Quercetin From Ocimum Basilicum L. Differentially Affects PC‐12 Survival in 2D and 3D Culture

ABSTRACT Alteration of cellular environment from 3D body conditions to traditional 2D culture is one of the main contributors to failure in the transition of many drug candidates into clinical success as it is associated with bioavailability, activity, and toxicity. As a well‐known challenge for drugs, it is also a significant obstacle for secondary metabolites such as flavonoids, with current interest as dietary supplements and nutraceuticals. Previous research on quercetin focused on 2D culture tests, drug carrier platforms, spheroids, and animal models, yet the survival response to quercetin in an ECM‐mimicking environment was not explored, and the investigated quercetins were mainly commercially available quercetin in the literature. Here, we described an isolation strategy for quercetin from purple basil ( Ocimum basilicum L.) with 93% purity, and its effect is examined on collagen‐hydrogel encapsulated PC‐12 cells as well as on PC‐12 cells cultured on collagen‐treated surfaces. Results indicate that the 3D system had greater IC50 values (up to 2.33‐fold of 2D culture) with similar toxicity compared to commercial quercetin, showing promise for clinical and food applications.