Hou Yi, Li Hong, Zhu Luochen, Quan Tian, Feng Xianhu, Li Yue, Bian Yuan, Wei Yuxun
Pharmacy Department, The Center of Clinical Trials, The People's Hospital of Zhongjiang, Deyang, China.
West China School of Medicine, Sichuan University, Chengdu, China.
Front Pharmacol. 2025 Sep 3;16:1614429. doi: 10.3389/fphar.2025.1614429. eCollection 2025.
Paeoniflorin (PF) is widely present in species of the genus. In recent years, numerous preclinical studies have shown that PF has preventive and therapeutic effects on various neurological diseases, particularly in the prevention and treatment of depression. Additionally, some classic traditional Chinese medicine formulas containing PF, such as Xiaoyao San, Chaihu Shugan San, and Sini San, have been proven to significantly improve depressive symptoms. However, the antidepressant mechanisms of PF and its containing classic traditional Chinese medicine formulas are not yet fully understood. PF, as a natural glycoside metabolite with a wide margin of safety and good tolerance, exhibits certain toxicity at high concentrations. The differences in standardized methods between the traditional formulations, such as extraction processes, dosages, and inherent metabolite variability in formulations, may affect the interpretation of results and clinical applications. Therefore, this article reviews the antidepressant mechanisms of PF from the perspectives of inhibiting the hypothalamic-pituitary-adrenal axis, increasing the levels of monoamine neurotransmitters, suppressing oxidative stress and apoptosis, regulating calcium homeostasis, inhibiting neuroinflammation, modulating mitochondrial function, regulating cellular autophagy, and increasing the levels of brain-derived neurotrophic factor, and elucidates the antidepressant effects and mechanisms of traditional Chinese medicine formulations containing PF. Additionally, we describe the physicochemical properties, toxinology, pharmacokinetic characteristics, and the transformation of PF . This review may contribute to the application of PF and its formulations in depression.
芍药苷（PF）广泛存在于该属植物中。近年来，大量临床前研究表明，PF对多种神经系统疾病具有预防和治疗作用，尤其是在抑郁症的预防和治疗方面。此外，一些含有PF的经典中药方剂，如逍遥散、柴胡疏肝散和四逆散，已被证明能显著改善抑郁症状。然而，PF及其所含经典中药方剂的抗抑郁机制尚未完全明确。PF作为一种安全性高、耐受性好的天然糖苷代谢产物，在高浓度时会表现出一定毒性。传统方剂之间在标准化方法上的差异，如提取工艺、剂量以及方剂中固有代谢物的变异性，可能会影响结果的解读和临床应用。因此，本文从抑制下丘脑 - 垂体 - 肾上腺轴、提高单胺类神经递质水平、抑制氧化应激和细胞凋亡、调节钙稳态、抑制神经炎症、调节线粒体功能、调节细胞自噬以及提高脑源性神经营养因子水平等方面综述了PF的抗抑郁机制，并阐明了含PF的中药方剂的抗抑郁作用及机制。此外，我们还描述了PF的理化性质、毒理学、药代动力学特征以及转化情况。本综述可能有助于PF及其制剂在抑郁症治疗中的应用。
