Novel anticancer mechanisms of JinYingZi-derived oleanolic acid against renal cell carcinoma: an in silico analysis

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for 90% of all estimated cases. Advanced RCC often carries poor prognosis due to its high metastases rate, the lack of early-warning signs, as well as its complex clinical manifestations and its resistance to chemotherapy. Ethnopharmacologically, Fructus Rosae laevigata (JinYingZi) has been employed by Chinese medicine to treat various urinary tract and gastrointestinal dis¬orders. This study aimed at performing a series of mechanistic analyses in order to unlock the anticancer potential of JinYingZi-derived bioactive components against RCC. Several network pharmacology tools were employed so as to analyse the drug-disease interactions. Our data revealed that more than 2,214 genes were dysregulated in RCC, whereas the JinYingZi-derived bioactive compounds modulated 347 genes. The intersecting between RCC and the bioactive compounds revealed 132 cross targets. Our results were further validated by conducting molecular docking, which revealed a stable association between oleanolic acid with each of the following targets: androgen receptor (AR), dipeptidyl peptidase (DPP), estradiol (ESR1), nitric oxide synthase 2 (NOS2), and cyclooxygenase-2 (PTGS2). Our approach is being used successfully in order to evaluate a panel of novel medicinal plant-derived bioactive com¬pounds, and may lead to the identification of safe and effective chemical scaffolds that could act as templates for drug discovery or yield potential drug candidates.