Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
Institute of Medicinal Plant Development, State Key Laboratory of Basis and New Drug Development of Natural and Nuclear Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Fitoterapia. 2024 Sep;177:106087. doi: 10.1016/j.fitote.2024.106087. Epub 2024 Jun 17.
Herbal medicine pair, composed of two single herbs, is a relatively fixed minimum prescription unit in the traditional Chinese medicine's formula and has special significance in clinic. The combination of Xiangfu (the rhizoma of Cyperus rotundus L, XF) and Chuanxiong (the rhizoma of Ligusticum chuanxiong Hort, CX) has been recoded as an herbal medicine pair XF-CX in the Yuan Dynasty (1347 CE) of China and widely used in traditional Chinese medicine formula, including Chaihu Shugan San, which has been clinically used for treatment of depression. However, the optimal ratio of the XF-CX herbal medicine pair and its antidepressant constituents are still unclear. Herein, the antidepressive-like effects of XF-CX herbal medicine pairs with different ratios of XF and CX (2:1, 1:1, 1:2) were evaluated using behavioral despair animal models in mice, and then its potential antidepressant constituents were recognized by spectrum-effect relationship analyses. Finally, the potential antidepressant constituents of the XF-CX herbal medicine pair were validated by molecular docking with glucocorticoid receptor and corticosterone (CORT)-induced PC12 cell injury model. The results indicated that different ratios of XF-CX pairs had antidepressive-like effects, and the XF-CX (2:1) exhibited a more significant effect. Thirty-two potential antidepressant constituents in the XF-CX herbal medicine pair were screened out from the spectrum-effect relationship combined molecular docking analyses. Among them, senkyunolide A, cyperotundone, Z-ligustilide, and levistilide A were validated to have protective effects against CORT-induced injury in PC12 cells. Our findings not only obtained the optimal ratio of XF-CX in the herbal medicine pair for the treatment of depression but also its potential antidepressant constituents, which will benefit in elucidating the mechanism of action and promoting the application of the herbal medicine pair in the clinic.
中药对药由两味单味中药组成，是中药方剂中相对固定的最小处方单元，在临床上具有特殊意义。香附（Cyperus rotundus L. 的根茎，XF）和川芎（Ligusticum chuanxiong Hort. 的根茎，CX）的组合在元代（公元 1347 年）被记录为中药对药 XF-CX，并广泛应用于中药方剂中，包括柴胡疏肝散，已在临床上用于治疗抑郁症。然而，XF-CX 中药对药的最佳比例及其抗抑郁成分仍不清楚。在此，通过行为绝望动物模型评估了不同比例的 XF-CX 中药对药（2:1、1:1、1:2）的抗抑郁样作用，然后通过谱效关系分析识别其潜在的抗抑郁成分。最后，通过与糖皮质激素受体和皮质酮（CORT）诱导的 PC12 细胞损伤模型的分子对接验证了 XF-CX 中药对药的潜在抗抑郁成分。结果表明，不同比例的 XF-CX 对药具有抗抑郁样作用，XF-CX（2:1）的作用更为显著。从谱效关系结合分子对接分析筛选出 XF-CX 中药对药中的 32 种潜在抗抑郁成分。其中，藁本内酯 A、环维黄杨星 D、Z-藁本内酯和升麻素 A 被验证对 CORT 诱导的 PC12 细胞损伤具有保护作用。我们的研究结果不仅获得了治疗抑郁症的 XF-CX 中药对药的最佳比例，还获得了其潜在的抗抑郁成分，这将有助于阐明其作用机制并促进该中药对药在临床上的应用。
