En Hu, Teng Li, Zhilin Li, Hong Su, Qiuju Yan, Lei Wang, Haigang Li, Wei Zhang, Tao Tang, Yang Wang
{"title":"Metabolomics reveals the effects of hydroxysafflor yellow A on neurogenesis and axon regeneration after experimental traumatic brain injury.","authors":"En Hu, Teng Li, Zhilin Li, Hong Su, Qiuju Yan, Lei Wang, Haigang Li, Wei Zhang, Tao Tang, Yang Wang","doi":"10.1080/13880209.2023.2229379","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of safflower (<i>Carthamus tinctorius</i> L., [Asteraceae]) for traumatic brain injury (TBI) treatment.</p><p><strong>Objective: </strong>To explore the therapeutic effects and underlying mechanisms of HSYA on post-TBI neurogenesis and axon regeneration.</p><p><strong>Materials and methods: </strong>Male Sprague-Dawley rats were randomly assigned into Sham, controlled cortex impact (CCI), and HSYA groups. Firstly, the modified Neurologic Severity Score (mNSS), foot fault test, hematoxylin-eosin staining, Nissl's staining, and immunofluorescence of Tau1 and doublecortin (DCX) were used to evaluate the effects of HSYA on TBI at the 14th day. Next, the effectors of HSYA on post-TBI neurogenesis and axon regeneration were screened out by pathology-specialized network pharmacology and untargeted metabolomics. Then, the core effectors were validated by immunofluorescence.</p><p><strong>Results: </strong>HSYA alleviated mNSS, foot fault rate, inflammatory cell infiltration, and Nissl's body loss. Moreover, HSYA increased not only hippocampal DCX but also cortical Tau1 and DCX following TBI. Metabolomics demonstrated that HSYA significantly regulated hippocampal and cortical metabolites enriched in 'arginine metabolism' and 'phenylalanine, tyrosine and tryptophan metabolism' including l-phenylalanine, ornithine, l-(+)-citrulline and argininosuccinic acid. Network pharmacology suggested that neurotrophic factor (BDNF) and signal transducer and activator of transcription 3 (STAT3) were the core nodes in the HSYA-TBI-neurogenesis and axon regeneration network. In addition, BDNF and growth-associated protein 43 (GAP43) were significantly elevated following HSYA treatment in the cortex and hippocampus.</p><p><strong>Discussion and conclusions: </strong>HSYA may promote TBI recovery by facilitating neurogenesis and axon regeneration through regulating cortical and hippocampal metabolism, BDNF and STAT3/GAP43 axis.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"61 1","pages":"1054-1064"},"PeriodicalIF":3.9000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332220/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13880209.2023.2229379","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Context: Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of safflower (Carthamus tinctorius L., [Asteraceae]) for traumatic brain injury (TBI) treatment.
Objective: To explore the therapeutic effects and underlying mechanisms of HSYA on post-TBI neurogenesis and axon regeneration.
Materials and methods: Male Sprague-Dawley rats were randomly assigned into Sham, controlled cortex impact (CCI), and HSYA groups. Firstly, the modified Neurologic Severity Score (mNSS), foot fault test, hematoxylin-eosin staining, Nissl's staining, and immunofluorescence of Tau1 and doublecortin (DCX) were used to evaluate the effects of HSYA on TBI at the 14th day. Next, the effectors of HSYA on post-TBI neurogenesis and axon regeneration were screened out by pathology-specialized network pharmacology and untargeted metabolomics. Then, the core effectors were validated by immunofluorescence.
Results: HSYA alleviated mNSS, foot fault rate, inflammatory cell infiltration, and Nissl's body loss. Moreover, HSYA increased not only hippocampal DCX but also cortical Tau1 and DCX following TBI. Metabolomics demonstrated that HSYA significantly regulated hippocampal and cortical metabolites enriched in 'arginine metabolism' and 'phenylalanine, tyrosine and tryptophan metabolism' including l-phenylalanine, ornithine, l-(+)-citrulline and argininosuccinic acid. Network pharmacology suggested that neurotrophic factor (BDNF) and signal transducer and activator of transcription 3 (STAT3) were the core nodes in the HSYA-TBI-neurogenesis and axon regeneration network. In addition, BDNF and growth-associated protein 43 (GAP43) were significantly elevated following HSYA treatment in the cortex and hippocampus.
Discussion and conclusions: HSYA may promote TBI recovery by facilitating neurogenesis and axon regeneration through regulating cortical and hippocampal metabolism, BDNF and STAT3/GAP43 axis.
期刊介绍：
Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine.
Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
