PMID: 

Behav Pharmacol. 2019 12 ;30(8):700-711. PMID: 31703032

Abstract Title: 

Biochanin A protects against angiotensin II-induced damage of dopaminergic neurons in rats associated with the increased endophilin A2 expression.

Abstract: 

The brain renin-angiotensin system plays a vital role in the modulation of the neuroinflammatory responses and the progression of dopaminergic (DA) degeneration. Angiotensin II (Ang II) induces microglia activation via angiotensin II type 1 receptor (AT1R), which in turn affects the function of DA neurons. Endophilin A2 (EPA2) is involved in fast endophilin-mediated endocytosis and quickly endocytoses several G-protein-coupled receptor (GPCR), while AT1R belongs to GPCR family. Therefore, we speculated that EPA2 may modulate microglia activation via endocytosing AT1R. Biochanin A is an O-methylated isoflavone, classified as a kind of phytoestrogen due to its chemical structure that is similar to mammalian estrogens. In this study, we investigated the protective effects of biochanin A on Ang II-induced DA neurons damage in vivo, and molecular mechanisms. The results showed that biochanin A treatment for 7 days attenuated the behavioral dysfunction, inhibited the microglial activation, and prevented DA neuron damage in Ang II-induced rats. Furthermore, biochanin A increased EPA2 expression and decreased the expression of AT1R, gp91phox, p22 phox, NLRP3, ASC, Caspase-1, IL-1β, IL-6, IL-18, and TNF-α. In summary, these results suggest that biochanin A exerts protective effects in Ang II-induced model rats, and the mechanisms may involve inhibition of inflammatory responses, an increase in EPA2 expression and a decrease in AT1R expression.

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PMID: 

Med Sci Monit. 2019 Nov 26 ;25:8975-8983. Epub 2019 Nov 26. PMID: 31767824

Abstract Title: 

Biochanin A Provides Neuroprotection Against Cerebral Ischemia/Reperfusion Injury by Nrf2-Mediated Inhibition of Oxidative Stress and Inflammation Signaling Pathway in Rats.

Abstract: 

BACKGROUND Oxidative stress and neuroinflammation are 2 pivotal mechanisms in the progression of cerebral ischemia/reperfusion injury. Biochanin A, a natural phytoestrogen, has been reported to protect against ischemic brain injury in animal experiments, but the possible pharmacological mechanisms of its neuroprotection remain elusive. In this research, we sought to investigate the neuroprotective effects of biochanin A in experimental stroke rats and the probable mechanisms underlying oxidative stress and inflammation signaling pathways. MATERIAL AND METHODS An ischemic stroke model was induced by inserting thread into the middle cerebral artery. Rats were pre-administered intraperitoneallywith a vehicle solution or biochanin A (10, 20, or 40 mg·kg·d–⁻¹) for 14 days prior to ischemic stroke. Neurological score, infarct volume, and cerebral edema were assessed after 2 h of ischemia and 24 h of reperfusion. The activities of SOD and GSH-Px and MDA content were measured. The expressions of Nrf2, HO-1, and NF-kappaB and the activity of phosphor-IkappaBalpha were detected by Western blotting. RESULTS Biochanin A pretreatment significantly improved neurological deficit and decreased infarct size and brain edema. Biochanin A also enhanced SOD and GSH-Px activities and suppressedthe production of MDA. Additionally, biochanin A promoted Nrf2 nuclear translocation, promoted the expression of HO-1, and inhibited NF-kappaB activation in ischemic brain injury. CONCLUSIONS The results indicated that biochanin A protected the brain against ischemic injury in rats by anti-oxidativeand anti-inflammatory actions. The activation of the Nrf2 pathway and the inhibition of the NF-kappaB pathway may contribute to the neuroprotective effects of biochanin A.

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PMID: 

Acta Cir Bras. 2019 ;34(11):e201901104. Epub 2019 Dec 20. PMID: 31859817

Abstract Title: 

Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway.

Abstract: 

PURPOSE: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism.METHODS: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues.RESULTS: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway.CONCLUSION: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.

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PMID: 

J Sci Food Agric. 2020 Feb 22. Epub 2020 Feb 22. PMID: 32086808

Abstract Title: 

Black tea polyphenol theaflavin as promising antioxidant and potential copper chelator.

Abstract: 

BACKGROUND: In this work, we investigated the antioxidant and copper chelating abilities of theaflavin, a polyphenol responsible for astringency, color and sensation present in black tea. Using voltammetric techniques, the analyses were conducted at disposable electrochemical printed carbon chips in conjunction with a portable hand-held potentiostat.RESULTS: Voltammograms of theaflavin showed five separate oxidation peaks, corresponding to the oxidation of five individual functional groups. Electroanalytical data of theaflavin after interaction with copper indicates that the flavonoid has higher antioxidant potential and is a better copper chelator than epigallocatechin gallate, a major polyphenol present in green tea and a well-known antioxidant. This could be attributed to the extra fused ring and larger number of OH groups in theaflavin.CONCLUSIONS: Our findings introduce another natural compound as a potential nutraceutical in oxidation- and copper-modulated illnesses. In addition, this simple and fast approach would be highly pertinent to inspect health benefits of natural food products. To the best of our knowledge, this is the first report of electrochemical analysis of Cu (II) chelation by theaflavin. This article is protected by copyright. All rights reserved.

