A Ru-Han, Gong Qin, Tuo Yan-Jun, Zhai Shu-Ting, He Bei-Lan, Zou En-Guo, Wang Mu-Lan, Huang Tian-Yu, Zha Chen-Liang, He Ming-Zhen, Zhong Guo-Yue, Feng Yu-Lin, Li Jun
Jiangxi University of Chinese Medicine, Nanchang, 330006, PR China.
Jiangxi University of Chinese Medicine, Nanchang, 330006, PR China; National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Nanchang, 330006, PR China.
J Ethnopharmacol. 2025 Feb 11;341:119274. doi: 10.1016/j.jep.2024.119274. Epub 2025 Jan 3.
Syringa oblata Lindl (ZDX) is a plant in the Oleaceae family that is the primary ingredient in the classic Tibetan medicine AKARU sinensis. The plant's stem is used as a medicine, and Tibetan doctors often use it as a sedative, a use with a history of nearly 100 years. Tibetan medicine mainly uses lilac to treat headache, forgetfulness, insomnia, irritability and other symptoms. Depression is a chronic mental disorder characterized by low mood, cognitive impairments, and physical discomfort, and it has become a significant public health issue. Given the limitations of existing treatments, interest in alternative therapies, including herbal medicines, is increasing.
To elucidate the mechanism of ZDX extract in the treatment of depression.
A depression-like mouse model was established via the subcutaneous injection of corticosterone (CORT) into the groin, and a model of PC12 cell injury was established via CORT treatment. The antidepressant effect of the ZDX extract was subsequently evaluated via weight measurements, the sucrose preference test (SPT), the forced swimming test (FST), the open field test(OFT), the tail suspension test (TST), HE staining, Nissl staining and ELISA. Moreover, immunofluorescence staining, qRT‒PCR and Western blotting were used to determine whether ZDX extract can regulate the cAMP/PKA-CREB-BDNF pathway to prevent depression and neuronal apoptosis.
ZDX extract significantly improved depression-like behaviours; inhibited decreases in the protein levels of cAMP, PKA, CREB and BDNF; and increased proliferative activity in the hippocampus and cortex. In addition, in vitro, ZDX extract attenuated CORT-induced injury and apoptosis in hippocampal neurons and inhibited CORT-induced decreases in the mRNA expression levels of cAMP, PKA, CREB and BDNF.
These findings suggest that ZDX extract has potential as a novel antidepressant therapeutic agent, offering a complementary approach to current treatments by targeting multiple pathways involved in the pathogenesis of depression. Further research is warranted to explore the clinical applications of ZDX extract in the treatment of depression.
紫丁香(ZDX)是木犀科植物,是经典藏药中华阿咖如的主要成分。该植物的茎用作药物,藏医经常将其用作镇静剂,这种用法已有近百年历史。藏药主要用丁香治疗头痛、健忘、失眠、易怒等症状。抑郁症是一种慢性精神障碍,其特征为情绪低落、认知障碍和身体不适,已成为一个重大的公共卫生问题。鉴于现有治疗方法的局限性,人们对包括草药在内的替代疗法的兴趣日益增加。
阐明ZDX提取物治疗抑郁症的机制。
通过向腹股沟皮下注射皮质酮(CORT)建立抑郁症样小鼠模型,并通过CORT处理建立PC12细胞损伤模型。随后通过体重测量、蔗糖偏好试验(SPT)、强迫游泳试验(FST)、旷场试验(OFT)、悬尾试验(TST)、苏木精-伊红(HE)染色、尼氏染色和酶联免疫吸附测定(ELISA)评估ZDX提取物的抗抑郁作用。此外,采用免疫荧光染色、定量逆转录-聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法来确定ZDX提取物是否可以调节环磷酸腺苷/蛋白激酶A-环磷腺苷反应元件结合蛋白-脑源性神经营养因子(cAMP/PKA-CREB-BDNF)通路以预防抑郁症和神经元凋亡。
ZDX提取物显著改善了抑郁症样行为;抑制了cAMP、PKA、CREB和BDNF蛋白水平的降低;并增加了海马体和皮质的增殖活性。此外,在体外,ZDX提取物减轻了CORT诱导的海马神经元损伤和凋亡,并抑制了CORT诱导的cAMP、PKA、CREB和BDNF mRNA表达水平降低。
这些发现表明,ZDX提取物具有作为新型抗抑郁治疗药物的潜力,通过靶向参与抑郁症发病机制的多种途径,为当前治疗提供了一种补充方法。有必要进一步研究以探索ZDX提取物在抑郁症治疗中的临床应用。