Sharma Ikshit, Khan Mohammad Umar, Zahiruddin Sultan, Basist Parakh, Ahmad Sayeed
Centre of Excellence (CoE) in Unani Medicine (Pharmacognosy and Pharmacology), Bioactive Natural Product Laboratory, Jamia Hamdard, New Delhi 110062, India.
AIMIL Pharmaceuticals (India) Ltd., Saini Majra, Ropar Nalagarh Road, Solan District, Nalagarh 174101, India.
Biomedicines. 2023 Jan 9;11(1):168. doi: 10.3390/biomedicines11010168.
Based on traditional therapeutic claims, NEERI KFT (a traditional Ayurvedic polyherbal preparation) has been innovatively developed in recent time on the decades of experience for treating kidney dysfunction. Due to the lack of scientific evidence, the present investigations are needed to support the rationale use of NEERI KFT. Considering the facts, the study investigated the nephroprotective effect of NEERI KFT against kidney dysfunction using in silico, in vitro and in vivo approaches. In this study, phytochemical and network pharmacology studies were performed for the developed formulation to evaluate the molecular mechanism of NEERI KFT in the amelioration of kidney disease. In vitro nephroprotective and antioxidant effect of NEERI KFT was determined on HEK 293 cells against cisplatin-induced cytotoxicity and oxidative stress. In vivo nephroprotective effect of NEERI KFT was determined against cisplatin-induced nephrotoxicity in Wistar rats, via assessing biochemical markers, antioxidant enzymes and inflammatory cytokines such as TNF-α, IL-1β, CASP-3, etc. The results showed that the compounds such as gallic acid, caffeic acid and ferulic acid are the major constituents of NEERI KFT, while network pharmacology analysis indicated a strong interaction between polyphenols and several genes (CASPs, ILs, AGTR1, AKT, ACE2, SOD1, etc.) involved in the pathophysiology of kidney disease. In vivo studies showed a significant (p < 0.05) ameliorative effect on biochemical markers and antioxidant enzymes (SOD, CAT, GSH, etc.), and regulates inflammatory cytokine (TNF-α, IL-1β, CASP-3) expression in kidney tissue. Hence, it can be concluded that NEERI KFT subsequently alleviates renal dysfunction mediated by cisplatin via attenuating oxidative and inflammatory stress, thus preserving the normalcy of kidney function.
基于传统治疗主张，NEERI KFT（一种传统阿育吠陀多草药制剂）近期在数十年治疗肾功能障碍经验的基础上进行了创新研发。由于缺乏科学证据，目前需要进行研究以支持NEERI KFT的合理使用。考虑到这些事实，本研究采用计算机模拟、体外和体内方法，研究了NEERI KFT对肾功能障碍的肾保护作用。在本研究中，对研发的制剂进行了植物化学和网络药理学研究，以评估NEERI KFT改善肾脏疾病的分子机制。在HEK 293细胞上测定了NEERI KFT对顺铂诱导的细胞毒性和氧化应激的体外肾保护和抗氧化作用。通过评估生化标志物、抗氧化酶和炎性细胞因子如TNF-α、IL-1β、CASP-3等，确定了NEERI KFT对Wistar大鼠顺铂诱导的肾毒性的体内肾保护作用。结果表明，没食子酸、咖啡酸和阿魏酸等化合物是NEERI KFT的主要成分，而网络药理学分析表明多酚与参与肾脏疾病病理生理学的几个基因（CASPs、ILs、AGTR1、AKT、ACE2、SOD1等）之间存在强烈相互作用。体内研究表明，对生化标志物和抗氧化酶（SOD、CAT、GSH等）有显著（p < 0.05）改善作用，并调节肾组织中炎性细胞因子（TNF-α、IL-1β、CASP-3）的表达。因此，可以得出结论，NEERI KFT随后通过减轻氧化和炎性应激来缓解顺铂介导的肾功能障碍，从而维持肾功能的正常。
