(RS)-bambuterol and its enantiomers: Potential improvement of (R)-bambuterol in mice with colitis

• Published in: International immunopharmacology 2022-02, Vol.103, p.108501-108501, Article 108501
• Main Authors: Deng, Liangjun, Wang, Shanping, Guo, Haihua, Liu, Xiaoming, Zou, Xinfeng, Zhang, Rui, Lin, Yue, Tan, Wen
• Format: Article
• Language: English
• Subjects: (R)-BMB; Animals; Asthma; Body weight; Body weight loss; Bronchodilation; Butyrilcholinesterase; Colitis - chemically induced; Colitis - drug therapy; Colitis - metabolism; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Colon; Colon - pathology; Cytokines; Dextran; Dextran sulfate; Dextran Sulfate - pharmacology; Dextrans; Disease Models, Animal; Enantiomers; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 17; Interleukin 6; Macrophages; Mice; Mice, Inbred C57BL; Oral administration; p-STAT3; Receptors; Retinoic acid; Signal Transduction; Spleen; Stat3 protein; Terbutaline - analogs & derivatives; Ulcerative colitis; Weight loss measurement; Western blotting; β2AR
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.108501

•(R)-bambuterol, but not (S)-bambuterol or (RS)-bambuterol, could significantly relieve gut inflammation.•(R)-bambuterol alleviated colitis by inhibiting IL-6, STAT3, and RORγt pathway activation and mitigating inflammatory responses.•(R)-bambuterol attenuated the colitis effect was superior to that of 5-ASA. Bambuterol (BMB) has been used clinically to treat asthma due to its bronchodilation activity. However, the effect of BMB on ulcerative colitis (UC) has not been examined. The present work focused on the effects of enantiomeric BMB on UC. Acute UC was induced in mice by 3% dextran sulfate sodium (DSS), and (R)-, (S) and (RS)-BMB were orally administered. Body weight loss and the disease activity index (DAI) were measured once a day. Inflammatory factors were detected by ELISA and qRT-PCR. Histological evaluations of colon samples were performed. IL-6, STAT3, and RORγt pathway-related proteins were analyzed by western blotting. The results verified that colitis severity was dramatically ameliorated by (R)-BMB, which was significantlybetter than the effect of (RS)-BMB or (S)-BMB, as evidenced by body weight loss, DAI, colon length, spleen/body weight ratio and histopathological manifestations. Furthermore, (R)-BMB treatment significantly diminished the levels of inflammatory cytokines and macrophages infiltration in mice with colitis. Besides, treated with (R)-BMB obviously elevated the level of β2AR. In addition, (R)-BMB decreased the expression of IL-6, IL-17, retinoic acid receptor-related orphan receptor-gamma t (RORt), and phosphorylated STAT3 (p-STAT3) in a dose-dependent manner in the colon tissues. The efficacy of (R)-BMB was more notable than aminosalicylic acid (5-ASA). (R)-BMB is either butyrilcholinesterase inhibitor or β2AR agonist which offers new treatment of colitis.