Combinatorial Chemistry & High Throughput ScreeningCombinatorial Chemistry & High Throughput ScreeningCombinatorial Chemistry & High Throughput Screening1386-20731875-5402Bentham Science64371710.2174/1386207326666230515151302ChemistryResearch ArticleStudy on Fu-Fang-Jin-Qian-Cao Inhibiting Autophagy in Calcium Oxalate-induced Renal Injury by UHPLC/Q-TOF-MS-based Metabonomics and Network Pharmacology ApproachesLiuWen-Ruiinfo@benthamscience.netLiMao-Tinginfo@benthamscience.netZhouQiinfo@benthamscience.netGaoSong-Yaninfo@benthamscience.netHouJie-Bininfo@benthamscience.netYangGuo-Bininfo@benthamscience.netLiuNan-Meiinfo@benthamscience.netJia-Yaninfo@benthamscience.netYuJian-Penginfo@benthamscience.netChengJininfo@benthamscience.netGuoZhi-Yonginfo@benthamscience.netDepartment of Nephrology, Changhai Hospital, Navy Medical UniversityInstitute of Translational Medicine, Shanghai UniversityDepartment of Nephrology, the Second Medical Centre, Chinese PLA General HospitalDepartment of Nephrology, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese MedicineInternational Medicine III (Nephrology & Endocrinology), Navy Medical Center of PLA, Navy Medical University010120242719010007012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://rjpbr.com/1386-2073/article/view/643717

Introduction:Fu-Fang-Jin-Qian-Cao is a Chinese herbal preparation used to treat urinary calculi. Fu-Fang-Jin-Qian-Cao can protect renal tubular epithelial cells from calcium oxalateinduced renal injury by inhibiting ROS-mediated autopathy. The mechanism still needs further exploration. Metabonomics is a new subject; the combination of metabolomics and network pharmacology can find pathways for drugs to act on targets more efficiently.

Methods:Comprehensive metabolomics and network pharmacology to study the mechanism of Fu-Fang-Jin-Qian-Cao inhibiting autophagy in calcium oxalate-induced renal injury. Based on UHPLC-Q-TOF-MS, combined with biochemical analysis, a mice model of Calcium oxalateinduced renal injury was established to study the therapeutic effect of Fu-Fang-Jin-Qian-Cao. Based on the network pharmacology, the target signaling pathway and the protective effect of Fu- Fang-Jin-Qian-Cao on Calcium oxalate-induced renal injury by inhibiting autophagy were explored. Autophagy-related proteins LC3-II, BECN1, ATG5, and ATG7 were studied by immunohistochemistry.

Results:Combining network pharmacology and metabolomics, 50 differential metabolites and 2482 targets related to these metabolites were found. Subsequently, the targets enriched in PI3KAkt, MAPK and Ras signaling pathways. LC3-II, BECN1, ATG5 and ATG7 were up-regulated in Calcium oxalate-induced renal injury. All of them could be reversed after the Fu-Fang-Jin-Qian- Cao treatment.

Conclusions:Fu-Fang-Jin-Qian-Cao can reverse ROS-induced activation of the MAPK signaling pathway and inhibition of the PI3K-Akt signaling pathway, thereby reducing autophagy damage of renal tubular epithelial cells in Calcium oxalate-induced renal injury.

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