PMID: 

Curr Diabetes Rev. 2019 Oct 4. Epub 2019 Oct 4. PMID: 31584372

Abstract Title: 

A molecular approach on the protective effects of mangiferin against diabetes and diabetes-related complications.

Abstract: 

BACKGROUND: Diabetic and its related complications are now a global health problem without an effective therapeutic approach. There are many herbal medicines which have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets.AIM: The aim of this study is to review currently available knowledge of mangiferin focusing on its mode of action.METHOD: Mangiferin was extensively reviewed for its antidiabetic activity using online database like Scopus, PubMed, and Google Scholar as well as some offline textbooks. A critical discussion based on the mechanism of action and the future perspectives is also given in the present manuscript.RESULTS: Mangiferin is a natural C-glucoside and mainly obtained from its primary source, the leaves of mango tree (Mangifera indica L.). Therapeutic and preventive properties of mangiferin include antimicrobial, anti-inflammatory, antioxidative, antiallergic, neuroprotective, and cognition-enhancing effects. It dissolves well in water, so it can be easily extracted into infusions and decoctions and hence, many research has been made on the therapeutic effect of this molecule. Recently, mangiferin has been proved to be an effective remedy in diabetes and diabetes-related complications. It is a beneficial natural compound for type 2 diabetes mellitus as it improves insulin sensitivity, modulates lipid profile and reverts adipokine levels to normal.CONCLUSION: This study concludes that mangiferin has the potential to treat diabetes and it can be developed as a therapeutic agent for diabetes and the complications caused by diabetes.

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PMID: 

Free Radic Biol Med. 2019 Sep ;141:59-66. Epub 2019 Jun 1. PMID: 31163256

Abstract Title: 

Myricetin prevents thapsigargin-induced CDK5-P66Shc signalosome mediated pancreaticβ-cell dysfunction.

Abstract: 

Chronic endoplasmic reticulum (ER) stress has deleterious effects on pancreaticβ-cell function and survival in type 2 diabetes (T2D). Cyclin-dependent kinase 5 (CDK5) plays a critical role in β-cell failure under diabetic milieu conditions. However, little information is available on CDK5's ability to impair the function of β-cells via a chemical ER stress inducer thapsigargin. Myricetin, a natural flavonoid, has therapeutic potential for the treatment of type 2 diabetes mellitus. Therefore, we examined the effect of CDK5 on thapsigargin-induced β-cell apoptosis, and explored the relationship between myricetin and CDK5. Exposure of beta cells with thapsigargin, induced a Src-mediated redox signaling (VAV2-Rac1-NOX) formation and CDK5 activation. Activated CDK5 induced antiapoptotic protein myeloid cell leukemia sequence 1 (Mcl-1) degradation which was associated with p66Shc serine 36 phosphorylation, causing beta cell apoptosis via mitochondrial dysfunction. Exposure of beta cells to myricetin resulted in an acute inhibition of Src-mediated redox signaling (VAV2-Rac1-NOX) formation and CDK5 activation. Myricetin inhibited CDK5 activation by directly binding to its ATP-binding pocket. Treatment with myricetin also enhanced the stability of Mcl-1 after thapsigargin treatment. Inhibition of CDK5 with myricetin or roscovitine, a CDK5 inhibitor attenuates thapsigargin induced p66Shc serine 36 phosphorylation and also reduced mitochondrial dysfunction by decreasing mitochondrial ROS and caspase-3 activation. In addition, myricetin was observed to enhancePDX-1 and insulin mRNA expression and potentiate glucose stimulated insulin secretion (GSIS). Taken together, these findings indicate that thapsigargin-induced early molecular events lead to CDK5-p66Shc signalosome contributes to thapsigargin-induced pancreatic β-cell dysfunction. Myricetin blockedthapsigargin induced CDK5-p66Shc signalosome formation and prevented pancreatic beta cell dysfunction. In this study, we demonstrated for the first time that thapsigargin initiated CDK5-p66Shc signalosome mediates the pancreatic beta cell dysfunction and myricetin protects the pancreatic beta cellsthrough the inhibition of CDK5-p66Shc signalosome.

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PMID: 

Prev Nutr Food Sci. 2019 Jun ;24(2):202-209. Epub 2019 Jun 30. PMID: 31328126

Abstract Title: 

Myricetin Inhibition of Peptidoglycan-Induced COX-2 Expression in H9c2 Cardiomyocytes.

