Kuttiappan Anitha, Chenchula Santenna, Vanangamudi Murugesan, Bhatt Shvetank, Chikatipalli Radhika, Shaila Bhanu P, Bandaru Nagaraju
Department of Pharmacology, School of Pharmacy and Technology Management (SPTM), SVKM's Narsee Monjee Institute of Management Studies (NMIMS) Deemed-to-University, Shirpur 425405, Maharashtra, India.
Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhopal 462020, Madhya Pradesh, India.
J Ayurveda Integr Med. 2024 Sep-Oct;15(5):101036. doi: 10.1016/j.jaim.2024.101036. Epub 2024 Sep 6.
Phytochemicals and their derivatives are promising target drugs for various ailments and have served as therapeutic agents for several decades. Using in vivo and in vitro models and molecular docking, this study investigated the pharmacological potential of a flavonoid-rich fraction of the ethanolic extract of Sesbania grandiflora (SG).
This research aimed to determine whether flavonoid-rich whole-plant extracts of SGs have any cytoprotective or in vivo hepatoprotective effects. Additionally, the study was intended to elucidate the molecular connections between the discovered flavonoid flavonols and PPARα target proteins linked to liver problems, for which an in silico molecular docking investigation was performed.
To separate the flavonoid components, the entire Sesbania grandiflora plant was first extracted using ethanol as a solvent by soxhlet extraction. The resulting ethanolic extract was then fractionated. The cytoprotective and hepatoprotective properties were evaluated via in vitro and in vivo experiments. SGOT, SGPT, triglyceride, bilirubin, and total protein levels were used to evaluate hepatotoxicity in animal models. In vitro studies on Hepatocellular Carcinoma G2 (HepG2) cell lines have examined their cytotoxic effects and antioxidant activity. The most promising flavonoid-flavanol compounds were identified by conducting molecular docking studies against PPARα target protein (PDB ID: 3VI8) using MOE software.
In vivo, the serum levels of SGOT, SGPT, total triglyceride and total bilirubin were measured in experimental animals treated with the flavonoid-rich ethanolic extract of SG. Significant reductions in the levels of these hepatic injury markers were observed, indicating the hepatoprotective potential of the extract. Elevated levels of liver biomarkers in the untreated group indicated liver injury or dysfunction. The treated groups showed significant restoration of these biomarkers, suggesting the hepatoprotective potential of SG. The IC value for the total flavonoid content of SG was 190.28 μg/ml, indicating its safety in inhibiting HepG2 cell growth. Flavonoid treatment decreased cell viability but did not affect antioxidant parameters in hepatocytes. In addition, SG restored the damaged hepatocyte architecture. Molecular docking studies revealed the binding affinities of flavonoids for PPARα. These findings suggest that a promising lead candidate for the development of therapeutic medicines against anti-TB drug-induced hepatotoxicity has been identified.
Our findings demonstrate the hepatoprotective potential of the flavonoid-rich fraction of Sesbania grandiflora both in vivo and in vitro. This study provides valuable insights into its mechanism of action, highlighting its promising therapeutic application in the management of liver disorders. This study highlights the hepatoprotective and cytoprotective potential of the total flavonoid-rich fraction of SG.
植物化学物质及其衍生物是治疗各种疾病的潜在靶向药物,并且已经作为治疗药物使用了几十年。本研究利用体内和体外模型以及分子对接技术,研究了大花田菁(SG)乙醇提取物中富含黄酮类化合物的部分的药理潜力。
本研究旨在确定SG富含黄酮类化合物的全株提取物是否具有任何细胞保护或体内肝脏保护作用。此外,该研究旨在阐明所发现的黄酮醇类黄酮与与肝脏问题相关的PPARα靶蛋白之间的分子联系,为此进行了计算机分子对接研究。
为了分离黄酮类成分,首先使用乙醇作为溶剂通过索氏提取法提取整个大花田菁植株。然后对所得乙醇提取物进行分离。通过体外和体内实验评估细胞保护和肝脏保护特性。使用谷草转氨酶(SGOT)、谷丙转氨酶(SGPT)、甘油三酯、胆红素和总蛋白水平来评估动物模型中的肝毒性。对肝癌G2(HepG2)细胞系的体外研究考察了它们的细胞毒性作用和抗氧化活性。使用MOE软件对PPARα靶蛋白(PDB ID:3VI8)进行分子对接研究,鉴定出最有前景的黄酮-黄烷醇化合物。
在体内,对用SG富含黄酮类化合物的乙醇提取物处理的实验动物测定了SGOT、SGPT、总甘油三酯和总胆红素的血清水平。观察到这些肝损伤标志物水平显著降低,表明该提取物具有肝脏保护潜力。未处理组中肝脏生物标志物水平升高表明肝脏损伤或功能障碍。处理组这些生物标志物显著恢复,表明SG具有肝脏保护潜力。SG总黄酮含量的半数抑制浓度(IC)值为190.28μg/ml,表明其在抑制HepG2细胞生长方面的安全性。黄酮类处理降低了细胞活力,但不影响肝细胞中的抗氧化参数。此外,SG恢复了受损的肝细胞结构。分子对接研究揭示了黄酮类化合物与PPARα的结合亲和力。这些发现表明,已确定一种有前景的先导化合物,可用于开发抗结核药物诱导的肝毒性的治疗药物。
我们的研究结果证明了大花田菁富含黄酮类化合物的部分在体内和体外均具有肝脏保护潜力。本研究为其作用机制提供了有价值的见解,突出了其在肝脏疾病管理中的有前景的治疗应用。本研究突出了SG总黄酮富集部分的肝脏保护和细胞保护潜力。