Berberine improves ulcerative colitis in mice by inhibiting JAK2/STAT3 signal pathway

WANG Hongqing; ZHANG Lijun; LIN Chuan; HUANG Cheng; FAN Shengjie; AN Rui

doi:10.16306/j.1008-861x.2023.02.003

您当前的位置：

首页 >

文章列表页 >

Berberine improves ulcerative colitis in mice by inhibiting JAK2/STAT3 signal pathway

Special column on anti-inflammatory of traditional Chinese medicine | 更新时间：2023-03-24

- Berberine improves ulcerative colitis in mice by inhibiting JAK2/STAT3 signal pathway
- Academic Journal of Shanghai University of Traditional Chinese Medicine Vol. 37, Issue 2, Pages: 14-21(2023)
- 作者机构：
  
  1.上海中医药大学中药学院（上海　201203）
- 作者简介：
- 基金信息：
- DOI：10.16306/j.1008-861x.2023.02.003
  CLC：
扫描看全文
王鸿卿,张丽君,林川等.小檗胺通过抑制JAK2/STAT3信号通路改善小鼠溃疡性结肠炎[J].上海中医药大学学报,2023,37(02):14-21.

WANG Hongqing,ZHANG Lijun,LIN Chuan,et al.Berberine improves ulcerative colitis in mice by inhibiting JAK2/STAT3 signal pathway[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2023,37(02):14-21.
王鸿卿,张丽君,林川等.小檗胺通过抑制JAK2/STAT3信号通路改善小鼠溃疡性结肠炎[J].上海中医药大学学报,2023,37(02):14-21. DOI： 10.16306/j.1008-861x.2023.02.003.

WANG Hongqing,ZHANG Lijun,LIN Chuan,et al.Berberine improves ulcerative colitis in mice by inhibiting JAK2/STAT3 signal pathway[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2023,37(02):14-21. DOI： 10.16306/j.1008-861x.2023.02.003.

摘要

目的,2,观察小檗胺（BBM）对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）小鼠的干预作用及其可能机制。,方法,2,①采用RAW264.7巨噬细胞炎症模型，考察BBM对其细胞活力、一氧化氮（NO）释放、肿瘤坏死因子-α（,TNF,⁃,α,）、白介素-1β（,IL,⁃,1β,）、,IL,⁃,6,和诱导型NO合酶（,iNOS,）炎症基因表达的影响。②雄性C57BL/6小鼠随机分为正常组、模型组、BBM组（50 mg/kg）和柳氮磺胺吡啶（SASP）阳性药组（250 mg/kg），每组8只。建立DSS诱导的UC小鼠模型，连续9 d灌胃给予相应药物。记录小鼠的体质量、脾脏系数、结肠长度及表观，评估疾病活动指数，HE染色观察结肠病理损伤；RT-qPCR检测小鼠结肠中炎症基因,TNF,⁃,α、IL,⁃,1β、IL,⁃,6、iNOS,的表达；Western blot检测小鼠结肠中紧密连接蛋白Claudin-4、Occludin及JAK2/STAT3通路蛋白的表达。,结果,2,①BBM对RAW264.7细胞活力没有明显影响（,P,>,0.05），但能呈剂量依赖性地减少细胞中NO的释放量（,P,<,0.05，,P,<,0.01）及炎症基因,TNF,⁃,α、IL,⁃,1β、IL,⁃,6、iNOS,的表达（,P,<,0.05，,P,<,0.01）；②BBM能改善UC小鼠的体质量下降和脾脏系数升高（,P,<,0.05）、抑制结肠的缩短（,P,<,0.05）、降低疾病活动指数评分和改善结肠病理损伤（,P,<,0.05）；③BBM能减少小鼠结肠中炎症基因,TNF,⁃,α、IL,⁃,1β、IL,⁃,6、iNOS,的表达（,P,<,0.05，,P,<,0.01）；④BBM能增加小鼠结肠中Claudin-4、Occludin的表达以及抑制JAK2和STAT3的磷酸化（,P,<,0.05，,P,<,0.01）。,结论,2,BBM能改善DSS诱导小鼠的UC，其作用机制可能为通过抑制JAK2/STAT3信号通路、减少炎症基因的表达，从而增强肠黏膜屏障功能。

