| Stroke is an acute cerebrovascular disease,mainly divided into ischemic stroke and hemorrhagic stroke.Stroke is the second leading cause of death and disability globally,causing a huge social and medical burden.Currently,effective drugs for acute stroke treatment and prognostic rehabilitation are still in short supply.Traditional Chinese medicine(TCM)has a long history in treating stroke.Some TCM and its natural products have been proved to be effective in stroke treatment and rehabilitation.Due to the complex composition and variety of small molecule compounds,only a few extracts and active compounds in traditional Chinese medicine have been discovered and verified.And the synergism between active ingredients in traditional Chinese medicine compounds has not been studied deeply.In vGivens,the aim othis study aimsesize bioinformatics and systemic pharmacology approaches to construct a new computational model of the network,screen and confirm the active components of Chinese herbal combinations for stroke treatment and explore the active compounds that may have synergistic effects.In addition,it supplies methodological refa erence for the optimization of traditional Chinese medicine prescriptions and the secondary development of its synergism.It consists mainly of the following two parts:(1)Screening of Active Components of Suhexiang Wan for strokeSuhexiang Wan(SHXW),as a formulation recorded in the Chinese Pharmacopoeia,is also a warm and enlightened prescription used in the acute stage of stroke.In this study,data on the main components of SHXW and their small molecule compounds recorded in several Chinese herbal databases were collected and initially filtered.Combining apoplexy transcriptome data,stroke-causing genes,compound-target prediction and protein-protein interaction network data to construct a compound-target-pathogenic gene network and screen key components of SHXW to awaken and protect nerve cells througa h multi-target optimization model,we performed a preliminary validation of the efficacy and safety of novel small molecule compounds.(2)Synergy Study on the Treatment of Stroke by Ditan Decoction,Xuefu Zhuyu Decoction,and Xiao Xuming DecoctionIn the clinical practice of traditional Chinese medicine,due to the complexity of stroke and the change in the patient's condition,the combination of multiple prescriptions is a common method.However,the synergies in these formulations are unclear.Using Ditan Decoction(DTD),Xuefu Zhuyu Decoction(XFZYD),and Xiao Xuming Decoction(XXMD)as examples,we collected herbs and their chemical components from a database and filtered them through ADMET,making target predictions for each chemical composition and constructing a synergistic network of compound targets for each recipe with a collaborative recommendation algorithm.Then,active small molecules with potential synergistic effects were screened through molecular docking,compound similarity analysis,and a combined network of formula-herbal-compound-target-pathway.Validation of active small molecules and synergistic effects using oxythe gen-deprivation/reperfusion(OGD/R)model proved that quercetin,baicalin and ginseng saponin Rg1 alone and synergistically increase cell viability.In this study,a comprehensive approach of systematic pharmacology and chemical informatics was used to construct a TCM prescription-specific compound-target interaction network and filter out a subset of compounds with potential therapeutic effeffectsr stroke.In addition,this study supplies a new methodological reference for the screening acof tive ingredients and synergisticeffectst in traditional Chinese medicine prescriptions and supplies important information for further research on pharmacological mechanisms. |
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