Metabolite profiling and nephroprotective potential of Glycyrrhiza glabra L. roots against cisplatin-induced nephrotoxicity in vitro and in vivo

Objective(s): The present study was conducted to investigate the phytochemical analysis and demonstrate the nephroprotective potential of root extract of Glycyrrhiza glabra L. against cisplatin (CP) - induced nephrotoxicity in vitro and in vivo. Materials and Methods: The HPTLC analysis and UPLC-MS were carried out for standardizing and metabolite profiling of methanolic extract of roots of G. glabra (GGE). Further, in vitro studies were conducted in human embryonic kidney (HEK)-293 cells to evaluate the cytotoxicity and anti-oxidant potential of GGE with CP as a toxicant and ascorbic acid as standard. Also, in vivo nephroprotective potential at doses of 31.5, 63, and 126 mg/kg/day on CP (6 mg/kg, bw, IP) induced nephrotoxicity was evaluated on rodents. Results: Phytochemical analysis by HPTLC and UPLC-MS revealed the presence of glycyrrhizin, glabridin, and liquiritin along with other bioactive constituents. The in vitro assay of GGE showed significant (P 0.001 nephroprotective, cellular anti-oxidant potential and improvement in morphological changes induced by CP. Further, administration of CP caused significant (P 0.001) elevation in biochemical, inflammatory, oxidative stress, caspase-3, as well as histopathological changes in kidney tissue. Pre-treatment with GGE attenuated the elevated biochemical markers significantly, improved histopathological damage, and showed a comparable result to ascorbic acid and α- ketoanalogue. Conclusion: Present study concluded the nephroprotective potential of GGE which supports the traditional claim of G. glabra roots in various kidney and its related disorders. The nephroprotective activity may be attributed to its anti-oxidant, anti-inflammatory, and anti-apoptosis effects. Thus, it holds promising potential in management of nephrotoxicity.