Ginkgetin Alleviates Inflammation and Senescence by Targeting STING
Ginkgo biloba extract is reported to have therapeutic effects on aging-related disorders. However, the specific component responsible for this biological function and its mechanism of action remain largely unknown. This study finds that Ginkgetin, an active ingredient of Ginkgo biloba extract, can alleviate cellular senescence and improve pathologies in multiple tissues of aging mice. To reveal the molecular mechanism of Ginkgetin's anti-aging effect, a graph convolutional network-based drug "on-target" pathway prediction algorithm for prediction is employed. The results indicate that the cGAS-STING pathway may be a potential target for Ginkgetin. Subsequent cell biological and biophysical data confirmed that Ginkgetin directly binds to the carboxy-terminal domain of STING protein, thereby inhibiting STING activation and signal transduction. Furthermore, in vivo pharmacodynamic data showed that Ginkgetin effectively alleviates systemic inflammation in Trex1<sup>-/-</sup> mice and inhibits the abnormally activated STING signaling in aging mouse model. In summary, this study, utilizing an artificial intelligence algorithm combined with pharmacological methods, confirms STING serves as a critical target for Ginkgetin in alleviating inflammation and senescence. Importantly, this study elucidates the specific component and molecular mechanism underlying the anti-aging effect of Ginkgo biloba extract, providing a robust theoretical basis for its therapeutic use.
Authors
- Yuanyuan Zhu
- Zisheng Fan
- Bing Jiang (ORCID: https://orcid.org/0000-0001-5389-3293)
- Jingyi Zhou (ORCID: https://orcid.org/0000-0002-7020-598X)
- Jialin Ye (ORCID: https://orcid.org/0000-0002-6520-8844)
- Mingyue Zheng (ORCID: https://orcid.org/0000-0002-3323-3092)
- Min Wu (ORCID: https://orcid.org/0000-0003-1205-982X)
- Yichuan Xiao (ORCID: https://orcid.org/0000-0001-7804-6971)
- Yadan Liu (ORCID: https://orcid.org/0000-0002-4686-095X)
- Yajie Wang (ORCID: https://orcid.org/0000-0002-9793-8956)
- Yinghui Zhang (ORCID: https://orcid.org/0000-0001-6980-2384)
- Xiaolong Wu (ORCID: https://orcid.org/0009-0003-7150-808X)
- Sulin Zhang (ORCID: https://orcid.org/0000-0002-9167-4689)
- Zhiming Ge (ORCID: https://orcid.org/0000-0003-4812-0696)
- Guizhen Zhou
- Ruirui Yang (ORCID: https://orcid.org/0000-0002-7480-5077)
- Jingyi Meng
Institutions
- Nanjing University of Chinese Medicine (CN)
- East China University of Science and Technology (CN)
- Chinese Academy of Sciences (CN)
- ShanghaiTech University (CN)
- Shanghai Institute of Nutrition and Health (CN)
- Shanghai Institute of Materia Medica (CN)
- Hangzhou Academy of Agricultural Sciences (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-11-19
- DOI
- https://doi.org/10.1002/advs.202407222
- Citations
- 30
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 7.21
Funders
- Natural Science Foundation of Shanghai
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
- Youth Innovation Promotion Association of the Chinese Academy of Sciences
- Nanjing University
- Shanghai University of Traditional Chinese Medicine
- ShanghaiTech University
- Directorate for Biological Sciences
- National Key Research and Development Program of China
- Youth Innovation Promotion Association