Ginkgo biloba extract has been widely used in clinical settings to treat central nervous system and cardiovascular diseases. Accumulating evidence has revealed that Ginkgo extract possesses anti-inflammatory and anti-oxidant properties, making it effective in treating aging-related diseases. However, the specific component responsible for its anti-aging activity remains unclear. 

In a study published in Advanced Science, a research team led by Prof. ZHENG Mingyue from the Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences, in collaboration with Prof. XIAO Yichuan from the Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences, utilized artificial intelligence algorithms (AI) combined with pharmacological methods to predict and confirm that the stimulator of interferon genes (STING) is key target of Ginkgetin, an active ingredients in Ginkgo biloba extract, for alleviating aging.

The researchers discovered that Ginkgetin can alleviate aging phenotype in aging model mice, but molecular mechanism underlying its anti-aging activity remains unclear. They employed a graph convolutional network-based drug “on-target” pathway prediction algorithm (GDOP) to identify potential target pathways of Ginkgetin. This algorithm integrates structural information and biological characterization (gene expression profiles) of active molecules as input. After training with LINCS datasets, GDOP demonstrated superior generalization ability and predictive performance. 

Using this algorithm, researchers predicted that Ginkgetin may target cGAS-STING signaling pathway, whose abnormal activation is a critical driver of aging. Subsequent molecular and cellular experiments confirmed that Ginkgetin directly targets STING and inhibits its activation. In vivo pharmacodynamic studies further revealed that Ginkgetin effectively alleviates systemic inflammation in Trex1-deficient mice and suppresses abnormally activated STING signaling in multiple tissues of aging model mice.

This study utilized AI algorithms combined with pharmacological methods to predict and confirm that STING is the key target of Ginkgetin in alleviating inflammation and aging. These findings not only provided experimental evidence for advancing new clinical applications of Ginkgo biloba extract but also serve as a valuable example of modernizing traditional Chinese medicine research.

Ginkgetin alleviates inflammation and senescence by targeting STING (Image by ZHENG Mingyue’s Laboratory)

Contact:

JIANG Qingling

Shanghai Institute of Materia Medica, Chinese Academy of Sciences

E-mail: qljiang@stimes.cn