Habiba Sarmin Ummey, Choi Ho Jin, Munni Yeasmin Akter, Yang In-Jun, Haque Md Nazmul, Moon Il Soo
Department of Anatomy, College of Medicine, Dongguk University, Gyeongju 38066, Republic of Korea.
Medical Institute of Dongguk University, Gyeongju 38066, Republic of Korea.
Int J Mol Sci. 2024 Nov 26;25(23):12701. doi: 10.3390/ijms252312701.
Mill, commonly known as fennel, is an aromatic herb traditionally used for culinary and medicinal purposes, with potential therapeutic effects on neurological disorders. However, limited research has focused on its neurotrophic impact, particularly on neuronal maturation and synaptic development. This study investigates the neurotrophic effects of ethanol extracts (FVSE) on the maturation of rat primary hippocampal neurons. Results show that FVSE and its prominent component, anethole, significantly promote neurite outgrowth in a dose-dependent manner. Optimal axonal and dendritic growth occurred at concentrations of 40 µg/mL FVSE and 20 µM anethole, respectively, without causing cytotoxicity, underscoring the safety of FVSE for neuronal health. Additionally, FVSE enhances the formation of synapses, essential for neuronal communication. Network pharmacology analysis revealed that FVSE components influence critical neurotrophic pathways, including PI3K-AKT and Alzheimer's disease pathways. Specifically, FVSE modulates key proteins, including tropomyosin receptor kinase (Trk), glycogen synthase kinase 3 (GSK3β), phosphatidylinositol 3-kinase (PI3K), and extracellular signal-regulated protein kinase (Erk1/2). Anethole was found to play a key role in regulating these pathways, which was confirmed by immunocytochemistry experiments demonstrating its effect on promoting neuronal growth and synaptic development. In conclusion, this study highlights the neurotrophic properties of FVSE, with anethole emerging as a critical bioactive compound. These findings provide valuable insights into the therapeutic potential of fennel in treating neurological disorders, offering a basis for future research into interventions promoting neuronal growth and survival.
小茴香，通常被称为茴香，是一种芳香草本植物，传统上用于烹饪和药用，对神经系统疾病具有潜在的治疗作用。然而，有限的研究集中在其神经营养作用上，特别是对神经元成熟和突触发育的影响。本研究调查了乙醇提取物（FVSE）对大鼠原代海马神经元成熟的神经营养作用。结果表明，FVSE及其主要成分茴香脑以剂量依赖的方式显著促进神经突生长。最佳轴突和树突生长分别发生在FVSE浓度为40µg/mL和茴香脑浓度为20µM时，且不会引起细胞毒性，这突出了FVSE对神经元健康的安全性。此外，FVSE增强了突触的形成，这对神经元通讯至关重要。网络药理学分析表明，FVSE成分影响关键的神经营养途径，包括PI3K-AKT和阿尔茨海默病途径。具体而言，FVSE调节关键蛋白，包括原肌球蛋白受体激酶（Trk）、糖原合酶激酶3（GSK3β）、磷脂酰肌醇3激酶（PI3K）和细胞外信号调节蛋白激酶（Erk1/2）。发现茴香脑在调节这些途径中起关键作用，免疫细胞化学实验证实了其对促进神经元生长和突触发育的作用，从而证实了这一点。总之，本研究突出了FVSE的神经营养特性，茴香脑成为一种关键的生物活性化合物。这些发现为小茴香在治疗神经系统疾病方面的治疗潜力提供了有价值的见解，为未来促进神经元生长和存活的干预措施的研究提供了基础。
