Berberine Prevents NSAID-Induced Small Intestinal Injury by Protecting Intestinal Barrier and Inhibiting Inflammasome-Associated Activation

被引：0

作者：

Ishiguro, Mikako ^{[1
]}

Takahara, Masahiro ^{[1
]}

Takaki, Akinobu ^{[1
]}

Hiraoka, Sakiko ^{[1
]}

Toyosawa, Jyunki ^{[1
]}

Aoyama, Yuki ^{[1
]}

Igawa, Shoko ^{[1
]}

Yamasaki, Yasushi ^{[1
]}

Inokuchi, Toshihiro ^{[1
]}

Kinugasa, Hideaki ^{[1
]}

Otsuka, Motoyuki ^{[1
]}

机构：

[1] Okayama Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Dent & Pharmaceut Sci, 2-5-1 Shikata Cho,Kita Ku, Okayama 7008558, Japan

来源：

DIGESTIVE DISEASES AND SCIENCES | 2025年

关键词：

Nonsteroidal anti-inflammatory drugs-induced small intestinal injury; Berberine; Tight junction protein; Inflammasomes; SMALL-BOWEL INJURY; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RHEUMATOID-ARTHRITIS; AGENTS; DAMAGE;

D O I：

10.1007/s10620-025-09276-5

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BackgroundNonsteroidal anti-inflammatory drugs (NSAID), which are commonly used to manage pain and inflammation, often cause gastrointestinal injuries, including small intestinal damage. Berberine (BBR) is a traditional Chinese medicine that protects against these injuries. However, the mechanism of action is not fully understood.AimsThis study aimed to evaluate the protective effects of BBR against NSAID-induced intestinal injury and elucidate the underlying molecular mechanisms.MethodsWe evaluated the effects of BBR on NSAID-induced intestinal injury using a combination of mouse models and human gut organoids. Mice were treated with indomethacin with or without BBR to induce small intestinal injury. Human gut organoids were exposed to NSAID, with or without BBR, to assess their direct epithelial effects. Histological analyses, cytokine measurements, and Western blotting were performed to evaluate intestinal damage, tight junction integrity, and inflammasome-associated activation.ResultsIn NSAID-treated mice, BBR markedly reduced ulcers and adhesions and preserved ileal Claudin-1, Occludin, and Zonula Occludens-1 (ZO-1) levels. BBR inhibited both NOD-like receptor family pyrin domain-containing 6 and NOD-like receptor family caspase recruitment domain-containing protein 4 inflammasome activation, reducing Caspase-1 maturation and downstream interleukin-1 beta and tumor necrosis factor-alpha release. In human gut organoids, BBR demonstrated comparable protective effects by directly mitigating NSAID-induced epithelial barrier disruption caused by Claudin-1 and Occludin downregulation, although it did not restore ZO-1 expression.ConclusionsBBR effectively prevented NSAID-induced small intestinal injury by maintaining tight junction integrity and inhibiting inflammasome-associated activation, indicating its potential as a therapeutic agent against such damage.

引用

页数：12

共 37 条

[1] Amelioration of IFN-γ and TNF-α-Induced Intestinal Epithelial Barrier Dysfunction by Berberine via Suppression of MLCK-MLC Phosphorylation Signaling Pathway [J].