Targeted production of desired minor ginsenosides based on the hydrolytic selectivity of β-glucosidase and their enhanced anti-neuroinflammatory activity

Abstract

Abstract Despite the inhibitory effect of various ginsenosides on neuroinflammation, pharmacological activity of ginsenosides varies depending on their hydrolysis by individual intestinal microbial flora and may not appear in individuals with intestinal microbial deficiency. Herein, we investigated the hydrolytic selectivity of β-glucosidase from Lactobacillus antri toward sugar residues in ginsenoside to selectively enhance the effective minor ginsenoside contents and improve their anti-neuroinflammatory activity in BV2 microglia. The hydrolytic selectivity of β-glucosidase was dependent on the position and linkage type of sugar residues. Hydrolysis of ginseng extract and its mimic indicated that the predominant hydrolytic selectivity of β-glucosidase toward P1 (β1→6 linkage), P4, and P2 residues led to the selective production of minor ginsenoside Rd at the early stage and Rg3, Rh1, and A-PPD at the late stage, which resulted in the enhanced anti-neuroinflammatory activity of hydrolyzed ginseng mimic by inhibiting the production of inflammatory mediators in BV2 microglial cells, particularly at the late stage of hydrolysis. This study suggests that the insight into the hydrolytic selectivity of β-glucosidase will help in selecting appropriate substrates hydrolyzed well and in enhancing the contents of desired deglycosylated compounds, including minor ginsenosides, to improve their efficacy on specific target diseases, including those caused by neuroinflammation.