Bidirectional Fermentation of Monascus and Ginseng Enhances Pigment and Ginsenoside Rg3 Contents: Process Optimization and Antioxidant Mechanism Analysis

Oxidative stress is a key contributor to aging and chronic diseases, highlighting the need for safe and effective natural antioxidants. Monascus yellow pigments (MYPs) and ginsenoside Rg3 exhibit antioxidant activity, but their applications are restricted by low solubility and limited natural abundance. In this research, a bidirectional liquid fermentation system of Monascus ruber using ginseng decoction was established for the simultaneous production of water-soluble MYPs (WSMYPs) and ginsenoside Rg3. Process conditions were optimized to enhance the yields and the antioxidant activity of the system. Antioxidant assays and H2O2-induced RAW264.7 cell models confirmed that WSMYPs were strongly correlated with antioxidant capacity, with ABTS and DPPH scavenging activities showing 2.28-fold and 3.33-fold increases, respectively, compared to the control. Their combination with Rg3 exerted synergistic protective effects by enhancing the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). Network pharmacology and molecular docking further revealed that Monapurone C, a representative WSMYP, and Rg3 act through a multi-target, multi-pathway antioxidant network involving signaling pathways such as PI3K-Akt. This study demonstrates a cost-effective strategy for co-producing WSMYPs and Rg3, providing new insights into the value-added utilization of edible and medicinal resources.