PMID- 24637189 OWN - NLM STAT- MEDLINE DCOM- 20150115 LR - 20161125 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 154 IP - 1 DP - 2014 May 28 TI - Intervention effects of QRZSLXF, a Chinese medicinal herb recipe, on the DOR-beta-arrestin1-Bcl2 signal transduction pathway in a rat model of ulcerative colitis. PG - 88-97 LID - S0378-8741(14)00198-6 [pii] LID - 10.1016/j.jep.2014.03.021 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Qingre Zaoshi Liangxue Fang (QRZSLXF) is a Chinese medicinal herb recipe that is commonly prescribed for the treatment of ulcerative colitis. It includes 5 quality assured herbs: Sophora flavescens Aiton., Baphicacanthus cusia (Nees) Bremek., Bletilla striata Rchb.f., Glycyrrhiza uralensis Fisch. and Coptis chinensis Franch. The main phytochemical ingredient of QRZSLXF includes ammothamnine, sophocarpidine, liquiritin, berberine and indirubin. QRZSLXF has been clinically proven for use in the treatment of ulcerative colitis for over twenty years. In the past ten years, research has confirmed the therapeutic effect of QRZSLXF in ulcerative colitis and partially revealed its mechanism of action. Here, we further reveal the therapeutic mechanism of QRZSLXF in ulcerative colitis. To investigate the role of the DOR-beta-arrestin1-Bcl-2 signal transduction pathway in ulcerative colitis and to determine the effects of QRZSLXF on this signal transduction pathway. MATERIALS AND METHODS: Eighty-four Sprague-Dawley rats were randomly divided into six groups: normal control group, model group, mesalazine group, and QRZSLXF high-dose, medium-dose group and low-dose groups (n=14). Experimental colitis was induced by trinitrobenzenesulfonic acid (TNBS) in each group, except the normal control group. After modeling, bloody stool, mental state and diarrhea were observed and recorded. Two rats were randomly selected from the model groups adfnd sacrificed on day 3 to observe pathological changes in the colon tissue by microscopy. The rats in the QRZSLXF-treated groups received intramuscular injections of different concentrations of QRZSLXF for 15 days. The rats in the mesalazine group were treated with mesalazine solution (0.5 g/kg/day) by gastric lavage for 15 days. The rats in the normal control group and the model group were treated with 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the remaining rats were sacrificed and their colon tissues were used to detect the mRNA and protein expressions of DOR, beta-arrestin1 and Bcl-2 by Real-time PCR and immunohistochemistry, respectively. Histological changes in the colon tissues were also examined. RESULTS AND CONCLUSIONS: The expressions of DOR, beta-arrestin1 and Bcl-2 were significantly different among the four groups. The expressions of DOR, beta-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group compared with the other groups (P<0.05). In contrast to the model group, the expressions of DOR, beta-arrestin1 and Bcl-2 were significantly decreased in the mesalazine group and the groups that received different doses of QRZSLXF (P<0.05), and there were no statistically significant differences among the mesalazine and QRZSLXF-treated groups (P>0.05). This study indicates that the DOR-beta-arrestin1-Bcl-2 signal transduction pathway may participate in the pathologic course of ulcerative colitis. Moreover, QRZSLXF could attenuate ulcerative colitis by regulating the DOR-beta-arrestin1-Bcl-2 signal transduction pathway. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Fan, Heng AU - Fan H AD - Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. FAU - Liu, Xing-xing AU - Liu XX AD - Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. FAU - Zhang, Li-juan AU - Zhang LJ AD - Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. FAU - Hu, Hui AU - Hu H AD - Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. FAU - Tang, Qing AU - Tang Q AD - Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. Electronic address: 122022188@qq.com. FAU - Duan, Xue-yun AU - Duan XY AD - Xueyun Duan, Department of Pharmacy, the Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan 430061, Hubei Province, China. FAU - Zhong, Min AU - Zhong M AD - Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. FAU - Shou, Zhe-xing AU - Shou ZX AD - Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140315 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Arrestins) RN - 0 (DOR protein, rat) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Muscle Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (RNA, Messenger) RN - 0 (beta-Arrestins) RN - 0 (qingre zaoshi liangxue fang) RN - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) SB - IM MH - Animals MH - Arrestins/genetics/*metabolism MH - Colitis, Ulcerative/chemically induced/*metabolism/pathology MH - Colon/drug effects/metabolism/pathology MH - Disease Models, Animal MH - Drugs, Chinese Herbal/*pharmacology MH - Male MH - Muscle Proteins/genetics/*metabolism MH - Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism MH - RNA, Messenger/metabolism MH - Rats, Sprague-Dawley MH - Signal Transduction MH - Trinitrobenzenesulfonic Acid/metabolism MH - beta-Arrestins OTO - NOTNLM OT - B-cell lymphoma-2 OT - Delta opioid receptor OT - Qingre Zaoshi Liangxue Fang OT - Signal transduction pathway OT - Ulcerative colitis OT - beta-Arrestin1 EDAT- 2014/03/19 06:00 MHDA- 2015/01/16 06:00 CRDT- 2014/03/19 06:00 PHST- 2013/04/14 00:00 [received] PHST- 2014/03/06 00:00 [revised] PHST- 2014/03/09 00:00 [accepted] PHST- 2014/03/19 06:00 [entrez] PHST- 2014/03/19 06:00 [pubmed] PHST- 2015/01/16 06:00 [medline] AID - S0378-8741(14)00198-6 [pii] AID - 10.1016/j.jep.2014.03.021 [doi] PST - ppublish SO - J Ethnopharmacol. 2014 May 28;154(1):88-97. doi: 10.1016/j.jep.2014.03.021. Epub 2014 Mar 15.