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PMID: 

Complement Ther Med. 2019 Oct ;46:210-216. Epub 2019 Aug 27. PMID: 31519281

Abstract Title: 

The effect of green tea on C-reactive protein and biomarkers of oxidative stress in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

Abstract: 

INTRODUCTION: The beneficial effects of green tea on regulating insulin sensitivity and preventing the development of type 2 diabetes mellitus (T2DM) have been identified.OBJECTIVES: We aimed to investigate the effect of green tea on serum levels of C-reactive protein (CRP) and biomarkers of oxidative stress in patients with T2DM.METHODS: A systematic search was performed in the ISI Web of science, PubMed and Scopus to find articles related to the effect of the green tea on CRP, malondealdehyde (MDA) and total antioxidant capacity (TAC) in T2DM patients, up to June 2019. There was no language and time limitation. Meta-analyses were performed using both the random and fixed effects model where appropriate, and I2 index was used to evaluate the heterogeneity.RESULTS: Initial search yielded 780 publications. Eight articles with 614 T2DM patients were eligible. Following green tea consumption, CRP levels significantly decreased (weighted mean difference (WMD): -5.51 mg/dl, 95% CI: -9.18 to -1.83, p = 0.003) compared with the controlled group. Green tea consumption had no significant effect on plasma levels of TAC and MDA (0.02 mg/dl, CI: -0.06 to 0.10; -0.14 mg/dl, CI: -0.40 to 0.12; respectively).CONCLUSION: This systematic review and meta-analysis indicated that green tea significantly reduced the circulating levels of CRP, whereas, it had no significant effect on MDA and TAC. Overall, green tea can be considered as a healthy drink to reduce CRP levels in T2DM patients.

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PMID: 

J Biochem Mol Toxicol. 2019 Nov ;33(11):e22393. Epub 2019 Sep 13. PMID: 31518035

Abstract Title: 

Mitigative effects of epigallocatechin gallate in terms of diminishing apoptosis and oxidative stress generated by the combination of lead and amyloid peptides in human neuronal cells.

Abstract: 

Environmental exposure to lead (Pb) is reported to associate with the development of Alzheimer's disease, where the formation ofβ-amyloid peptides (APs) of (1-40), (1-42), and (25-35) is considered as the major risk factor. In this context, we aimed at investigating the effect of epigallocatechin gallate (EGCG), a major flavonoid polyphenol available in green tea, in mitigating the individual and combined toxicity generatedby Pb and β-APs in terms of oxidative stress and apoptosis in human neuronal cells. SH-SY5Y cells were exposed to Pb and β-APs of (1-40) and (25-35) individually and in different combinations in the presence and absence of EGCG. The results indicated that EGCG mitigated both Pb- and β-AP-inducedoxidative stress in scavenging reactive oxygen species and apoptosis by improving the expression levels of Bax and bcl2 and inhibiting annexin V and caspase-3. Thus, our study shows that EGCG protects SH-SY5Y cells against the cytotoxicity induced by Pb and β-APs by decreasing oxidative stress andinhibiting apoptosis.

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PMID: 

Neuromolecular Med. 2020 Mar ;22(1):81-99. Epub 2019 Oct 12. PMID: 31606849

Abstract Title: 

Butanol Extract of Tinospora cordifolia Ameliorates Cognitive Deficits Associated with Glutamate-Induced Excitotoxicity: A Mechanistic Study Using Hippocampal Neurons.

Abstract: 

Overstimulation of glutamate receptors leads to development of excitotoxicity, which is implicated as final destructive pathway in neurodegenerative diseases. Development of alternative therapeutic strategies effective against glutamate-induced excitotoxicity is much in demand. Herbal drug development is emerging as a major research area for the treatment of various debilitating diseases due to multimodal action and least side effects of herbal products. The current study was aimed to investigate neuroprotective potential of butanol extract of Tinospora cordifolia (B-TCE) against glutamate-induced excitotoxicity using primary hippocampal neurons as in vitro and Wistar strain albino rats as in vivo model systems. Molecular and behavioral parameters were studied to elucidate the underlying mechanism of beneficial effects of B-TCE. B-TCE treatment was also effective in prevention of anxiety, cognition, and motor-coordination deficits induced by glutamate. B-TCE pre-treatment protected the hippocampal neurons from glutamate-induced neurodegeneration and impaired plasticity. At molecular level, B-TCE was observed to attenuate overactivation of glutamate receptors. B-TCE promoted upregulation of ERK and AKT pathways of synaptic plasticity and cell survival in the hippocampus region of brain. This study provides first evidence of neuroprotective potential of B-TCE against glutamate-induced excitotoxicity in hippocampus region and suggests that B-TCE may act as a potential candidate for neuroprotective therapeutic approaches. A single compound 'tinosporicide' was further isolated from B-TCE, which was found to be effective at 800× lower concentration against glutamate-induced neurodegeneration under in vitro conditions.

