Effects and mechanism of asperuloside on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis

XU Chao; TAN Xiaoping; LI Jie; AI Minghua; LU Yueyue; LIU Chaoyong

doi:10.6039/j.issn.1001-0408.2025.02.06

您当前的位置：

首页 >

文章列表页 >

Effects and mechanism of asperuloside on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis

更新时间：2025-09-25

- Effects and mechanism of asperuloside on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis
- ZHONGGUO YAOFANG Vol. 36, Issue 2, Pages: 166-171(2025)
- 作者机构：
  
  荆州市第一人民医院消化内科，湖北荆州　434000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.02.06
  CLC： R965;R574.1
- Received：29 May 2024，
  
  Revised：2024-10-11，
  
  Accepted：11 October 2024，
  
  Published：30 January 2025
- 稿件说明：
移动端阅览
徐超,谭小平,李杰,等.车叶草苷对溃疡性结肠炎大鼠肠上皮细胞焦亡的影响及机制[J].中国药房,2025,36(02):166-171.

XU Chao,TAN Xiaoping,LI Jie,et al.Effects and mechanism of asperuloside on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis[J].ZHONGGUO YAOFANG,2025,36(02):166-171.
徐超,谭小平,李杰,等.车叶草苷对溃疡性结肠炎大鼠肠上皮细胞焦亡的影响及机制[J].中国药房,2025,36(02):166-171. DOI： 10.6039/j.issn.1001-0408.2025.02.06.

XU Chao,TAN Xiaoping,LI Jie,et al.Effects and mechanism of asperuloside on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis[J].ZHONGGUO YAOFANG,2025,36(02):166-171. DOI： 10.6039/j.issn.1001-0408.2025.02.06.

摘要

目的

探讨车叶草苷（Asp）对溃疡性结肠炎（UC）大鼠肠上皮细胞焦亡的影响及机制。

方法

将雄性SD大鼠随机分为对照组（Control组），模型组（UC组），ASP低、高剂量组[Asp-L、Asp-H组，Asp 35、70 mg/（kg·d）]，ASP高剂量+AMPK抑制剂Compound C组[Asp-H+Compound C组，Asp 70 mg/（kg·d）+Compound C 0.2 mg/（kg·d）]，每组12只。除Control组外，其余各组均以肠腔灌入50%乙醇（0.25 mL）+5% 2，4，6-三硝基苯磺酸溶液（2 mL/kg）的方式构建UC模型。造模后，各药物组大鼠灌胃或（和）尾静脉注射相应药液，每天1次，连续14 d。末次给药后，称定各组大鼠体重，测量其结肠长度，并进行疾病活动指数（DAI）评分、结肠黏膜损伤指数（CMDI）评分，检测其血清中炎症因子[白细胞介素18（IL-18）、IL-1β、IL-6]水平，观察结肠组织病理改变，检测结肠组织中焦亡相关蛋白[胱天蛋白酶1（caspase-1）、消皮素D（GSDMD）]及通路相关蛋白[腺苷一磷酸活化的蛋白激酶（AMPK）、硫氧还蛋白互作蛋白（TXNIP）、NOD样受体蛋白3（NLRP3）、凋亡相关斑点样蛋白（ASC）]的表达情况。

结果

与Control组比较，UC组大鼠结肠组织结构受损，炎症细胞浸润、水肿明显；体重、结肠长度及AMPK蛋白的磷酸化水平均显著降低或缩短（

＜0.05）；DAI、CMDI评分，血清中炎症因子水平以及结肠组织中caspase-1、GSDMD、TXNIP、NLRP3、ASC蛋白的表达均显著升高

或上调（

＜0.05）。与UC组比较，Asp-L、Asp-H组大鼠结肠组织病理损伤均有所减轻，各定量指标均显著改善（

＜0.05），且Asp-H组的改善效果更明显（

＜0.05）；Compound C可显著逆转高剂量Asp对UC大鼠上述指标的改善作用（

＜0.05）。

结论

Asp可改善UC大鼠结肠组织炎症性损伤，抑制其肠上皮细胞焦亡，上述作用可能与激活AMPK进而抑制TXNIP/NLRP3信号通路有关。

Abstract

OBJECTIVE

To investigate the effects and mechanism of asperuloside （Asp） on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis （UC）.

