Abstract
Background: Drynaria Fortunei and Cuscuta Chinensis are among the most used traditional Chinese medicine herbal prescriptions and have a significant therapeutic effect on osteoarthritis. However, the purpose of this study intends to elaborate the molecular mechanism of action through network pharmacology. The active ingredients of TCM and the potential targets for the treatment of osteoarthritis were selected through the TCMSP, OMIM and Genecards. Results: The 27 components and 85/117 targets of Drynaria Fortunei and/or Cuscuta Chinensis were identified for osteoarthritis. Pharmacological and PPI network analysis identified top 3 active components (kaempferol, luteolin, and quercetin) and core proteins (IL6, AKT1, and VEGFA). GO and KEGG analysis identified the top 3 functions (cytokine and cell/nuclear receptor) and pathways (PI3K-Akt, TNF and IL-17). Molecular docking showed strong binding ability between quercetin-AKT1 and luteolin-IL6/VEGFA. Interaction analysis mapped the quercetin-AKT1 and luteolin-IL6/VEGFA binding to specific hydrogen and hydrophobic bonds. Conclusions: The main active components, common target proteins, functional activities, and signaling pathways of TCM Drynaria Fortunei and Cuscuta Chinensis for the treatment of osteoarthritis were identified by Network pharmacology. We found, for the first time, that drynariae rhizoma and cuscuta chinensis suppress osteoarthritis by quercetin-AKT1/IL6 and luteolin-VEGFA direct binding. Our findings have significant implication for our understanding of the molecular mechanism of action in the treatment of osteoarthritis and future development of osteoarthritis treatment using quercetin and luteolin.