PMID: 

Environ Sci Pollut Res Int. 2020 Jan 8. Epub 2020 Jan 8. PMID: 31916151

Abstract Title: 

Protective role of lycopene against metabolic disorders induced by chronic bisphenol A exposure in rats.

Abstract: 

This study was conducted to elucidate the ameliorative potential of lycopene (LYC) against the metabolic toxicity induced by bisphenol A (BPA) in rats. Male rats (n = 28) were divided into 4 equal groups: control group, LYC group was given lycopene (10 mg/kg BW), BPA group was given 10 mg/kg BW of BPA, and the last group was administered BPA and LYC at 10 mg/kg via gavage for 90 consecutive days. Body weight (BW) gain, lipid profile, and total antioxidant capacity (TAC) were assessed. Oral glucose tolerance test (OGTT), homeostasis model assessment-estimated insulin resistance (HOMA-IR), thyroid hormones, interleukin-1 beta (IL-1β), leptin, and resistin were assayed. Moreover, immunohistochemistry of TNF-α was performed in adipose tissue. BPA-treated rats showed significant reduction in BW gain and deteriorations in lipid profile, TAC, OGTT, and thyroid hormones as well as significant increases in HOMA-IR, IL-1β, leptin, and resistin. While, improvement of metabolic parameters was observed when LYC was administrated with BPA. Intense TNF-α immunostaining was detected in the fat of BPA-treated rats but the intensity decreased when LYC was administrated with BPA. In conclusion, LYC ameliorated the adverse effects of BPA on metabolism through its antioxidant potential and its reduction of TNF-α expression in adipose tissue.

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PMID: 

Biomolecules. 2019 Dec 6 ;9(12). Epub 2019 Dec 6. PMID: 31817791

Abstract Title: 

Benzyl Isothiocyanate Induces Apoptosis via Reactive Oxygen Species-Initiated Mitochondrial Dysfunction and DR4 and DR5 Death Receptor Activation in Gastric Adenocarcinoma Cells.

Abstract: 

Benzyl isothiocyanate (BITC) is known to inhibit the metastasis of gastric cancer cells but further studies are needed to confirm its chemotherapeutic potential against gastric cancer. In this study, we observed cell shrinkage and morphological changes in one of the gastric adenocarcinoma cell lines, the AGS cells, after BITC treatment. We performed 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2H-tetrazolium bromide (MTT) assay, a cell viability assay, and found that BITC decreased AGS cell viability. Reactive oxygen species (ROS) analyses using 2',7'-dichlorofluorescin diacetate (DCFDA) revealed that BITC-induced cell death involved intracellular ROS production, which resulted in mitochondrial dysfunction. Additionally, cell viability was partially restored when BITC-treated AGS cells were preincubated with glutathione (GSH). Western blotting indicated that BITC regulated the expressions of the mitochondria-mediated apoptosis signaling molecules, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cytochrome c (Cyt c). In addition, BITC increased death receptor DR5 expression, and activated the cysteine-aspartic proteases (caspases) cascade. Overall, our results showed that BITC triggers apoptosis in AGS cells via the apoptotic pathways involved in ROS-promoted mitochondrial dysfunction and death receptor activation.

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PMID: 

Biomolecules. 2019 Dec 30 ;10(1). Epub 2019 Dec 30. PMID: 31905923

Abstract Title: 

Neuroprotective Effects of Quercetin in Alzheimer's Disease.

Abstract: 

Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. It is widely distributed among plants and found commonly in daily diets predominantly in fruits and vegetables. Neuroprotection by quercetin has been reported in several in vitro studies. It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation. In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways. In this review, we provide a synopsis of the recent literature exploring the relationship between quercetin and cognitive performance in Alzheimer's disease and its potential as a lead compound in clinical applications.

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PMID: 

Int J Biol Sci. 2020 ;16(1):147-161. Epub 2020 Jan 1. PMID: 31892852

Abstract Title: 

Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis.

Abstract: 

Colorectal carcinoma (CRC) is the third most common malignant tumor pathology worldwide. Despite progress in surgical procedures and therapy options, CRC is still a considerable cause of cancer-related mortality. In this study, we tested the antitumor effects of shikonin in CRC and tried to identify its potential mechanism. The potential target, molecular mechanism as well asandantitumor effects of shikonin in CRC cells were determined by an integrative protocol including quantitative proteomics, RT-PCR, western blotting, RNA interference and overexpression, apoptosis and autophagy assays, etc. Galectin-1 was a potential target of shikonin from the iTRAQ-based proteomic analysis in shikonin-treated SW620 cell. The overexpression and RNA silencing of galectin-1 in two CRC cells suggested that the shikonin sensitivity was correlation to galectin-1 levels. The ROS accumulation induced by shikonin was important to the formation of galectin-1 dimers. Dimer galectin-1 was found to be associated with the activation of JNK and downstream apoptosis or autophagy. Moreover, through functionalstudies, we showed that differences in galectin-1 level affected tumor cell proliferation, migration, and invasion. In summary, shikonin induced CRC cells apoptosis and autophagy by targeting galectin-1 and JNK signaling pathway bothand, which suggested a potential novel therapy target for CRC.

