supplement.

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PMID:  Front Pharmacol. 2022 ;13:1038802. Epub 2023 Jan 9. PMID: 36699054 Abstract Title:  Malvidin alleviates mitochondrial dysfunction and ROS accumulation through activating AMPK-/UCP2 axis, thereby resisting inflammation and apoptosis in SAE mice. Abstract:  This study aimed to explore the protective roles of malvidin in life-threatened sepsis-associated encephalopathy (SAE) and illustrate the underlying mechanism. SAE mice models were developed and treated with malvidin for subsequently protective effects evaluation. Malvidin restored neurobehavioral retardation, declined serum S100and NSE levels, sustained cerebrum morphological structure, improved blood-brain barrier integrity with elevated tight junction proteins, and decreased evans blue leakage, and finally protect SAE mice from brain injury. Mechanistically, malvidin prevented cerebrum from mitochondrial dysfunction with enhanced JC-1 aggregates and ATP levels, and ROS accumulation with decreased lipid peroxidation and increased antioxidant enzymes. UCP2 protein levels were found to be decreased after LPS stimulation in the cerebrum and BV-2 cells, and malvidin recovered its levels in a ROS dependent manner.inhibition of UCP2 with genipin orinterference with siRNA UCP2 both disrupted the mitochondrial membrane potential, decreased ATP levels and intensified DCF signals, being a key target for malvidin. Moreover, dorsomorphin block assays verified that malvidin upregulated UCP2 expression through phosphorylating AMPK in SAE models. Also, malvidin alleviated SAE progression through inhibition of ROS-dependent NLRP3 inflammasome activation mediated serum pro-inflammatory cytokines secretion and mitochondrial pathway mediated apoptosis with weakened apoptosis body formation and tunel positive signals, and decreased Bax, cytochrome C, caspase-3 and increased Bcl-2 protein levels. Overall, this study illustrated that malvidin targeted AMPK-/UCP2 axis to restore LPS-induced mitochondrial dysfunction and alleviate ROS accumulation, which further inhibits NLRP3 inflammasome activation and mitochondrial apoptosis in a ROS dependent way, and ultimately protected SAE mice, providing a reference for the targeted development of SAE prophylactic approach.

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PMID:  Metabolites. 2022 Nov 3 ;12(11). Epub 2022 Nov 3. PMID: 36355145 Abstract Title:  Antiadhesive and Antibiofilm Effect of Malvidin-3-Glucoside and Malvidin-3-Glucoside/Neochlorogenic Acid Mixtures upon. Abstract:  Several reports on the biological activity of anthocyanin-rich extracts have been made. However, despite the association of said activity with their anthocyanin content, to the best of our knowledge, there are no previous works regarding the antimicrobial, antibiofilm and/or antiadhesive properties of anthocyanins alone. Therefore, the present work aimed to determine the effects of malvidin-3-glucoside, a major component of a previously reported extract, and the impact of its association with neochlorogenic acid (the only non-anthocyanin phenolic present in said extract), upon severalstrains with varying resistance profiles. Results show that, while malvidin-3-glucoside and malvidin-3-glucoside/neochlorogenic acid mixtures were unable to considerably inhibit bacterial growth after 24 h, they still possessed an interesting antibiofilm activity (with reductions of biofilm entrapped cells up to 2.5 log cycles, metabolic inhibition rates up to 81% and up to 51% of biomass inhibition). When considering the bacteria's capacity to adhere to plain polystyrene surfaces, the inhibition ranges were considerably lower (21% maximum value). However, when considering polystyrene surfaces coated with plasmatic proteins this value was considerably higher (45% for adhesion in the presence of extract and 39% for adhesion after the surface was exposed to extract). Overall, the studied anthocyanins showed potential as future alternatives to traditional antimicrobials in adhesion and biofilm formation prevention.

