The molecular mechanisms of <italic style="font-style: italic">Jiang Tang San Hao</italic> Formula alleviating inflammatory responses in diabetic mice via the NLPR3 inflammasome

ZHAO Yi; LI Runqi; XU Bingrui; YE Zimengwei; MO Fangfang; TIAN Tian; DONG Guangtong; MA Rufeng; YANG Xiaoda; GAO Sihua; ZHAO Dandan

doi:10.3969/j.issn.1006-2157.2024.11.009

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The molecular mechanisms of Jiang Tang San Hao Formula alleviating inflammatory responses in diabetic mice via the NLPR3 inflammasome

Experimental Studies | 更新时间：2024-12-02

- The molecular mechanisms of Jiang Tang San Hao Formula alleviating inflammatory responses in diabetic mice via the NLPR3 inflammasome
- Journal of Beijing University of Traditional Chinese Medicine Vol. 47, Issue 11, Pages: 1541-1549(2024)
- 作者机构：
  
  1.北京中医药大学中医学院　北京　100029
  2.北京大学医学部
- 作者简介：
  
  ZHAO Dandan, Ph.D., Associate Researcher. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No.11, Beisanhuan Donglu Road, Chaoyang District, Beijing 100029. E-mail: bucmzhaodandan@163.com
- 基金信息：
  
  National Natural Science Foundation of China(82174329)
- DOI：10.3969/j.issn.1006-2157.2024.11.009
  CLC： R285.5
- Received：23 May 2024，
  
  Published Online：12 October 2024，
  
  Published：30 November 2024
- 稿件说明：
移动端阅览
ZHAO Yi, LI Runqi, XU Bingrui, et al. The molecular mechanisms of Jiang Tang San Hao Formula alleviating inflammatory responses in diabetic mice via the NLPR3 inflammasome[J]. Journal of beijing university of traditional chinese medicine, 2024, 47(11): 1541-1549.
DOI：

ZHAO Yi, LI Runqi, XU Bingrui, et al. The molecular mechanisms of Jiang Tang San Hao Formula alleviating inflammatory responses in diabetic mice via the NLPR3 inflammasome[J]. Journal of beijing university of traditional chinese medicine, 2024, 47(11): 1541-1549. DOI： 10.3969/j.issn.1006-2157.2024.11.009.

摘要

目的

观察降糖3号方对2型糖尿病(T2DM)小鼠机体与肠道炎症反应及NLRP3炎症小体的影响，揭示其抗糖尿病的分子机制。

方法

选取4周龄C57BL/6 N雄性小鼠，高脂饲料联合链脲佐菌素腹腔注射构建T2DM小鼠模型，将成模小鼠随机数字表法分成模型组、二甲双胍组、降糖3号方组，同时设置正常组。各组小鼠每日灌胃相应药液，二甲双胍组灌胃二甲双胍0.20 g/kg，降糖3号方组灌胃降糖3号方4.26 g/kg，正常组、模型组灌胃等量灭菌水，连续给药8周。药物干预结束后，酶联免疫吸附法检测血清及结肠组织中脂多糖(LPS)、肿瘤坏死因子－α(TNF-α)、白细胞介素－1β(IL-1β)、白细胞介素－6(IL-6)含量，苏木素－伊红染色观察结肠组织病理形态，免疫组织化学法检测结肠组织中NOD样受体热蛋白结构域相关蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、半胱氨酸蛋白酶－1(Caspase-1)、G蛋白偶联受体43(GPR43)、闭锁小带蛋白－1(ZO-1)、闭合蛋白(Occludin)蛋白表达，实时荧光PCR法检测结肠组织中NLRP3、ASC、Caspase-1、GPR43、ZO-1、Occludin mRNA表达。

结果

各组间血清、结肠炎性因子表达差异具有统计学意义，与模型组比较，降糖3号方组LPS、TNF-α、

IL-1β、IL-6表达降低(均

0.05)；降糖3号方可上调结肠中ZO-1、Occludin、GPR43的蛋白及mRNA表达，降低NLRP3、ASC、Caspase-1的蛋白及mRNA表达(均

0.05)，同时改善结肠组织病理损伤。

结论

T2DM小鼠呈现慢性炎症反应状态，降糖3号方能够通过抑制NLRP3炎症小体，缓解T2DM小鼠机体与肠道炎症反应，修复肠黏膜屏障，这可能是其抗糖尿病的分子机制之一。

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 (

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 (

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.