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PMID: 

Plants (Basel). 2019 Dec 24 ;9(1). Epub 2019 Dec 24. PMID: 31878169

Abstract Title: 

Myricetin Abrogates Cisplatin-Induced Oxidative Stress, Inflammatory Response, and Goblet Cell Disintegration in Colon of Wistar Rats.

Abstract: 

Cisplatin [cis-diamminedichloroplatinum II] is an extensively prescribed drug in cancer chemotherapy; it is also useful for the treatment of diverse types of malignancies. Conversely, cisplatin is associated with a range of side effects such as nephrotoxicity, hepatotoxicity, gastrointestinal toxicity, and so on. Myricetin (3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)-4chromenone) is a very common natural flavonoid found in fruits, tea, and plants. It has been found to have high-value pharmacological properties and strong health benefits. To examine the role of myricetin in colon toxicity induced by cisplatin, we conducted a concurrent prophylactic study in experimental animals that were treated orally with myricetin for 14 days at two doses-25 and 50 mg/kg of body weight. On the 14th day, a single intraperitoneal injection of cisplatin (7.5 mg/kg body weight) was administered in all groups except control. The effects of myricetin in cisplatin-induced toxicity in the colon were assessed in terms of antioxidant status, phase-II detoxification enzymes, the level of inflammatory markers, and goblet cell disintegration. Myricetin was found to restore the level of all the antioxidant enzymes analyzed in the study. In addition, the compound ameliorated cisplatin-induced lipid peroxidation, increase in xanthine oxidase activity, and phase-II detoxifying enzyme activity. Myricetin also attenuated deteriorative effects induced by cisplatin by regulating the level of molecular markers of inflammation (NF-κB, Nrf-2, IL-6, and TNF-α), restoring Nrf-2 levels, and controlling goblet cell disintegration. The current study reinforces the conclusion that myricetin exerts protection in colon toxicity via up-regulation of inflammatory markers, improving anti-oxidant status, and protecting tissue damage.

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PMID: 

Oxid Med Cell Longev. 2019 ;2019:6304058. Epub 2019 Dec 6. PMID: 31885808

Abstract Title: 

Myricetin Alleviates Pathological Cardiac Hypertrophy via TRAF6/TAK1/MAPK and Nrf2 Signaling Pathway.

Abstract: 

Myricetin (Myr) is a common plant-derived polyphenol and is well recognized for its multiple activities including antioxidant, anti-inflammation, anticancer, and antidiabetes. Our previous studies indicated that Myr protected mouse heart from lipopolysaccharide and streptozocin-induced injuries. However, it remained to be unclear whether Myr could prevent mouse heart from pressure overload-induced pathological hypertrophy. Wild type (WT) and cardiac Nrf2 knockdown (Nrf2-KD) mice were subjected to aortic banding (AB) surgery and then administered with Myr (200 mg/kg/d) for 6 weeks. Myr significantly alleviated AB-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction in both WT and Nrf2-KD mice. Myr also inhibited phenylephrine- (PE-) induced neonatal rat cardiomyocyte (NRCM) hypertrophy and hypertrophic markers' expression. Mechanically, Myr markedly increased Nrf2 activity, decreased NF-B activity, and inhibited TAK1/p38/JNK1/2 MAPK signaling in WT mouse hearts. We further demonstrated that Myr could inhibit TAK1/p38/JNK1/2 signaling via inhibiting Traf6 ubiquitination and its interaction with TAK1 after Nrf2 knockdown in NRCM. These results strongly suggested that Myr could attenuate pressure overload-induced pathological hypertrophyand PE-induced NRCM hypertrophy via enhancing Nrf2 activity and inhibiting TAK1/P38/JNK1/2 phosphorylation by regulating Traf6 ubiquitination. Thus, Myr might be a potential strategy for therapy or adjuvant therapy for malignant cardiac hypertrophy.

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PMID: 

J Nutr Sci Vitaminol (Tokyo). 2019 ;65(6):470-476. PMID: 31902859

Abstract Title: 

The Protective Effects of Myricetin against Cardiovascular Disease.

Abstract: 

Cardiovascular disease (CVD) is the leading cause of death globally, except Africa, and poses a severe health burden worldwide. Both in vitro and in vivo studies have demonstrated the protective effects of myricetin for preventing CVD. For this review, we have assessed the literature from 2009 to 2019 at home and abroad to uncover the protective roles of myricetin for preventing CVD. Myricetin exhibits cardioprotective, anti-hypertensive, anti-atherosclerotic, anti-hyperglycemic, and anti-hyperlipidemic effects. In addition, myricetin may alleviate some of the complications caused by adult-onset diabetes. The combined functions of myricetin allow for the prevention of CVD. This review describes the possible therapeutic benefits of myricetin, along with its potential mechanisms of action, to support the clinical use of the myricetin for the prevention of CVD.

