GC–MS Metabolomics and Network Pharmacology‑Based Investigation of Molecular Mechanism of Identified Metabolites from Tinospora cordifolia (Willd.) Miers for the Treatment of Kidney Diseases

Background: Tinospora cordifolia (Willd.) Miers (T. cordifolia) is a well‑known Indian medicinal plant containing several nonpolar and polar constituents that play an important role to mitigate various ailments, such as diabetes, urinary disorders, and hepatoprotective. Due to the lack of evidence on phytopharmacological relevance to the unpredicted nonpolar matrix of T. cordifolia, the present study aimed to evaluate the metabolomic pattern of different fractions obtained from aqueous extract of T. cordifolia, which has been recommended in AYUSH for various ailments including kidney disorders. Materials and Methods: High‑performance thin‑layer chromatography and gas chromatography–mass spectrometry (GC–MS) analyses were performed on aqueous extracts and hexane, dichloromethane, and methanolic fraction of T. cordifolia aqueous extract to evaluate fingerprinting and metabolomic profile. Principal components and pharmacokinetic analysis were performed using XLSTAT and in‑silico SwissADME tool to determine metabolite variability and pharmacokinetic relationship based on lipophilicity and drug‑likeness. Further, network pharmacology analysis was performed to determine the exact biomolecular relationship of T. cordifolia in alleviating kidney disease. Results: The GC–MS metabolomics results showed several metabolites in different fractions with high variability of phytoconstituents in the methanolic fraction. In pharmacokinetics, each metabolite exhibited a direct correlation between drug lipophilicity and permeability. Network pharmacological suggested five fatty acids, which significantly interacted with the genes such as AGTR1, ATG, RELA, NOS3, NOS2, REN, INS, IL6, TNF, MAPK1, and CASP3, which could potentially regulate various pathophysiological conditions, such as hypertension, insulin resistance, oxidative and inflammatory stress, and electrolyte homeostasis, thereby strengthening the normal function of the kidney. Conclusion: The study showed that six metabolites of T. cordifolia play a multimechanistic role in alleviating kidney disease.