A Novel Approach Based on Gut Microbiota Analysis and Network Pharmacology to Explain the Mechanisms of Action of Cichorium intybus L. Formula in the Improvement of Hyperuricemic Nephropathy in Rats

Mukaram Amatjan; Na Li; Pengke He; Boheng Zhang; Xianyan Mai; Qianle Jiang; Haochen Xie; Xiaoni Shao

doi:10.2147/DDDT.S389811

A Novel Approach Based on Gut Microbiota Analysis and Network Pharmacology to Explain the Mechanisms of Action of Cichorium intybus L. Formula in the Improvement of Hyperuricemic Nephropathy in Rats

Drug Des Devel Ther. 2023 Jan 20:17:107-128. doi: 10.2147/DDDT.S389811. eCollection 2023.

Authors

Mukaram Amatjan¹, Na Li¹, Pengke He¹, Boheng Zhang¹, Xianyan Mai¹, Qianle Jiang¹, Haochen Xie², Xiaoni Shao¹

Affiliations

¹ Immunotherapy Laboratory, College of Pharmacology, Southwest Minzu University, Chengdu, 610225, People's Republic of China.
² Qinghai Tibet Plateau Research Institute, Southwest Minzu University, Chengdu, 610225, People's Republic of China.

Abstract

Background: Cichorium intybus L. formula (CILF) is a traditional Chinese medicine (TCM) widely used in the treatment of gout and hyperuricemic nephropathy (HN). The aim of this research was to investigate the potential protective effect of CILF against HN and elucidated the underlying mechanism.

Methods: CILF water extract was administered to an HN rat model established by adenine combined with ethambutol. The levels of uric acid (UA), serum urea nitrogen (UREA), and creatinine (CREA) were detected. Changes in the pathology and histology of the kidney were observed by hematoxylin-eosin staining. The 16S rRNA of the gut microbiota was sequenced. The binding ability of the main ingredients of CILF to key targets was analyzed by network pharmacology and molecular docking. The expression levels of the related mRNAs and proteins in the kidney were evaluated by RT-qPCR and immunohistochemistry analysis.

Results: CILF administration significantly alleviated increases in UA, UREA, and CREA, structural damage, and kidney dysfunction. Gut microbiota analysis was applied to explore the pharmacological mechanism of the effects of CILF on bacterial diversity and microbiota structure in HN. CILF decreased the abundance of Bacteroides. In addition, it increased the abundance of Lactobacillaceae, Erysipelotrichaceae, Lachnospiraceae, Ruminococcaceae, and Bifidobacterium. Based on network pharmacology and molecular docking analysis, CILF profoundly influenced the IL17, TNF and AGE-RAGE signaling pathway. Additionally, CILF inhibited the expression of STAT3, VEGFA and SIRT1 to improve the symptoms of nephropathy. Our research suggested that CILF protects against kidney dysfunction in rats with HN induced by adenine combined with ethambutol.

Conclusion: Our findings on the anti-HN effects of CILF and its mechanism of action, from the viewpoint of systems biology, and elaborated that CILF can alter the diversity and community structure of the gut microbiota in HN, providing new approaches for the prevention and treatment of HN.

Keywords: Cichorium intybus L. formula; gut microbiota; hyperuricemic nephropathy; molecular docking; network pharmacology.

MeSH terms

Adenine
Animals
Cichorium intybus*
Creatinine
Drugs, Chinese Herbal* / pharmacology
Ethambutol
Gastrointestinal Microbiome*
Hyperuricemia* / drug therapy
Molecular Docking Simulation
Network Pharmacology
RNA, Ribosomal, 16S
Rats
Urea
Uric Acid

Substances

Uric Acid
Ethambutol
RNA, Ribosomal, 16S
Adenine
Creatinine
Urea
Drugs, Chinese Herbal

Grants and funding

This work was supported by National Natural Science Foundation of China (No. 81801086); Natural Science Foundation of Sichuan, China (No.2022NSFSC1574) and the innovative research project for graduate students of Southwest Minzu University in 2022 (No. ZD2022168).