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

Abstract

Plants belonging to the Launaea 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 L. mucronate ethanolic extract (LME), along with assessing the mechanistic protective actions of LME and its nano-silver formulation (LMNS) against K2Cr2O7-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 (K2Cr2O7, 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-O-hexoside reported for the first time in LME. The findings revealed that the serum kidney function indicators (urea and creatinine) were markedly elevated in K2Cr2O7-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 K2Cr2O7 in the kidneys. In contrast, the administration of LME and LMNS prior to K2Cr2O7 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 K2Cr2O7-induced toxicity.

Citrus clementine Peel Essential Oil Ameliorates Potassium Dichromate-Induced Lung Injury: Insights into the PI3K/AKT Pathway

“…Swiss albino mice were administered gradient oral doses of CCEO, up to 2000 mg/kg bw, without any observable signs of toxicity or mortality within 24 h. From these observations, it can be concluded that the median lethal dose (LD50) of CCEO in mice is expected to be higher than 2000 mg/kg. According to classification criteria, as reported in previous literature, substances with LD50 values exceeding 50 mg/kg body weight are generally considered to be non-toxic [ 13 , 17 ].…”

“…The lungs were washed with saline and placed in ice-cold phosphate buffer (pH 7.4) to prepare 20% homogenate using a homogenizer (Heidolph, DIAX 900, Burladingen, Germany). The homogenates were centrifuged at 2000× g for 20 min at 4 • C. The supernatant was collected and stored at −80 • C [13] and then used for estimation of lung contents of TNF-α and TGF-β using NOVA (Beijing, China) ELISA kits and of IP3k using SunRed Biotechnology Company ELISA kits. Another part of lung tissue was kept in 10% formalin-saline for histopathological examination.…”

Enhancement of Female Rat Fertility via Ethanolic Extract from Nigella sativa L. (Black Cumin) Seeds Assessed via HPLC-ESI-MS/MS and Molecular Docking

“…The macerated plant with ethanol was filtered using a Buchner funnel lined with gauze between small pieces of cotton; the beaker was attached with a vacuum pump to facilitate the filtration process; the filtrate of N. sativa was dried using a rotary evaporator at 40 • C (Heidolph, Schwabach, Germany). The evaporated extract (75 g) was collected and kept in the refrigerator until it was used for phytochemical analysis and biological assays [46].…”