Abstract: 

Peptidoglycan (PGN) is a cell wall constituent in dental plaque bacteria that triggers inflammatory responses. PGN binds Toll-like receptors, leading to increases in prostaglandin E2 and interleukin-1β, which play crucial roles in the inflammatory response and tissue destruction. Dental surgery can give plaque bacteria access to blood circulation, thereby creating a risk of septic inflammation of the endocardium. Plant-derived flavonoids have been reported to reduce inflammatory cytokine secretion by host cells. In the present study, we investigated the effects of flavonoid myricetin on expression of cyclooxygenase 2 (COX-2) in the H9c2 cells treated with PGN from, a bacterial constituent of dental plaque associated with infective endocarditis. Myricetin exposure resulted in dose-dependent suppression of PGN-induced COX-2 expression, diminished phosphorylation of p38, extracellular signal regulated kinase 1/2, and c-Jun N-terminal kinase, and reduced IκB-α degradation, consistent with decreased COX-2 activity. In conclusion, the aforementioned results suggest that myricetin is useful for moderating the inflammatory response in infective endocarditis.

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PMID: 

Life Sci. 2016 Feb 1 ;146:52-7. Epub 2016 Jan 5. PMID: 26764231

Abstract Title: 

Effects of short term and long term Extremely Low Frequency Magnetic Field on depressive disorder in mice: Involvement of nitric oxide pathway.

Abstract: 

AIMS: Previous reports on the possible effects of Extremely Low Frequency Magnetic Fields (ELF MF) on mood have been paradoxical in different settings while no study has yet been conducted on animal behavior. In addition, it was shown that ELF MF exposure makes an increase in brain nitric oxide level. Therefore, in the current study, we aimed to assess the possible effect(s) of ELF MF exposure on mice Forced Swimming Test (FST) and evaluate the probable role of the increased level of nitric oxide in the observed behavior.MAIN METHODS: Male adult mice NMRI were recruited to investigate the short term and long term ELF MF exposure (0.5 mT and 50 Hz, single 2h and 2 weeks 2h a day). Locomotor behavior was assessed by using open-field test (OFT) followed by FST to evaluate the immobility time. Accordingly, NΩ-nitro-l-arginine methyl ester 30 mg/kg was used to exert anti-depressant like effect.KEY FINDINGS: According to the results, short term exposure did not alter the immobility time, whereas long term exposure significantly reduces immobility time (p

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PMID: 

Electromagn Biol Med. 2014 Jan ;33(1):51-7. Epub 2013 Jun 19. PMID: 23781994

Abstract Title: 

Effect of long-term 50 Hz magnetic field exposure on the micronucleated polychromatic erythrocytes of mice.

Abstract: 

In recent years extremely low-frequency magnetic fields (ELF-EMF) have become widely used in human activities, leading to an increased chance of exposure to ELF-EMF. There are few reports on in vivo mammalian genotoxic effects using micronucleus (MN) assays, which generally have been used as a short-term screening system. We analyzed the possible genotoxic effect induced by long-term exposure (7, 14, 21, 28 d) of a 50 Hz ELM-MF to mice by measuring the increase in frequency of micronucleated polychromatic erythrocyte in their bone marrow (MNPCEs) and we compared it with that induced by 50 cGy of X-rays. Subsequently, we tried to reduce this chromosomal damage by administering four antioxidants substances with radioprotective capacities: dimethyl sulfoxide (DMSO), 6-n-propyl-2-thiouracil (PTU), grape-procyanidins (P) and citrus flavonoids extract (CE). The increase in micronucleated cells was higher in both physical treatments (Control 

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PMID: 

Br J Nutr. 2019 Jun ;121(12):1389-1397. Epub 2019 Apr 22. PMID: 31006420

Abstract Title: 

Substituting brown rice for white rice on diabetes risk factors in India: a randomised controlled trial.

Abstract: 

India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI≥ 23 kg/m2) adults aged 25-65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin,glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (-0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in thebrown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI< 25 kg/m2 (P-for-heterogeneity< 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.

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PMID: 

Electromagn Biol Med. 2016 ;35(3):245-59. Epub 2016 Apr 12. PMID: 27070942

Abstract Title: 

Effects of pre- and postnatal exposure to extremely low-frequency electric fields on mismatch negativity component of the auditory event-related potentials: Relation to oxidative stress.

