Liang Hongbao, Yao Jingchun, Miao Yu, Sun Ying, Gao Yanbing, Sun Chenghong, Li Rui, Xiao He, Feng Qun, Qin Guofei, Lu Xiaoyan, Liu Zhong, Zhang Guimin, Li Feng, Shao Mingguo
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.
Center for Drug Safety Evaluation, Shandong New Time Pharmaceutical Co., Ltd., Linyi, China.
Front Pharmacol. 2023 Mar 10;14:1151447. doi: 10.3389/fphar.2023.1151447. eCollection 2023.
As a potential drug candidate for the treatment of hypertension and complications, it is speculated that the component-based Chinese medicine of leaves (GBCCM) which mainly composed of flavonoid aglycones (FAs) and terpene lactones (TLs) may have different pharmacological effects at different doses or ratios. Taking the normal mice as the study object, metabonomics was conducted by giving different doses of GBCCM. Based on the components of GBCCM absorbed into the blood, the network pharmacological prediction was carried out. By integrating the results of metabonomics and network pharmacology, predict the possible pharmacological effects of GBCCM and conduct experimental verification. It was found that eight of the 19 compounds in GBCCM could be absorbed into the blood. GBCCM mainly affected the signal pathways of unsaturated fatty acid, pyruvate, bile acid, melanin and stem cells. It was speculated that GBCCM might have activities such as lowering blood pressure, regulating stem cell proliferation and melanogenesis. By establishing the models of mushroom tyrosinase, rat bone marrow mesenchymal stem cells (BMSCs) and spontaneously hypertensive rats (SHRs), we found that FAs and TLs showed synergistic effect in hypertension and tyrosinase models, and the optimal ratio was 3:2 (4.4 mg/kg) and 1:1 (0.4 mg/ml), respectively. As effective substances, FAs significantly promoted the proliferation of rat BMSCs on the third and fifth days at the concentration of 0.2 μg/ml ( < 0.05). GBCCM showed a variety of pharmacological effects at different doses and ratios, which provided an important reference for the druggability of GBCCM.
作为一种治疗高血压及其并发症的潜在候选药物,推测主要由黄酮苷元(FAs)和萜类内酯(TLs)组成的银杏叶组分中药(GBCCM)在不同剂量或比例下可能具有不同的药理作用。以正常小鼠为研究对象,给予不同剂量的GBCCM进行代谢组学研究。基于吸收进入血液的GBCCM成分,进行网络药理学预测。通过整合代谢组学和网络药理学的结果,预测GBCCM可能的药理作用并进行实验验证。结果发现GBCCM中的19种化合物中有8种可被吸收进入血液。GBCCM主要影响不饱和脂肪酸、丙酮酸、胆汁酸、黑色素和干细胞的信号通路。推测GBCCM可能具有降低血压、调节干细胞增殖和黑色素生成等活性。通过建立蘑菇酪氨酸酶、大鼠骨髓间充质干细胞(BMSCs)和自发性高血压大鼠(SHRs)模型,发现FAs和TLs在高血压和酪氨酸酶模型中表现出协同作用,最佳比例分别为3:2(4.4 mg/kg)和1:1(0.4 mg/ml)。作为有效物质,FAs在浓度为0.2 μg/ml时在第3天和第5天显著促进大鼠BMSCs的增殖(<0.05)。GBCCM在不同剂量和比例下表现出多种药理作用,为GBCCM的成药性提供了重要参考。