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PMID:  Eur J Pharmacol. 2022 Oct 15 ;933:175252. Epub 2022 Sep 2. PMID: 36063870 Abstract Title:  Malvidin protects against lipopolysaccharide-induced acute liver injury in mice via regulating Nrf2 and NLRP3 pathways and suppressing apoptosis and autophagy. Abstract:  Sepsis-related acute liver injury (ALI) is a fatal disease associated with many complications. Recent studies indicate that malvidin, an active flavonoid, has multiple bioactivities including anti-oxidant and anti-inflammation. However, the protective roles of malvidin against LPS-induced ALI are unknown. The purpose of this research is to explore whether malvidin has biological activities on LPS-induced ALI in mice and the underlying mechanisms. Male C57 mice were injected intraperitoneally with malvidin for five days and the mice were euthanized 6 h after LPS (10 mg/kg body weight) intraperitoneal injection. Multiple methods of H&E staining, biochemical kits, qRT-PCR assay, western blotting analysis, TUNEL and transmission electron microscope (TEM) were used. Results showed that decreased ALT, AST levels and alleviated histopathological damage of liver tissue were observed in malvidin pretreatment group in mice. Then, malvidin prevented LPS-induced reduction of antioxidant enzyme activities such as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) via up-regulating nuclear factor E2-related factor2 (Nrf2) pathway. In addition, in malvidin pretreatment groups, mRNA levels of pro-inflammatory cytokines (TNF-IL-1, IL-6) and protein levels of NOD-like receptor protein 3 (NLRP3) inflammasome in the liver were significantly down-regulated. We also found that the malvidin could reduce the expression of apoptosis key protein and TUNEL-labeled apoptotic hepatocytes. Furthermore, malvidin inhibited the protein expression of ATG5, p62 and the ratio of LC3-II/LC3-I. In conclusion, our study firstly suggests that malvidin is a potentially protective agent against LPS-induced ALI through up-regulating Nrf2 signaling pathway, suppressing NLRP3 inflammasome and inhibiting apoptosis and autophagy.

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PMID:  J Sci Food Agric. 2023 Jul ;103(9):4638-4648. Epub 2023 Mar 31. PMID: 36935348 Abstract Title:  Blueberry extract alleviated lipopolysaccharide-induced inflammation responses in mice through activating the FXR/TGR5 signaling pathway and regulating gut microbiota. Abstract:  BACKGROUND: Blueberry extract (BE) is rich in phenols, especially anthocyanins. Anthocyanins regulate the inflammatory response in mice and may be related to gut microbiota and bile acid receptors. The aim of the present study was to explore the effects of BE on the inflammatory response by regulating gut microbiota and bile acid receptors in mice administered Escherichia coli lipopolysaccharide (LPS).METHOD: Thirty male KM mice were randomly divided into three groups: CON (control diet) group; LPS (LPS stimulation) group; and LPS+BE (LPS stimulation, 5% BE intervention) group.RESULTS: our results showed that, compared with the LPS group, the addition of BE decreased the level of inflammatory factors in serum and tissues, inhibited the TLR4/MyD88 signaling pathway, protected the intestinal barrier and activated FXR/TGR5, which was related to gut microbiota (especially Akkermansia). The active component (e.g., cyanidin 3-O-glucoside, C3G) in BE may be an important factor in regulating gut microbiota.CONCLUSION: BE alleviated the inflammatory response mainly by activating bile acid receptor expression and regulating the gut microbiota; this effect may be related to the composition of bioactive substances in BE.2023 Society of Chemical Industry.