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PMID: 

Biol Pharm Bull. 2019 ;42(12):2109-2112. PMID: 31787726

Abstract Title: 

Sulforaphane Exhibits Cytotoxic Effects against Primary Effusion Lymphoma Cells by Suppressing p38MAPK and AKT Phosphorylation.

Abstract: 

Primary effusion lymphoma (PEL) is a rare subtype of non-Hodgkin's B-cell lymphoma and is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) in immunosuppressed patients. PEL is an aggressive lymphoma and is frequently resistant to conventional chemotherapies. Sulforaphane (SFN), a natural compound found in cruciferous vegetables and broccoli sprouts, modulates signaling pathways and epigenetic gene expression. However, the anti-proliferative effects of SFN on PEL cells and the underlying mechanisms have not been identified. Here, we found that SFN decreased the viability of KSHV-infected PEL cells compared to KSHV-uninfected B-lymphoma cells. The anti-proliferative effects of SFN on PEL cells were mediated by apoptosis with activating caspases. In addition, SFN inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and AKT in PEL cells. We also showed that p38MAPK and AKT inhibitors reduced PEL cell growth. The constitutive and/or transient activation of p38MAPK and AKT signaling are necessary for the survival and proliferation of PEL cells. Our data and previous literature indicate that SFN represses the phosphorylation of p38MAPK and AKT, which results in PEL cell apoptosis. Moreover, we investigated whether MG132 or sangivamycin (Sangi) in combination with SFN potentiated the cytotoxic effects of SFN on PEL cells. Compared to treatment with SFN alone, the addition of MG132 or Sangi enhanced the cytotoxic activity of SFN in a synergistic manner. In conclusion, the anti-proliferative effects of SFN indicate its potential as a new substance for the treatment of PEL.

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PMID: 

Heliyon. 2020 Jan ;6(1):e03112. Epub 2019 Dec 31. PMID: 31909276

Abstract Title: 

Methanol soluble fraction of fruits ofpossesses significant antidiarrheal activities.

Abstract: 

Medicinal plants are the major sources of traditional treatment of disease in Indian subcontinent due to abundant presence of plants and vast side effects of synthetic drug. The present study was subjected to observethrombolytic, antibacterial, andantidiarrheal activities of methanol soluble fraction of fruits of. In thrombolytic activity assay, various concentrations (2─ 10 mg/ml) of methanol soluble fraction was used and dose dependently less potent activity was found. The maximum clot lysis 18.33% () was achieved at 10 mg/ml of methanolic fruit extract, whereas standard drug streptokinase showed 55.50% () clot lysis. In antibacterial assay, disc diffusion method was used comprising two gram positive () and two gram negative () bacteria. None of four (0.25, 0.5, 1, and 5 mg/disc) concentration of fruit extract showed antibacterial potentiality, whereas standard amikacin (3 mg/disc) revealed strong antibacterial activities (=~ 23─ 24 mm of MIC). To evaluate antidiarrheal activity, castor oil induced diarrhea was created in Swiss albino mice and different doses (100, 200, and 400 mg/kgbw) of fruit extract was introduced post orally. All of three different doses of fruit extract showed significant (p

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PMID: 

J Toxicol Environ Health A. 2019 ;82(19):1045-1051. Epub 2019 Nov 18. PMID: 31735125

Abstract Title: 

Mechanisms Associated with Protective Effects of Ginkgo Biloba Leaf Extracton in Rat Cerebral Ischemia Reperfusion Injury.

Abstract: 

Cerebral infarction occurs as a consequence of cerebral ischemia-reperfusion injury (CIRI).leaf extract (GbE) is composed predominantly of active ingredients such as flavonoids and terpene lactones and often used to treat cerebrovascular diseases. However, the mechanisms underlying the use of this herbal extract to treat cerebrovascular-mediated damage are not known. The aim of this study was to examine the effectiveness of administration GbE to ameliorate the observed consequences of CIRI. The following parameters were measured: (1) behavioral score (2) infarct area (3) the content of serum malondialdehyde (MDA) as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and (4) interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression levels in the infarcted brain tissue. Data demonstrated that treatment with GbE to CIRI rats resulted in significant reduction in cerebral-infarcted area associated with improvement in behavioral score. GbE was found to decrease serum MDA levels concomitant with elevated activity levels of SOD and GSH-PX. Immunohistochemistry and Western blot analysis showed that GbE significantly lowered the levels of IL-6 and TNF-α in the infarcted brain tissue. Data suggest that GbE may be therapeutically effective in improving behavioral score in CIRI rats through reduction of oxidative stress and anti-inflammation in the cerebral infarction region.

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