基于与肠道菌群相互作用的壮药五指那藤皂苷治疗RA作用机制的研究

Stauntonia obovatifoliola Hayata subsp. intermedia is used for the treatment of rheumatic arthritis and rheumatoid arthritis in southwest China. The effective parts of analgesic and anti-inflammatory are rich in triterpenoid saponins. It was proved that multi-component is effective. However, the bioavailability of the main active ingredient was very low, and the metabolite aglycone was also not detected in the blood. This phenomenon is difficult to explain the efficacy of this herb. In order to clarify its effective material basis and mechanism of action, the following research is proposed. First, the pharmacokinetic study after multi-dose administration and the study of intestinal metabolism of the main components of Stauntonia obovatifoliola will be carried out on the rat model of immune arthritis. Secondly, the saponins will be incubated with the gut microbiota of RA model rats in vitro, and the prototypes of metabolites will be monitored. Finally, the effects of saponins on the structure of gut microbiota of RA model rats will be observed and the possible new mechanism of anti-rheumatoid arthritis will be explored. This study will provide a reference for clarifying the mechanism of saponins with poor absorption and high activity, and to provide a reference for the mechanism of the study of the pharmacological substances of the constituent synergistic effect in traditional Chinese medicine, focusing on the interaction between the body and the drug.

五指那藤是我国西南民族地区治疗风湿、类风湿性关节炎的有效药物，镇痛抗炎有效部位富含三萜皂苷，研究证实为多组分起效。但主要有效成分生物利用度极低，代谢物苷元在血中也未检测到，难以解释药效。为阐明其有效物质基础及作用机理，拟开展以下研究。首先，建立免疫性类风湿关节炎大鼠模型，观察口服给予五指那藤皂苷后进行其在大鼠体内多剂量给药的药代动力学研究及肠内代谢研究；其次，将五指那藤皂苷与RA模型大鼠的肠道菌共孵育，进行原型成分代谢产物研究。最后，测定皂苷成分群对模型大鼠肠道菌群结构的影响，探究难吸收的皂苷类成分抗类风湿性关节炎的可能的新机制。课题的完成，为建立“符合中药多成分协同起效特点，重视机体与药物相互作用”的药效物质研究模式奠定基础，为阐明吸收差、活性高的皂苷类成分起效机制提供参考。