Huang Jin-Lu, Tang Chen-Yue, Fu Yao, Wan Li-Li, Li Jie, Sun Xi-Peng, Hu Jia-Lu, Zhang Yue-Yi, Qu Li-Ying, Fu Miao-Jia, Zhang Yuan-Yuan, Ma Le, Guo Cheng, Chen Jiu-Geng
Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, China.
Pharm Biol. 2025 Dec;63(1):275-287. doi: 10.1080/13880209.2025.2492872. Epub 2025 Apr 23.
Matrine has antinociceptive properties, and spinal cord ionomic changes are involved in bone cancer pain.
To investigate the relationship between ionomic metabolism in cerebrospinal fluid (CSF) and spinal cord and matrine's analgesic efficacy.
The antinociceptive effects of matrine were identified in rats intraperitoneal (i.p.) injection using the tail-immersion and formalin tests. Pharmacodynamic parameters for matrine against formalin-induced pain were calculated with nonlinear regression analysis. Inductively coupled plasma mass spectrometry (ICP-MS) technology was utilized to detect contents of the ionome in CSF and spinal cord. Variations in ionomic metabolism in different treated groups were examined using Pearson's correlation coefficients and principal component analysis (PCA).
In the tail-immersion test, matrine significantly prolonged tail-flick latency in rats. Matrine also dose-dependently yielded analgesia against formalin-induced biphasic pain, with an onset at around 10 min post-injection and a duration of 100 min. The ED and E values were 19.01 mg/kg and 71.86% for phase I and 40.30 mg/kg and 81.51% for phase II, respectively. Pearson's correlation coefficient study and PCA revealed significant reprogramming of ionomic metabolism in the CSF and the spinal cord in the NM (normal saline + matrine), NF (normal saline + formalin), and FM (formalin + matrine) groups, compared to the NN (normal saline + normal saline) group.
These findings broaden the known analgesic spectrum of matrine and provide novel insights into the involvement of ionomic metabolism in its analgesic efficacy.
苦参碱具有抗伤害感受特性,脊髓离子组学变化与骨癌疼痛有关。
研究脑脊液(CSF)和脊髓中的离子组学代谢与苦参碱镇痛效果之间的关系。
采用尾浸法和福尔马林试验,通过腹腔注射确定苦参碱对大鼠的抗伤害感受作用。用非线性回归分析计算苦参碱对抗福尔马林诱导疼痛的药效学参数。利用电感耦合等离子体质谱(ICP-MS)技术检测脑脊液和脊髓中离子组的含量。使用Pearson相关系数和主成分分析(PCA)检查不同治疗组中离子组学代谢的变化。
在尾浸试验中,苦参碱显著延长了大鼠的甩尾潜伏期。苦参碱还对福尔马林诱导的双相疼痛产生剂量依赖性镇痛作用,注射后约10分钟起效,持续100分钟。第一阶段的ED和E值分别为19.01mg/kg和71.86%,第二阶段分别为40.30mg/kg和81.51%。Pearson相关系数研究和PCA显示,与NN(生理盐水+生理盐水)组相比,NM(生理盐水+苦参碱)、NF(生理盐水+福尔马林)和FM(福尔马林+苦参碱)组的脑脊液和脊髓中的离子组学代谢发生了显著的重新编程。
这些发现拓宽了已知的苦参碱镇痛谱,并为离子组学代谢在其镇痛效果中的作用提供了新的见解。