关键词

Keywords

references

GBD 2021 Diabetes Collaborators . Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021 [J ] . Lancet , 2023 , 402 ( 10397 ): 203 － 234 .

中华医学会糖尿病学分会 . 中国2型糖尿病防治指南(2020年版)(上) [J ] . 中国实用内科杂志， 2021 , 41 ( 8 ): 668 － 695 .

ZHAO LJ , LOU HX , PENG Y , et al . Elevated levels of circulating short-chain fatty acids and bile acids in type 2 diabetes are linked to gut barrier disruption and disordered gut microbiota [J ] . Diabetes Res Clin Pract , 2020 ， 169 ： 108418 .

LIU LL , ZHANG JH , CHENG Y , et al . Gut microbiota: a new target for T2DM prevention and treatment [J ] . Front Endocrinol , 2022 , 13 : 958218 .

SIKALIDIS AK , MAYKISH A . The gut microbiome and type 2 diabetes mellitus: discussing a complex relationship [J ] . Biomedicines , 2020 , 8 ( 1 ): 8 .

高思华，龚燕冰，倪青，等 . 肝脾肾同治法辨证治疗2型糖尿病的临床研究 [J ] . 中华中医药杂志， 2009 , 24 ( 8 ): 1007 － 1010 .

白颖，暴雪丽，赵丹丹，等 . 降糖3号方改善饮食诱导肥胖小鼠糖脂代谢的机制研究 [J ] . 中华中医药杂志， 2020 , 35 ( 5 ): 2253 － 2258 .

YE ZMW , MA JK , LIU YG , et al . Jiangtang Sanhao formula ameliorates skeletal muscle insulin resistance via regulating GLUT4 translocation in diabetic mice [J ] . Front Pharmacol , 2022 , 13 : 950535 .

白煜，姚乃礼，郝钰，等．基于肠道微生态探讨脾胃气化内涵及中医药的作用途径 [J ] . 中华中医药杂志， 2022 ， 37 ( 3 )： 1790 － 1793 .

郭文茜，王琦，郭刚，等 . 基于人体肠道菌群探讨“脾为后天之本” [J ] . 中华中医药杂志， 2021 , 36 ( 9 ): 5165 － 5168 .

MOHAMMAD S , THIEMERMANN C . Role of metabolic endotoxemia in systemic inflammation and potential interventions [J ] . Front Immunol , 2020 , 11 : 594150 .

EGUCHI K , NAGAI R . Islet inflammation in type 2 diabetes and physiology [J ] . J Clin Invest , 2017 , 127 ( 1 ): 14 － 23 .

MENINI S , IACOBINI C , VITALE M , et al . The inflammasome in chronic complications of diabetes and related metabolic disorders [J ] . Cells , 2020 , 9 ( 8 ): 1812 .

YANG D , WANG ZX , CHEN YX , et al . Interactions between gut microbes and NLRP3 inflammasome in the gut-brain axis [J ] . Comput Struct Biotechnol J , 2023 , 21 : 2215 － 2227 .

MONTEIRO-SEPULVEDA M , TOUCH S , MENDES-SÁ C , et al . Jejunal T cell inflammation in human obesity correlates with decreased enterocyte insulin signaling [J ] . Cell Metab , 2015 , 22 ( 1 ): 113 － 124 .

