Abstract
Berberine (BER), a natural isoquinoline alkaloid, has been demonstrated to have appreciable anticolitis effects. Nevertheless, the protective mechanism of BER in ulcerative colitis (UC) is barely understood. The present study was aimed at exploring the therapeutic efficacy of BER on UC in experimental colitis rat model. Rats were orally administered with BER for seven days at low and high doses (25 and 50 mg/kg/day) before AcOH intracolonic instillation. BER significantly retrieved colon inflammation and mucosal damage indicated by inhibition of macroscopic score and lessened the levels of inflammatory biomarkers (IL-1β, IL-6, TNF-α, MPO, and PGE2). Notable downregulation of mRNA expression of p38 MAPK and increased protein expression of TGF-β were achieved by BER treatment. The anti-inflammatory potential of BER was supported by the histopathological screening of colon mucosa. In addition, BER restored colonic antioxidant capacity through elevation of GSH level and antioxidant enzymatic activities (SOD, CAT, GPx, and GR) together with reductions of both MDA and NO levels. Marked downregulation of Nos2 mRNA expression is accompanied by increased Nrf2 and Hmox-1 expressions in colon specimens treated by BER. Furthermore, BER exhibited noticeable antiapoptotic activities through decreasing proapoptotic proteins (Bax and caspase-3) and lessening antiapoptotic Bcl-2 protein in the colon mucosa. Based on these findings, BER may improve colitis markedly which may be mediated by its striking antioxidant, anti-inflammatory, and antiapoptotic properties.
Highlights
Inflammatory bowel disease is an umbrella term which includes mainly two subtypes, ulcerative colitis (UC) and Crohn’s disease, and clinically characterized by severe abdominal pain, diarrhea, fatigue, and weight loss [1]
Macroscopic picture of experimental colitis revealed transmural inflammation of the colon accompanied by signs of hyperemia, necrosis, corrosion, mucosal edema, and ulcerations (Figure 1(a))
A seven-day administration of BER at low (25 mg/kg) and high (50 mg/kg) doses (p < 0:05) showed less severe necrosis, corrosion, and ulceration with a significantly decreased in the degree of colonic injure, by about 28% and 43% correspondingly in comparison with the UC-untreated rats (Figure 1(b))
Summary
Inflammatory bowel disease is an umbrella term which includes mainly two subtypes, ulcerative colitis (UC) and Crohn’s disease, and clinically characterized by severe abdominal pain, diarrhea, fatigue, and weight loss [1]. UC is associated with chronic relapsing nonspecific inflammation and ulcer formation in the rectum and sigmoid colon with architectural epithelial damage and mucosal barrier dysfunction [2]. Some manifestations were associated with UC such as enteropathic arthritis, primary sclerosing cholangitis, and ocular and skin damage [4]. Exaggerated inflammatory response and overproduction of inflammatory mediators such as tumour necrosis factor (TNF)-α and cytokines (interleukin (IL)-6 and IL1β) play a pivotal role in colon inflammation [5]. Prostaglandin E2 (PGE2) is the main PG in the gastrointestinal tract and physiologically influences on acid and mucus secretion, blood flow, intestinal motility, and mucosal health. High levels of PGE2 have proinflammatory effects and are involved in progress of UC pathogenesis [6].
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