METHODS

The male SD rats were randomly divided into Control group， model group （UC group）， ASP low-dose and high-dose groups [Asp-L， Asp-H groups， Asp 35， 70 mg/（kg·d）]， ASP high-dose group+AMPK inhibitor Compound C group [Asp-H+Compound C group， Asp 70 mg/（kg·d）+Compound C 0.2 mg/（kg·d）]， with 12 rats in each group. Except for Control group， the other groups were injected with 50% ethanol （0.25 mL）+5% 2，4， 6-trinitrobenzene sulfonic acid solution （2 mL/kg） into the intestinal cavity to construct UC model. After modeling， the rats in each drug group were given corresponding drug solution by gavage or （and） tail vein injection， once a day， for 14 consecutive days. After the last administration， the weight of rats in each group was measured， and the length of their colons was measured； disease activity index （DAI） score and colonic mucosal damage index （CMDI） score were performed， and the serum levels of inflammatory factors （interleukin-18， -1β， -6） were detected. The pathological changes of the colon tissue were observed. The expressions of pyroptosis-related proteins [caspase-1， gasdermin D （GSDMD）] in colon tissue， and pathway-related proteins such as adenosine monophosphate-activated protein kinase （AMPK）， thioredoxin-interacting protein （TXNIP）， NOD-like receptor protein 3 （NLRP3） and apoptosis-associated speck-like protein containing a CARD （ASC） were all detected.

RESULTS

Compared with Control

group， the colon tissue structure of rats in UC group was damaged， with obvious infiltration of inflammatory cells and edema. Their body weight， colon length and phosphorylation level of AMPK protein were significantly reduced or shortened； DAI and CMDI scores， serum levels of inflammatory factors， and the protein expressions of caspase-1， GSDMD， TXNIP， NLRP3 and ASC in colon tissue were increased or upregulated significantly （

＜0.05）. Compared with UC group， the pathological damage of colon tissue in rats was relieved in Asp-L and Asp-H groups， and all quantitative indicators were significantly improved （

＜0.05）； the improvement effect of Asp-H group was more significant （

＜0.05）. Compound C could significantly reverse the improvement effect of high-dose of Asp on the above indicators in UC rats （

＜0.05）.

CONCLUSIONS

Asp can improve inflammatory damage in colon tissue and inhibit pyroptosis of intestinal epithelial cells in UC rats， which is associated with the activation of AMPK and inhibition of TXNIP/NLRP3 signaling pathway.

关键词

Keywords

references

SEGAL J P ， LEBLANC J F ， HART A L . Ulcerative colitis：an update [J ] . Clin Med ， 2021 ， 21 （ 2 ）： 135 - 139 .

BUIE M J ， QUAN J ， WINDSOR J W ， et al . Global hospitalization trends for Crohn’s disease and ulcerative colitis in the 21st century：a systematic review with temporal analyses [J ] . Clin Gastroenterol Hepatol ， 2023 ， 21 （ 9 ）： 2211 - 2221 .

BEAUGERIE L ， KIRCHGESNER J . Balancing benefit vs. risk of immunosuppressive therapy for individual patients with inflammatory bowel diseases [J ] . Clin Gastroenterol Hepatol ， 2019 ， 17 （ 3 ）： 370 - 379 .

CHAN Y H ， NG S W ， XIN TAN J Z ， et al . Emerging therapeutic potential of the iridoid molecule，asperuloside：a snapshot of its underlying molecular mechanisms [J ] . Chem Biol Interact ， 2020 ， 315 ： 108911 .

