Noni (Morinda citrifolia L.) is a natural source of antioxidants whose bioactivity can be enhanced through fermentation.Quercetin, a representative exogenous flavonoid, exhibits potent antioxidant properties; however, its interaction within complex phytochemical systems such as noni remains insufficiently understood.This study aimed to investigate the antioxidant effects and underlying molecular mechanisms of quercetin supplementation in noni-based formulations using an integrated in vitro and in silico approach.A mixture of noni juice and probiotic-fermented noni juice was established as a baseline matrix to incorporate both intrinsic and fermentation-derived bioactivities.Quercetin (10 g/mL) was added to this matrix to evaluate its effects on phytochemical composition and antioxidant capacity.The formulations were optimized using a mixture design approach, followed by response surface methodology (RSM) and principal component analysis (PCA).In vitro analyses showed that quercetin supplementation enhanced antioxidant activity in a ratiodependent manner.A 5:1 ratio of noni: fermented noni significantly increased total phenolic content (P < 0.001), while the 3:1 ratio exhibited the highest 3:1 for 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity.The 8:1 ratio showed maximal 2,2'-azino-bis(3ethylbenzothiazoline-6-sulfonic acid) activity and increased total flavonoid content (P < 0.05).RSM and PCA analyses identified non-additive interaction regions, suggesting potential synergistic effects between quercetin and the noni matrices.Liquid chromatography-tandem mass spectrometry based metabolite profiling indicated that quercetin supplementation modulates the metabolic composition of noni, leading to the formation of metabolites such as dimethyl D-malate and peroxyoctanoic acid.In silico molecular docking suggested that these metabolites exhibit high binding affinity toward nuclear factor erythroid-2-related factor 2 and RAC-alpha serine/threonine-protein kinase, key regulators of oxidative stress and metabolic signaling pathways.In conclusion, quercetin supplementation significantly enhances the antioxidant capacity of noni-based matrices by increasing antioxidant levels, promoting radical scavenging activity and modulating oxidative stress-associated metabolites, supporting the potential of quercetin-enriched noni as a functional food or nutraceutical candidate.
Park et al. (Thu,) studied this question.