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芥子酸通过调节NLRP3炎性小体激活和自噬途径减轻慢性右旋糖酐硫酸钠诱导的C57BL/6J小鼠肠道纤维化。

Sinapic Acid Attenuates Chronic DSS-Induced Intestinal Fibrosis in C57BL/6J Mice by Modulating NLRP3 Inflammasome Activation and the Autophagy Pathway.

作者信息

Li Wan-Ying, Liu Jun-Yang, Wang Zi-Xian, Wang Ke-Ying, Huang Chun-Xiang, He Wen, Song Jia-Le

机构信息

Department of Nutrition and Food Hygiene, School of Public Health, Guilin Medical University, Guilin 541100, Guangxi, China.

Department of Clinical Nutrition, Liuzhou People's Hospital, Liuzhou 545006, Guangxi, China.

出版信息

ACS Omega. 2023 Dec 26;9(1):1230-1241. doi: 10.1021/acsomega.3c07474. eCollection 2024 Jan 9.


DOI:10.1021/acsomega.3c07474
PMID:38222654
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10785090/
Abstract

Ulcerative colitis (UC) is a chronic gastrointestinal disease that results from repeated inflammation and serious complications. Sinapic acid (SA) is a hydroxycinnamic acid present in a variety of plants that has antioxidant, anti-inflammatory, anticancer, and other protective effects. This study investigated the antifibrotic effect of SA on chronic colitis induced by dextran sulfate sodium salt (DSS) in mice. We observed that SA could significantly reduce clinical symptoms (such as improved body weight loss, increased colon length, and decreased disease activity index score) and pathological changes in mice with chronic colitis. SA supplementation has been demonstrated to repair intestinal mucosal barrier function and maintain epithelial homeostasis by inhibiting activation of the NLRP3 inflammasome and decreasing the expression of IL-6, TNF-α, IL-17A, IL-18, and IL-1β. Furthermore, SA could induce the expression of antioxidant enzymes (, , , ) by activating the Nrf2/keap1 pathway, thus improving antioxidant capacity. Additionally, SA could increase the protein expression of downstream LC3-II/LC3-I and Beclin1 and induce autophagy by regulating the AMPK-Akt/mTOR signaling pathway, thereby reducing the production of intestinal fibrosis-associated proteins Collagen-I and α-SMA. These findings suggest that SA can enhance intestinal antioxidant enzymes, reduce oxidative stress, expedite intestinal epithelial repair, and promote autophagy, thereby ameliorating DSS-induced colitis and intestinal fibrosis.

摘要

溃疡性结肠炎(UC)是一种由反复炎症和严重并发症引起的慢性胃肠疾病。芥子酸(SA)是一种存在于多种植物中的羟基肉桂酸,具有抗氧化、抗炎、抗癌和其他保护作用。本研究调查了SA对葡聚糖硫酸钠(DSS)诱导的小鼠慢性结肠炎的抗纤维化作用。我们观察到SA可显著减轻慢性结肠炎小鼠的临床症状(如改善体重减轻、增加结肠长度和降低疾病活动指数评分)及病理变化。已证明补充SA可通过抑制NLRP3炎性小体的激活和降低IL-6、TNF-α、IL-17A、IL-18和IL-1β的表达来修复肠黏膜屏障功能并维持上皮稳态。此外,SA可通过激活Nrf2/keap1途径诱导抗氧化酶(、、、)的表达,从而提高抗氧化能力。此外,SA可增加下游LC3-II/LC3-I和Beclin1的蛋白表达,并通过调节AMPK-Akt/mTOR信号通路诱导自噬,从而减少肠道纤维化相关蛋白I型胶原蛋白和α-平滑肌肌动蛋白的产生。这些发现表明,SA可增强肠道抗氧化酶、减轻氧化应激、加速肠上皮修复并促进自噬,从而改善DSS诱导的结肠炎和肠道纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/ae61314b7841/ao3c07474_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/696ef74be7b5/ao3c07474_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/3edc41d63d2f/ao3c07474_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/3722d1e97273/ao3c07474_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/71fae729a0bc/ao3c07474_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/bdc12d7fee00/ao3c07474_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/714b6ebc1eb8/ao3c07474_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/413c0c1e9c34/ao3c07474_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/ae61314b7841/ao3c07474_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/696ef74be7b5/ao3c07474_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/3edc41d63d2f/ao3c07474_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/3722d1e97273/ao3c07474_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/71fae729a0bc/ao3c07474_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/bdc12d7fee00/ao3c07474_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/714b6ebc1eb8/ao3c07474_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/413c0c1e9c34/ao3c07474_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c17f/10785090/ae61314b7841/ao3c07474_0008.jpg

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引用本文的文献

[1]
Therapeutic potential of alpha-lipoic acid on mitochondrial dynamics, oxidative/nitrosative stress, and histopathological changes in rat ulcerative colitis model.

Inflammopharmacology. 2025-9-1

[2]
Sinapic Acid Ameliorates Cadmium-Induced Hepatotoxicity: Modulation of Oxidative Stress, Inflammation, and Apoptosis.

Biomedicines. 2025-4-28

[3]
Regulation of pyroptosis by natural products in ulcerative colitis: mechanisms and therapeutic potential.

Front Pharmacol. 2025-4-9

[4]
Harnessing the Anti-Inflammatory Properties of Polyphenols in the Treatment of Inflammatory Bowel Disease.

Int J Biol Sci. 2024

[5]
Rutin Ameliorates Inflammation and Oxidative Stress in Ulcerative Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway.

Cell Biochem Biophys. 2024-12

[6]
Li-Hong Tang alleviates dextran sodium sulfate-induced colitis by regulating NRF2/HO-1 signaling pathway and gut microbiota.

Front Pharmacol. 2024-5-30

[7]
Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats.

Food Sci Nutr. 2024-1-24

本文引用的文献

[1]
Excessive ER-phagy contributes to ochratoxin A-induced apoptosis.

Food Chem Toxicol. 2023-6

[2]
Lonp1 and Sig-1R contribute to the counteraction of ursolic acid against ochratoxin A-induced mitochondrial apoptosis.

Food Chem Toxicol. 2023-2

[3]
CD147 Targeting by AC-73 Induces Autophagy and Reduces Intestinal Fibrosis Associated with TNBS Chronic Colitis.

J Crohns Colitis. 2022-11-23

[4]
Rhamnocitrin Attenuates Ovarian Fibrosis in Rats with Letrozole-Induced Experimental Polycystic Ovary Syndrome.

Oxid Med Cell Longev. 2022

[5]
Dietary sinapic acid attenuated high-fat diet-induced lipid metabolism and oxidative stress in male Syrian hamsters.

J Food Biochem. 2022-11

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Front Immunol. 2022

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Perfluorooctanoic acid induces hepatocellular endoplasmic reticulum stress and mitochondrial-mediated apoptosis in vitro via endoplasmic reticulum-mitochondria communication.

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Caveolin-1 Alleviates Crohn's Disease-induced Intestinal Fibrosis by Inhibiting Fibroblasts Autophagy Through Modulating Sequestosome 1.

Inflamm Bowel Dis. 2022-6-3

[9]
Procyanidin A1 alleviates DSS-induced ulcerative colitis via regulating AMPK/mTOR/p70S6K-mediated autophagy.

J Physiol Biochem. 2022-2

[10]
Hook polysaccharide ameliorates dextran-sodium-sulfate-induced colitis in mice improving intestinal barrier function, modulating intestinal microbiota, and reducing oxidative stress and inflammatory responses.

Food Funct. 2022-1-4

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