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PMID:  Eur J Med Res. 2022 Nov 28 ;27(1):267. Epub 2022 Nov 28. PMID: 36437468 Abstract Title:  The combination of olive oil and Lepidium sativum improves the deleterious effects resulting from dexamethasone-induced osteoporosis in rats. Abstract:  INTRODUCTION: Osteoporosis is characterized by deterioration of bone microarchitecture and reduced bone mass and can increase the risk of fracture. To reduce this risk, the aim of this study was to compare the combination effects of olive oil and Lepidium sativum compared to the conventional drug therapy alendronate.METHODS: Osteoporosed-induced rat model was established by administration of dexamethasone in female adult albino rats. The serum level of Ca, P, and osteocalcin was assessed. In addition, histopathological changes and immunohistochemical expression of osteopontin within bone specimens were performed.RESULTS: Our results showed that a combination of olive oil and Lepidium sativum had a beneficial therapeutic effect in the treatment of osteoporosis as compared to alendronate therapy. This was demonstrated by increase of serum Ca, P, and osteocalcin levels in treated compared to control groups. Intriguingly, the highest effect was noticed in rats that received a combination of olive oil and Lepidium sativum compared to the individual treatment. This was reflected by an increase in the cortical bone thickness and a decrease in immunohistochemical expression of osteopontin compared to individual treated groups.CONCLUSION: We concluded that the administration of a combination of olive oil and Lepidium sativum improves bone mineral health and intensity and reduces the risk of osteoporosis in a rat model.

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PMID:  Nutrients. 2023 Mar 9 ;15(6). Epub 2023 Mar 9. PMID: 36986069 Abstract Title:  Effects of Wild Blueberries on Fat Oxidation Rates in Aerobically Trained Males. Abstract:  Wild blueberries (WBs) have been documented to decrease oxidative stress in active and sedentary populations as well as influence lipolytic enzymes and increase the rate of fat oxidation (FAT-ox) during rest. To examine the effect of WBs on the rate of FAT-ox and lipid peroxidation during submaximal exercise, 11 healthy, aerobically trained males (267.5 years, 74.97.54 kg, 10.53.2% BF) completed a 2-week washout avoiding foods high in anthocyanins, then completed a control exercise protocol cycling at 65% of VOfor 40 min. Participants then consumed 375 g/d of anthocyanins for two weeks before repeating the exercise protocol. WBs increased FAT-ox when cycling at 65% of VOby 19.7% at 20, 43.2% at 30, and 31.1% at 40 min, and carbohydrate oxidation (CHO-ox) decreased by 10.1% at 20, 19.2% at 30, and 14.8% at 40 min of cycling at 65% of VO. Lactate was lower with WBs at 20 (WB: 2.61.0, C: 3.01.1), 30 (WB: 2.20.9, C: 2.91.0), and 40 min (WB: 1.90.8, C: 2.50.9). Results indicate that WBs may increase the rate of FAT-ox during moderate-intensity activity in healthy, active males.

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PMID:  Molecules. 2023 Mar 22 ;28(6). Epub 2023 Mar 22. PMID: 36985822 Abstract Title:  The Extraction and High Antiproliferative Effect of Anthocyanin from Gardenblue Blueberry. Abstract:  Blueberries are rich in flavonoids, anthocyanins, phenolic acids, and other bioactive substances. Anthocyanins are important functional components in blueberries. We collected 65 varieties of blueberries to investigate their nutritional and functional values. Among them, Gardenblue had the highest anthocyanin content, with 2.59 mg/g in fresh fruit. After ultrasound-assisted solvent extraction and macroporous resin absorption, the content was increased to 459.81 mg/g in the dried powder. Biological experiments showed that Gardenblue anthocyanins (L) had antiproliferative effect on cervical cancer cells (Hela, 51.98g/mL), liver cancer cells (HepG2, 23.57g/mL), breast cancer cells (MCF-7, 113.39g/mL), and lung cancer cells (A549, 76.10g/mL), and no apparent toxic effects were indicated by methyl thiazolyl tetrazolium (MTT) assay, especially against HepG2 cells both in vitro and in vivo. After combining it with DDP (cisplatin) and DOX (doxorubicin), the antiproliferative effects were enhanced, especially when combined with DOX against HepG2 cells; the ICvalue was 0.02g/mL. This was further evidence that Lcould inhibit cell proliferation by inducing apoptosis. The detailed mechanism might be Linteracting with DNA in an intercalation mode that changes or destroys DNA, causing apoptosis and inhibiting cell proliferation. The findings of this study suggest that Lextract can be used as a functional agent against hepatoma carcinoma cells.

