School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610000, P.R. China.
Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ, 86001, USA.
Comb Chem High Throughput Screen. 2023;26(12):2201-2225. doi: 10.2174/1386207326666230130091802.
Depressive disorder (DD) is a common chronic and highly disabling disease. (PMC), a traditional Chinese medicine, has been listed in the 2020 edition of the Chinese Pharmacopoeia. Here, the antidepressant effects and mechanisms of PMC were explored for the first time.
We observed the safety of PMC at a 10-fold clinically equivalent dose. Depressed mice were induced by chronic unpredictable mild stress (CUMS) and were used to evaluate the antidepressant effects of PMC the sucrose preference test and the tail suspension test. The composition of PMC was identified by ultra-high performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometer, and the active components, important targets, and potential mechanism of PMC in DD treatment were predicted network pharmacology. Investigation included active compounds and DD-related targets screening, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, PMC-compound-target-pathway- DD network construction, and Molecular docking.
In the safety evaluation of PMC, no toxic side effects or deaths occurred. There were no significant differences in liver function (ALT, AST, and TP; > 0.05) and kidney function (BUN, CRE, and UA; > 0.05) in each group of mice. Compared to the control group, the model group of mice showed significantly decreased sucrose preference and significantly increased immobility time ( < 0.01 or < 0.05). Compared with the model group, the mice in the PMC low, medium, and high dose groups showed a significant decrease in immobility time and a significant increase in sucrose preference. In the PMC-Compound-Target-Pathway-DD network, 54 active compounds, 83 common targets, and 13 major signaling pathways were identified for the treatment of DD. Molecular docking verified that the active compounds could effectively bind with the hub targets.
PMC is a relatively safe antidepressant herbal medicine with its potential mechanism involving multiple compounds, targets, and pathways.
抑郁障碍（DD）是一种常见的慢性、高致残性疾病。（PMC），一种中药，已被列入 2020 年版《中国药典》。在这里，我们首次探索了 PMC 的抗抑郁作用及其机制。
我们观察了 PMC 在临床等效剂量的 10 倍时的安全性。采用慢性不可预测轻度应激（CUMS）诱导抑郁小鼠，通过蔗糖偏好试验和悬尾试验评价 PMC 的抗抑郁作用。采用超高效液相色谱-四极杆精确轨道阱质谱联用技术鉴定 PMC 的成分，通过网络药理学预测 PMC 治疗 DD 的活性成分、重要靶点及潜在机制。包括筛选活性化合物和 DD 相关靶点、基因本体（GO）分析、京都基因与基因组百科全书（KEGG）注释、PMC-化合物-靶点-通路-DD 网络构建和分子对接。
在 PMC 的安全性评价中，各组小鼠均未出现毒性副作用或死亡。各组小鼠的肝功能（ALT、AST 和 TP；>0.05）和肾功能（BUN、CRE 和 UA；>0.05）均无显著差异。与对照组相比，模型组小鼠的蔗糖偏好显著降低，不动时间显著增加（<0.01 或<0.05）。与模型组相比，PMC 低、中、高剂量组小鼠的不动时间显著减少，蔗糖偏好显著增加。在 PMC-化合物-靶点-通路-DD 网络中，共鉴定出 54 个活性化合物、83 个共同靶点和 13 个主要信号通路，用于治疗 DD。分子对接验证了活性化合物可有效与枢纽靶点结合。
PMC 是一种相对安全的抗抑郁草药，其潜在机制涉及多种化合物、靶点和通路。