Abstract

Objective： To observe the intervention effect and possible mechanism of berbamine （BBM） on ulcerative colitis （UC） mice induced by dextran sulfate sodium （DSS）.,Methods,2,①RAW264.7 macrophage inflammation model was used to investigate the effect of BBM on its cell viability， nitric oxide （NO） release， and the expression of tumor necrosis factor-α （,TNF,-,α,）， interleukin-1β （,IL,-,1β,）， ,IL,-,6, and inducible NO synthase （,iNOS,） inflammatory genes. ②Male C57BL/6 mice were randomly divided into normal group， model group， BBM group （50 mg/kg） and sulfasalazine （SASP） positive group （250 mg/kg）， with 8 mice in each group. DSS induced UC mouse model was established， and corresponding drugs were given by gavage for 9 d consecutively. The body mass， spleen coefficient， colon length and appearance of the mice were recorded， disease activity index was evaluated， and pathological injury of colon was observed by HE staining. The expression of inflammatory genes ,TNF,-,α， IL,-,1 β， IL,-,6 ,and ,iNOS, in the colon of mice were detected by RT-qPCR and the expression of tight junction proteins Claudin-4 and Occludin as well as JAK2/STAT3 pathway proteins were detected by Western blot.,Results,2,①BBM had no effect on RAW264.7 cells viability， but could reduce the NO release （,P,<,0.05，,P,<,0.01） and the expression of inflammatory genes, TNF,-,α,， ,IL,-,1β,，, IL,-,6 ,and, iNOS, in a dose-dependent manner （,P,<,0.05，,P,<,0.01）. ②BBM could improve the body mass loss and spleen coefficient increase of UC mice （,P,<,0.05）， inhibit the shortening of the colon （,P,<,0.05）， decrease the score of disease activity index and improve the pathological injury of colon in mice （,P,<,0.05）. ③BBM could reduce the expression of inflammatory genes ,TNF,-,α,， ,IL,-,1 β， IL,-,6, and, iNOS, in the colon of mice （,P,<,0.05，,P,<,0.01）. ④BBM could increase the expression of Claudin-4 and Occludin， and reduce the phosphorylation of JAK2 and STAT3 in the colon of mice （,P,<,0.05，,P,<,0.01）.,Conclusion,2,BBM can improve UC in mice induced by DSS， its mechanism may be related to the inhibition of JAK2/STAT3 signal pathway and the reduction of inflammatory genes expression， thus enhancing the intestinal mucosal barrier function.

关键词

小檗胺溃疡性结肠炎JAK2/STAT3信号通路

Keywords

berbamineulcerative colitisJAK2/STAT3 signal pathway

references

DREWES A M，FROKJAER J B，LARSEN E，et al. Pain and mechanical properties of the rectum in patients with active ulcerative colitis［J］. Inflamm Bowel Dis， 2006， 12（4）： 294-303.

张彦成，张小元，崔龙，等. 溃疡性结肠炎中医治疗进展及相关优势探讨［J］. 甘肃科技， 2021， 37（6）： 130-133.

ZHANG Y C，ZHANG X Y，CUI L，et al. Progress and related advantages of traditional Chinese Medicine in the treatment of Ulcerative Colitis［J］. Gansu Science and Technology， 2021， 37（6）： 130-133.

PIECHOTA-POLANCZYK A， FICHNA J. Review article： the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases［J］. Naunyn Schmiedebergs Arch Pharmacol， 2014， 387（7）： 605-620.

SOUFLI I， TOUMI R， RAFA H， et al. Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases［J］. World J Gastrointest Pharmacol Ther， 2016， 7（3）： 353-360.

WANG L， HU Y， SONG B， et al. Targeting JAK/STAT signaling pathways in treatment of inflammatory bowel disease［J］. Inflamm Res， 2021， 70（7）： 753-764.

ZHAO W， BAI B， HONG Z， et al. Berbamine （BBM）， a Natural STAT3 Inhibitor， Synergistically Enhances the Antigrowth and Proapoptotic Effects of Sorafenib on Hepatocellular Carcinoma Cells［J］. ACS Omega， 2020， 5（38）： 24838-24847.

郭治彬，付金国. 小檗胺的心血管药理作用研究进展［J］. 中国中西医结合杂志，2005， 25（8）： 765-768.

GUO Z B，FU J G. Research progress on cardiovascular pharmacological effects of berbamine［J］. Chinese Journal of Integrated Traditional and Western Medicine， 2005， 25（8）： 765-768.

YIN L， ZHANG L，LUO L，et al. Berbamine reduces body weight via suppression of small GTPase Rab8a activity and activation of paraventricular hypothalamic neurons in obese mice［J］. Eur J Pharmacol， 2022， 9（16）： 174679.

衡宇，李晰，孙涛，等. 葡聚糖硫酸钠自由饮用与灌胃诱导小鼠溃疡性结肠炎模型的对比研究［J］. 中国药师，2017， 20（4）： 603-606.

HENG Y， LI X， SUN T， et al. Comparative study on the model of ulcerative colitis induced by free drinking and intragastric administration of sodium dextran sulfate in mice ［J］. China Pharmacist， 2017， 20（4）： 603-606.

樊锋. 美沙拉嗪联合甲硝唑对溃疡性结肠炎炎症反应及疾病活动指数的影响［J］. 社区医学杂志，2017， 15（19）： 45-46.