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PMID:  Am J Clin Nutr. 2023 Jun ;117(6):1306-1319. Epub 2023 Mar 25. PMID: 36972800 Abstract Title:  Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial. Abstract:  BACKGROUND: Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown.METHODS: A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry.RESULTS: A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P

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PMID:  J Chem Neuroanat. 2023 Jul ;130:102260. Epub 2023 Mar 24. PMID: 36965643 Abstract Title:  The effects of curcumin and blueberry on axonal regeneration after peripheral nerve injury. Abstract:  The purpose of this study was to analyze the axonal regeneration and therapeutic effects of curcumin and blueberry administration following peripheral nerve injury using stereological, electron microscopic and electrophysiological methods. Animals in were assigned into one of four groups - control (Cont), injury (Inj), injury+curcumin (Cur) and injury+blueberry (Blue). Following the induction of sciatic nerve crush injury (75 Newtons for 5 s) in the Inj, Cur, and Blue groups, the rats in the Cur group received intraperitoneal injection of 30 mg/kg curcumin (Sigma C1386) and the rats in the Blue group received 4 g/kg blueberry by gavage over a four-week period. The rats in the Cont and Inj groups were not exposed to any substance. All animals were given standard chow. Sciatic functional index analyses were performed on the 14th and 28th days after injury, and electromyography (EMG) results were recorded. Stereological analysis of the nerve was performed under light microscopy. Light and electron microscopies were used for the histopathological evaluation of the sciatic nerve. Analysis of myelinated axon numbers revealed no significant differences between the Inj group and the Cur and Blue groups. However, a significant difference was observed between the Blue and Inj groups in terms of axonal areas. EMG test results differed between the Blue and the Inj groups (p 

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PMID:  Inflammopharmacology. 2023 Jan 20. Epub 2023 Jan 20. PMID: 36662400 Abstract Title:  Pterostilbene attenuates hemin-induced dysregulation of macrophage M2 polarization via Nrf2 activation in experimental hyperglycemia. Abstract:  Macrophages exhibit a high degree of plasticity that is physiologically relevant in wound healing, and disruption in normal macrophage response leads to delayed wound closure resulting in chronic wounds. Here, we attempt to discern macrophage responses to hemin via regulation of the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) that could help us better understand the pathophysiology of diabetic foot ulcers (DFU). We demonstrate the alleviation of hemin-mediated Nrf2 suppression and M2 macrophage polarization by pterostilbene (PTS), a proven Nrf2 activator. IC-21 macrophages were treated with hemin under the normoglycemic or hyperglycemic environment with or without PTS and the expression levels of various markers, such as Nrf2 and its downstream target Heme Oxygenase-1 (HO-1), CD206, Ferroportin-1 among others were analyzed using qPCR and Western blot. Our results revealed that hemin under hyperglycemia reduced Nrf2 activation and its downstream targets, M2 polarization, and the induction of a proinflammatory cellular environment, and interestingly all of these were remedied by PTS treatment. Gelatin zymography of matrix metalloproteinase2 (MMP2) expression revealed that hemin under hyperglycemic condition significantly elevated MMP2 expression, which was reversed by PTS treatment. Further proteomic analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS) revealed a heightened cellular stress profile accompanying inflammation that was suppressed by PTS. This study has furthered our understanding on the role of Nrf2 in attenuating hemin-induced perturbations in macrophage responses and suggests a potential therapeutic target in the management of DFU.

