Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions

Heng Li; Chen Fan; Huimin Lu; Chunlan Feng; Peilan He; Xiaoqian Yang; Caigui Xiang; Jianping Zuo; Wei Tang

doi:10.1016/j.apsb.2019.08.006

Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions

Acta Pharm Sin B. 2020 Mar;10(3):447-461. doi: 10.1016/j.apsb.2019.08.006. Epub 2019 Sep 5.

Authors

Heng Li^{1

2}, Chen Fan¹, Huimin Lu^{1

2}, Chunlan Feng¹, Peilan He¹, Xiaoqian Yang¹, Caigui Xiang^{1

2}, Jianping Zuo^{1

2

3}, Wei Tang^{1

2}

Affiliations

¹ Laboratory of Anti-inflammation and Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
² School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China.
³ Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Abstract

Ulcerative colitis (UC) manifests as an etiologically complicated and relapsing gastrointestinal disease. The enteric nervous system (ENS) plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract. Berberine, an isoquinoline alkaloid, is known as its anti-inflammatory and therapeutic effects in experimental colitis. However, little research focused on its regulatory function on ENS. Therefore, we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro-immune interactions. Functional defects of enteric glial cells (EGCs), with decreased glial fibrillary acidic protein (GFAP) and increased substance P expression, were observed in DSS-induced murine UC. Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC, closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation. In vitro, berberine showed direct protective effects on monoculture of EGCs, bone marrow-derived dendritic cells (BMDCs), T cells, and intestinal epithelial cells (IECs) in the simulated inflammatory conditions. Furthermore, berberine could modulate gut EGCs-IECs-immune cell interactions in the co-culture systems. In summary, our study indicated the EGCs-IECs-immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.

Keywords: APCs, antigen-presenting cells; BDNF, brain-derived neurotrophic factor; BMDCs, bone marrow-derived dendritic cells; Berberine; CGRP, calcitonin gene-related peptide; DSS, dextran sulfate sodium; EGCs, enteric glial cells; ENS, enteric nervous system; Enteric glial cells; Enteric nervous system; GDNF, glial cell derived neurotrophic factor; GFAP, glial fibrillary acidic protein; IBD, inflammatory bowel diseases; IECs, intestinal epithelial cells; LMPC, lamina propria mononuclear cells; MAPK, mitogen-activated protein kinases; MLNs, mesenteric lymph nodes; MPO, myeloperoxidase; Mucosal inflammation; UC, ulcerative colitis; Ulcerative colitis; VIP, vasoactive intestinal polypeptide.