Oral administration of hydrolyzed red ginseng extract improves learning and memory capability in cognitive‐decline models

Korean red ginseng ( Panax ginseng C.A. Meyer) contains various pharmacologically active constituents including ginsenosides. Recently we found that red ginseng extract has a strong antioxidant activity and that pectinase‐mediated hydrolysis augments its radical‐scavenging activity. In addition, the content of compound‐K, a bioavailable and bioactive ginsenoside, was significantly increased in the hydrolyzed red ginseng extract compared to the non‐hydrolyzed extract. We further investigated neuroprotective and cognitive‐enhancing effects of the hydrolyzed red ginseng extract in vitro and in vivo . To induce oxidative stress‐induced neurotoxicity, mouse hippocampal HT22 cells and C57BL/6 mice were exposed to an excess glutamate and D‐galactose, respectively. For behavioral assessments, the passive avoidance, Y‐maze, and Morris water maze tasks were performed following treatment with the extracts or compound‐K. Our results from the in vitro and in vivo tests demonstrate that (1) red ginseng extract (containing compound‐K) protects neuronal cells from oxidative damage through the induction of Nrf2 and antioxidant enzymes, (2) the learning and memory impairments induced by oxidative stress were alleviated by treatment with the hydrolyzed red ginseng extract, (3) the hippocampi (particularly cell counts and nuclear arrangement) of the stressed mice was histologically pathologic, which was rarely observable from the hippocampi of the extract‐treated mice. Our findings suggest that red ginseng extract hydrolyzed by pectinase may effectively alleviate oxidative stress‐mediated memory deficits possibly through Nrf2‐related detoxification. Support or Funding Information This work was supported by the Food Functionality Evaluation program funded by the Ministry of Agriculture, Food and Rural Affairs through Korea Food Research Institute.