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PMID:  Mol Pharm. 2023 Feb 6 ;20(2):1189-1201. Epub 2023 Jan 16. PMID: 36647568 Abstract Title:  Pterostilbene-Loaded Soluplus/Poloxamer 188 Mixed Micelles for Protection against Acetaminophen-Induced Acute Liver Injury. Abstract:  Excessive acetaminophen (APAP) induces excess reactive oxygen species (ROS), leading to liver damage. Pterostilbene (PTE) has excellent antioxidant and anti-inflammatory activities, but poor solubility limits its biological activity. In this study, we prepared PTE-loaded Soluplus/poloxamer 188 mixed micelles (PTE-MMs), and the protective mechanism against APAP-induced liver injury was investigated. In vitro results showed that PTE-MMs protected HO-induced HepG2 cell proliferation inhibition, ROS accumulation, and mitochondrial membrane potential destruction. Immunofluorescence results indicated that PTE-MMs significantly inhibited HO-induced DNA damage and cGAS-STING pathway activation. For in vivo protection studies, PTE-MMs (25 and 50 mg/kg) were administered orally for 5 days, followed by APAP (300 mg/kg). The results showed that APAP significantly induced injury in liver histopathology as well as an increase in serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, the above characteristics of APAP-induced acute liver injury were inhibited by PTE-MMs. In addition, APAP-induced changes in the activities of antioxidant enzymes such as SOD and GSH in liver tissue were also inhibited by PTE-MMs. Immunohistochemical results showed that PTE-MMs inhibited APAP-induced DNA damage and cGAS-STING pathway activation in liver tissues. For in vivo therapeutic effect study, mice were first given APAP (300 mg/kg), followed by oral administration of PTE-MMs (50 mg/kg) for 3 days. The results showed that PTE-MMs exhibited promising therapeutic effects on APAP-induced acute liver injury. In conclusion, our study shows that the Soluplus/poloxamer 188 MM system has the potential to enhance the biological activity of PTE in the protection and therapeutic of liver injury.

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PMID:  Nutr Neurosci. 2023 Feb ;26(2):127-137. Epub 2022 Jan 4. PMID: 36692990 Abstract Title:  Blueberry treatment administered before and/or after lipopolysaccharide stimulation attenuates inflammation and oxidative stress in rat microglial cells. Abstract:  Microglia are key regulators of inflammation and oxidative stress (OS) in the CNS. Microglia activation can lead to chronic inflammation, OS, and neurodegeneration. Blueberries (BB) reduce inflammation and OS when administered to microglia before stressors such as lipopolysaccharide (LPS), but the therapeutic value of BBs administered after activation by stressors has not been examined. Therefore, this study investigated the differential effects of pre-, post-, and pre-/post-BB on inflammation and OS in LPS-activated microglia. Rat microglia were pretreated with BB (0.5 mg/mL) or control media (C) for 24 hours, incubated overnight with LPS (0 or 200 ng/mL), and post-treated with BB or C for 24 hours. Biomarkers of inflammation (e.g. nitrite [NO], tumor necrosis factor-[TNF], inducible nitric oxide synthase [iNOS], cyclooxygenase-2 [COX-2], phosphorylated IB-[pIB-]) and OS (e.g. NADPH oxidase [NOX2]) were assessed. LPS increased NO, TNF, COX-2, iNOS, pIB-, and NOX2 compared to non-stressed conditions (

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PMID:  Antioxidants (Basel). 2023 Mar 3 ;12(3). Epub 2023 Mar 3. PMID: 36978880 Abstract Title:  Antioxidant and Anti-Tumor Effects of Dietary Vitamins A, C, and E. Abstract:  Oxidative stress, a condition characterized by an imbalance between pro-oxidant molecules and antioxidant defense systems, is increasingly recognized as a key contributor to cancer development. This is because the reactive oxygen species (ROS) generated during oxidative stress can damage DNA, proteins, and lipids to facilitate mutations and other cellular changes that promote cancer growth. Antioxidant supplementation is a potential strategy for decreasing cancer incidence; by reducing oxidative stress, DNA damage and other deleterious cellular changes may be attenuated. Several clinical trials have been conducted to investigate the role of antioxidant supplements in cancer prevention. Some studies have found that antioxidant supplements, such as vitamin A, vitamin C, and vitamin E, can reduce the risk of certain types of cancer. On the other hand, some studies posit an increased risk of cancer with antioxidant supplement use. In this review, we will provide an overview of the current understanding of the role of oxidative stress in cancer formation, as well as the potential benefits of antioxidant supplementation in cancer prevention. Additionally, we will discuss both preclinical and clinical studies highlighting the potentials and limitations of preventive antioxidant strategies.