巩静 . 从肠道黏膜屏障与免疫系统探讨小檗碱改善糖脂代谢紊乱的机制 [D ] . 武汉：华中科技大学， 2018 .

KODI T , SANKHE R , GOPINATHAN A , et al . New insights on NLRP3 inflammasome: mechanisms of activation, inhibition, and epigenetic regulation [J ] . J Neuroimmune Pharmacol , 2024 , 19 ( 1 ): 7 .

FU JN , WU H . Structural mechanisms of NLRP3 inflammasome assembly and activation [J ] . Annu Rev Immunol , 2023 ， 41 ： 301 － 316 .

LI Y , ZHANG HF , LIU MY , et al . Microglia NLRP3 inflammasomes activation involving diabetic neuroinflammation in diabetic mice and BV2 cells [J ] . Curr Pharm Des , 2021 , 27 ( 24 ): 2802 － 2816 .

ZHANG LJ , JING MM , LIU Q . Crocin alleviates the inflammation and oxidative stress responses associated with diabetic nephropathy in rats via NLRP3 inflammasomes [J ] . Life Sci , 2021 , 278 : 119542 .

ZHANG C , LI X , HU X , et al . Epigallocatechin－3－gallate prevents inflammation and diabetes-induced glucose tolerance through inhibition of NLRP3 inflammasome activation [J ] . Int Immunopharmacol , 2021 , 93 : 107412 .

LIANG BJ , LIAO SR , HUANG WX , et al . Intermittent fasting therapy promotes insulin sensitivity by inhibiting NLRP3 inflammasome in rat model [J ] . Ann Palliat Med , 2021 , 10 ( 5 ): 5299 － 5309 .

JONES N , BLAGIH J , ZANI F , et al . Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation [J ] . Nat Commun , 2021 , 12 ( 1 ): 1209 .

李嘉鑫，王庆峰，安继仁，等 . 基于“燥热怫郁”理论探讨2型糖尿病肠黏膜屏障损伤 [J ] . 北京中医药大学学报， 2023 , 46 ( 7 ): 992 － 998 .

PANWAR S , SHARMA S , TRIPATHI P . Role of barrier integrity and dysfunctions in maintaining the healthy gut and their health outcomes [J ] . Front Physiol , 2021 , 12 : 715611 .

IYER SS , GENSOLLEN T , GANDHI A , et al . Dietary and microbial oxazoles induce intestinal inflammation by modulating aryl hydrocarbon receptor responses [J ] . Cell , 2018 , 173 ( 5 ): 1123 － 1134 .

GURUNG M , LI ZP , YOU H , et al . Role of gut microbiota in type 2 diabetes pathophysiology [J ] . EBioMedicine , 2020 , 51 : 102590 .

AN YC , DAI HY , DUAN YH , et al . The relationship between gut microbiota and susceptibility to type 2 diabetes mellitus in rats [J ] . Chin Med , 2023 , 18 ( 1 ): 49 .

王梓宇，张智慧，吴鹏，等．基于肠道菌群和短链脂肪酸代谢探讨甘草制远志降低肠道炎症的作用机制 [J ] . 中草药， 2023 ， 54 ( 14 )： 4556 － 4563 .

MCKENZIE CI , MACKAY CR , MACIA L . GPR43 － A prototypic metabolite sensor linking metabolic and inflammatory diseases [J ] . Trends Endocrinol Metab , 2015 , 26 ( 10 ): 511 － 512 .

MCNELIS JC , LEE YS , MAYORAL R , et al . GPR43 potentiates β－cell function in obesity [J ] . Diabetes , 2015 , 64 ( 9 ): 3203 － 3217 .

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The molecular mechanisms of Jiang Tang San Hao Formula alleviating inflammatory responses in diabetic mice via the NLPR3 inflammasome

DOI：10.3969/j.issn.1006-2157.2024.11.009

摘要

Abstract

关键词

Keywords

references