Berberine alleviates dextran sodium sulfate-induced colitis by improving intestinal barrier function and reducing inflammation and oxidative stress

Abstract

Berberine has demonstrated efficacy in alleviating experimental colitis in vivo and in vitro. However, the anti-colitis mechanisms of berberine that enable it to promote intestinal barrier function in vivo remain unclear. The present study aimed to evaluate the effect of berberine on intestinal epithelial barrier function, expression of tight junction proteins and the levels of inflammatory and oxidative stress factors in the intestinal mucosa of dextran sulfate sodium (DSS)-induced colitis mice. Berberine (100 mg/kg) was administered for five days to mice with established colitis, induced by administration of DSS (3% w/v) for six days. Intestinal barrier function and the presence of proinflammatory factors, oxidative stress and active signaling pathways in the colon were determined principally by western blotting and reverse transcription-quantitative polymerase chain reaction. It was observed that berberine reduced weight loss, shortening of the colon and colon damage in DSS-colitis mice. In addition, berberine significantly inhibited the increase of fluorescein isothiocyanate-dextran in serum and the decrease of zonula occluden-1 (also known as tight junction protein-1), occludin and epithelial cadherin expression in colonic tissue, relative to a DSS-treated control group. Berberine also significantly inhibited the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α mRNA and phosphorylation of signal transducer and activator of transcription 3. Furthermore, berberine reduced the levels of myeloperoxidase and increased the levels of superoxide dismutase and catalase in colon and serum samples relative to the control group. The expression of cluster of differentiation 68 in the colon of colitis mice was also reduced by berberine. Collectively, these data suggest that berberine alleviates colitis principally by improving intestinal barrier function and promoting anti-inflammatory and antioxidative stress responses. In turn these effects inhibit macrophage infiltration into the colon and thus may be central to the anti-colitis activity of berberine.

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

“…UC manifested as an idiopathic, relapsing and etiologically complicated inflammatory disorder, involving the interaction between environment factors, genetic emotivity, perturbation of immune homeostasis, and dysfunction of intestinal mucosal barrier 5,6,18 . Over the past decades, oral administration of berberine has been demonstrated to exert protective capacity on DSSinduced experimental acute UC, which dominantly attributed to the critical role of berberine in modulating the inflammatory responses from immune cell and epithelial cells, maintaining the intestinal barrier function, and regulating gut microbiota 24,41,42 . Besides, berberine could also attenuate colonic macromorphological and histopathological inflammation through suppressing the expansion and overaction of Th17 cells in DSS-induced murine chronic UC 43,44 .…”

“…Increasing evidence has suggested that berberine possessed numerous pharmacological activities, including anti-microbial, anti-diabetic, anti-colorectal cancer, analgesic, lipid modulatory, anti-depressant, and blood glucose and anti-inflammatory effects 21 . Particularly, berberine has been suggested to function as an effective agent in treating experimental colitis, including UC and CD, which were largely due to the role of berberine in modulating gut microbiota, neurogenic inflammation, mucosal immunity, and barrier function 20,[22][23][24] . Though the underlying mechanism of berberine has been focused on activation of adenosine 5′-monophosphate (AMP)activated protein kinase (AMPK) 23 , we revealed a new molecular mechanism of berberine in attenuating chronic UC.…”

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

“…As a main ingredient of C. chinensis Franch., berberine (100 mg/kg) treatment inhibits the activations of NF-κB and mitogen-activated protein kinase (MAPK), which contributes to down-regulation of tumor necrosis factor (TNF), interferon gamma (IFN-γ) and IL-17 expressions in colonic macrophages and epithelial cells from DSS-induced mice, showing the reductions of crypt injury and severe inflammatory damage [50]. In addition, berberine (100 mg/kg or 100 μM) treatment improves intestinal barrier function through suppression of the phosphorylated colonic signal transducer and activator of transcription (STAT) 3 and myosin light chain (MLC) kinase-MLC signaling pathway, as well as inhibition of IFN-γ and TNF-α expressions and macrophage infiltration into the intestinal mucosa in DSS-colitis mice [51,52].…”

Improvement of Oxazolone-Induced Ulcerative Colitis in Rats Using Andrographolide

“…Unfortunately, no particular effective clinical treatment is reported because of undefined pathogenesis. Notably, the chemical components of traditional Chinese medicine, including baicalin [25], curcumin [26], berberine [27], oxymatrine [28], and astragalus polysaccharides [29], have shown significant progress in UC treatment. In addition, some studies have focused on the improvement of UC by using dietary supplements (e.g., anthocyanins, flavan-3-ols and green tea, proanthocyanidins and cocoa, isoflavones and soy, flavonols, gingerols and ginger, and hydroxycinnamic acids), nutraceutical supplements (e.g., prebiotics, probiotics, synbiotics, and fish oil), and other natural compounds in recent years [30][31][32].…”