基于网络药理学研究解析气血和胶囊治疗气滞血瘀证的活性成分及作用机制
Deciphering the Active Compounds and Mechanisms of Qixuehe Capsule on Qi Stagnation and Blood Stasis Syndrome: A Network Pharmacology Study.
作者信息
Huang Yu-Xi, Xu Ding-Qiao, Yue Shi-Jun, Chen Yan-Yan, Tao Hui-Juan, Fu Rui-Jia, Xing Li-Ming, Wang Taiyi, Ma Yu-Ling, Wang Bao-An, Tang Yu-Ping, Duan Jin-Ao
机构信息
Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China.
Oxford Chinese Medicine Research Centre, University of Oxford, Oxford, UK.
出版信息
Evid Based Complement Alternat Med. 2020 Feb 27;2020:5053914. doi: 10.1155/2020/5053914. eCollection 2020.
BACKGROUND
Qixuehe capsule (QXH), a Chinese patent medicine, has been demonstrated to be effective in the treatment of menstrual disorders. In traditional Chinese medicine (TCM) theory, qi stagnation and blood stasis syndrome (QS-BSS) is the main syndrome type of menstrual disorders. However, the pharmacodynamic effect of QXH in treating QS-BSS is not clear, and the main active compounds and underlying mechanisms remain unknown.
METHODS
A rat model of QS-BSS was established to evaluate the pharmacodynamic effect of QXH. Thereafter, a network pharmacology approach was performed to decipher the active compounds and underlying mechanisms of QXH.
RESULTS
QXH could significantly reduce the rising whole blood viscosity (WBV) and plasma viscosity (PV) but also normalize prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) content in QS-BSS rats. Based on partial least-squares-discriminant analysis (PLS-DA), the low-dose QXH-intervened (QXH-L) and the high-dose QXH-intervened (QXH-H) groups seemed the most effective by calculating the relative distance to normality. Through network pharmacology, QXH may improve hemorheological abnormality mainly via 185 compounds-51 targets-28 pathways, whereas 184 compounds-68 targets-28 pathways were associated with QXH in improving coagulopathy. Subsequently, 25 active compounds of QXH were verified by UPLC-Q/TOF-MS. Furthermore, 174 active compounds of QXH were shared in improving hemorheological abnormality and coagulopathy in QS-BSS, each of which can act on multiple targets to be mainly involved in complement and coagulation cascades, leukocyte transendothelial migration, PPAR signaling pathway, VEGF signaling pathway, and arachidonic acid metabolism. The attribution of active compounds indicated that Angelicae Sinensis Radix (DG), Paeoniae Radix Rubra (CS), Carthami Flos (HH), Persicae Semen (TR), and Corydalis Rhizoma (YHS) were the vital herbs of QXH in treating QS-BSS.
CONCLUSION
QXH can improve the hemorheology abnormality and coagulopathy of QS-BSS, which may result from the synergy of multiple compounds, targets, and pathways.
背景
气血和胶囊（QXH）是一种中成药，已被证明在治疗月经失调方面有效。在中医理论中，气滞血瘀证（QS - BSS）是月经失调的主要证型。然而，QXH治疗QS - BSS的药效作用尚不清楚，其主要活性成分及潜在机制仍不明确。
方法
建立QS - BSS大鼠模型以评估QXH的药效作用。此后，采用网络药理学方法解析QXH的活性成分及潜在机制。
结果
QXH可显著降低QS - BSS大鼠升高的全血粘度（WBV）和血浆粘度（PV），还可使凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）和纤维蛋白原（FIB）含量恢复正常。基于偏最小二乘判别分析（PLS - DA），通过计算与正常状态的相对距离，低剂量QXH干预组（QXH - L）和高剂量QXH干预组（QXH - H）似乎最为有效。通过网络药理学，QXH可能主要通过185种化合物 - 51个靶点 - 28条通路改善血液流变学异常，而184种化合物 - 68个靶点 - 28条通路与QXH改善凝血功能障碍有关。随后，通过超高效液相色谱 - 四极杆飞行时间质谱联用仪（UPLC - Q/TOF - MS）验证了QXH的25种活性成分。此外，QXH有174种活性成分在改善QS - BSS的血液流变学异常和凝血功能障碍方面存在共享，每种成分可作用于多个靶点，并主要参与补体和凝血级联反应、白细胞跨内皮迁移、过氧化物酶体增殖物激活受体（PPAR）信号通路、血管内皮生长因子（VEGF）信号通路和花生四烯酸代谢。活性成分的归属表明，当归（DG）、赤芍（CS）、红花（HH）、桃仁（TR）和延胡索（YHS）是QXH治疗QS - BSS的关键药材。
结论
QXH可改善QS - BSS的血液流变学异常和凝血功能障碍，这可能是多种化合物、靶点和通路协同作用的结果。
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