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PMID:  Antioxidants (Basel). 2023 Feb 25 ;12(3). Epub 2023 Feb 25. PMID: 36978824 Abstract Title:  Low Levels of Vitamin C during Pregnancy; a Risk Marker of Progression of Diabetic Retinopathy in Type 1 Diabetic Women? Abstract:  Pregnancy is a risk factor for the development or aggravation of diabetic retinopathy. Here, we suggest a relationship between plasma vitamin C (vitC) status during pregnancy and into postpartum in type 1 diabetes and the possible progression of diabetic retinopathy based on data of 29 women. VitC was measured in first, second, and third trimesters and three months postpartum. The women had visual acuity testing and fundus photography performed at least twice during pregnancy and onto four months after birth. An overall retinopathy grade was assigned on a scale from 0 (no retinopathy) to four according to the International Clinical Diabetic Retinopathy scale. At baseline in 1st trimester, 12 women had no retinopathy; seventeen women had retinopathy in grade 1-3. The retinopathy grade increased in nine women; remained unchanged in 17 women, and improved in three women. No women had or developed proliferative retinopathy (grade 4). The level of vitC in 1st trimester predicted the possible progression of retinopathy-the lower the vitC, the more probable the progression (= 0.03; OR 1.6 (95% CI:1.06-3.2);= 29 (multiple logistic regression))-while the combined levels of 1st and 2nd trimesters and the mean vitC level of the whole pregnancy did not. The diabetes duration, retinopathy grade per se in 1st trimester, 24-h blood pressure measurements, kidney function, urinary protein, HbA1c, or lipid profile were not independent predictors of progression of retinopathy during pregnancy. Retrospectively, the women who experienced progression of their retinopathy during and into postpartum had significantly lower vitC levels in 1st trimester (= 0.02;= 9/20), combined level of vitC in 1st and 2nd trimester (= 0.032;= 7/18), and mean vitC level of the whole pregnancy (= 0.036;= 7/9), respectively. In conclusion, our results suggest that low vitC status in pregnancy could be associated with progression of diabetic retinopathy.

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PMID:  Sci Rep. 2017 Mar 21 ;7:44815. Epub 2017 Mar 21. PMID: 28322293 Abstract Title:  Tea polyphenols inhibit the growth and virulence properties of Fusobacterium nucleatum. Abstract:  Fusobacterium nucleatum plays a key role in creating the pathogenic subgingival biofilm that initiates destructive periodontitis. It is also a common resident of the human gastrointestinal tract and has been associated with inflammatory bowel disease. The aim of the present study was to investigate the effects of green and black tea extracts as well as two of their bioactive components, EGCG and theaflavins, on the growth and virulence properties of F. nucleatum. The tea extracts and components displayed various degrees of antibacterial activity that may involve damage to the bacterial cell membrane and the chelation of iron. They also prevented biofilm formation by F. nucleatum at concentrations that did not interfere with bacterial growth. In addition, the treatment of a pre-formed F. nucleatum biofilm with the green tea extract and EGCG caused a time-dependent decrease in biofilm viability. The green and black tea extracts, EGCG, and theaflavins decreased the adherence of F. nucleatum to oral epithelial cells and matrix proteins. Moreover, these tea components also attenuated F. nucleatum-mediated hemolysis and hydrogen sulfide production, two other virulence factors expressed by this bacterium. In summary, this study showed that tea polyphenols may be of interest for treating F. nucleatum-associated disorders.

