Tetramethylpyrazine is an alkaloid isolated from Chuanxiong rhizome, which has anti-inflammatory, antioxidant, anti-tumor, autophagy regulation, vasodilation, angiogenesis regulation, mitochondrial damage inhibition, endothelial protection, and neuroprotection activities[1, 2]. Tetramethylpyrazine has certain therapeutic effects on central nervous system diseases by inhibiting calcium overload and glutamate excitotoxicity, anti-oxidative/nitrosative stress, reducing inflammatory response, anti-apoptosis, protecting blood-brain barrier (BBB) integrity and promoting synaptic plasticity[3, 4].
In vitro, Tetramethylpyrazine (200, 400, 800µg/mL) treatment of A549 cells for 72h inhibited cell viability in a dose-dependent manner, induced the aggregation of cells in the G0-G1 phase (increased from 55.06% to 72.61%), and reduced the number of cells in the S phase (decreased from 34.52% to 18.22%)[5].
In vivo, Tetramethylpyrazine (5-40mg/kg) was injected intraperitoneally to treat rats with ischemic brain injury, which significantly reduced the infarct volume, alleviated brain edema, and significantly reduced the activation of inflammatory cells and the production of proinflammatory mediators induced by cerebral ischemia/reperfusion[6]. Tetramethylpyrazine (5, 10mg/kg) was injected intravenously to treat rats with myocardial ischemia/reperfusion injury, which significantly reduced the myocardial infarct size and induced the expression of heme oxygenase 1 (HO-1)[7].
References:
[1] Lin J, Wang Q, Zhou S, et al. Tetramethylpyrazine: a review on its mechanisms and functions[J]. Biomedicine & Pharmacotherapy, 2022, 150: 113005.
[2] Yang S, Wu S, Dai W, et al. Tetramethylpyrazine: a review of its antitumor potential and mechanisms[J]. Frontiers in Pharmacology, 2021, 12: 764331.
[3] Liu Y, Yang G, Cui W, et al. Regulatory mechanisms of tetramethylpyrazine on central nervous system diseases: a review[J]. Frontiers in Pharmacology, 2022, 13: 948600.
[4] Feng F, Xu D Q, Yue S J, et al. Neuroprotection by tetramethylpyrazine and its synthesized analogues for central nervous system diseases: A review[J]. Molecular Biology Reports, 2024, 51(1): 159.
[5] Zheng C Y, Xiao W, Zhu M X, et al. Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects on A549 cell invasion and metastasis[J]. International journal of oncology, 2012, 40(6): 2029-2037.
[6] Liao S L, Kao T K, Chen W Y, et al. Tetramethylpyrazine reduces ischemic brain injury in rats[J]. Neuroscience letters, 2004, 372(1-2): 40-45.
[7] Chen S Y, Hsiao G, Hwang H R, et al. Tetramethylpyrazine induces heme oxygenase-1 expression and attenuates myocardial ischemia/reperfusion injury in rats[J]. Journal of biomedical science, 2006, 13(5): 731-740.
Tetramethylpyrazine是一种从川芎中分离出来的生物碱，具有抗炎、抗氧化、抗肿瘤、自噬调节、血管舒张、血管生成调节、线粒体损伤抑制、内皮保护、神经保护等活性[1, 2]。Tetramethylpyrazine通过抑制钙离子超载和谷氨酸兴奋毒性、抗氧化/硝化应激、减轻炎症反应、抗细胞凋亡、保护血脑屏障（BBB）完整性和促进突触可塑性等作用，对中枢神经系统疾病具有一定的治疗作用[3, 4]。
在体外，Tetramethylpyrazine（200, 400, 800µg/mL）处理A549细胞72h，以剂量依赖性方式抑制了细胞活力，诱导了G0-G1期细胞聚集（从55.06%增至72.61%），减少了S期细胞（从34.52%降至18.22%）[5]。
在体内，Tetramethylpyrazine（5-40mg/kg）通过腹腔注射治疗缺血性脑损伤大鼠，显著减少了大鼠脑梗死体积，减轻了脑水肿，显著降低了脑缺血/再灌注诱导的炎症细胞活化和促炎介质的产生[6]。Tetramethylpyrazine（5, 10mg/kg）通过静脉注射治疗心肌缺血/再灌注损伤大鼠，显著减少了大鼠心肌梗死面积，诱导了血红素加氧酶1（HO-1）的表达[7]。