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.