肠道微生物与三七皂苷互作抗炎性肠病药效物质及作用机制研究

Oral administration of Panax notoginseng saponins (PNS) can be used for the prevention and treatment of inflammatory bowel disease, and the pharmacodynamic substances and mechanism of PNS in anti-inflammatory bowel disease are not clear. This project is aiming to investigate the pharmacodynamics of PNS on anti-inflammatory bowel disease and clarify its mechanism based on the interaction between gut microbiota and PNS. Studies have shown that most of PNS have low bioavailability. PNS can be transformed by gut microbiota after oral administration, while the anti-inflammatory activity of the bio-converted products is obviously enhanced. The steady-state health of gut microbiota is important to the prevention and treatment of inflammatory bowel diseases, while PNS can regulate the profile of gut microbiota. Therefore, it will provide a scientific basis for the clinical use of P. notoginseng for inflammatory bowel disease to study the key components of the pharmacodynamics of PNS using gut microbiota mediated pharmacokinetics. Inflammatory bowel disease causes gut microbial dysregulation to promote the malignant development of the disease. This project will use 16s RNA and metagenomic sequencing to analyze the gut microbiota regulated by PNS, and elucidate the relevance between PNS on inflammatory bowel disease and gut microbiota. The project will clarify the basis and mechanism of the interaction between PNS and gut microbiota against anti-inflammatory bowel disease, provide theoretical guidance for its rational development and use in inflammatory bowel disease, and further establish a useful exploration for the research methods with multi-component and multi-target low bioavailable natural products in traditional Chinese medicine.

三七皂苷口服可用于炎性肠病的治疗，而三七皂苷体内抗炎性肠病药效物质及作用机制尚不明确。本项目基于肠道微生物与三七皂苷互作研究三七体内抗炎性肠病药效物质及作用机制。研究表明三七总皂苷中多数皂苷单体生物利用度低，但经口服可被肠道微生物转化成抗炎活性强的产物；炎性肠病导致肠道微生物失调反向促使疾病恶性发展，所以肠道微生物的稳态健康对炎性肠病的治疗有重要影响，而三七皂苷可调节肠道微生物的轮廓。因此，利用肠道微生物介导结合药物代谢动力学研究三七皂苷筛选药效关键成分将为三七临床用于炎性肠病提供科学依据。本课题将利用16s RNA和宏基因组测序的方法检测三七皂苷对失调肠道微生物的调节作用，探寻其与三七皂苷对炎性肠病作用的相关性。项目将阐明三七皂苷与肠道微生物互作体内抗炎性肠病物质基础及作用机制，为其合理开发及用于炎性肠病提供理论指导，为建立符合生物利用度低中药多成分多靶点的研究方法做出探索。

三七皂苷口服可用于炎性肠病的预防与治疗，而三七皂苷体内抗炎性肠病药效物质及作用机制尚不明确。本项目基于肠道微生物与三七皂苷互作研究三七体内抗炎性肠病药效物质及明确其作用机制。研究表明三七总皂苷中多数皂苷单体生物利用度低，其经口服可被肠道微生物转化，转化产物抗炎活性明显增强；肠道微生物的稳态健康对炎性肠病预防与治疗有重要影响，而三七皂苷可调节肠道微生物的轮廓。因此，利用肠道微生物介导结合药物代谢动力学研究三七皂苷筛选药效关键成分将为三七临床用于炎性肠病提供科学依据。炎性肠病导致肠道微生物失调反向促使疾病恶性发展，本课题将利用16s RNA和宏基因组测序的方法检测三七皂苷对失调肠道微生物调节作用，探寻其与三七皂苷对炎性肠病作用的相关性。项目将阐明三七皂苷与肠道微生物互作体内抗炎性肠病物质基础及作用机制，为其合理开发及用于炎性肠病提供理论指导，为建立符合生物利用度低中药多成分多靶点的研究方法做出有益探索。课题主要研究内容包括：<1> 三七皂苷肠道微生物代谢成分确证、制备及活性菌株鉴定; <2> 三七皂苷肠道微生物体内代谢物分析鉴定; <3> 三七皂苷口服后体内抗炎性肠病的活性及对肠道微生物影响的研究; <4>三七皂苷肠道微生物代谢物药代动力学研究; <5> 三七皂苷肠道微生物代谢物抗炎性肠病作用分子机制研究。研究证实，①三七皂苷体内外可被肠道菌群代谢，不同个体肠道菌群差异会导致三七皂苷代谢差异；②利用炎性肠病动物模型，发现三七皂苷肠抗炎性肠病活性与肠道菌互作相关，明确GCK、GRh2等单体内药效成分；③解析三七皂苷肠道微生物代谢物体内生物利用度明显提升；④证明肠道微生物结构、功能变化与炎性肠病发生发展的关系,及其对三七皂苷肠道微生物代谢物抗炎性肠病活性有影响；⑤阐明了三七皂苷肠道微生物代谢物体内抗炎性肠病分子机制。课题已经支持发表7篇SCI论文，培养硕士生3人。