The molecular mechanisms of Jiang Tang San Hao Formula alleviating inflammatory responses in diabetic mice via the NLPR3 inflammasome
10.3969/j.issn.1006-2157.2024.11.009
- VernacularTitle:基于NLRP3炎症小体探讨降糖3号方缓解糖尿病小鼠炎症反应的分子机制
- Author:
Yi ZHAO
1
;
Runqi LI
;
Bingrui XU
;
Zimengwei YE
;
Fangfang MO
;
Tian TIAN
;
Guangtong DONG
;
Rufeng MA
;
Xiaoda YANG
;
Sihua GAO
;
Dandan ZHAO
Author Information
1. 北京中医药大学中医学院 北京 100029
- Keywords:
type 2 diabetes;
Jiang Tang San Hao Formula;
inflammatory reaction;
NLPR3 inflammasome;
intestinal mucosal barrier;
mice
- From:
Journal of Beijing University of Traditional Chinese Medicine
2024;47(11):1541-1549
- CountryChina
- Language:Chinese
-
Abstract:
Objective This study aimed to observe the effect of Jiang Tang San Hao Formula(JTSHF)on systemic and intestinal inflammation,as well as on the NLRP3 inflammasome in type 2 diabetic mice(T2DM),and to elucidate its anti-diabetic molecular mechanisms.Methods Four-week-old male C57BL/6 N mice were used to establish the T2DM model using a high-fat diet combined with streptozotocin injection.The diabetic mice were randomly divided into the model,metformin,and JTSHF groups.A control group was also set to provide baseline comparisons.Each group of mice was orally administered with the corresponding medication daily.The metformin group was orally administered with 0.20 g/kg metformin,the JTSHF group was orally administered with 4.26 g/kg JTSHF,and the control group and model group were orally administered with an equal amount of sterile water continuously for 8 weeks.After an 8-week drug intervention via gavage,the lipopolysaccharide(LPS),tumor necrosis factor-alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6)serum and colon levels were quantified using an enzyme-linked immunosorbent assay(ELISA).The pathological morphology of the colon was observed using hematoxylin and eosin staining.NOD-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),caspase-1,zonula occludens-1(ZO-1),occludin,and G-protein coupled receptor 43(GPR43)protein expression in the colon were assessed using immunohistochemistry.The mRNA expression levels of NLRP3,ASC,caspase-1,ZO-1,Occludin,and GPR43 in the colon were detected using Real-time PCR.Results The ELISA data revealed significant differences in inflammatory markers among the groups.Compared with the model group,the JTSHF group exhibited notably reduced LPS,TNF-α,IL-1β,and IL-6 levels(P<0.05).Moreover,compared with the model group,JTSHF treatment upregulated ZO-1,occludin,and GPR43 protein and mRNA expression in the colon and downregulated NLRP3,ASC,and Caspase-1 protein and mRNA expression(P<0.05).Conclusion The inflammatory reaction of T2DM mice is apparent.JTSHF effectively alleviates the systemic and intestinal inflammatory response of T2DM mice by inhibiting the NLRP3 inflammasome and repairing the intestinal mucosal barrier,highlighting the potential molecular mechanisms of the anti-diabetes effects of JTSHF.
