Gastrodiae rhizoma attenuates brain aging via promoting neuritogenesis and neurodifferentiation

Gastrodiae Rhizoma (Tianma), the dried tuber of Gastrodia elata Bl. (Orchidaceae), is listed as a top-grade herbal medicine in Shen-nong Ben-ts'ao Jing and has been used for treating headaches, dizziness, vertigo and convulsion. It has a neuroprotective effect and extends the lifespan in mouse models of Huntington's disease and Niemann-Pick type C disease. However, its effect on senescence remains unknown. This study aimed to investigate the anti-aging effects and the underlying mechanism of Gastrodiae Rhizoma. D-galactose (D-gal)- and BeSO4-induced cellular senescence and senescence-associated β-galactosidase (SA-β-gal) activity were evaluated in SH-SY5Y and PC12 cells. D-gal–induced aging mice were used as an in vivo model. Animal behaviors including nesting and burrowing and Morris water maze were conducted. Neurogenesis in the hippocampus was assessed by immunohistochemistry and confocal microscopy, and the aging-related proteins were assessed by Western blot analysis. The potential neuritogenesis activity of the partially purified fraction of Gastrodiae Rhizoma (TM-2) and its major ingredients were investigated in PC12 cells. TM-2 could improve D-gal-induced learning and memory impairement by inhibiting oxidative stress, increasing hippocampal neurogenesis and regulating the SH2B1-Akt pathway. Moreover, N6-(4-hydroxybenzyl)adenine riboside (T1-11) and parishins A and B, three constituents of TM-2, had anti-aging activity, as did T1-11 and parishin A induced neuritogenesis. Our data suggested that TM-2 slowed down D-gal-induced cellular and mouse brain aging. These results indicate that Gastrodiae Rhizoma has a beneficial effect on senescence. It may be used for neuroprotection and promoting neurogenesis.