CHEN Y E ， XU S J ， LU Y Y ， et al . Asperuloside suppres-sing oxidative stress and inflammation in DSS-induced chronic colitis and RAW 264.7 macrophages via Nrf2/HO-1 and NF-κB pathways [J ] . Chem Biol Interact ， 2021 ， 344 ： 109512 .

ZHANG Q ， WANG S F ， JI S Y . Trifolirhizin regulates the balance of Th17/Treg cells and inflammation in the ulcera-tive colitis mice through inhibiting the TXNIP-mediated activation of NLRP3 inflammasome [J ] . Clin Exp Pharmacol Physiol ， 2022 ， 49 （ 8 ）： 787 - 796 .

孙立燕，刘泽茹，苏永胜，等 . 车叶草苷调节NLRP3/caspase-1/GSDMD信号通路对脓毒症大鼠肺组织细胞焦亡的影响 [J ] . 天津医药， 2023 ， 51 （ 6 ）： 607 - 613 .

SUN L Y ， LIU Z R ， SU Y S ， et al . Effect of asperuloside on pyroptosis of lung tissue in septic rats by regulating NLRP3/caspase-1/GSDMD signaling pathway [J ] . Tianjin Med J ， 2023 ， 51 （ 6 ）： 607 - 613 .

ZHU L ， XU L Z ， ZHAO S ， et al . Protective effect of bai-calin on the regulation of Treg/Th17 balance，gut microbiota and short-chain fatty acids in rats with ulcerative colitis [J ] . Appl Microbiol Biotechnol ， 2020 ， 104 （ 12 ）： 5449 - 5460 .

李浩田，李梦丽，张臣，等 . 基于AMPK/mTOR信号通路介导的自噬途径研究黄芪多糖对急性放射性肠炎大鼠肠黏膜的保护作用 [J ] . 中国病理生理杂志， 2022 ， 38 （ 2 ）： 311 - 317 .

LI H T ， LI M L ， ZHANG C ， et al . Astragalus polysaccharide protects against intestinal mucosal injury in rats with acute radiation enteritis through AMPK/mTOR-mediated autophagy pathway [J ] . Chin J Pathophysiol ， 2022 ， 38 （ 2 ）： 311 - 317 .

HUANG Y C ， ZHENG Y H ， YANG F M ， et al . Lycium barbarum glycopeptide prevents the development and progression of acute colitis by regulating the composition and diversity of the gut microbiota in mice [J ] . Front Cell Infect Microbiol ， 2022 ， 12 ： 921075 .

陈泰宇，唐学贵，蒋小东，等 . 基于Nrf2/ARE信号通路探讨硫氢化钠对溃疡性结肠炎大鼠肠黏膜损伤的影响 [J ] . 中国现代医学杂志， 2022 ， 32 （ 19 ）： 38 - 43 .

CHEN T Y ， TANG X G ， JIANG X D ， et al . Effects of NaHS on intestinal mucosal injury in ulcerative colitis rats based on Nrf2/ARE signaling pathway [J ] . China J Mod Med ， 2022 ， 32 （ 19 ）： 38 - 43 .

DU L ， HA C . Epidemiology and pathogenesis of ulce-rative colitis [J ] . Gastroenterol Clin North Am ， 2020 ， 49 （ 4 ）： 643 - 654 .

LU Y Y ， GUAN T ， XU S X ， et al . Asperuloside inhibited epithelial-mesenchymal transition in colitis-associated cancer via activation of vitamin D receptor [J ] . Phytomedicine ， 2022 ， 101 ： 154070 .

SHEN Q ， CHEN Y E ， SHI J X ， et al . Asperuloside alle-viates lipid accumulation and inflammation in HFD-induced NAFLD via AMPK signaling pathway and NLRP3 inflammasome [J ] . Eur J Pharmacol ， 2023 ， 942 ： 175504 .

