Catechin–Folate nano-niosomes from Osbeckia parvifolia Arn. induce apoptotic cell death in Ovarian cancer

The current study establishes the mechanism on how dietary flavonoid, catechin fractions of Osbeckia parvifolia Arn. could be used as a therapeutic treatment for ovarian cancer, using a combination of network pharmacology, molecular validation and nano-formulations. From network modelling analysis, 420 protein targets linked to ovarian cancer, including five that act as major regulatory hubs – AKT1, STAT3, IL6, ESR1 and CASP3 were found. Catechin had the strongest binding affinity to all of these five hub proteins, especially for ESR1 (-11.089 kcal/mol) and AKT1 (-9.221 kcal/mol). In molecular dynamics simulation studies over 100 ns, catechin bonded strongly with its target proteins. HPLC guided fractionation (RT: 3.887 min) LC-MS/MS (RT:6.51 min), HPTLC (Rf: 0.973) were performed, which resulted in the confirmation of the presence of both catechin and epicatechin and verified the biosynthetic pathway of both through the measurement of the expression of their respective biosynthetic genes LAR (0.3637 folds) and ANR (0.2746 folds) in O. parvifolia . The evaluation of the six different nano-formulations of phytoniosomes led to F5 being the most stable with uniform spherical architecture, having an optimal particle size (229.2 nm), a high positive zeta potential (+ 42.7mV), and having the highest cytotoxicity (93.17%) in SKOV3 cells, the mechanism of action being through apoptosis induction and cell-cycle arrest. Hence, this study supports the hypothesis that catechin extracted from O. parvifolia can serve as an effective therapeutic candidate for the targeted treatment of ovarian cancer.