Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation

Abstract

The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4 + T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro , using lamina propria (LP) CD4 + T cells in T cell transfer IBD models in which SCID mice had been injected with CD4 + CD45RB high T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4 + T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo . BBR-fed mice showed AMPK activation in the LPCD4 + T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4 + T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.

Anticolitic Effect of Berberine in Rat Experimental Model: Impact of PGE2/p38 MAPK Pathways

“…Disturbance of such tight junctions gives rise to further inflammatory reactions and oversecretions of chemokines and adhesive molecules [ 28 ]. Additionally, elevated levels of inflammatory cytokines exaggerate the innate and acquired immune reactions, involving activation of inflammatory CD4 + T cells [ 29 ].…”

“…Zhang et al [ 11 ] stated that BER restored the intestinal barrier function in experimental colitis induced by dextran sodium sulfate in mice through upregulation of expression of tight junction proteins (zonula occluden-1, occludin, and epithelial cadherin) in colonic tissue. Further, BER exhibited noteworthy suppression of the UC-associated inflammatory response on lamina propria CD4 + T cells via activation of AMP-activated protein kinase and inhibition of oxidative phosphorylation [ 29 ]. In the present study, treatment of rats with BER significantly alleviated the colonic inflammation due to suppression of overproduction of MPO and inflammatory cytokines such as TNF- α , IL-1 β , and IL-6.…”

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

“…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.…”

Effects of Dietary Inclusion of Dry Hydrastis canadensis on Laying Performance, Egg Quality, Serum Biochemical Parameters and Cecal Microbiota in Laying Hens

“…Hydrastis canadensis is a natural plant with a long history of use, and berberine is considered its most effective ingredient [ 20 ]. It has been confirmed that Hydrastis canadensis can ameliorate several pathological statuses and has anti-inflammation [ 35 ], anti-cancer [ 36 ], anti-diabetic [ 37 ], anti-obesity, and anti-hyperlipidemia properties [ 38 , 39 ], in addition to offering myocardial protection [ 40 ]. Our results indicate that laying hens fed with diets containing goldenseal root, leaf, or a mixture of leaf and root (1:1) showed no mortality throughout the experiments.…”