"Exploring the anti-ferroptosis mechanism of Kai-Xin-San against Alzheimer's disease through integrating network pharmacology, bioinformatics, and experimental validation strategy in vivo and in vitro"

作者全名："Yan, Chenchen; Yang, Song; Shao, Simai; Zu, Runru; Lu, Hao; Chen, Yuanzhao; Zhou, Yangang; Ying, Xiran; Xiang, Shixie; Zhang, Peixu; Li, Zhonghua; Yuan, Ye; Zhang, Zhenqiang; Wang, Pan; Xie, Zhishen; Wang, Wang; Ma, Huifen; Sun, Yiran"

作者地址："[Yan, Chenchen; Shao, Simai; Zu, Runru; Chen, Yuanzhao; Xiang, Shixie; Zhang, Peixu; Li, Zhonghua; Yuan, Ye; Zhang, Zhenqiang; Wang, Pan; Xie, Zhishen; Ma, Huifen] Henan Univ Chinese Med, Acad Chinese Med Sci, Henan Engn Res Ctr Prevent & Treatment Major Chron, Zhengzhou 450046, Peoples R China; [Lu, Hao; Zhou, Yangang; Ying, Xiran; Sun, Yiran] Chengdu Med Coll, Sch Pharm, Chengdu 610500, Peoples R China; [Yang, Song] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Wang, Wang] Nanchang Med Coll, Sch Basic Med, Nanchang 330052, Jiangxi, Peoples R China; [Zhang, Zhenqiang; Wang, Pan; Xie, Zhishen; Ma, Huifen] Henan Univ Chinese Med, Collaborat Innovat Ctr Res & Dev Whole Ind Chain Y, Zhengzhou 450046, Peoples R China"

通信作者："Xie, ZS; Ma, HF (通讯作者)，Henan Univ Chinese Med, Acad Chinese Med Sci, Henan Engn Res Ctr Prevent & Treatment Major Chron, Zhengzhou 450046, Peoples R China.; Sun, YR (通讯作者)，Chengdu Med Coll, Sch Pharm, Chengdu 610500, Peoples R China.; Wang, W (通讯作者)，Nanchang Med Coll, Sch Basic Med, Nanchang 330052, Jiangxi, Peoples R China."

来源：JOURNAL OF ETHNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001199483200001

JCR分区：Q1

影响因子：5.4

年份：2024

卷号：326

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Alzheimer 's disease; Neuronal ferroptosis; Kai Xin San; FSP1; SIRT1

摘要："Ethnopharmacological relevance: Kai Xin San (KXS), first proposed by Sun Simiao during the Tang Dynasty, has been utilized to treat dementia by tonifying qi and dispersing phlegm. Aim of the study: This study aimed to elucidate the mechanism by which KXS exerts its therapeutic effects on Alzheimer's disease (AD) by targeting ferroptosis, using a combination of network pharmacology, bioinformatics, and experimental validation strategies. Materials and methods: The active target sites and the further potential mechanisms of KXS in protecting against AD were investigated through molecular docking, molecular dynamics simulation, and network pharmacology, and combined with the validation of animal experiments. Results: Computational and experimental findings provide the first indication that KXS significantly improves learning and memory defects and inhibits neuronal ferroptosis by repairing mitochondria damage and upregulating the protein expression of ferroptosis suppressor protein 1 (FSP1) in vivo APP/PS1 mice AD model. According to bioinformatics analysis, the mechanism by which KXS inhibits ferroptosis may involve SIRT1. KXS notably upregulated the mRNA and protein expression of SIRT1 in both vivo APP/PS1 mice and in vitro APPoverexpressed HT22 cells. Additionally, KXS inhibited ferroptosis induced by APP-overexpression in HT22 cells through activating the SIRT1-FSP1 signal pathway. Conclusions: Collectively, our findings suggest that KXS may inhibit neuronal ferroptosis through activating the SIRT1/FSP1 signaling pathway. This study reveals the scientific basis and underlying modern theory of replenishing qi and eliminating phlegm, which involves the inhibition of ferroptosis. Moreover, it highlights the potential application of SIRT1 or FSP1 activators in the treatment of AD and other ferroptosis-related diseases."

基金机构："Henan Youth Science Foundation of Henan Province [232300421310]; Postdoctoral Foundation of China [2022M711080]; General project of natural sciences foundation of Chongqing [cstc2020jcyj-msxmX0306]; Jiangxi Provincial Natural Science Foundation [20232BAB215022]; Henan Province key research and development project [231111312900]; National Natural Science Foundation of China [82274612, 32301030, 82305087]; Program for Science & Technology Innovation Talents in Universities of Henan Province [23HASTIT044]; Innovative Research Team (in Science and Technology) in University of Henan Province [21IRTSTHN026]; Henan Province Traditional Chinese Medicine Scientific Research Special Project [2022ZYZD21]; Joint Research Fund of Science and Technology R &D Plan of Henan Province [222301420068]"

基金资助正文："This study was financially supported by Henan Youth Science Foundation of Henan Province (No. 232300421310) ; Postdoctoral Foundation of China (No. 2022M711080) ; The general project of natural sciences foundation of Chongqing (cstc2020jcyj-msxmX0306) ; Jiangxi Provincial Natural Science Foundation (20232BAB215022) ; Henan Province key research and development project (231111312900) ; The National Natural Science Foundation of China (No. 82274612, 32301030, 82305087) ; Program for Science & Technology Innovation Talents in Universities of Henan Province (No. 23HASTIT044) ; Innovative Research Team (in Science and Technology) in University of Henan Province (21IRTSTHN026) ; Henan Province Traditional Chinese Medicine Scientific Research Special Project (No. 2022ZYZD21) ; Joint Research Fund of Science and Technology R & D Plan of Henan Province (NO. 222301420068) ."