Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran.
Sci Rep. 2021 Jan 11;11(1):336. doi: 10.1038/s41598-020-79472-y.
Aging is correlated with several complex diseases, including type 2 diabetes, neurodegeneration diseases, and cancer. Identifying the nature of this correlation and treatment of age-related diseases has been a major subject of both modern and traditional medicine. Traditional Persian Medicine (TPM) embodies many prescriptions for the treatment of ARDs. Given that autophagy plays a critical role in antiaging processes, the present study aimed to examine whether the documented effect of plants used in TPM might be relevant to the induction of autophagy? To this end, the TPM-based medicinal herbs used in the treatment of the ARDs were identified from modern and traditional references. The known phytochemicals of these plants were then examined against literature for evidence of having autophagy inducing effects. As a result, several plants were identified to have multiple active ingredients, which indeed regulate the autophagy or its upstream pathways. In addition, gene set enrichment analysis of the identified targets confirmed the collective contribution of the identified targets in autophagy regulating processes. Also, the protein-protein interaction (PPI) network of the targets was reconstructed. Network centrality analysis of the PPI network identified mTOR as the key network hub. Given the well-documented role of mTOR in inhibiting autophagy, our results hence support the hypothesis that the antiaging mechanism of TPM-based medicines might involve autophagy induction. Chemoinformatics study of the phytochemicals using docking and molecular dynamics simulation identified, among other compounds, the cyclo-trijuglone of Juglans regia L. as a potential ATP-competitive inhibitor of mTOR. Our results hence, provide a basis for the study of TPM-based prescriptions using modern tools in the quest for developing synergistic therapies for ARDs.
衰老与多种复杂疾病相关，包括 2 型糖尿病、神经退行性疾病和癌症。确定这种相关性的本质和治疗与年龄相关的疾病一直是现代医学和传统医学的主要课题。传统的波斯医学（TPM）包含了许多治疗 ARD 的处方。鉴于自噬在抗衰老过程中起着关键作用，本研究旨在探讨 TPM 中记载的植物的作用是否与诱导自噬有关？为此，从现代和传统文献中确定了用于治疗 ARD 的 TPM 药用植物。然后，检查这些植物的已知植物化学物质是否有诱导自噬的作用。结果发现，几种植物有多种活性成分，这些成分确实可以调节自噬或其上游途径。此外，对鉴定靶点的基因集富集分析证实了鉴定靶点在自噬调节过程中的集体贡献。还重建了靶点的蛋白质-蛋白质相互作用（PPI）网络。对 PPI 网络的网络中心性分析确定了 mTOR 为关键网络枢纽。鉴于 mTOR 在抑制自噬方面的作用有充分的文献记载，我们的结果支持这样一种假设，即 TPM 药物的抗衰老机制可能涉及自噬诱导。使用对接和分子动力学模拟对植物化学物质进行化学生物信息学研究，除其他化合物外，鉴定出核桃 Juglans regia L.中的环三萜内酯为 mTOR 的潜在 ATP 竞争性抑制剂。因此，我们的结果为使用现代工具研究 TPM 处方提供了依据，以期为 ARD 开发协同治疗方法。
