Butylphthalide (3-n-Butylphthalide) is a natural compound with a wide range of pharmacological activities, primarily used for the treatment of acute ischemic stroke[1]. The mechanisms of action of Butylphthalide include antioxidant effects and mitochondrial protection[2]. Butylphthalide can also improve symptoms of myocardial infarction[3]. In addition, Butylphthalide has the potential to treat tissue damage induced by ischemia-reperfusion[4].
In vitro, pretreatment of SV40-transformed rat aortic endothelial cells with Butylphthalide (1μM) for 6 hours, followed by oxygen-glucose deprivation (OGD) for 6 hours, significantly enhances PGC-1α expression and protects cells from OGD-induced damage, increasing cell viability[5]. Pretreatment of SH-SY5Y cells with Butylphthalide (5μM) for 6 hours, followed by stimulation with 6-OHDA (100μM) for 24 hours, significantly increases cell viability, reduces cell apoptosis and ROS production, inhibits NLRP3 inflammasome activation and related inflammatory factor expression, alleviates mitochondrial damage, and decreases abnormal aggregation of α-synuclein (α-Syn)[6].
In vivo, Butylphthalide (200mg/kg) is administered intraperitoneally once daily to C57BL/6 mice starting at 8 weeks of age until the 10th week. Butylphthalide significantly alleviates behavioral deficits induced by Rotenone, reduces the loss of dopaminergic neurons, and inhibits microglial activation[7]. Butylphthalide (4mg/kg) is administered intraperitoneally as a single dose to rats with middle cerebral artery occlusion/reperfusion (MCAO/R) model. Butylphthalide significantly alleviates behavioral deficits induced by MCAO/R, reduces brain infarct volume, inhibits microglial activation, suppresses ferroptosis by activating the Nrf2/HO-1 signaling pathway, and alleviates lipid peroxidation, iron accumulation, and mitochondrial damage induced by ischemia-reperfusion[8].
References:
[1] Chen XQ, Qiu K, Liu H, et al. Application and prospects of butylphthalide for the treatment of neurologic diseases. Chin Med J (Engl). 2019 Jun 20;132(12):1467-1477.
[2] Zhu T, Wang L, Feng Y, et al. Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke. Oxid Med Cell Longev. 2021 Mar 13;2021:8868941.
[3] Bai M, Pan CL, Jiang GX, et al. Effects of butylphthalide on oxidative stress and inflammatory response in rats with myocardial infarction through Akt/Nrf2 signaling pathway. Eur Rev Med Pharmacol Sci. 2019 Nov;23(21):9642-9650.
[4] Lu P, Li WP, Zhou BJ, et al. N-butylphthalide (NBP) ameliorated ischemia/reperfusion-induced skeletal muscle injury in male mice via activating Sirt1/Nrf2 signaling pathway. Physiol Rep. 2024 Dec;12(23):e70149.
[5] Wei H, Zhan LP, Zhang B, et al. dl-3n-butylphthalide reduces oxygen-glucose deprivation-induced endothelial cell damage by increasing PGC-1α. Eur Rev Med Pharmacol Sci. 2019 May;23(10):4481-4490.
[6] Que R, Zheng J, Chang Z, et al. Dl-3-n-Butylphthalide Rescues Dopaminergic Neurons in Parkinson's Disease Models by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment. Front Immunol. 2021 Dec 1;12:794770.
[7] Liu Y, Duan R, Li P, et al. 3-N-butylphthalide attenuates neuroinflammation in rotenone-induced Parkinson's disease models via the cGAS-STING pathway. Int J Immunopathol Pharmacol. 2024 Jan-Dec;38:3946320241229041.
[8] Sun M, Chen J, Liu F, et al. Butylphthalide inhibits ferroptosis and ameliorates cerebral Ischaemia-Reperfusion injury in rats by activating the Nrf2/HO-1 signalling pathway. Neurotherapeutics. 2024 Sep;21(5):e00444.
Butylphthalide (3-n-Butylphthalide) 具有广泛的药理活性的天然化合物，主要被用于治疗急性缺血性中风 [1]。Butylphthalide的作用机制包括抗氧化、保护线粒体机制等[2]。Butylphthalide还可改善心肌梗死的症状[3]。此外，Butylphthalide还具有治疗缺血再灌注诱导组织损伤的潜力[4]。
在体外，Butylphthalide（1μM）预处理SV40转化的大鼠主动脉内皮细胞6h，随后进行氧糖剥夺（OGD）处理6h，可显著增强PGC-1α表达，同时保护细胞免受OGD诱导的损伤，提高细胞存活率[5]。Butylphthalide（5μM）预处理SH-SY5Y细胞6h，随后以6-OHDA（100μM）刺激24h，可显著提高细胞存活率，降低细胞凋亡率和ROS产生，同时抑制NLRP3炎症体激活及相关炎症因子表达，减轻线粒体损伤，减少α-突触核蛋白（α-Syn）异常聚集[6]。
在体内，Butylphthalide（200mg/kg）每天一次腹腔注射，用于处理8周龄开始直至第10周的C57BL/6小鼠。Butylphthalide显著减轻了由Rotenone诱导的行为障碍，减少了多巴胺能神经元的损失，并抑制了小胶质细胞的激活[7]。Butylphthalide（4mg/kg）在通过单次腹腔给药，用于处理脑缺血-再灌注（MCAO/R）大鼠模型。Butylphthalide显著减轻了由MCAO/R诱导大鼠的行为障碍，减少了脑梗死体积，并抑制了小胶质细胞的激活，通过激活Nrf2/HO-1信号通路抑制铁死亡，减轻了缺血再灌注诱导的脂质过氧化、铁积累和线粒体损伤[8]。