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

被引:8
|
作者
Li, Na [1 ]
Amatjan, Mukaram [1 ]
He, Pengke [1 ]
Zhang, Boheng [1 ]
Mai, Xianyan [1 ]
Jiang, Qianle [1 ]
Xie, Haochen [2 ]
Shao, Xiaoni [1 ,3 ]
机构
[1] Southwest Minzu Univ, Coll Pharmacol, Immunotherapy Lab, Chengdu, Peoples R China
[2] Southwest Minzu Univ, Qinghai Tibet Plateau Res Inst, Chengdu, Peoples R China
[3] Southwest Minzu Univ, Coll Pharmacol, Immunotherapy Lab, 168 Dajian St, Chengdu 610225, Peoples R China
基金
中国国家自然科学基金;
关键词
traditional Chinese medicine formula; molecular docking; nephroprotective effect; gut microorganisms; CHRONIC KIDNEY-DISEASE; URIC-ACID LEVEL; GARDENIAE FRUCTUS; XANTHINE-OXIDASE; UPLC-MS/MS; TNF-ALPHA; GENIPOSIDE; MODULATION; INHIBITION; EXPRESSION;
D O I
10.1080/13880209.2022.2147551
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
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 mu Mol/L, from 15.87 to 11.05 mMol/L and from 64.83 to 54.83 mu Mol/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.
引用
收藏
页码:2338 / 2354
页数:17
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  • [1] 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
    Amatjan, Mukaram
    Li, Na
    He, Pengke
    Zhang, Boheng
    Mai, Xianyan
    Jiang, Qianle
    Xie, Haochen
    Shao, Xiaoni
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