Cadmium is an environmentally toxic metal that has deleterious effects on both animals and humans due to its accumulation in different body tissues. Physalis peruviana L. fruit and calyx contain many active constituents which are used traditionally for their different biological activities. Based on the traditional uses of P. peruviana L. calyx, we aimed to evaluate the nephroprotective effect of their 80% aqueous methanol extract (AME) and n-butanol fraction (Bu.F.) against cadmium chloride-induced nephrotoxicity in rats and to correlate this activity with phytoconstituents isolated using molecular docking studies.

The AME and its butanol fraction of P. peruviana L calyx showed potential nephroprotective activity against cadmium chloride-induced nephrotoxicity which is correlated at least in part to its considerable withanolides content.

The n-butanol fraction of P. peruviana L. calyx was fractionated using various chromatographic techniques and the isolated compounds were identified based on their chemical and spectroscopic data. The nephroprotective activity was assessed using cadmium chloride-induced nephrotoxicity in the rat model, by measuring some important parameters such as body weight, kidney weight, serum urea, and creatinine levels, oxidative stress markers, inflammatory markers, and histopathological examinations of kidney tissue. Molecular docking studies of the isolated compounds were performed.

Three withanolides named 4 β-hydroxywithanolide E (1), Physalin B (2) and 3α, 14β-dihydroxywithaphysalin N (3) were isolated and identified from the n-butanol fraction of P. peruviana L calyx extract. The extract and its butanol fraction significantly improved the serum kidney function markers and tissue oxidative status including malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT). Additionally, the extracts significantly decreased the levels of tumor necrosis factor-alpha (TNF-α) and nuclear factor kappaB (NF-κβ). Moreover, the histological changes were ameliorated by the extracts. The molecular docking study showed that the isolated compounds displayed a remarkable inhibitory activity against IκB kinase.