岗茶microRNA类药效物质的新发现及其抗流感病毒作用机制

Pharmacodynamic material basis is the difficulty and the emphasis of Chinese medicine research. Using breakthroughs in gene sequencing technology over the past 2 years, plant miRNAs as new natural active substances are verified to enter the body through daily diet to regulate human genes, and have been focused by international pharmacy enterprises. However, studies on its applications in the field of traditional Chinese medicine are still lacking. In previous studies, we found that miRNA-719, a small RNA sequenced from Eurya chinensis, can be absorbed orally into the blood, and possesses anti-inflammatory activity in influenza virus-infected mice, thus proving the existence of miRNA substance in Eurya chinensis. This study is aimed to obtain 2 to 5 new miRNAs from Eurya chinensis (ech-miRs) on influenza virus-induced lung injury mouse model and cell model by high-flux sequencing, gene knockout, and microdialysis analysis. In addition, betulinic acid, a well-known active ingredient of Eurya chinensis, is used as control to illustrate the potency and structure-activity relationship of ech-miRs, as well as their network regulation mechanism on influenza virus-induced lung injury from histopathology, cell function, signal transduction and gene structure. The present study first reveals the effects of Chinese herb miRNAs on the body, and demonstrates a new perspective and method for traditional Chinese medicine, providing evidence for development of new herbal miRNA drugs.

药效物质是中药研究的重点和难点。随着近2年基因测序技术的突破，证实植物微小核糖核酸(miRNA)可通过日常饮食进入体内，调控人体基因，是一类全新的天然活性物质，已成为国际制药企业关注焦点，但在中药研究领域尚属空白。我们前期发现，岗茶miRNA-719可口服吸收入血，具有抗流感病毒性肺炎活性，提示岗茶中miRNA类药效物质的存在。本项目采用高通量测序、基因敲除及微透析技术，通过构建流感病毒小鼠模型和细胞模型，获取2-5个新的岗茶miRNA类药效物质，并与岗茶抗炎成分白桦酸作比较，从组织病理、细胞功能、信号转导和基因构象4个层次，阐明岗茶miRNA类药效物质的作用强弱、构效关系及对病毒性肺损伤修复的网络调控机制，从miRNA角度揭示岗茶抗流感病毒作用的药效物质基础，首次揭示中药核酸类物质对机体的影响，为中药药效物质研究提供一种全新的研究视角和方法，为中药miRNA新药研发提供依据。

药效物质是中药研究的重点和难点。随着近2年基因测序技术的突破，证实植物微小核糖核酸(miRNA)可通过日常饮食进入体内，调控人体基因，是一类全新的天然活性物质，已成为国际制药企业关注焦点，但在中药研究领域尚属空白。本项目采用高通量测序技术，通过构建流感病毒小鼠模型和细胞模型，鉴定得到5个岗茶miRNA类药效物质；其中，以miR-719活性最强，可抑制MDCK细胞中流感病毒的增殖，并且可显著改善流感病毒引起的小鼠急性肺损伤，其机制可能是miR-719靶向作用于NLRP3，调控NLRP3/Caspase-1通路关键蛋白的表达，降低体内过度的炎症反应，抑制流感病毒诱导的细胞焦亡。本项目从miRNA角度揭示岗茶抗流感病毒作用的药效物质基础，首次揭示中药核酸类物质对机体的影响，为中药药效物质研究提供一种全新的研究视角和方法，为中药miRNA新药研发提供依据。