Li Xue, Chen Miaoqi, Wei Decheng, Wei Pengsheng, Jiang Yanzong, Chen Jiaqi, Duan Xiaomeng, Wang Zitong, Zhang Yuchuan, Bai Dafeng, Jia Hui, Jin Ge
Basic Medical School, Shenyang Medical College, 146 Huanghe North Street, Yuhong District, Shenyang, 110034, Liaoning, China.
School of Traditional Chinese Medicine, Shenyang Medical College, 146 Huanghe North Street, Yuhong District, Shenyang, 110034, Liaoning, China.
Neurochem Res. 2025 May 26;50(3):171. doi: 10.1007/s11064-025-04419-6.
Depression is a chronic and recurrent neuropsychiatric disorder with complex pathophysiology. Dihydromyricetin (DMY), a bioactive flavonoid compound isolated from Ampelopsis grossedentata (commonly known as rattan tea), has demonstrated multiple pharmacological properties including anti-inflammatory, antioxidant, antitumor, and antimicrobial activities. In the present study, a well-established rodent model of depression was generated through chronic unpredictable mild stress (CUMS) paradigm combined with social isolation. Following eight weeks of DMY intervention, comprehensive behavioral assessments were conducted to validate both the successful establishment of the depression model and the therapeutic efficacy of DMY treatment. We employed network pharmacology approaches to systematically predict potential antidepressant targets of DMY. Further mechanistic investigations were performed to elucidate the underlying molecular pathways, providing novel perspectives for developing innovative antidepressant therapeutics.Integrating network pharmacology prediction with molecular biology validation, our findings revealed that DMY exerts significant antidepressant-like effects through suppression of the advanced glycosylation end products (AGEs)-RAGE signaling pathway, activation of the nuclear factor E2-related factor 2 (NRF2)-mediated antioxidant defense system, and upregulation of synaptic plasticity-related proteins including postsynaptic density protein 95 (PSD95) and synaptophysin (SYP). These results suggest that DMY may represent a promising natural therapeutic candidate for depression treatment.
抑郁症是一种具有复杂病理生理学的慢性复发性神经精神障碍。二氢杨梅素（DMY）是从显齿蛇葡萄（俗称藤茶）中分离出的一种生物活性黄酮类化合物，已显示出多种药理特性，包括抗炎、抗氧化、抗肿瘤和抗菌活性。在本研究中，通过慢性不可预测轻度应激（CUMS）范式结合社会隔离建立了一种成熟的抑郁症啮齿动物模型。经过八周的DMY干预后，进行了全面的行为评估，以验证抑郁症模型的成功建立以及DMY治疗的疗效。我们采用网络药理学方法系统地预测DMY的潜在抗抑郁靶点。进行了进一步的机制研究以阐明潜在的分子途径，为开发创新的抗抑郁疗法提供了新的视角。将网络药理学预测与分子生物学验证相结合，我们的研究结果表明，DMY通过抑制晚期糖基化终产物（AGEs）-RAGE信号通路、激活核因子E2相关因子2（NRF2）介导的抗氧化防御系统以及上调包括突触后密度蛋白95（PSD95）和突触素（SYP）在内的突触可塑性相关蛋白，发挥显著的抗抑郁样作用。这些结果表明，DMY可能是一种有前途的抑郁症治疗天然候选药物。
