Mechanism Prediction of Astragalus membranaceus against Cisplatin-Induced Kidney Damage by Network Pharmacology and Molecular Docking

Author:

Jia Congchao1ORCID,Pan Xianchao2ORCID,Wang Binyou3ORCID,Wang Pengyu1ORCID,Wang Yiwei45ORCID,Chen Rong6ORCID

Affiliation:

1. Clinical Medical College, Southwest Medical University, Luzhou, Sichuan 646000, China

2. Department of Medicinal Chemistry, College of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China

3. College of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China

4. State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China

5. College of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China

6. Department of Pathophysiology, College of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China

Abstract

Background. Cisplatin is a frequently used and effective chemotherapy drug in clinical practice, but severe side effects limit its use, among which nephrotoxicity is considered the most serious and prolonged damage to the body. Astragalus membranaceus (AM) is a well-known herbal medicine, and modern pharmacological studies have confirmed its antioxidant, immunomodulatory, and antiapoptotic effects. Clinical studies have shown that AM and its active components can attenuate cisplatin-induced kidney damage, but the molecular mechanism has not been fully expounded. Materials and Methods. First, the components and targets information of AM were collected from the TCMSP, and the relevant targets of cisplatin-induced kidney damage were accessed from the GeneCards and OMIM databases. Then, the core targets were selected by the Venn diagram and network topology analysis, which was followed by GO and KEGG pathway enrichment analysis. Finally, we construct a component-target-pathway network. Furthermore, molecular docking was carried out to identify the binding activity between active components and key targets. Results. A total of 20 active components and 200 targets of AM and 646 targets related to cisplatin-induced kidney damage were obtained. 91 intersection targets were found between AM and cisplatin-induced kidney damage. Then, 16 core targets were identified, such as MAPK1, TNF-α, and p53. Furthermore, GO and KEGG pathway enrichment analysis suggested that MAPK, Toll-like receptor, and PI3K-Akt signaling pathways may be of significance in the treatment of cisplatin-induced kidney damage by AM. Molecular docking indicated that quercetin and kaempferol had high binding affinities with many core targets. Conclusion. In summary, the active components, key targets, and signaling pathways of AM in the treatment of cisplatin-induced kidney damage were predicted in this study, which contributed to the development and application of AM.

Funder

Natural Science Project of Sichuan Provincial Health Department

Publisher

Hindawi Limited

Subject

Complementary and alternative medicine

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