PMID- 36164881 OWN - NLM STAT- MEDLINE DCOM- 20220928 LR - 20221013 IS - 1001-5302 (Print) IS - 1001-5302 (Linking) VI - 47 IP - 17 DP - 2022 Sep TI - [Mechanism of total flavonoids from Ampelopsis grossedentata against gouty arthritis based on multi-level interactive network and in vivo experimental validation]. PG - 4733-4743 LID - 10.19540/j.cnki.cjcmm.20220223.701 [doi] AB - The present study investigated the mechanism of total flavonoids from Ampelopsis grossedentata(AGTF) against gouty arthritis(GA) by network pharmacology and experimental validation. The main active ingredients and targets of AGTF, as well as disease targets, were screened out using relevant databases and literature data. The "protein-protein interaction"(PPI) network and "drug-ingredient-target-pathway" network were constructed, and the potential targets and mechanism of AGTF against GA were predicted. The hyperuricemia(HUA) combined with GA model was induced in rats. The gait behaviors of rats were scored, and ankle swelling degree was observed. The uric acid(UA) level and xanthine oxidase(XOD) activity in the rat serum were detected, and the levels of interleukin-1beta(IL-1beta), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-alpha) were measured. The protein expression of toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), and nuclear factor-kappa B(NF-kappaB) in the synovial tissues of the rat ankle joint was determined by immunohistochemistry. Ten active ingredients of AGTF and 73 candidate targets of AGTF against GA were screened out by network pharmacology. Eighty-six signaling pathways were enriched, including TNF signaling pathway, NF-kappaB signaling pathway, TLR signaling pathway, Nod-like receptor signaling pathway, and purine metabolism signaling pathway, which were closely related to AGTF against GA. Animal experimental results showed that AGTF could effectively improve the abnormal gait behaviors of GA rats, relieve ankle inflammation, and reduce ankle joint swelling. In addition, AGTF could significantly reduce UA level, inhibit XOD activity, decrease TNF-alpha, IL-6, and IL-1beta content, and down-regulate the expression of TLR4, MyD88, and NF-kappaB in ankle synovial tissues(P<0.05, P<0.01). The results of network pharmacology and experimental validation are consistent, indicating that AGTF exerts its therapeutic effect on GA by regulating UA metabolism, improving abnormal UA level, reducing the release of inflammatory factors, and regulating immunity and the TLR4/MyD88/NF-kappaB inflammatory pathway. FAU - Li, Jia-Chuan AU - Li JC AD - College of Pharmacy, Southwest Minzu University Chengdu 610041, China. FAU - Li, Si-Ying AU - Li SY AD - College of Pharmacy, Southwest Minzu University Chengdu 610041, China. FAU - Song, Qin AU - Song Q AD - College of Pharmacy, Southwest Minzu University Chengdu 610041, China. FAU - Ma, Er-Xiu AU - Ma EX AD - College of Pharmacy, Southwest Minzu University Chengdu 610041, China College of Forestry and Health, the Open University of Sichuan Chengdu 610075, China. FAU - Aimaijiang, Mu-Karan AU - Aimaijiang MK AD - College of Pharmacy, Southwest Minzu University Chengdu 610041, China. LA - chi PT - Journal Article PL - China TA - Zhongguo Zhong Yao Za Zhi JT - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica JID - 8913656 RN - 0 (Flavonoids) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (NLR Proteins) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 268B43MJ25 (Uric Acid) RN - EC 1.17.3.2 (Xanthine Oxidase) SB - IM MH - *Ampelopsis/chemistry MH - Animals MH - *Arthritis, Gouty/drug therapy MH - *Flavonoids/pharmacology/therapeutic use MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - Myeloid Differentiation Factor 88/genetics/metabolism MH - NF-kappa B/genetics/metabolism MH - NLR Proteins/metabolism MH - Rats MH - Toll-Like Receptor 4/genetics/metabolism MH - Tumor Necrosis Factor-alpha/genetics/metabolism MH - Uric Acid MH - Xanthine Oxidase OTO - NOTNLM OT - gouty arthritis OT - mechanism of action OT - network pharmacology OT - total flavonoids from Ampelopsis grossedentata EDAT- 2022/09/28 06:00 MHDA- 2022/10/14 06:00 CRDT- 2022/09/27 04:22 PHST- 2022/09/27 04:22 [entrez] PHST- 2022/09/28 06:00 [pubmed] PHST- 2022/10/14 06:00 [medline] AID - 10.19540/j.cnki.cjcmm.20220223.701 [doi] PST - ppublish SO - Zhongguo Zhong Yao Za Zhi. 2022 Sep;47(17):4733-4743. doi: 10.19540/j.cnki.cjcmm.20220223.701.