Abstract: 

In our previous study, the developmental effects of extremely low-frequency electric fields (ELF-EF) on visual and somatosensory evoked potentials in adult rats were studied. There is no study so far examining the effects of 50 Hz electric field (EF) on mismatch negativity (MMN) recordings after exposure of rats during development. Therefore, our present study aimed to investigate MMN and oxidative brain damage in rats exposed to EF (12 kV/m, 1 h/day). Rats were divided into four groups, namely control (C), prenatal (Pr), postnatal (Po), and prenatal+postnatal (PP). Pregnant rats of Pr and PP groups were exposed to EF during pregnancy. Following birth, rats of PP and Po groups were exposed to EF for three months. After exposure to EF, MMN was recorded by electrodes positioned stereotaxically to the surface of the dura, and then brain tissues were removed for histological and biochemical analyses. The MMN amplitude was higher to deviant tones than to standard tones. It was decreased in all experimental groups compared with the C group. 4-Hydroxy-2-nonenal (4-HNE) levels were significantly increased in the Po group with respect to the C group, whereas they were significantly decreased in the PP group compared with Pr and Po groups. Protein carbonyl levels were significantly decreased in the PP group compared with C, Pr, and Po groups. EF decreased MMN amplitudes were possibly induced by lipid peroxidation.

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PMID: 

Electromagn Biol Med. 2012 Dec ;31(4):436-48. Epub 2012 Oct 9. PMID: 23045992

Abstract Title: 

The effect of different strengths of extremely low-frequency electric fields on antioxidant status, lipid peroxidation, and visual evoked potentials.

Abstract: 

The aim of the study was to investigate the effects of extremely low-frequency electric field (ELF EF) on visual evoked potential (VEP), thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS), total oxidant status (TOS), and oxidant stress index (OSI). Thirty female Wistar rats, aged 3 months, were divided into three equal groups: Control (C), the group exposed to EF at 12 kV/m strength (E12), and the group exposed to EF at 18 kV/m strength (E18). Electric field was applied to the E12 and E18 groups for 14 days (1 h/day). Brain and retina TBARS, TOS, and OSI were significantly increased in the E12 and E18 groups with respect to the control group. Also, TBARS levels were significantly increased in the E18 group compared with the E12 group. Electric fields significantly decreased TAS levels in both brain and retina in E12 and E18 groups with respect to the control group. All VEP components were significantly prolonged in rats exposed to electric fields compared to control group. In addition, all latencies of VEP components were increased in the E18 group with respect to the E12 group. It is conceivable to suggest that EF-induced lipid peroxidation may play an important role in changes of VEP parameters.

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PMID: 

Biomed Pharmacother. 2019 Oct 3 ;120:109506. Epub 2019 Oct 3. PMID: 31586904

Abstract Title: 

Anti-tumor effects and associated molecular mechanisms of myricetin.

Abstract: 

Myricetin (3, 5, 7, 3', 4', 5'-hexahydroxyflavone) is a natural flavonol compound found in a large variety of plants, including berries, oranges, grapes, herbs, teas, and wine. In the last decade, a convergence of evidence has demonstrated that myricetin has good biological activity as an anti-tumor, anti-inflammatory, and anti-oxidation agent. In studies involving various types of cancer cells, myricetin has been shown to suppress cancer cell invasion and metastasis, to induce cell cycle arrest and apoptosis of cancer cells, and to inhibit their proliferation. These findings have raised interest in myricetin as a potential tumor inhibitor in human patients. In this review, evidence of myricetin's anti-tumor activity and its underlying molecular mechanisms published in the last decade are summarized.

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PMID: 

Int J Radiat Biol. 2013 Dec ;89(12):1053-60. Epub 2013 Jul 15. PMID: 23786626

Abstract Title: 

Can safe and long-term exposure to extremely low frequency (50 Hz) magnetic fields affect apoptosis, reproduction, and oxidative stress?

Abstract: 

PURPOSE: To determine whether 50 Hz extremely low frequency-magnetic fields (ELF-MF) affects apoptotic processes, oxidative damage, and reproductive characteristics such as sperm count and morphology in rat testes.MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were used in the present study, which were divided into three groups (sham group, n = 10, and two experimental groups, n = 10 for each group). Rats in the experimental group were exposed to 100 and 500μT ELF-MF (2 h/day, 7 days/week, for 10 months) corresponding to exposure levels that are considered safe for humans. The same experimental procedures were applied to the sham group, but the ELF generator was turned off. Tissues from the testes were immunohistochemically stained for active (cleaved) caspase-3 in order to measure the apoptotic index by a semi-quantitative scoring system. The levels of catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidative capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) were also measured. Additionally, epididymal sperm count and sperm morphology was evaluated.RESULTS: There were no significant differences in the reproductive and oxidative stress parameters between the sham group and the exposed groups (p>0.05). While no difference was observed between the final apoptosis score of the sham and the 100μT ELF-MF group (p>0.05), the final apoptosis score was higher in the 500μT ELF-MF exposure group than in the sham group (p

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