Ginkgetin Alleviates Inflammation and Senescence by Targeting STING

doi:10.1002/advs.202407222

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	Ginkgetin Alleviates Inflammation and Senescence by Targeting STING
	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
	2024-11-01
发表期刊	ADVANCED SCIENCE (IF:14.3[JCR-2023],16.3[5-Year])
EISSN	2198-3844
卷号	12 期号:2
发表状态	已发表
DOI	10.1002/advs.202407222
摘要	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.
关键词	cGAS-STING signaling Ginkgetin senescence STING inhibitor target identification
URL	查看原文
收录类别	SCI ; EI
语种	英语
资助项目	National Natural Science Foundation of China["T2225002","82273855","81903639","82304379"] ; National Key Research and Development Program of China["2023YFC2305904","2022YFC3400504"] ; Youth Innovation Promotion Association CAS[2023296] ; Open fund of state key laboratory of Pharmaceutical Biotechnology, Nanjing University, China[KF-202301] ; SIMM-SHUTCM Traditional Chinese Medicine Innovation Joint Research Program[E2G805H] ; Natural Science Foundation of Shanghai[22ZR1474300] ; Young Elite Scientists Sponsorship Program by CAST[2023QNRC001]
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science
WOS类目	Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS记录号	WOS:001357868600001
出版者	WILEY
EI入藏号	20244717413322
EI主题词	Mammals
EI分类号	101.1 ; 102.1 ; 103 ; 821 Agricultural Equipment and Methods ; Vegetation and Pest Control
原始文献类型	Article in Press
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/449041
专题	免疫化学研究所生命科学与技术学院_博士生物质科学与技术学院_博士生
共同第一作者	Jialin Ye; Zisheng Fan; Xiaolong Wu; Yinghui Zhang
通讯作者	Yichuan Xiao; Mingyue Zheng; Sulin Zhang
作者单位	1.Drug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203, China 2.School of Chinese Materia Medica Nanjing University of Chinese Medicine Nanjing 210023, China 3.CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health Chinese Academy of Sciences Shanghai 200031, China 4.University of Chinese Academy of Sciences Beijing100049,China 5.Shanghai Institute for Advanced Immunochemical Studies School of Life Science and Technology ShanghaiTech University Shanghai 201210, China 6.Lingang Laboratory Shanghai 200031, China 7.School of Pharmacy East China University of Science and Technology Shanghai 200237, China
推荐引用方式 GB/T 7714	Yadan Liu,Jialin Ye,Zisheng Fan,et al. Ginkgetin Alleviates Inflammation and Senescence by Targeting STING[J]. ADVANCED SCIENCE,2024,12(2).
APA	Yadan Liu.,Jialin Ye.,Zisheng Fan.,Xiaolong Wu.,Yinghui Zhang.,...&Sulin Zhang.(2024).Ginkgetin Alleviates Inflammation and Senescence by Targeting STING.ADVANCED SCIENCE,12(2).
MLA	Yadan Liu,et al."Ginkgetin Alleviates Inflammation and Senescence by Targeting STING".ADVANCED SCIENCE 12.2(2024).