Astilbin exerts anti-hypersensitivity by regulating metabolic demand and neuronal activity in rodent model of neuropathic pain.

Annals of medicine Pub Date : 2024-12-01 Epub Date: 2024-12-03 DOI:10.1080/07853890.2024.2396561
Qiru Wang, Dongxia Duan, Chao Luo, Jinlu Huang, Jinbao Wei, Yang Zhang, Ke Zhang, Tong Zhou, Wei Wang, Shaoxin Yang, Le Ma
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Abstract

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.

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。
目的:黄芪是治疗疼痛的常用中药。然而,它的主要活性成分仍然是一个有争议的话题。方法:采用脊髓神经结扎(SNL)和福尔马林疼痛模型。利用网络药理学和生物信息学鉴定靶点。通过脊髓双免疫荧光染色、定量PCR和全细胞记录技术进行验证。结果:在对神经病大鼠进行的实验中,全身和鞘内给药,一种重要成分,显示出明显的剂量依赖性慢性和急性疼痛行为的减少。ED50值为7.59 μg,表示达到50%有效的剂量,而Emax值表示可达到的最大效果,为最大可能效果(% MPE)的60%。我们发现了42个共同的靶点,丰富了网络药理学分析中的代谢和突触通路,转录组学分析也证实了这一点。加权基因共表达网络分析(加权基因共表达网络分析,WGCNA)显示,降糖素的抗伤害性作用与神经元代谢过程有很强的相关性。脊髓功能超声(FUS)分析显示,神经病变大鼠脊髓血流强度增加,代谢相关酶活性发生变化,包括硬脂酰辅酶a去饱和酶(Scd)、17 β -羟基类固醇脱氢酶(Hsd17b7)和甾醇14 α -去甲基化酶(Cyp51)。通过降低微型兴奋性突触后电流(mEPSCs)的频率和振幅,而不影响微型抑制性突触后电流(mIPSCs),体外应用降糖素可剂量依赖性地抑制神经元活动。结论:总之,本研究提供的证据表明,通过调节神经元的代谢过程和突触的稳态,降黄素减轻疼痛。
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