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

Amany A El-Fadaly; Inas Y Younis; Mohamed F Abdelhameed; Yasmine H Ahmed; Tamer I M Ragab; Abd El-Nasser G El Gendy; Mohamed A Farag; Abdelsamed I Elshamy; Abdelbaset M Elgamal

doi:10.3390/metabo13070786

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

Metabolites. 2023 Jun 23;13(7):786. doi: 10.3390/metabo13070786.

Authors

Amany A El-Fadaly¹, Inas Y Younis², Mohamed F Abdelhameed¹, Yasmine H Ahmed³, Tamer I M Ragab⁴, Abd El-Nasser G El Gendy⁵, Mohamed A Farag², Abdelsamed I Elshamy⁶, Abdelbaset M Elgamal⁴

Affiliations

¹ Pharmacology Department, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt.
² Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo 11562, Egypt.
³ Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
⁴ Chemistry of Natural and Microbial Products Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt.
⁵ Medicinal and Aromatic Plants Research Department, National Research Centre, Dokki, Giza 12622, Egypt.
⁶ Chemistry of Natural Compounds Department, National Research Centre, 33 El Bohouth St., Dokki, Giza 12622, Egypt.

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.

Keywords: Launaea mucronata; UPLC-MS; oxidative stress; potassium dichromate toxicity; renal injury; secondary metabolites.

Grants and funding

This research received no external funding.