ZHANG Y F ， ZHANG Y Q ， ZHAO Y ， et al . Protection against ulcerative colitis and colorectal cancer by evo-diamine via anti-inflammatory effects [J ] . Mol Med Rep ， 2022 ， 25 （ 5 ）： 188 .

田琳，王鑫，黄晓峰，等 . 清化肠饮对溃疡性结肠炎大鼠NLRP3/caspase-1细胞焦亡通路的影响 [J ] . 实用中医内科杂志， 2023 ， 37 （ 11 ）： 86 - 89 .

TIAN L ， WANG X ， HUANG X F ， et al . Effect of Qinghuachang yin on NLRP3/caspase-1 cell scorching pathway in ulcerative colitis rats [J ] . J Pract Tradit Chin Intern Med ， 2023 ， 37 （ 11 ）： 86 - 89 .

唐立，陆岩，欧阳满照 . 细胞焦亡与溃疡性结肠炎研究的最新进展 [J ] . 广东医学， 2021 ， 42 （ 11 ）： 1393 - 1399 .

TANG L ， LU Y ， OUYANG M Z . The latest progress in the study of cell death and ulcerative colitis [J ] . Guangdong Med J ， 2021 ， 42 （ 11 ）： 1393 - 1399 .

周伯乐，徐卫东 . NLRP3炎症小体在自身免疫疾病中的作用及机制 [J ] . 国际免疫学杂志， 2024 ， 47 （ 3 ）： 300 - 305 .

ZHOU B L ， XU W D . The role and mechanism of NLRP3 inflammasome in autoimmune diseases [J ] . Int J Immunol ， 2024 ， 47 （ 3 ）： 300 - 305 .

YUAN B ， ZHOU X M ， YOU Z Q ， et al . Inhibition of AIM2 inflammasome activation alleviates GSDMD-induced pyroptosis in early brain injury after subarachnoid haemorrhage [J ] . Cell Death Dis ， 2020 ， 11 （ 1 ）： 76 .

李克亚，王真权，王军文 . 乌梅丸通过调控NLRP3炎症小体改善溃疡性结肠炎大鼠肠黏膜炎症反应及细胞焦亡 [J ] . 中国免疫学杂志， 2024 ， 40 （ 1 ）： 97 - 102，109 .

LI K Y ， WANG Z Q ， WANG J W . Wu-mei-wan improves colonic mucosal inflammation and pyroptosis in rats with ulcerative colitis via regulating NLRP3 inflammasome [J ] . Chin J Immunol ， 2024 ， 40 （ 1 ）： 97 - 102，109 .

CHEN Q L ， YIN H R ， HE Q Y ， et al . Targeting the NLRP3 inflammasome as new therapeutic avenue for inflammatory bowel disease [J ] . Biomedecine Pharmacother ， 2021 ， 138 ： 111442 .

YOUSSEF M E ， ABD EL-FATTAH E E ， ABDELHAMID A M ， et al . Interference with the AMPKα/mTOR/NLRP3 signaling and the IL-23/IL-17 axis effectively protects against the dextran sulfate sodium intoxication in rats：a new paradigm in empagliflozin and metformin reprofiling for the management of ulcerative colitis [J ] . Front Phar-macol ， 2021 ， 12 ： 719984 .

Views

1168

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mechanism of the alleviation of colonic mucosal injury and inflammatory response in rats with ulcerative colitis by asperuloside

Related Author

LI Xiufen

ZHAO Hanqing

JIA Huiyu

ZHANG Xia

DONG Liping

Related Institution

Graduate School of Hebei North University

Dept. of Geriatric Medicine， the Second Hospital Affiliated to Hebei North University

Dept. of Traditional Chinese Medicine， the Second Hospital Affiliated of Hebei North University

Dept. of Laboratory， the Second Hospital Affiliated of Hebei North University

Dept. of Geriatric Medicine， the First Hospital Affiliated of Hebei North University

Address：8th Floor, Sihuan Building, No. 129 Daping Main Street, Yuzhong District, Chongqing, China Postal code：400042
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