20(S)-protopanaxatriol inhibited D-galactose-induced brain aging in mice via promoting mitochondrial autophagy flow.
Jun-Jie ZhangRui-Yi HuKe-Cheng ChenYong-Bo LiuYun-Yi HouYu-Zhuo ZhangZi-Meng FengRi-Xin ChenYi-Nan ZhengShuang LiuWei LiPublished in: Phytotherapy research : PTR (2023)
Previous reports have confirmed that saponins (ginsenosides) derived from Panax ginseng. C. A. Meyer exerted obvious memory-enhancing and antiaging effects, and the simpler the structure of ginsenosides, the better the biological activity. In this work, we aimed to explore the therapeutic effect and underlying molecular mechanism of 20(S)-protopanaxatriol (PPT), the aglycone of panaxatriol-type ginsenosides, by establishing D-galactose (D-gal)-induced subacute brain aging model in mice. The results showed that PPT treatment (10 and 20 mg/kg) for 4 weeks could significantly restore the D-gal (800 mg/kg for 8 weeks)-induced impaired memory function, choline dysfunction, and redox system imbalance in mice. Meanwhile, PPT also significantly reduced the histopathological changes caused by D-gal exposure. Moreover, PPT could increase TFEB/LAMP2 protein expression to promote mitochondrial autophagic flow. Importantly, the results from molecular docking showed that PPT had good binding ability with LAMP2 and TFEB, suggesting that TFEB/LAMP2 might play an important role in PPT to alleviate D-gal-caused brain aging.
Keyphrases
- molecular docking
- oxidative stress
- diabetic rats
- high glucose
- white matter
- resting state
- high fat diet induced
- cell death
- drug induced
- endothelial cells
- functional connectivity
- loop mediated isothermal amplification
- molecular dynamics simulations
- working memory
- cerebral ischemia
- adipose tissue
- type diabetes
- insulin resistance
- brain injury
- binding protein
- metabolic syndrome
- combination therapy
- electronic health record
- preterm birth
- replacement therapy