Ginkgetin Alleviates Inflammation and Senescence by Targeting STING
Abstract 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 extra...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202407222 |
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| author | Yadan Liu Jialin Ye Zisheng Fan Xiaolong Wu Yinghui Zhang Ruirui Yang Bing Jiang Yajie Wang Min Wu Jingyi Zhou Jingyi Meng Zhiming Ge Guizhen Zhou Yuan Zhu Yichuan Xiao Mingyue Zheng Sulin Zhang |
| author_facet | Yadan Liu Jialin Ye Zisheng Fan Xiaolong Wu Yinghui Zhang Ruirui Yang Bing Jiang Yajie Wang Min Wu Jingyi Zhou Jingyi Meng Zhiming Ge Guizhen Zhou Yuan Zhu Yichuan Xiao Mingyue Zheng Sulin Zhang |
| author_sort | Yadan Liu |
| collection | DOAJ |
| description | Abstract 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−/− 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. |
| format | Article |
| id | doaj-art-3baca89929ce480b9f5e79d46702513b |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-3baca89929ce480b9f5e79d46702513b2025-01-13T15:29:43ZengWileyAdvanced Science2198-38442025-01-01122n/an/a10.1002/advs.202407222Ginkgetin Alleviates Inflammation and Senescence by Targeting STINGYadan Liu0Jialin Ye1Zisheng Fan2Xiaolong Wu3Yinghui Zhang4Ruirui Yang5Bing Jiang6Yajie Wang7Min Wu8Jingyi Zhou9Jingyi Meng10Zhiming Ge11Guizhen Zhou12Yuan Zhu13Yichuan Xiao14Mingyue Zheng15Sulin Zhang16Drug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health Chinese Academy of Sciences Shanghai 200031 ChinaShanghai Institute for Advanced Immunochemical Studies School of Life Science and Technology ShanghaiTech University Shanghai 201210 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaCAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health Chinese Academy of Sciences Shanghai 200031 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDrug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaAbstract 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−/− 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.https://doi.org/10.1002/advs.202407222cGAS‐STING signalingGinkgetinsenescenceSTING inhibitortarget identification |
| spellingShingle | Yadan Liu Jialin Ye Zisheng Fan Xiaolong Wu Yinghui Zhang Ruirui Yang Bing Jiang Yajie Wang Min Wu Jingyi Zhou Jingyi Meng Zhiming Ge Guizhen Zhou Yuan Zhu Yichuan Xiao Mingyue Zheng Sulin Zhang Ginkgetin Alleviates Inflammation and Senescence by Targeting STING Advanced Science cGAS‐STING signaling Ginkgetin senescence STING inhibitor target identification |
| title | Ginkgetin Alleviates Inflammation and Senescence by Targeting STING |
| title_full | Ginkgetin Alleviates Inflammation and Senescence by Targeting STING |
| title_fullStr | Ginkgetin Alleviates Inflammation and Senescence by Targeting STING |
| title_full_unstemmed | Ginkgetin Alleviates Inflammation and Senescence by Targeting STING |
| title_short | Ginkgetin Alleviates Inflammation and Senescence by Targeting STING |
| title_sort | ginkgetin alleviates inflammation and senescence by targeting sting |
| topic | cGAS‐STING signaling Ginkgetin senescence STING inhibitor target identification |
| url | https://doi.org/10.1002/advs.202407222 |
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