Quantitative and Systems Pharmacology 3. Network-Based Identification of New Targets for Natural Products Enables Potential Uses in Aging-Associated Disorders

Jiansong Fang, Li Gao, Huili Ma, Qihui Wu, Tian Wu, Jun Wu, Qi Wang, Feixiong Cheng
2017 Frontiers in Pharmacology  
Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new
more » ... ndications for aging-associated disorders by natural products. Specifically, we incorporated 411 high-quality aging-associated human genes or human-orthologous genes from mus musculus (MM), saccharomyces cerevisiae (SC), caenorhabditis elegans (CE), and drosophila melanogaster (DM). We constructed a global drug-target network of natural products by integrating both experimental and computationally predicted drug-target interactions (DTI). We further built the statistical network models for identification of new anti-aging indications of natural products through integration of the curated aging-associated genes and drug-target network of natural products. High accuracy was achieved on the network models. We showcased several network-predicted anti-aging indications of four typical natural products (caffeic acid, metformin, myricetin, and resveratrol) with new mechanism-of-actions. In summary, this study offers a powerful systems pharmacology infrastructure to identify natural products for treatment of aging-associated disorders.
doi:10.3389/fphar.2017.00747 pmid:29093681 pmcid:PMC5651538 fatcat:rv57vd54zzftrbjjhuh3x7xim4