Department of pharmacology, Fourth Military Medical University, Xian 710032, Shaanxi, People's Republic of China.
Eur J Pharmacol. 2011 Jan 25;651(1-3):187-96. doi: 10.1016/j.ejphar.2010.10.030. Epub 2010 Oct 20.
Ulcerative colitis involves complicated etiology and presents diverse symptoms including intestine inflammation, bowel pain and diarrhea. Anti-inflammatory drugs are the mainstay in patient care, accompanied with antidiarrhea and analgesic agents used as symptomatic treatment. A classic traditional Chinese medicine formula, Fructus Mume pill (FMP), showed remarkable therapeutic efficacy in treating ulcerative colitis. However, since it contains many herbs and countless chemicals, the underlying mechanism is not clear. In this study, we selected three alkaloids from FMP, namely, berberine, hypaconitine and skimmianine to study the individual drug effect and compare these results with the BHS combination on: 1) The recovery of ulcerative colitis rats induced by trinitrobenzene-sulfonic acid. 2) Mice with xylene-induced acute exudative edema and acetic acid-induced writhing. 3) Gastrointestinal transit inhibition, and 4) the response of HT29 cells after treatment with lipopolysaccharide. We found that the compound hypaconitine showed a potent analgesic effect, while skimmianine acted as an antidiarrhea agent and the component berberine was the key agent exerting anti-inflammatory effect. However, since berberine killed the commensal bacteria and induced lipopolysaccharide release, it could at the same time aggravate colon inflammation. The three-alkaloid combination BHS produced complementary and synergistic effects in colon inflammation recovery, relieving acetic acid-induced bowel pain and xylene-induced acute exudative edema. BHS also decreased lipopolysaccharide production and enhanced the therapeutic efficacy. It is hoped that this study will lay the foundation to further dissect and understand the FMP formula to improve the treatment with simplified and well defined drug combinations for this dreadful disease.
溃疡性结肠炎涉及复杂的病因，表现出多种症状，包括肠道炎症、腹痛和腹泻。抗炎药物是患者治疗的主要方法，同时还使用抗腹泻和镇痛药进行对症治疗。一种经典的中药方剂，乌梅丸（FMP），在治疗溃疡性结肠炎方面显示出显著的疗效。然而，由于它含有许多草药和无数的化学物质，其潜在机制尚不清楚。在这项研究中，我们从 FMP 中选择了三种生物碱，即小檗碱、乌头碱和斯皮诺宁，分别研究其单独的药物作用，并将这些结果与 BHS 组合进行比较：1）三硝基苯磺酸诱导的溃疡性结肠炎大鼠的恢复。2）二甲苯诱导的急性渗出性水肿和醋酸诱导的扭体反应。3）胃肠道转运抑制，以及 4）脂多糖处理后 HT29 细胞的反应。我们发现，化合物乌头碱具有很强的镇痛作用，而斯皮诺宁具有止泻作用，成分小檗碱是发挥抗炎作用的关键药物。然而，由于小檗碱杀死了共生菌并诱导了脂多糖的释放，它也可能同时加重结肠炎症。三碱组合 BHS 在结肠炎症恢复中产生了互补和协同作用，缓解了醋酸诱导的肠痛和二甲苯诱导的急性渗出性水肿。BHS 还降低了脂多糖的产生，增强了治疗效果。希望这项研究将为进一步剖析和理解 FMP 配方奠定基础，以改善对这种可怕疾病的简化和明确药物组合的治疗。
