Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 71, Issue 7, Pages 3484-3496Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.2c07889
Keywords
ginseng; 20(S)-protopanaxadiol; brain-type creatine kinase; target
Ask authors/readers for more resources
Ginseng is consumed as a dietary supplement and its metabolite PPD has been found to enhance cognitive performance. Through various experiments, it was found that PPD directly interacts with CK-BB and promotes its activity, leading to amelioration of cognitive deficits and alterations in oxidative stress and synaptic plasticity in mice.
Ginseng is an important medicinal herb consumed as dietary supplements. Ginsenosides and their metabolites have been reported to enhance cognitive performance, but their underlying mechanisms remain unclear. Brain-type creatine kinase (CK-BB) was previously screened out as one of the potential targets in brain tissues. In vitro, the strongest direct interaction between 20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, and CK-BB was detected using biolayer interferometry (BLI). Drug affinity responsive target stability, cellular thermal shift assay, BLI, and isothermal titration calorimetry were subsequently used, and the binding of PPD to CK-BB was verified. The binding sites of the CK-BB/PPD complex were clarified by molecular docking and site-directed mutagenesis. Enzyme activity assay showed that the binding of PPD to CK-BB in vitro enhanced its activity. In vivo, PPD increased CK-BB activity in D-gal-induced mice. PPD also improved the D-gal-induced cognitive deficits and ameliorated alterations in oxidative stress and hippocampal synaptic plasticity. Therefore, the integration of PPD with its target protein CK-BB may promote CK-BB activity, thereby ameliorating hippocampal synaptic plasticity and cognitive deficits in D-gal-treated mice.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available