Study on Fu-Fang-Jin-Qian-Cao Inhibiting Autophagy in Calcium Oxalate-induced Renal Injury by UHPLC/Q-TOF-MS-based Metabonomics and Network Pharmacology Approaches


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Abstract

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.

About the authors

Wen-Rui Liu

Department of Nephrology, Changhai Hospital, Navy Medical University

Email: info@benthamscience.net

Mao-Ting Li

Department of Nephrology, Changhai Hospital, Navy Medical University

Email: info@benthamscience.net

Qi Zhou

Department of Nephrology, Changhai Hospital, Navy Medical University

Email: info@benthamscience.net

Song-Yan Gao

Institute of Translational Medicine, Shanghai University

Email: info@benthamscience.net

Jie-Bin Hou

Department of Nephrology, the Second Medical Centre, Chinese PLA General Hospital

Email: info@benthamscience.net

Guo-Bin Yang

Department of Nephrology, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Email: info@benthamscience.net

Nan-Mei Liu

International Medicine III (Nephrology & Endocrinology), Navy Medical Center of PLA, Navy Medical University

Email: info@benthamscience.net

Jia-Yan

Department of Nephrology, Changhai Hospital, Navy Medical University

Email: info@benthamscience.net

Jian-Peng Yu

Department of Nephrology, Changhai Hospital, Navy Medical University

Email: info@benthamscience.net

Jin Cheng

International Medicine III (Nephrology & Endocrinology), Navy Medical Center of PLA, Navy Medical University

Author for correspondence.
Email: info@benthamscience.net

Zhi-Yong Guo

Department of Nephrology, Changhai Hospital, Navy Medical University

Author for correspondence.
Email: info@benthamscience.net

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