title: Berberine ameliorates pro-inflammatory cytokine-induced endoplasmic reticulum stress in human intestinal epithelial cells in vitro.
abstract: Endoplasmic reticulum stress (ER stress) in intestinal epithelial cells (IECs) plays an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD). The aim of this study is to explore the potential of berberine (BBR) in regulating pro-inflammatory cytokine-induced ER stress and apoptosis in IECs. ER stress in cultured Caco-2 cells was induced by IFN-γ/TNF-α and tunicamycin, respectively. The experimental groups were pretreated with BBR. Cell viability was determined by MTT assay. In vitro apoptosis was examined by flow cytometry using annexin V-FITC labeling. The molecular markers of ER stress, including GRP-78, p-JNK, caspase-12, and cleaved caspase-3 were analyzed by Western blot. Xbp-1 mRNA splicing was detected by RT-PCR. Pretreatment of BBR helped to survive in cytokine-induced Caco-2 cells. BBR significantly attenuated cytokine-induced Caco-2 apoptosis. GRP78 expression and xbp-1 mRNA splicing were enhanced significantly in the presence of IFN-γ/TNF-α and tunicamycin, and they could be dampened by BBR. Further study revealed BBR could downregulate JNK phosphorylation, and the level of caspase-12 and cleaved caspase-3. Berberine can ameliorate pro-inflammatory cytokines induced ER stress in vitro, and it might be one of the targeted therapeutic agents for IBD.
authors.affiliation: Department of General Surgery, Jinling Hospital, Second Military Medical University, Nanjing, China.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Hao
authors.forename: Anlong
authors.initials: A
authors.lastname: Yao
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Gong
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhu
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001599:Berberine / Q000494:pharmacology*; D018938:Caco-2 Cells; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000032:analysis; D006801:Humans; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007371:Interferon-gamma / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D001599:Berberine; D014415:Tunicamycin; D007371:Interferon-gamma; D048031:JNK Mitogen-Activated Protein Kinases; D053454:Caspase 12; D053148:Caspase 3