Boondam Yingrak, Pakaprot Narawut, Yang Meng Chieh, Sandech Nichawadee, Maiuthed Arnatchai, Samer Jutima, Prasittisa Kanjanawadee, Ruanpang Jutamas, Care Chit, Chuayboon Srirat
Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Centre of Biopharmaceutical Science for Healthy Ageing, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Sci Rep. 2025 Aug 11;15(1):29348. doi: 10.1038/s41598-025-12622-2.
ECa 233 is a standardized extract of Centella asiatica that contains the major active compounds madecassoside (MDS) and asiaticoside (ASS), which can strengthen hippocampal synapses, resulting in a memory-enhancing effect. This study explored the possible mechanisms of ECa 233 related to synaptic enhancement via proteomic analysis. Differentiated SH-SY5Y cells and hippocampal slices obtained from healthy male Wistar rats were treated with dimethyl sulfoxide, ECa 233, or the MDS + ASS mixture. Mitochondrial function and protein expression were examined via proteomic, western blot, and immunofluorescence analyses. Effects on synaptic plasticity were confirmed via electrophysiology using acute hippocampal slices. The treated groups exhibited a significant increase in mitochondrial activity and synaptic plasticity-related protein expression. Upstream Akt-mTOR signaling was significantly enhanced, with the most pronounced effects observed in the MDS + ASS group. However, the ECa 233 group still showed the highest hippocampal synaptic response. Based on our data, both ECa 233 and MDS + ASS were involved in mitochondrial metabolism, with the Akt-mTOR pathway as one of the targets promoting these activities. Furthermore, the synergistic effect of MDS + ASS was essential to achieve the same level of response obtained with ECa 233. Ultimately, the MDS + ASS mixture may enhance cellular plasticity, while the remaining components of ECa 233 may promote specific proteins that play a role in maintaining biological homeostasis.
ECa 233是积雪草的标准化提取物，含有主要活性化合物羟基积雪草苷（MDS）和积雪草苷（ASS），它们可以增强海马突触，从而产生记忆增强作用。本研究通过蛋白质组学分析探讨了ECa 233与突触增强相关的可能机制。用二甲基亚砜、ECa 233或MDS + ASS混合物处理从健康雄性Wistar大鼠获得的分化的SH-SY5Y细胞和海马切片。通过蛋白质组学、蛋白质印迹和免疫荧光分析检测线粒体功能和蛋白质表达。使用急性海马切片通过电生理学证实对突触可塑性的影响。处理组的线粒体活性和与突触可塑性相关的蛋白质表达显著增加。上游Akt-mTOR信号显著增强，在MDS + ASS组中观察到的效果最明显。然而，ECa 233组仍表现出最高的海马突触反应。根据我们的数据，ECa 233和MDS + ASS都参与线粒体代谢，Akt-mTOR途径是促进这些活动的靶标之一。此外，MDS + ASS的协同作用对于实现与ECa 233相同水平的反应至关重要。最终，MDS + ASS混合物可能增强细胞可塑性，而ECa 233的其余成分可能促进在维持生物稳态中起作用的特定蛋白质。
