Piperine, a functional food alkaloid, exhibits inhibitory potential against TNBS-induced colitis via the inhibition of IκB-α/NF-κB and induces tight junction protein (claudin-1, occludin, and ZO-1) signaling pathway in experimental mice

被引：51

作者：

Guo, G. ^{[1
]}

Shi, F. ^{[1
,2
]}

Zhu, J. ^{[3
]}

Shao, Y. ^{[4
]}

Gong, W. ^{[5
]}

Zhou, G. ^{[6
]}

Wu, H. ^{[1
]}

She, J. ^{[1
,2
]}

Shi, W. ^{[1
,3
]}

机构：

[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Talent Highland, Xian 710061, Shaanxi, Peoples R China

[2] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Gen Surg, Xian, Shaanxi, Peoples R China

[3] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Gastroenterol, Xian 710061, Shaanxi, Peoples R China

[4] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Nephrol, Xian, Shaanxi, Peoples R China

[5] Fourth Mil Med Univ, Xijing Hosp, Dept Ultrasound, Xian, Shaanxi, Peoples R China

[6] Sichuan Univ, West China Hosp, Dept Endocrinol & Metab, Chengdu, Sichuan, Peoples R China

来源：

HUMAN & EXPERIMENTAL TOXICOLOGY | 2020年 / 39卷 / 04期

基金：

中国博士后科学基金;

关键词：

Caspase-1; claudin-1; COX-2; I kappa B-alpha; NF-kappa B; occludin; piperine; TNBS; ulcerative colitis; ZO-1; INFLAMMATORY-BOWEL-DISEASE; INTESTINAL EPITHELIAL-CELLS; TNF-ALPHA; INDUCED UROLITHIASIS; ULCERATIVE-COLITIS; BLACK PEPPER; RAT MODEL; EXPRESSION; EXTRACT; MODULATION;

D O I：

10.1177/0960327119892042

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Background: Inflammatory bowel disease is a chronic immunoinflammatory disease of the gastrointestinal tract. Piperine, an alkaloid, has been reported to possess antioxidant, anti-inflammatory, antiapoptotic, and antiulcer potential. Aim: To elucidate the plausible mechanisms of action of piperine on experimental trinitrobenzenesufonic acid (TNBS)-induced colitis by assessing various biochemical, molecular, histological, and ultrastructural modifications. Methods: Colitis was induced in male Sprague-Dawley rats via intrarectal instillation of TNBS. Then, the rats were treated with piperine (10, 20, and 40 mg/kg, p.o.) for 14 days. Results: TNBS induced significant (p < 0.05) colonic damage, which was assessed by disease activity index, macroscopic score, and stool consistency. The administration of piperine (20 and 40 mg/kg) significantly inhibited (p < 0.05) these damages. Treatments with piperine (20 and 40 mg/kg) notably inhibited (p < 0.05) the TNBS-induced elevation of oxido-nitrosative stress (superoxide dismutase, glutathione, malondialdehyde, and nitric oxide), 5-hydroxytryptamine, and hydroxyproline content in the colon. Furthermore, colonic inducible nitric oxide synthase (iNOs), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6, interferon-gamma, and cyclooxygenase-2 (COX-2) messenger RNA (mRNA) expressions were upregulated after TNBS instillation and piperine (20 and 40 mg/kg) significantly attenuated (p < 0.05) these elevated mRNA expressions. TNBS decreased the expressions of tight junction (TJ) protein (claudin-1, occludin, and zonula occludens-1 (ZO-1)) and increased the expressions of proapoptotic (caspase-1) protein. These expressions were markedly inhibited (p < 0.05) by piperine treatment. Histological and ultrastructural studies of transmission electron microscopy suggested that piperine significantly ameliorated (p < 0.05) TNBS-induced colonic aberrations. Conclusion: Piperine ameliorated the progression of TNBS-induced colitis by modulating the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha/nuclear factor-kappa B signaling pathway, thus inhibiting the overexpression of proinflammatory cytokines (TNF-alpha and IL's), COX-2, iNOs, oxido-nitrosative stress, and proapoptotic proteins (caspase-1) that may improve the expression of TJ protein (claudin-1, occludin, and ZO-1).

引用

页码：477 / 491

页数：15