Network Pharmacology Integrated Experimental Validation Uncover Quercetin as the Key Ingredient of Hedyotis diffusa Anti‐BRCA

ABSTRACT Hedyotis diffusa , a famous Traditional Chinese Medicine (TCM), has been extensively used clinically for thousands of years. Although the therapeutic effect of Hedyotis diffusa on tumors has attracted wide attention, components, and mechanisms against breast cancer (BRCA) have not been fully understood. The study aims to explore the active components and molecular mechanisms of Hedyotis diffusa against BRCA using network pharmacology combined with experimental validation. The results of network pharmacology indicated that quercetin was the most core component of Hedyotis diffusa . BIRC5, CDK1, FOS, and HSP90AA1 were considered candidate key targets of Hedyotis diffusa against BRCA. KEGG enrichment analysis revealed that multiple cancer‐related pathways are enriched, including pathways in cancer, estrogen signaling pathway, and PI3K‐AKT signaling pathway, and the like. The results of in vitro experiments showed that quercetin inhibited the proliferation of both MCF‐7 cells and MDA‐MB‐231 cells in a dose‐dependent manner. Furthermore, the experimental data demonstrated quercetin may decrease the expression level of BIRC5, CDK1, and HSP90AA1 in MCF‐7 cells. Overall, results of the study indicated that quercetin may play a vital role in the anti‐BRCA effect of Hedyotis diffusa , and quercetin can affect the expression of BIRC5, CDK1, and HSP90AA1 in MCF‐7 cells. This study may provide new evidence for the use of Hedyotis diffusa in the treatment of BRCA.