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. 2023 Jul;37(7):2827-2840.
doi: 10.1002/ptr.7779. Epub 2023 Apr 10.

20(S)-protopanaxatriol inhibited D-galactose-induced brain aging in mice via promoting mitochondrial autophagy flow

Jun-Jie Zhang  1   2 , Rui-Yi Hu  1   2 , Ke-Cheng Chen  3 , Yong-Bo Liu  1   2 , Yun-Yi Hou  1   2 , Yu-Zhuo Zhang  1 , Zi-Meng Feng  1 , Ri-Xin Chen  3 , Yi-Nan Zheng  1 , Shuang Liu  4 , Wei Li  1   2
Affiliations

20(S)-protopanaxatriol inhibited D-galactose-induced brain aging in mice via promoting mitochondrial autophagy flow

Jun-Jie Zhang et al. Phytother Res. 2023 Jul.

Abstract

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.

Keywords: 20(S)-protopanaxatriol; D-galactose; TFEB/LAMP2; brain aging; mitochondrial autophagic flow.

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