Protective Action Mechanisms of Extract and Its Nano-Formulation against Nephrotoxicity in Rats as Revealed via Biochemical, Histopathological, and UPLC-QTOF-MS/MS Analyses.

Plants belonging to the genus have been extensively utilized ethnopharmacologically to treat a variety of diseases, including kidney disorders. Chromium is a common industrial pollutant that has been linked to kidney disease. The present work was designed for the investigation of the UPLC-QTOF-MS/MS metabolite profile of the ethanolic extract (LME), along with assessing the mechanistic protective actions of LME and its nano-silver formulation (LMNS) against KCrO-induced nephrotoxicity in rats. LMNE was successfully biosynthesized and confirmed using UV-Visible (UV-Vis) spectroscopy and transmission electron microscopy (TEM). The nephroprotective effects of LME and LMNE was assessed in rats exposed to potassium dichromate (KCrO, 15 mg/kg BW) to cause nephrotoxicity. LME and LMNS, separately, were administered twice daily for 14 days at doses of 200 and 400 mg/kg BW, respectively. The kidney function, catalase, UGT, Nrf2, PGE2, Cox-2, ERK, and MAPK levels in renal tissue were all assessed, along with histopathological examinations for exploring their ameliorative effects. Forty-five bioactive metabolites were annotated belonging to flavonoids, phenolic and organic acids, coumarins, and fatty acids. Metabolite profiling revealed that chlorogenic acid, apigenin, and luteolin glycosides were the main phenolics, with chlorogenic acid--hexoside reported for the first time in LME. The findings revealed that the serum kidney function indicators (urea and creatinine) were markedly elevated in KCrO-intoxicated rats. Furthermore, inflammatory indicators (COX-2 and PGE2), MAPK, and ERK were all markedly elevated in kidney tissue, whereas catalase, UGT, and Nrf2 levels were downregulated. Histological and immunohistochemical assays confirmed the toxic effects of KCrO in the kidneys. In contrast, the administration of LME and LMNS prior to KCrO considerably improved the architecture of the renal tissue, while also restoring levels of most biochemical markers. Functioning via the inhibition of the MAPK/ERK pathway, activating Nrf2, and modifying the antioxidant and metabolic enzymes, LME and LMNS exerted their nephroprotective effects against KCrO-induced toxicity.