Derris eriocarpa Extract Treats Gout via TLR4/NF-κB/NLRP3 Pathway
10.13422/j.cnki.syfjx.20230509
- VernacularTitle:基于TLR4/NF-κB/NLRP3通路探讨毛果鱼藤提取物抗痛风作用及机制
- Author:
Hongcun LIU
1
;
Zhenxin ZHU
1
;
Yue LU
1
;
Yang XIAO
2
;
Ying LIU
2
;
Guining WEI
2
;
Lifang YANG
2
Author Information
1. Guangxi Key Laboratory for Polysaccharide Materials and Modifications，School of Marine Sciences and Biotechnology，Guangxi Minzu University，Nanning 530008，China
2. Guangxi Key Laboratory of Chemistry and Engineering of Forest Products，School of Chemistry and Chemical Engineering，Guangxi Minzu University，Nanning 530008，China
- Publication Type:Journal Article
- Keywords:
Derris eriocarpa;
gout;
Toll-like receptor 4 （TLR4）;
NOD-like reception protein 3 （NLRP3）;
inflammation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(23):72-80
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the anti-gout effect and mechanism of Derris eriocarpa extract by network pharmacological analysis combined with in vivo and in vitro experimental verification. MethodThe chemical components and candidate targets of D. eriocarpa were obtained from the database. The key targets and potential active components of D. eriocarpa in the treatment of gout were screened by the protein-protein interaction analysis， and then the Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the key targets. A mouse model of hyperuricemia was established by intraperitoneal injection of hypoxanthine to observe the effect of D. eriocarpa alcohol extract on hyperuricemia. A rat model of gouty inflammation induced by the injection of microcrystalline sodium urate crystals into the foot and plantar was used to observe the effect of D. eriocarpa alcohol extract on gouty inflammation. A xylene-induced acute inflammation model was established to observe the anti-inflammatory effect of D. eriocarpa alcohol extract. The hot plate test and twisting test were performed to observe the pain-relieving effect of D. eriocarpa. The lipopolysaccharide （LPS）-induced RAW264.7 cells were used to study the anti-gout effect and mechanism of D. eriocarpa alcohol extract. ResultA total of 12 key targets and 15 potential active components were obtained from the D. eriocarpa-component-gout target network. The emodin， betulinic acid， and medicarpin endowed D. eriocarpa with anti-hyperuricemia， anti-inflammatory， and pain-relieving effects by acting on Toll-like receptor 4 （TLR4）， NOD-like reception protein 3 （NLRP3）， and nuclear factor （NF）-κB. Compared with the control group， the model groups showed elevated serum uric acid level in mice （P<0.01）， increased swelling degree of rats （P<0.05， P<0.01）， alleviated the auricular swelling of mice （P<0.05）， reduced the twisting times of mice （P<0.05， P<0.01）， and increased the hot plate pain threshold （P<0.05）. Moreover， the model group showed up-regulated mRNA level of TLR4 and protein levels of TLR4， NF-κB， and NLRP3 in cells （P<0.01）， and elevated levels of TLR4 and NF-κB in the cell supernatant （P<0.05， P<0.01）. Compared with the model group， the alcoholic extracts （20， 10， 5 g·kg-1） of D. eriocarpa lowered the serum uric acid level in hyperuricemic mice （P<0.01）， inhibited foot and plantar swelling in rats （P<0.05， P<0.01）， down-regulated the mRNA level of TLR4 and the protein levels of TLR4， NF-κB， NLRP3 in cells， and lowered the levels of TLR4， TNF-α， NF-κB， and IL-6 in cell supernatants （P<0.05， P<0.01）. ConclusionD. eriocarpa alcohol extract may exert the anti-gout， anti-inflammatory， and pain-relieving effects by regulating the TLR4/NF-κB/NLRP3 signaling pathway.
