Qiru Wang, Dongxia Duan, Chao Luo, Jinlu Huang, Jinbao Wei, Yang Zhang, Ke Zhang, Tong Zhou, Wei Wang, Shaoxin Yang, Le Ma
{"title":"在神经性疼痛啮齿动物模型中,降黄素通过调节代谢需求和神经元活动发挥抗超敏作用。","authors":"Qiru Wang, Dongxia Duan, Chao Luo, Jinlu Huang, Jinbao Wei, Yang Zhang, Ke Zhang, Tong Zhou, Wei Wang, Shaoxin Yang, Le Ma","doi":"10.1080/07853890.2024.2396561","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong><i>Astilbe chinensis</i>, is a traditional Chinese medicine commonly employed for pain management. However, its primary active ingredient remains a subject of debate.</p><p><strong>Methods: </strong>Spinal nerve ligation (SNL) and formalin-induced pain models were employed. Network pharmacology and bioinformatics were utilized to identify targets. Verification was performed through spinal cord double immunofluorescence staining, quantitative PCR and whole-cell recording techniques.</p><p><strong>Results: </strong>In experiments conducted on neuropathic rats, both systemic and intrathecal administration of astilbin, an essential constituent, exhibited a noteworthy and dose-dependently decrease in chronic and acute pain behaviours. The ED<sub>50</sub> value, which represents the dose at which 50% effectiveness is achieved, was measure at 7.59 μg, while the <i>E</i><sub>max</sub> value, indicating the maximum attainable effect, was found to be 60% of the maximal possible effect (% MPE). Forty-two shared targets were identified, enriching the metabolic and synaptic pathways in the network pharmacology analysis, as confirmed by transcriptomic analysis. Weighted gene co-expression network analysis (WGCNA) revealed a strong correlation between the anti-nociceptive effects of astilbin and neuronal metabolic processes. Spinal functional ultrasound (FUS) analysis indicated increased spinal blood flow intensity and changes in metabolism-related enzyme activity, including stearoyl-CoA desaturase (<i>Scd</i>), 17beta-hydroxysteroid dehydrogenase (<i>Hsd17b7</i>) and sterol 14alpha-demethylase (<i>Cyp51</i>) in neuropathic rats, pretreatment with astilbin decreased formalin-induced blood flow in acute pain. Bath application of astilbin dose-dependently inhibited neuronal activity by reducing the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) without affecting miniature inhibitory postsynaptic currents (mIPSCs).</p><p><strong>Conclusions: </strong>In summary, this study provides evidence that astilbin alleviates pain by modulating neuronal metabolic processes and synaptic homeostasis.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2396561"},"PeriodicalIF":0.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616750/pdf/","citationCount":"0","resultStr":"{\"title\":\"Astilbin exerts anti-hypersensitivity by regulating metabolic demand and neuronal activity in rodent model of neuropathic pain.\",\"authors\":\"Qiru Wang, Dongxia Duan, Chao Luo, Jinlu Huang, Jinbao Wei, Yang Zhang, Ke Zhang, Tong Zhou, Wei Wang, Shaoxin Yang, Le Ma\",\"doi\":\"10.1080/07853890.2024.2396561\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong><i>Astilbe chinensis</i>, is a traditional Chinese medicine commonly employed for pain management. However, its primary active ingredient remains a subject of debate.</p><p><strong>Methods: </strong>Spinal nerve ligation (SNL) and formalin-induced pain models were employed. Network pharmacology and bioinformatics were utilized to identify targets. Verification was performed through spinal cord double immunofluorescence staining, quantitative PCR and whole-cell recording techniques.</p><p><strong>Results: </strong>In experiments conducted on neuropathic rats, both systemic and intrathecal administration of astilbin, an essential constituent, exhibited a noteworthy and dose-dependently decrease in chronic and acute pain behaviours. The ED<sub>50</sub> value, which represents the dose at which 50% effectiveness is achieved, was measure at 7.59 μg, while the <i>E</i><sub>max</sub> value, indicating the maximum attainable effect, was found to be 60% of the maximal possible effect (% MPE). Forty-two shared targets were identified, enriching the metabolic and synaptic pathways in the network pharmacology analysis, as confirmed by transcriptomic analysis. Weighted gene co-expression network analysis (WGCNA) revealed a strong correlation between the anti-nociceptive effects of astilbin and neuronal metabolic processes. Spinal functional ultrasound (FUS) analysis indicated increased spinal blood flow intensity and changes in metabolism-related enzyme activity, including stearoyl-CoA desaturase (<i>Scd</i>), 17beta-hydroxysteroid dehydrogenase (<i>Hsd17b7</i>) and sterol 14alpha-demethylase (<i>Cyp51</i>) in neuropathic rats, pretreatment with astilbin decreased formalin-induced blood flow in acute pain. Bath application of astilbin dose-dependently inhibited neuronal activity by reducing the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) without affecting miniature inhibitory postsynaptic currents (mIPSCs).</p><p><strong>Conclusions: </strong>In summary, this study provides evidence that astilbin alleviates pain by modulating neuronal metabolic processes and synaptic homeostasis.</p>\",\"PeriodicalId\":93874,\"journal\":{\"name\":\"Annals of medicine\",\"volume\":\"56 1\",\"pages\":\"2396561\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616750/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/07853890.2024.2396561\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/07853890.2024.2396561","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/3 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Astilbin exerts anti-hypersensitivity by regulating metabolic demand and neuronal activity in rodent model of neuropathic pain.
Objective: Astilbe chinensis, is a traditional Chinese medicine commonly employed for pain management. However, its primary active ingredient remains a subject of debate.
Methods: Spinal nerve ligation (SNL) and formalin-induced pain models were employed. Network pharmacology and bioinformatics were utilized to identify targets. Verification was performed through spinal cord double immunofluorescence staining, quantitative PCR and whole-cell recording techniques.
Results: In experiments conducted on neuropathic rats, both systemic and intrathecal administration of astilbin, an essential constituent, exhibited a noteworthy and dose-dependently decrease in chronic and acute pain behaviours. The ED50 value, which represents the dose at which 50% effectiveness is achieved, was measure at 7.59 μg, while the Emax value, indicating the maximum attainable effect, was found to be 60% of the maximal possible effect (% MPE). Forty-two shared targets were identified, enriching the metabolic and synaptic pathways in the network pharmacology analysis, as confirmed by transcriptomic analysis. Weighted gene co-expression network analysis (WGCNA) revealed a strong correlation between the anti-nociceptive effects of astilbin and neuronal metabolic processes. Spinal functional ultrasound (FUS) analysis indicated increased spinal blood flow intensity and changes in metabolism-related enzyme activity, including stearoyl-CoA desaturase (Scd), 17beta-hydroxysteroid dehydrogenase (Hsd17b7) and sterol 14alpha-demethylase (Cyp51) in neuropathic rats, pretreatment with astilbin decreased formalin-induced blood flow in acute pain. Bath application of astilbin dose-dependently inhibited neuronal activity by reducing the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) without affecting miniature inhibitory postsynaptic currents (mIPSCs).
Conclusions: In summary, this study provides evidence that astilbin alleviates pain by modulating neuronal metabolic processes and synaptic homeostasis.