Dey Debendranath, Chaskar Sunetra, Bhatt Narendra, Chitre Deepa
Bioved Pharmaceuticals, Inc., 1929 OToole Way, San Jose, CA 95131, USA.
Bioved Pharmaceuticals Pvt. Ltd, 5-6/12, Vadgaon Khurd, Pune 411 041, India.
Evid Based Complement Alternat Med. 2020 Mar 25;2020:6428906. doi: 10.1155/2020/6428906. eCollection 2020.
Excessive alcohol consumption is a worldwide threat with severe morbidity and mortality. Other than abstinence, there is still no FDA-approved drug for alcoholic liver disease (ALD). Liver is the primary site of ethanol metabolism and hence gets the most damage from excessive drinking. It triggers multiple signalling events including inflammation, leading to an array of hepatic lesions like steatosis, hepatitis, fibrosis, and cirrhosis. Similarly, when medications or xenobiotic compounds are ingested orally, the liver gets the highest exposure of those metabolites, which in turn can cause severe liver toxicity. BV-7310 is a standardized mixture of four Ayurvedic plants, namely, , and In different systems of traditional medicine, each of these plants has been known to have use in gastrointestinal disorders. We wanted to assess the combined effect of these plant extracts on alcohol-induced liver damage. First, we investigated the hepatoprotective activity of BV-7310 against alcohol-induced toxicity in human liver HepG2 cells. Ethanol treatment (120 mM for 48 hours) significantly showed toxicity (around 42%) in these cells, and coincubation with BV-7310 prevented ethanol-induced cell death in a dose-dependent manner. Interestingly, the formulation BV-7310 showed synergistic activity than any individual extract tested in this assay. BV-7310 also showed potent antioxidant activity in 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. Next, we induced hepatitis in Sprague-Dawley (SD) rats using repeated alcohol (40%) dosing, and carbon tetrachloride (CCl) 24 hours before termination. Both oral doses of BV-7310 (250 and 500 mg/kg body weight) protected the alcohol-induced body weight loss and significantly improved the elevated levels of liver enzymes compared to the vehicle treated group. Thus, BV-7310 prevents alcohol-induced toxicity in both in-vitro and in-vivo models and could be beneficial for the treatment of ALD or other conditions, which may cause liver toxicity.
过量饮酒是一个全球性威胁，会导致严重的发病率和死亡率。除了戒酒之外，目前尚无美国食品药品监督管理局（FDA）批准用于治疗酒精性肝病（ALD）的药物。肝脏是乙醇代谢的主要场所，因此过量饮酒对肝脏的损害最大。它引发多种信号转导事件，包括炎症反应，进而导致一系列肝脏病变，如脂肪变性、肝炎、纤维化和肝硬化。同样，当口服药物或外源性化合物时，肝脏会接触到最高浓度的这些代谢产物，这反过来又可能导致严重的肝脏毒性。BV - 7310是四种阿育吠陀植物的标准化混合物，分别是[此处原文缺失植物名称]。在不同的传统医学体系中，已知这些植物各自都可用于治疗胃肠道疾病。我们想评估这些植物提取物对酒精性肝损伤的联合作用。首先，我们研究了BV - 7310对人肝癌HepG2细胞中酒精诱导的毒性的肝保护活性。乙醇处理（120 mM，持续48小时）在这些细胞中显著显示出毒性（约42%），而与BV - 7310共同孵育以剂量依赖的方式预防了乙醇诱导的细胞死亡。有趣的是，制剂BV - 7310在该试验中显示出比任何单独测试的提取物更强的协同活性。BV - 7310在2,2 - 二苯基 - 1 - 苦基肼（DPPH）试验中也显示出强大的抗氧化活性。接下来，我们通过反复给予酒精（40%）并在处死前24小时给予四氯化碳（CCl）在Sprague - Dawley（SD）大鼠中诱导肝炎。与载体处理组相比，口服剂量的BV - 7310（250和500 mg/kg体重）均能保护大鼠免受酒精诱导的体重减轻，并显著改善肝酶水平的升高。因此，BV - 7310在体外和体内模型中均能预防酒精诱导的毒性，可能对治疗ALD或其他可能导致肝脏毒性的病症有益。
