Investigation of the mechanism of nephrotoxicity of nux‐vomica by PTGS2/CYP2C9‐mediated arachidonic acid pathway and Jian Pi Tong Luo compound's protective effect

Abstract

AbstractThe clinical effectiveness of nux‐vomica in treating rheumatism and arthralgia is noteworthy; however, its nephrotoxicity has sparked global concerns. Hence, there is value in conducting studies on detoxification methods based on traditional Chinese medicine compatibility theory. Blood biochemistry, enzyme‐linked immunosorbent assay, and pathological sections were used to evaluate both the nephrotoxicity of nux‐vomica and the efficacy of the Jian Pi Tong Luo (JPTL) compound in mitigating this toxicity. Kidney metabolomics, using ultra‐high‐performance liquid chromatography–quadrupole‐time‐of‐flight–MS (UPLC–Q‐TOF–MS), was applied to elucidate the alterations in small‐molecule metabolites in vivo. In addition, network pharmacology analysis was used to verify the mechanism and pathways underlying the nephrotoxicity associated with nux‐vomica. Finally, essential targets were validated through molecular docking and western blotting. The findings indicated significant nephrotoxicity associated with nux‐vomica, while the JPTL compound demonstrated the ability to alleviate this toxicity. The mechanism potentially involves nux‐vomica activating the “PTGS2/CYP2C9–phosphatidylcholine–arachidonic acid metabolic pathway.” This study establishes a scientific foundation for the clinical use of nux‐vomica and lays groundwork for further research and safety assessment of toxic Chinese herbal medicines.