Immunomodulatory Potential of 6-Gingerol and 6-Shogaol in Lactobacillus plantarum-Fermented Zingiber officinale Extract on Murine Macrophages

In this study, we aimed to investigate whether the physiological activity of ethanol extracts of Zingiber officinale was improved after fermentation with Lactobacillus plantarum strains KCTC 3108 (FLP8) and KCL005 (FLP9). Total polyphenol and flavonoid content was substantially increased after fermentation with FLP8 and FLP9 for 48 h and 24 h, respectively, compared with the unfermented control. The 6-gingerol content was significantly increased in FLP9 after 24 h of fermentation, whereas in FLP8, it remained comparable to pre-fermentation levels. The 6-shogaol content significantly increased in FLP8 and FLP9 at 48 h and 24 h, respectively, compared with the pre-fermentation levels. The anti-inflammatory effects were evaluated using RAW 264.7 cells stimulated with lipopolysaccharides. The fermented product of FLP8 at 48 h and FLP9 at 24 h maintained over 80% cell viability at a concentration of 200 mu g/mL and significantly reduced nitric oxide production compared to the lipopolysaccharide-stimulated control. Moreover, each extract downregulated pro-inflammatory gene expression. Furthermore, the purified 6-gingerol and 6-shogaol, which were purchased as reference compounds, were included in the fermentation extracts of FLP8 at 48 h and FLP9 at 24 h, and both inhibited cell migration in a dose-dependent manner without any cytotoxicity. In conclusion, the fermentation of Z. officinale with these L. plantarum strains enhanced its antioxidant and anti-inflammatory activities, with significant increases in bioactive compound content.