Wang Qiru, Duan Dongxia, Luo Chao, Huang Jinlu, Wei Jinbao, Zhang Yang, Zhang Ke, Zhou Tong, Wang Wei, Yang Shaoxin, Ma Le
Department of Pharmacy, Shanghai Cancer Center, Fudan University, Minhang Branch, Shanghai, China.
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ann Med. 2024 Dec;56(1):2396561. doi: 10.1080/07853890.2024.2396561. Epub 2024 Dec 3.
, is a traditional Chinese medicine commonly employed for pain management. However, its primary active ingredient remains a subject of debate.
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.
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 value, which represents the dose at which 50% effectiveness is achieved, was measure at 7.59 μg, while the 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 (), 17beta-hydroxysteroid dehydrogenase () and sterol 14alpha-demethylase () 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).
In summary, this study provides evidence that astilbin alleviates pain by modulating neuronal metabolic processes and synaptic homeostasis.
是一种常用于疼痛管理的中药。然而，其主要活性成分仍是一个有争议的话题。
采用脊神经结扎（SNL）和福尔马林诱导的疼痛模型。利用网络药理学和生物信息学来识别靶点。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。
在对神经性大鼠进行的实验中，主要成分落新妇苷的全身给药和鞘内给药均显示出慢性和急性疼痛行为有显著且剂量依赖性的降低。代表达到50%有效性剂量的ED值为7.59μg，而代表最大可达到效果的 值为最大可能效果的60%（%MPE）。确定了42个共同靶点，在网络药理学分析中丰富了代谢和突触途径，转录组分析证实了这一点。加权基因共表达网络分析（WGCNA）显示落新妇苷的抗伤害感受作用与神经元代谢过程之间有很强的相关性。脊髓功能超声（FUS）分析表明神经性大鼠的脊髓血流强度增加以及代谢相关酶活性发生变化，包括硬脂酰辅酶A去饱和酶（）、17β-羟基类固醇脱氢酶（）和甾醇14α-脱甲基酶（），落新妇苷预处理可降低福尔马林诱导的急性疼痛中的血流。落新妇苷浴应用通过降低微小兴奋性突触后电流（mEPSCs）的频率和幅度剂量依赖性地抑制神经元活动，而不影响微小抑制性突触后电流（mIPSCs）。
总之，本研究提供了证据表明落新妇苷通过调节神经元代谢过程和突触稳态来减轻疼痛。
