Eupatilin

Eupatilin is a natural flavonoid compound with multiple biological activities. It is an agonist of peroxisome proliferator-activated receptor α (PPARα) and has anti-apoptotic, antioxidant, and anti-inflammatory effects^{[1, 2]}. Eupatilin has a significant effect in inhibiting tumor growth and can be used in cancer research^[3].

In vitro, pretreatment of retinal pigment epithelial (RPE) cells (ARPE-19 cells) with Eupatilin (10, 25, 50μM) for 24h reduced the generation of intracellular ROS induced by H2O2 in a dose-dependent manner, upregulated the expression of Bcl-2 and the phosphorylation levels of PI3K and Akt, downregulated the expression of Bax, and inhibited the activity of caspase-3^[4]. Eupatilin (0-400µg/mL) treated osteosarcoma U-2 cells for 96h inhibited cell growth in a dose- and time-dependent manner, changed cell cycle distribution, induced cell apoptosis, induced mitochondrial dysfunction and cytochrome c release^[5]. Eupatilin (0-100μM) treated human endometrial cancer cell lines (Hec1A and KLE cells) for 96h significantly inhibited cell viability, was more effective than cisplatin, and induced cell cycle G2/M phase arrest^[6].

In vivo, oral treatment of mice treated with transient middle cerebral artery occlusion/reperfusion (tMCAO) surgery with Eupatilin (10mg/kg) significantly reduced cerebral infarction and improved neurological function in tMCAO-challenged mice^[7]. Oral treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) with Eupatilin (10mg/kg) for 6 days improved the mice's motor deficits and reduced neuronal loss, inhibiting neuroinflammation and apoptosis^[8].

References:
[1] Zeng J, Bao T, Yang K, et al. The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review[J]. Frontiers in immunology, 2023, 13: 1047550.
[2] Mavrogonatou E, Kletsas D. Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging[J]. Metabolites, 2024, 14(3): 146.
[3] Wang Y, Hou H, Li M, et al. Anticancer effect of eupatilin on glioma cells through inhibition of the Notch-1 signaling pathway[J]. Molecular Medicine Reports, 2016, 13(2): 1141-1146.
[4] Du L, Chen J, Xing Y. Eupatilin prevents H2O2-induced oxidative stress and apoptosis in human retinal pigment epithelial cells[J]. Biomedicine & Pharmacotherapy, 2017, 85: 136-140.
[5] Li Y Y, Wu H, Dong Y G, et al. Application of eupatilin in the treatment of osteosarcoma[J]. Oncology Letters, 2015, 10(4): 2505-2510.
[6] Cho J H, Lee J G, Yang Y I, et al. Eupatilin, a dietary flavonoid, induces G2/M cell cycle arrest in human endometrial cancer cells[J]. Food and Chemical Toxicology, 2011, 49(8): 1737-1744.
[7] Sapkota A, Gaire B P, Cho K S, et al. Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation[J]. PLoS One, 2017, 12(2): e0171479.
[8] Zhang Y, Qin L, Xie J, et al. Eupatilin prevents behavioral deficits and dopaminergic neuron degeneration in a Parkinson's disease mouse model[J]. Life sciences, 2020, 253: 117745.

Eupatilin是一种具有多种生物活性的天然黄酮类化合物，是过氧化物酶体增殖物激活受体α（PPARα）的激动剂，具有抗凋亡，抗氧化，及抗炎等功效^{[1, 2]}。Eupatilin在抑制肿瘤生长方面具有显著效果，能够用于癌症研究^[3]。

在体外，Eupatilin（10, 25, 50μM）预处理视网膜色素上皮（RPE）细胞（ARPE-19细胞）24h，以剂量依赖性方式减少了H₂O₂诱导的细胞内ROS的生成，上调了Bcl-2的表达和PI3K、Akt的磷酸化水平，下调了Bax的表达，抑制了caspase-3的活性^[4]。Eupatilin（0-400µg/mL）处理骨肉瘤U-2细胞96h，以剂量和时间依赖性方式抑制了细胞的生长，改变了细胞周期分布，诱导了细胞凋亡，诱导了线粒体功能障碍和细胞色素c释放^[5]。Eupatilin（0-100μM）处理人子宫内膜癌细胞系（Hec1A和KLE细胞）96h，显著抑制了细胞活力，比顺铂更有效，诱导了细胞周期G2/M期停滞^[6]。

在体内，Eupatilin（10mg/kg）通过口服治疗暂时性大脑中动脉闭塞/再灌注 （tMCAO）手术处理的小鼠，显著减少了脑梗塞并改善tMCAO攻击小鼠的神经功能^[7]。Eupatilin（10mg/kg）通过口服治疗1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱发的帕金森（PD）小鼠6天，改善了小鼠的运动缺陷和，减少了神经元丢失，抑制了神经炎症和细胞凋亡^[8]。