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PMID: 

Phytother Res. 2019 Oct ;33(10):2765-2774. Epub 2019 Aug 5. PMID: 31385371

Abstract Title: 

Tinospora cordifolia preserves pancreatic beta cells and enhances glucose uptake in adipocytes to regulate glucose metabolism in diabetic rats.

Abstract: 

The purpose of this study was to evaluate the pancreatic beta cell protective and glucose uptake enhancing effect of the water extract of Tinospora cordifolia stem (TCSE) by using rat insulinoma (RIN)-m5F cells and 3 T3-L1 adipocytes. RIN-m5F cells were stimulated with interleukin-1β and interferon-γ, and the effect of TCSE on insulin secretion and cytokine-induced toxicity was measured by ELISA and MTT assay, respectively. The glucose uptake and protein expression were measured by fluorometry and western blotting. Antidiabetic effect of TCSE was measured using streptozotocin-induced diabetic rats. TCSE dose dependently increased cell viability and insulin secretion in RIN-m5F cells. In addition, TCSE increased both the glucose uptake and glucose transporter 4 translocation in 3 T3-L1 adipocytes via PI3K pathway. Finally, TCSE significantly lowered blood glucose and diet intake and increased body weight in streptozotocin-induced diabetic rats. The level of serum insulin and hepatic glycogen was increased, whereas the level of serum triglyceride, total cholesterol, dipeptidyl peptidase-4, and thiobarbituric acid reactive substances was decreased in TCSE-administered rats. TCSE also increased glucose transporter 4 protein expression in the adipose tissue and liver of TCSE-fed diabetic rats. Our results suggested that TCSE preserved RIN-m5F cells from cytokine-induced toxicity and enhanced glucose uptake in 3 T3-L1 adipocytes, which may regulate glucose metabolism in diabetic rats.

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PMID: 

Sci Rep. 2019 Jul 29 ;9(1):10969. Epub 2019 Jul 29. PMID: 31358831

Abstract Title: 

Tinospora cordifolia protects against inflammation associated anemia by modulating inflammatory cytokines and hepcidin expression in male Wistar rats.

Abstract: 

Systemic iron homeostasis dysregulation is primarily associated with inflammation- associated anemia (AI) due to hepcidin up-regulation. Tinospora cordifolia (TC) has shown remarkable anti-inflammatory properties and has been found useful in the treatment of inflammatory disorders. However, the effects and mechanisms of TC on AI have not been studied yet. We conducted in vivo and in vitro studies to evaluate the effect of TC on AI. HPLC studies were also carried out to find out active constituents in TC extract. Model system exhibiting AI was developed by repeated injections of HKBA in Wistar rats. TC treated groups showed significantly higher levels of Hb and RBC count compared to the inflammatory control group. TC treatment showed reduction in the expression of the HAMP (hepcidin) gene in the rat liver. TC extract also inhibited gene expression of inflammatory cytokines (TNF-α, IL-1β) and decreased NO production in RAW 264.7 cells. The HPLC analysis revealed the presence of tinosporaside, which could have synergistically contributed to the above findings. Overall results indicate that TC therapy was able to maintain circulating iron through reduction of inflammatory cytokines and expression of hepcidin in rats.

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PMID: 

Curr Pharm Biotechnol. 2019 ;20(12):1055-1063. PMID: 31333126

Abstract Title: 

Tinospora cordifolia Aqueous Extract Alleviates Cyclophosphamide- Induced Immune Suppression, Toxicity and Systemic Candidiasis in Immunosuppressed Mice: In vivo Study in Comparison to Antifungal Drug Fluconazole.

Abstract: 

OBJECTIVE: The present study was aimed to evaluate the effect of the aqueous extract of Tinospora cordifolia (AETC) against cyclophosphamide-induced immunosuppression and systemic Candida albicans infection in a murine model.METHODS: The protective effect of AETC against cyclophosphamide-induced leukopenia was evaluated by quantitative and qualitative analysis of the leukocytes. The immune-stimulating potential of AETC on macrophages was assessed by determining the levels of secreted cytokines. To determine the direct antifungal activity, AETC or fluconazole was administered to C. albicans infected mice. The efficacy of treatment was assessed by determining the survival rate, kidney fungal burden, the organ index and liver inflammation parameters.RESULTS: Cyclophosphamide administration resulted in substantial depletion of leukocytes, whereas AETC treatment induced the recovery of leukocytes in cyclophosphamide-injected mice. Moreover, AETC treatment of macrophages resulted in enhanced secretion of IFN-γ, TNF-α and IL-1β. C. albicans infected mice treated with AETC at the doses of 50 and 100 mg/kg exhibited 40% and 60% survival rate, whereas the mice treated with fluconazole at a dose of 50 mg/kg showed 20% survival rate. Like survival data, the fungal load was found to be the lowest in the kidney tissues of mice treated with AETC at a dose of 100 mg/kg. Interestingly, mice infected with C. albicans demonstrated improvement in the organ indices and liver functioning after AETC treatment.CONCLUSION: These results suggest that AETC may potentially be used to rejuvenate the weakened immune system and eliminate systemic candidiasis in mice.

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