Cellular Immunology Laboratory, Department of Zoology, University of North Bengal, Siliguri, West Bengal, India.
Molecular Genetics Laboratory, Department of Botany, University of North Bengal,Siliguri, West Bengal, India.
PLoS One. 2018 Apr 30;13(4):e0196411. doi: 10.1371/journal.pone.0196411. eCollection 2018.
The progress in industrialization has blessed mankind with a technologically superior lifestyle but poor management of industrial waste has in turn poisoned nature. One such chemical is carbon tetra chloride (CCl4), which is a potent environmental toxin emitted from chemical industries and its presence in the atmosphere is increasing at an alarming rate. Presence of CCl4 in human body is reported to cause liver damage through free radical mediated inflammatory processes. Kupffer cells present in the liver are potentially more sensitive to oxidative stress than hepatocytes. Kuffer cells produced tumor necrosis factor-α (TNF-α) in response to reactive oxygen species (ROS), that might further cause inflammation or apoptosis. In this study hepatoprotective capacity of antioxidant rich extract of Croton bonplandianus Baill. (CBL) was evaluated on CCl4 induced acute hepatotoxicity in murine model. Hydro-methanolic extract of C. bonplandianus leaf was used for evaluation of free radical scavenging activity. Liver cells of experimental mice were damaged using CCl4 and subsequently hepatoprotective potential of the plant extract was evaluated using series of in-vivo and in-vitro studies. In the hepatoprotective study, silymarin was used as a positive control. Antioxidant enzymes, pro-inflammatory markers, liver enzymatic and biochemical parameters were studied to evaluate hepatoprotective activity of Croton bonplandianus leaf extract. Free radical scavenging activity of CBL extract was also observed in WRL-68 cell line. The phytochemicals identified by GCMS analysis were scrutinized using in-silico molecular docking procedure. The results showed that CBL extract have potent free radical scavenging capacity. The biochemical parameters were over expressed due to CCl4 administration, which were significantly normalized by CBL extract treatment. This finding was also supported by histopathological evidences showing less hepatocellularnecrosis, inflammation and fibrosis in CBL and silymarin treated group, compared to CCl4 group. ROS generated due to H2O2 in WRL-68 cell line were normalize in the highest group (200 μg/ml) when compared with control and negative control (CCl4) group. After molecular docking analysis, it was observed that the compound α-amyrin present in the leaf extract of C. bonplandianus has better potentiality to protect hepatocellular damages than the standard drug Silymarin. The present study provided supportive evidence that CBL extract possesses potent hepatoprotective capacity by ameliorating haloalkane induced liver injury in the murine model. The antioxidant and anti-inflammatory activities also affirm the same. The synergistic effects of the phytochemicals present in CBL are to be credited for all the hepatoprotective activity claimed above.
工业化的进步使人类拥有了技术先进的生活方式，但工业废物管理不善却反过来毒害了自然。四氯化碳（CCl4）就是这样一种化学物质，它是化学工业排放的一种强效环境毒素，其在大气中的含量正以惊人的速度增加。据报道，CCl4 会在人体内通过自由基介导的炎症过程造成肝损伤。肝脏中的库普弗细胞比肝细胞更容易受到氧化应激的影响。库普弗细胞会产生肿瘤坏死因子-α（TNF-α）来应对活性氧（ROS），这可能会进一步导致炎症或细胞凋亡。在这项研究中，评估了富含抗氧化剂的巴豆 Croton bonplandianus Baill.（CBL）叶提取物对小鼠模型中 CCl4 诱导的急性肝毒性的肝保护作用。使用 C. bonplandianus 叶的水-甲醇提取物来评估其清除自由基的活性。用 CCl4 破坏实验小鼠的肝细胞，然后通过一系列体内和体外研究来评估植物提取物的肝保护作用。在这项肝保护研究中，水飞蓟素被用作阳性对照。研究了抗氧化酶、促炎标志物、肝酶和生化参数，以评估巴豆 Croton bonplandianus 叶提取物的肝保护活性。还在 WRL-68 细胞系中观察了 CBL 提取物的自由基清除活性。通过 GCMS 分析鉴定的植物化学物质使用计算机分子对接程序进行了仔细研究。结果表明，CBL 提取物具有很强的清除自由基能力。由于 CCl4 给药，生化参数表达过高，而 CBL 提取物处理则显著使这些参数正常化。这一发现也得到了组织病理学证据的支持，与 CCl4 组相比，CBL 和水飞蓟素治疗组的肝细胞坏死、炎症和纤维化程度较低。当与对照组和阴性对照组（CCl4）相比时，WRL-68 细胞系中由于 H2O2 产生的 ROS 在最高组（200μg/ml）中得到了正常化。通过分子对接分析发现，存在于 C. bonplandianus 叶提取物中的化合物 α-香树脂醇比标准药物水飞蓟素有更好的保护肝细胞损伤的潜力。这项研究提供了支持性证据，表明 CBL 提取物通过改善小鼠模型中的卤代烷烃诱导的肝损伤，具有很强的肝保护作用。抗氧化和抗炎活性也证实了这一点。应该归功于 CBL 中存在的植物化学物质的协同作用，从而实现了所有声称的肝保护作用。
