Multi-Mechanistic and Therapeutic Exploration of Nephroprotective Effect of Traditional Ayurvedic Polyherbal Formulation Using In Silico, In Vitro and In Vivo Approaches

Abstract

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.

Yellow Himalayan Raspberry (Rubus ellipticus Sm.): Ethnomedicinal, Nutraceutical, and Pharmacological Aspects

“…These extracts were able to normalize increased blood urea nitrogen, serum uric acid, creatinine, and serum urea levels induced by cisplatin and gentamicin [ 128 ]. Such a potent nephroprotective activity might be due to the presence of certain phytochemicals like phenols, tannins, flavonoids, and triterpenoids, which act as an antioxidant, reducing the risk of renal dysfunction [ 129 , 130 , 131 ]. Likewise, the ethanolic extract of R. ellipticus was found to be an effective nephroprotective agent compared to its petroleum ether and aqueous extract.…”

Advancement of Network Pharmacology in Multi-targeted Therapeutic Evaluation of Medicinal Plants

“…This approach plays a pivotal role in evaluating the multi-targeted therapeutic potential of medicinal plants, making it a promising tool for drug discovery and development. The integration of traditional knowledge with modern analytical techniques and computational methods has enabled the comprehensive exploration of the pharmacological properties of medicinal plants [3][4][5][6]. Medicinal plants have been an essential part of traditional medicine systems worldwide for centuries.…”

“…Unlike singletarget drugs, many diseases involve a network of interconnected molecular pathways. Medicinal plants, with their multiple bioactive components, can influence multiple points within these networks, providing a holistic approach to treatment [3,7,11,12]. In a recent study conducted on network pharmacological based exploration of therapeutic targets of Boerhaavia diffusa and Tinospora cordifolia herbal combination in chronic kidney disease, it has been reported that the major constituents of these plants such as quercetin, ferulic acid, gallic acid, ameliorates the different pathophysiological targets in treatment of kidney disease [4].…”

“…In a study published in Biomedicine journal, multi-mechanistic and therapeutic targets were determined of a India's polyherbal formulation "NEERI KFT" using network pharmacological approaches and reported that gallic acid, quercetin, ferulic acid, etc exhibits a significant role in alleviation of nephrotoxicity induce by cisplatin [3,14]. Tinospora cordifolia is one of the most india's famous medicinal plants used for several therapeutic effect.…”

Indian Medicinal Plants for the Management of Endometriosis: A Comprehensive Review on their phytopharmacology

“…Medicinal plants have been used for centuries in various traditional systems of medicine, and they continue to play a crucial role in modern healthcare. There are several approaches that makes medicinal plants enriched for treating various disease including natural source of therapeutic compounds, Medicinal plants contain a diversity of phytoconstituents such as alkaloids, flavonoids, terpenoids, and phenolics, which possess medicinal properties (Ahmad et al, 2021;Gaurav et al, 2023;Gautam et al, 2021). These natural compounds can be used as a source of drugs or serve as lead compounds for the development of synthetic drugs.…”