三奥汤(SAD)是一种著名的中药(TCM)配方,用于缓解呼吸道症状,包括哮喘.然而,其确切的作用机制在很大程度上仍然未知。在这项研究中,我们利用计算机辅助方法来探索这些机制。首先,我们对SAD的化学成分进行了全面的分析,这使我们能够确定28种主要成分。然后,我们采用计算机模拟研究了SAD的潜在活性成分和瞬时受体电位香草酸1(TRPV1)的相应结合位点.模拟显示D509和D647是TRPV1的潜在结合位点。值得注意的是,分子动力学(MD)研究表明,位点D509可能是TRPV1的变构位点。此外,为了验证计算机辅助预测,我们进行了实验研究,包括体外和体内测定。这些实验的结果证实了我们的计算模型所做的预测,为三奥汤治疗哮喘的作用机制提供了进一步的证据。我们的发现表明:i)TRPV1的D509和D647是SAD主要成分的关键结合位点;ii)SAD或其主要成分显着减少了Ca2通过TRPV1的流入,遵循“Jun”的中医原理,陈,左,Shi\";iii)SAD在全面的体内验证中显示出效率。总之,我们对三奥汤在哮喘治疗中的计算机辅助研究为该中药配方的治疗机制提供了有价值的见解。计算分析和实验验证的结合已被证明可以有效地增强我们对中医的理解,并可能为该领域的未来发现铺平道路。
The San-Ao Decoction (SAD) is a well-known Traditional Chinese Medicine (TCM) formula used to alleviate respiratory symptoms, including asthma. However, its precise mechanisms of action have remained largely unknown. In this study, we utilized computer-aided approaches to explore these mechanisms. Firstly, we conducted a comprehensive analysis of the chemical composition of SAD, which allowed us to identify the 28 main ingredients. Then, we employed computer simulations to investigate the potential active ingredients of SAD and the corresponding binding sites of transient receptor potential vanilloid 1 (TRPV1). The simulations revealed that D509 and D647 were the potential binding sites for TRPV1. Notably, molecular dynamics (MD) studies indicated that site D509 may function as an allosteric site of TRPV1. Furthermore, to validate the computer-aided predictions, we performed experimental studies, including in vitro and in vivo assays. The results of these experiments confirmed the predictions made by our
computational models, providing further evidence for the mechanisms of action of San-Ao Decoction in asthma treatment. Our findings demonstrated that: i) D509 and D647 of TRPV1 are the key binding sites for the main ingredients of SAD; ii) SAD or its main ingredients significantly reduce the influx of Ca2+ through TRPV1, following the TCM principle of \"Jun, Chen, Zuo, Shi\"; iii) SAD shows efficiency in comprehensive in vivo validation. In conclusion, our computer-aided investigation of San-Ao Decoction in asthma treatment has provided valuable insights into the therapeutic mechanisms of this TCM formula. The combination of
computational analysis and experimental validation has proven effective in enhancing our understanding of TCM and may pave the way for future discoveries in the field.