FAN F. Effects of mesalazine combined with metronidazole on inflammatory response and disease activity index in patients with ulcerative colitis［J］. Journal of Community Medicine， 2017， 15（19）： 45-46.

陈阳. 基于肠道菌群的葛根芩连汤干预急性肠炎模型大鼠的作用机制研究［D］. 上海：上海中医药大学，2019.

CHEN Y. Study on the Mechanism of Gegen Qinlian Decoction Based on Gut Microbiota in Model Rats with Acute Enteritis［D］. Shanghai：Shanghai University of Traditional Chinese Medicine，2019.

张帅，刘英媛.中医治疗溃疡性结肠炎的研究进展［J］.中国实用乡村医生杂志，2022， 29（5）： 29-32.

ZHANG S， LIU Y Y. Research Progress in the treatment of Ulcerative Colitis with traditional Chinese Medicine ［J］. Chinese Practical Journal of Rural Doctor， 2022， 29（5）： 29-32.

胡元利. 黄连总生物碱治疗溃疡性结肠炎及其结肠靶向制剂研究［D］. 广州：南方医科大学，2012.

HU Y L. Study on total alkaloids of Coptis chinensis in the treatment of ulcerative colitis and its colon targeting preparation ［D］. Guangzhou： Southern Medical University， 2012.

舒德忠，万先惠，刘华蓉，等. 黄连总碱对实验性溃疡性结肠炎的作用研究［J］. 儿科药学杂志，2005（3）： 7-9.

SHU D Z，WAN X H，LIU H R， et al. Effect of total alkaloids of Coptis chinensis on experimental ulcerative colitis ［J］. Journal of Pediatric Pharmacy， 2005（3）： 7-9.

BANERJEE S，BIEHL A， GADINA M， et al. JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases： Current and Future Prospects［J］. Drugs， 2017， 77（11）： 1261.

石磊，向海燕，朱玲华. 小檗胺对糖尿病肾病大鼠肾损伤和炎性细胞因子产生的影响［J］.免疫学杂志，2020， 36（7）： 599-605.

SHI L，XIANG H Y，ZHU L H. Effects of berbamine on Renal injury and production of inflammatory cytokines in Diabetic Nephropathy Rats ［J］. Immunological Journal， 2020， 36（7）： 599-605.

LIU X Y，CHEN G N，DU G M，et al. Berbamine ameliorates ethanol-induced liver injury by inhibition of hepatic inflammation in mice［J］. Chin J Nat Med， 2020， 18（3）： 186-195.

ZHONG Y，YIN B，YE Y，et al. The bidirectional role of the JAK2/STAT3 signaling pathway and related mechanisms in cerebral ischemia-reperfusion injury［J］. Exp Neurol， 2021， 3（41）： 113690.

YEUNG Y T，AZIZ F，GUERRERO-CASTILLA A，et al. Signaling Pathways in Inflammation and Anti-inflammatory Therapies［J］. Curr Pharm Des， 2018， 24（14）： 1449-1484.

卫江鹏，刘刚，张霆，等. 溃疡性结肠炎患者肠道机械屏障变化与STAT3信号通路关系的研究［J］. 胃肠病学和肝病学杂志，2016， 25（1）： 47-50.

WEI J P，LIU G，ZHANG T， et al. Study on the relationship between the changes of intestinal mechanical barrier and STAT3 signal pathway in patients with ulcerative colitis ［J］. Chinese Journal of Gastroenterology and Hepatology， 2016， 25（1）： 47-50.

WATARI A，SAKAMOTO Y， HISAIE K，et al. Rebeccamycin Attenuates TNF-α-Induced Intestinal Epithelial Barrier Dysfunction by Inhibiting Myosin Light Chain Kinase Production［J］. Cell Physiol Biochem， 2017， 41（5）： 1924-1934.

Views

543

下载量

CSCD

CNKI被引量

Alert me when the article has been cited

提交

Tools

Publicity Resources

Understanding， diagnosis and treatment of ulcerative colitis with Chinese and western medicine

Exploration on mechanism of Shaoyao Gancao Decoction in treating ulcerative colitis based on network pharmacology and in vitro cell experiments

Effects of Yiyi Fuzi Baijiang Powder on intestinal mucosal repair in mice with acute ulcerative colitis

Effects of Lichang Decoction on intestinal microecology and brain-gut peptide in rats of ulcerative colitis with syndrome of dampness stagnancy due to spleen deficiency

Therapeutic mechanism of traditional Chinese medicine on ulcerative colitis based on theory of “liver and spleen being related”

Related Author

No data

Related Institution

Anorectal Department， Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine

Center for Pharmaceutics Research， Shanghai Institute of Materia Medica， Chinese Academy of Sciences

Xiangshan TCM， Huangpu District

Shanghai University of Traditional Chinese Medicine

Department of Medical Administration,Suzhou Hospital of Traditional Chinese Medicine

⁰