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PMID:  Front Nutr. 2023 ;10:1110405. Epub 2023 Mar 6. PMID: 36969825 Abstract Title:  Can plasma vitamin C predict survival in stage IV colorectal cancer patients? Results of a prospective cohort study. Abstract:  BACKGROUND AND AIMS: In light of the inconclusive evidence on the association between vitamin C status and colorectal cancer (CRC) outcome, this study assessed the prognostic value of vitamin C in participants with metastatic CRC (mCRC).METHODS: Adults with mCRC and cancer-free controls were recruited in this prospective cohort study to allow for comparison of vitamin C levels with healthy individuals from the same population. Sociodemographic, lifestyle, medical variables, BRAF and KRAS mutations, as well as Vitamin C plasma level and food intake were evaluated. Predictors of diminished vitamin C level were assessedmultivariate logistic regression. Mortality and progression free survival (PFS) among mCRC participants were analyzed based on plasma vitamin C level.RESULTS: The cancer group (=46) was older (mean age: 6014 vs. 429.6,=0.047) and included more males (29% vs. 19%,

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PMID:  Nutr Neurosci. 2023 Mar 24:1-13. Epub 2023 Mar 24. PMID: 36961747 Abstract Title:  Vitamin C, vitamin E,-carotene and risk of Parkinson's disease: a systematic review and dose-response meta-analysis of observational studies. Abstract:  OBJECTIVE: This study aimed to explore the relationship between the intake of vitamin C, vitamin E and-carotene, and the risk of Parkinson's disease (PD).METHODS: Web of Science, Embase, PubMed, Cochrane library, CNKI, and WanFang databases were searched from inception to 29 August 2022 for observational studies reporting the odds ratios (ORs) or relative risks (RRs) or hazard ratios (HRs) and 95% confidence intervals (CIs) of PD by Vitamin C/Vitamin E/-carotene intake. Random-effects models, publication bias assessment, subgroup, sensitivity and dose-response analyses were were included. There was no significant association between high-dose vitamin C intake and the risk of PD compared with low-dose vitamin C intake (RR=0.98, 95%CI:0.89,1.08). Compared with low-dose intake, high-dose intake of vitamin E can prevent the risk of PD (RR=0.87, 95%CI:0.77,0.99). Compared with lower-carotene intake, there was a borderline non-significant correlation between higher intake and PD risk (RR=0.91, 95%CI:0.82,1.01), and high dose-carotene intake was found to be associated with a lower risk of PD in women (RR=0.78, 95%CI:0.64,0.96).CONCLUSION: This study shows that vitamin E intake can reduce the risk of PD and play a preventive role.

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PMID:  Pharmaceuticals (Basel). 2023 Mar 2 ;16(3). Epub 2023 Mar 2. PMID: 36986484 Abstract Title:  The Role of Tocotrienol in Arthritis Management-A Scoping Review of Literature. Abstract:  Arthritis is a cluster of diseases impacting joint health and causing immobility and morbidity in the elderly. Among the various forms of arthritis, osteoarthritis (OA) and rheumatoid arthritis (RA) are the most common. Currently, satisfying disease-modifying agents for arthritis are not available. Given the pro-inflammatory and oxidative stress components in the pathogenesis of arthritis, tocotrienol, a family of vitamin E with both anti-inflammatory and antioxidant properties, could be joint-protective agents. This scoping review aims to provide an overview of the effects of tocotrienol on arthritis derived from the existing scientific literature. A literature search using PubMed, Scopus and Web of Science databases was conducted to identify relevant studies. Only cell culture, animal and clinical studies with primary data that align with the objective of this review were considered. The literature search uncovered eight studies investigating the effects of tocotrienol on OA= 4) and RA (= 4). Most of the studies were preclinical and revealed the positive effects of tocotrienol in preserving joint structure (cartilage and bone) in models of arthritis. In particular, tocotrienol activates the self-repair mechanism of chondrocytes exposed to assaults and attenuates osteoclastogenesis associated with RA. Tocotrienol also demonstrated strong anti-inflammatory effects in RA models. The single clinical trial available in the literature showcases that palm tocotrienol could improve joint function among patients with OA. In conclusion, tocotrienol could be a potential anti-arthritic agent pending more results from clinical studies.

