Effect of Berberine from Coptis chinensis on Apoptosis of Intestinal Epithelial Cells in a Mouse Model of Ulcerative Colitis: Role of Endoplasmic Reticulum Stress.

Shen Yan,Wang Zhangliu,Zhong Jihong,Ni Siyi,Liu Yingchao,Li Si,Ruan Xianli

doi:10.1155/2020/3784671

Abstract

The purpose of this study was to verify the effect of berberine (BBR) on endoplasmic reticulum stress (ERS) and apoptosis of intestinal epithelial cells (IECs) in mice with ulcerative colitis (UC). BALB/c mice were randomly divided into five groups as follows: blank control, model, and low-, medium-, and high-dose BBR. A dextran sodium sulfate- (DSS-) induced model of UC was prepared, and the low-, medium-, and high-dose BBR groups were simultaneously gavaged with a BBR suspension for 7 d. Disease activity index (DAI) was assessed, and tissue damage index (TDI) was assessed from colon samples after the last administration. TUNEL assays were used to detect apoptosis of IECs. Immunohistochemistry and/or real-time PCR were applied to determine the expression of GRP78, caspase-12, and caspase-3. In all BBR treatment groups, clinical symptoms of colitis and histopathological damage were significantly reduced. The high-dose BBR group exhibited particularly pronounced decrease (p < 0.01) in both DAI (0.48 ± 0.36) and TDI (1.62 ± 0.64) relative to the model group (1.50 ± 0.65 and 3.88 ± 0.04, respectively). In colon tissues of the model group, the number of apoptotic IECs was significantly increased; the expression of GRP78, caspase-12, and caspase-3 proteins was significantly increased; and the expression of the GRP78 mRNA was upregulated. In low-, medium-, and high-dose BBR groups, the number of apoptotic IECs was significantly reduced. Moreover, GRP78 and caspase-3 expression levels were significantly decreased in the medium- and high-dose BBR groups, caspase-12 expression was significantly decreased in the high-dose BBR group, and the GRP78 mRNA expression level was significantly decreased in the high-dose BBR group. BBR can effectively reduce the rate of IEC apoptosis in UC mice and alleviate the inflammatory response in the colon. The underlying mechanism seems to involve ERS modulation and inhibition of ERS-mediated activation of the caspase-12/caspase-3 apoptosis signaling pathway.

Highlights

Ulcerative colitis (UC) is a chronic colonic inflammatory disease primarily characterized by mucosal inflammation and ulceration
In the low-dose Berberine hydrochlorideEvidence-Based Complementary and Alternative Medicine (BBR) group, there was major loss of crypt glands, submucosal inflammatory cell infiltration, and partial edema of the mucosal epithelium. e medium-dose BBR group had a reduced extent of lesions compared to the low-dose group. e tissue damage index (TDI) of the high-dose BBR group was significantly lower (p < 0.01) compared to the model group, whereas in the lowand medium-dose BBR groups the decrease was not statistically significant (p > 0.05). e results are shown in Table 2 and Figure 1
Of a series of intracellular processes involved in homeostasis [15]

Summary

Introduction

Ulcerative colitis (UC) is a chronic colonic inflammatory disease primarily characterized by mucosal inflammation and ulceration. It is often recurrent with slow recovery and is currently a refractory disorder of the digestive tract [1, 2]. Evidence-Based Complementary and Alternative Medicine (BBR) is an effective active ingredient extracted from the traditional Chinese medicine Coptis chinensis. It may exert a therapeutic action in UC [6], which most likely is dependent on adjustment of the intestinal flora composition [7], preservation of intestinal barrier function [8], regulation of immune response, and other protective actions [9]. An exploration of the mechanisms underlying BBR treatment of UC from the perspective of regulating ERS and affecting apoptosis of IECs has not been attempted

Methods

Results

Conclusion