Nephroprotective potential of Sharbat-e-Bazoori Motadil (sugar-free) in HEK-293 cells and Wistar rats against cisplatin induced nephrotoxicity

Abstract

Sharbat-e-Bazoori Motadil (SBM) is a traditional Unani syrupy formulation, widely used for the management of kidney diseases. Due to lack of scientific evidence, the present work prospective is aimed to evaluate the protective effect of sugar-free SBM against cisplatin (CP)-induced nephrotoxicity using in vitro and in vivo followed by phytochemical studies. The sugar-free SBM formulation was chromatographically characterized for chemical analysis through HPTLC and evaluated for its metabolic contents. Thereafter, in vitro phytochemicals and free radical scavenging assays were performed to evaluate the total phenols and flavonoid content and antioxidant potential of sugar-free SBM. Human embryonic kidney-293 (HEK-293) cell was used to assess nephroprotective and antioxidant studies of sugar-free SBM. Further, in vivo nephroprotective studies were performed in female Wistar albino rats at different dose (32.1, 64.2, 128.4 mg/kg/day, p.o.) of SBM by assessment of biochemical markers, antioxidants status, inflammatory cytokines, and histopathological analysis. Qualitative and quantitative HPTLC analysis of SBM revealed eleven and eight metabolites at 254 and 366 nm, respectively, while the content of caffeic acid and trans ferulic acid was found as 5.63 ± 0.29 and 12.64 ± 0.71 µg/mg, respectively. In vitro free radical scavenging assays showed the significant antioxidant potential of sugar-free SBM. The in vitro assay for nephroprotective and cellular antioxidant analysis of SBM showed significant (p < 0.001) nephroprotective and antioxidant potential. Additionally, in vivo studies of different doses of SBM showed significant (p < 0.001) amelioration in kidney and liver biomarkers. Besides, it also manifests antioxidant, anti-inflammatory and anti-apoptosis activity confirmed by regulation of CAT, GPx, GSH, SOD, TNF-α, IL-1β, NO and caspase-3 levels. Additionally, normalization in histopathological changes of kidney tissue against cisplatin toxicity was also observed in SBM. The sugar-free SBM significantly ameliorated cisplatin induced nephrotoxicity by exerting normalcy in biochemical markers, antioxidant, and anti-inflammatory activity. These findings indicated an opportunity to develop a sugar-free formulation from SBM composition, as well as scientific validation of its traditional claim in the Unani system of medicine.

Keywords

• Sharbat-e-Bazoori
• Kidney
• Cisplatin
• Nephrotoxicity
• HEK-293
• α-Ketoanalogue