动脉粥样硬化、介入术后再狭窄等血管增殖疾病，其显著特征是血管平滑肌细胞（VSMC）过度增殖。辛能行血，前期我们选取活血作用的辛味中药，应用建立的血管增殖体内、外模型，筛选并发现了吴茱萸碱、姜烯酚、胡椒碱和辣椒素等活性成分。它们能高效并有选择性的抑制VSMC增殖，且在体内能抑制血管内膜增生。文献显示：上述成分都是TRPV1激动剂；有的激动剂能抑制动脉粥样硬化；TRPV1在VSMC有表达，亦是辛味中药的潜在作用靶点之一。故本项目提出“TRPV1通道介导辛味中药抑制VSMC增殖”的假设，拟：通过体外活性筛选结合计算预测等手段，发现辛效团和更多新颖活性辛成分；采用分子药理学方法研究TRPV1调控VSMC增殖的机制；再用动物模型评价体内药效，基因敲除动物模型确证机制；等。本项目基于TRPV1通道研究辛味中药“味-效”发生机制，既有助于揭示“辛能行血”的科学内涵，更有望发现调控VSMC增殖的新靶点。

Vascular smooth muscle cell (VSMC) abnormal proliferation is the predominant property of vascular proliferative disease including atherosclerosis, restenosis, etc. Pungency promotes blood circulation; hence we selected some pungent TCMs and screened them on vascular proliferative disease related in vivo and in vitro models. Evodiamine, shogaol, piperine, capsaicin and some others were identified as active components, which showed very potent and selective anti-proliferative activities on VSMC in vitro, and anti-neointima formation potencies in vivo. It has been reported that all the above active compounds are known TRPV1 agonists; some agonists could attenuate atherosclerosis; the expression of TRPV1 on VSMC is well studied, and TRPV1 is one of the potential targets of pungent TCMs. Thus, we hypothesized that “TRPV1 channel mediated inhibitory effect of pungent TCMs on VSMC proliferation”. Therefore, we plan to identify the “pungent” pharmacophore and more active components from pungent TCMs by using in vitro activity screening assays, computer aided drug design and other techniques. Meanwhile, we will investigate the regulatory effect of TRPV1 on VSMC proliferation by molecular pharmacological techniques. Furthermore, we will evaluate the in vivo potency by animal models, and use gene knockout mice to confirm the mechanism. Investigating TCM “flavor- efficacy” generation mechanism based on TRPV1 channel, will be valuable for elucidating connotation of Chinese medicine theory “pungency promotes blood circulation”, as well as for exploring new target of regulating VSMC proliferation.