Bioactive protopanaxadiol-enriched rice (DJ-PPD) exerts potent anti-inflammatory and antioxidant effects via dual regulation of NF-κB/MAPK/Akt and NRF2/HO-1 signalling.
Monmai Chaiwat, Tangonan Aimee Carol, Kim Jin-Suk, Rha Eui-Shik, Baek So-Hyeon
Abstract
Protopanaxadiol (PPD) is a bioactive ginsenoside with significant anti-inflammatory potential; however, its low natural abundance and dependence on inefficient intestinal microbial bioconversion hinder pharmaceutical development. To overcome these supply and bioavailability constraints, we developed a metabolically engineered rice variety, DJ-PPD, capable of directly biosynthesizing the aglycone PPD. This study investigated the anti-inflammatory and antioxidant mechanisms of DJ-PPD extract in lipopolysaccharide (LPS)-stimulated BV2 cells. DJ-PPD treatment significantly reduced nitric oxide (NO) production, pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and the expression of iNOS and COX-2. Its efficacy surpassed conventional ginseng extract and was comparable to synthetic PPD (S-PPD). Mechanistically, DJ-PPD inhibited NF-κB, MAPKs, and Akt phosphorylation while activating the NRF2/HO-1 antioxidant pathway. These findings demonstrate that DJ-PPD simultaneously inhibits pro-inflammatory cascades and reinforces intrinsic antioxidant defences. By effectively bypassing the need for gut microbiota metabolism, this genetically engineered rice represents a sustainable, bioavailable, and commercially viable multi-target therapeutic candidate for neuroinflammatory conditions.
Key Findings
- DJ-PPD treatment significantly reduced nitric oxide production and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in LPS-stimulated BV2 cells.
- DJ-PPD inhibited NF-κB, MAPKs, and Akt phosphorylation while activating the NRF2/HO-1 antioxidant pathway.
- DJ-PPD showed greater efficacy than conventional ginseng extract and comparable effects to synthetic PPD, bypassing the need for gut microbiota metabolism.
Clinical Significance
The genetically engineered DJ-PPD rice provides a sustainable and bioavailable therapeutic candidate that simultaneously reduces inflammation and enhances antioxidant defenses, offering potential for treating neuroinflammatory and oxidative stress-related conditions.
Citation
Monmai Chaiwat, Tangonan Aimee Carol, Kim Jin-Suket al.. Bioactive protopanaxadiol-enriched rice (DJ-PPD) exerts potent anti-inflammatory and antioxidant effects via dual regulation of NF-κB/MAPK/Akt and NRF2/HO-1 signalling. Natural product research. 2026-Jun-21.