Integration of network pharmacology and intestinal flora to investigate the mechanism of action of Chinese herbal Cichorium intybus formula in attenuating adenine and ethambutol hydrochloride-induced hyperuricemic nephropathy in rats. (31st December 2022)

• Record Type: Journal Article
• Authors: Li, Na; Amatjan, Mukaram; He, Pengke; Zhang, Boheng; Mai, Xianyan; Jiang, Qianle; Xie, Haochen; Shao, Xiaoni
• Is Part Of: Pharmaceutical biology. Volume 60:Number 1(2022)
• Page Start: 2338
• Page End: 2354
• Publication Date: 2022-12-31
• Subjects: traditional Chinese medicine formula -- molecular docking -- nephroprotective effect -- gut microorganisms; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.1080/13880209.2022.2147551
• Languages: English
• ISSNs: 1388-0209

Abstract

Abstract: Context: Cichorium intybus L. (Asteraceae) formula (CF) has been applied as a folk medicine to treat hyperuricemic nephropathy (HN). However, the exact mechanism remains unclear. Objective: To explore the therapeutic effect and mechanism of CF on HN. Materials and methods: Through network pharmacological methods, the targets of the active component of CF against HN were obtained. Subsequently, Male Wistar rats were divided into control, HN, allopurinol (50 mg/kg), CF high-dose (8.64 g/kg) and CF low-dose (2.16 g/kg) groups. The HN model was induced via intragastric administration of adenine (100 mg/kg) and ethambutol hydrochloride (250 mg/kg) for 3 weeks. After CF treatment, biochemical indicators including UA, UREA and CREA were measured. Then, HE staining, qRT-PCR and gut microbiota analysis were conducted to further explore the mechanism. Results: The network pharmacology identified 83 key targets, 6 core genes and 200 signalling pathways involved in the treatment of HN. Compared to the HN group, CF (8.64 g/kg) significantly reduced the levels of UA, UREA and CREA (from 2.4 to 1.57 μMol/L, from 15.87 to 11.05 mMol/L and from 64.83 to 54.83 μMol/L, respectively), and mitigated renal damage. Furthermore, CF inhibited the expression of IL-6, TP53, TNF and JUN. It also altered the composition of gut microbiota, and ameliorated HN by increasing the relative abundance of some probiotics. Conclusions: This work elucidated the therapeutic effect and underlying mechanism by which CF protects against HN from the view of the biodiversity of the intestinal flora, thus providing a scientific basis for the usage of CF.