Exploring the impact of Gastrodin on brain aging in mice: Unraveling mechanisms through network pharmacology

Background

With the intensification of global aging, slowing down the aging process has become a topic of significant interest. Brain aging, as one of the prominent changes in the aging process, urgently requires the exploration of new therapeutic methods to delay its progression. Gastrodia, a traditional Chinese medicine, has been widely recognized for its medicinal value, particularly in its pronounced neuroprotective effects. Although previous studies have demonstrated the protective effects of Gastrodin (GAS), an active compound in Gastrodia, on the mouse nervous system, its underlying mechanisms remain unclear.

Objective

This study aims to investigate comprehensively the impact and mechanisms of GAS in delaying brain aging through the combined approach of network pharmacology and animal experiments, providing a theoretical basis for the clinical application of GAS in treating age-related decline.

Methods

A D-galactose (D-gal)-induced aging mouse model was employed, and the anti-aging effects of GAS were evaluated through behavioral experiments and morphological observations. A “compound-target-pathway” network was constructed using network pharmacology. Gene and protein expression related to potential targets and pathways were verified and analyzed using RT-qPCR and immunohistochemistry (IHC) methods.

Results

GAS exposure significantly alleviated signs of brain aging in mice, including reduced body weight index, improved behavioral memory, mitigation of hippocampal morphological damage due to aging, and relief of oxidative stress levels in the mouse brain. Target screening through network pharmacology identified four key targets related to the AMPK/mTOR pathway and autophagy: AMPK, ULK1, ATG5, and Beclin1. Validation of the network pharmacology results using RT-qPCR and IHC confirmed that GAS upregulates cellular autophagy levels through the AMPK/mTOR/ULK1 signaling pathway.

Conclusion

GAS demonstrates a pronounced alleviating effect on age-related symptoms in D-galactose-induced brain aging mice by suppressing oxidative stress in the mouse brain. The mechanism involves the upregulation of cellular autophagy through the AMPK/mTOR/ULK1 signaling pathway.