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PMID:  Diabetes Obes Metab. 2023 Jul ;25(7):1985-1994. Epub 2023 Apr 20. PMID: 36999233 Abstract Title:  Astaxanthin, a natural antioxidant, lowers cholesterol and markers of cardiovascular risk in individuals with prediabetes and dyslipidaemia. Abstract:  AIM: To determine the effects of astaxanthin treatment on lipids, cardiovascular disease (CVD) markers, glucose tolerance, insulin action and inflammation in individuals with prediabetes and dyslipidaemia.MATERIALS AND METHODS: Adult participants with dyslipidaemia and prediabetes (n=34) underwent baseline blood draw, an oral glucose tolerance test and a one-step hyperinsulinaemic-euglycaemic clamp. They were then randomized (n=22 treated, 12 placebo) to receive astaxanthin 12mg daily or placebo for 24weeks. Baseline studies were repeated after 12 and 24weeks of therapy.RESULTS: After 24weeks, astaxanthin treatment significantly decreased low-density lipoprotein (-0.330.11mM) and total cholesterol (-0.300.14mM) (both P

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PMID:  Toxins (Basel). 2023 Mar 21 ;15(3). Epub 2023 Mar 21. PMID: 36977123 Abstract Title:  Astaxanthin Alleviates Aflatoxin B1-Induced Oxidative Stress and Apoptosis in IPEC-J2 Cells via the Nrf2 Signaling Pathway. Abstract:  Aflatoxin B1 (AFB1), a typical fungal toxin found in feed, is highly carcinogenic. Oxidative stress is one of the main ways it exerts its toxicity; therefore, finding a suitable antioxidant is the key to reducing its toxicity. Astaxanthin (AST) is a carotenoid with strong antioxidant properties. The aim of the present research was to determine whether AST eases the AFB1-induced impairment in IPEC-J2 cells, and its specific mechanism of action. AFB1 and AST were applied to IPEC-J2 cells in different concentrations for 24 h. The AST (80M) significantly prevented the reduction in the IPEC-J2 cell viability that was induced by AFB1 (10M). The results showed that treatment with AST attenuated the AFB1-induced ROS, and cytochrome C, the Bax/Bcl2 ratio, Caspase-9, and Caspase-3, which were all activated by AFB1, were among the pro-apoptotic proteins which were diminished by AST. AST activates the Nrf2 signaling pathway and ameliorates antioxidant ability. This was further evidenced by the expression of the HO-1, NQO1, SOD2, and HSP70 genes were all upregulated. Taken together, the findings show that the impairment of oxidative stress and apoptosis, caused by the AFB1 in the IPEC-J2 cells, can be attenuated by AST triggering the Nrf2 signaling pathway.

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PMID:  Biomedicines. 2023 Mar 22 ;11(3). Epub 2023 Mar 22. PMID: 36979970 Abstract Title:  Vitamin A Deficiency and Its Association with Visceral Adiposity in Women. Abstract:  Body adiposity is associated with increased metabolic risk, and evidence indicates that vitamin A is important in regulating body fat. The aim of this study was to evaluate serum concentrations of vitamin A and its association with body adiposity in women with the recommended intake of vitamin A. A cross-sectional study was designed with 200 women divided into four groups according to Body Mass Index (BMI): normal weight (NW), overweight (OW), class I obesity (OI), and class 2 obesity (OII). The cut-off points to assess inadequate participants were retinol

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PMID:  bioRxiv. 2023 Mar 10. Epub 2023 Mar 10. PMID: 36945561 Abstract Title:  -carotene accelerates resolution of atherosclerosis by promoting regulatory T cell expansion in the atherosclerotic lesion. Abstract:  -carotene oxygenase 1 (BCO1) catalyzes the cleavage of-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that-carotene also accelerates atherosclerosis resolution in two independent murine models, independently of changes in body weight gain or plasma lipid profile. Experiments inmice implicate vitamin A production in the effects of-carotene on atherosclerosis resolution. To explore the direct implication of dietary-carotene on regulatory T cells (Tregs) differentiation, we utilized anti-CD25 monoclonal antibody infusions. Our data show that-carotene favors Treg expansion in the plaque, and that the partial inhibition of Tregs mitigates the effect of-carotene on atherosclerosis resolution. Our data highlight the potential of-carotene and BCO1 activity in the resolution of atherosclerotic cardiovascular disease.

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