背景:半夏白术天麻汤(BBTD)起源于清代中医著作《医心武》,已有300多年的临床应用历史。这是经典的祛痰处方,熄灭风,健脾(中医,ie,TCM,指脾通道)和根据中医理论消散过多的液体。BBTD在治疗痰湿过度高血压方面特别有效。然而,尚未完全了解BBTD每种草药对高血压治疗的确切药理作用。
目的:研究BBTD中各中药治疗高血压的药理作用,并探讨其作用机制。
方法:建立了高脂饮食喂养的动物模型,以评估BBTD中不同药物组治疗高血压的功效。使用非靶向代谢检测建模和药物干预后的代谢变化。然后,豆甾醇(STI)和天麻素(GAS),半夏和天麻的主要成分,选择在HepG2细胞脂肪变性模型上进行治疗。采用实时定量聚合酶链反应和免疫印迹法检测药物干预后相应基因和蛋白的变化,探讨STI与GAS联合应用的抗高脂血症机制。
结果:体重增加,高脂饮食引起的血压升高和血脂升高均以剂量依赖性方式显著降低(p<0.05)。此外,造模后检测到28种差异代谢产物(DMs),各药物组治疗后均不同程度调至正常。此外,28例DMs中有8例与模型组比较,主要与四种代谢途径有关,而无原则药物干预后,只有两种代谢产物与模型组差异显著,与一种代谢途径有关。在HepG2高脂血症细胞模型中,STI,GAS及其组合显着降低TC,TG水平和脂质积累(p<0.05),和减少固醇调节元件结合蛋白1c(SREBP-1c),脂肪酸合成酶(FAS),硬脂酰辅酶A去饱和酶-1(SCD1)及其蛋白表达(p<0.05),磷酸腺苷活化蛋白激酶(AMPK)及其蛋白表达增加(p<0.05)。两种药物联合使用比单独使用效果更好。
结论:BBTD已被证明可有效减少高脂大鼠模型的脂质积累,以及以剂量依赖性方式将模型诱导的异常代谢物恢复到正常水平。半夏和天麻,BBTD的主要组成部分,可能通过脂肪酸生物合成来调节脂质代谢,精氨酸和脯氨酸代谢。他们的主要活性剂,STI和气体,能有效降低细胞内的脂质积累和脂质含量,调节与脂质代谢相关的基因和蛋白的表达水平。这些结果表明BBTD可能通过AMPK/SREBP-1c通路调节脂质代谢。
BACKGROUND: Banxia baizhu tianma decoction (BBTD) originated from the Qing Dynasty Chinese medicine book \"Medical Xinwu\", which has a clinical application history of more than 300 years. It\'s a classic prescription for expelling phlegm, extinguishing wind, strengthening the spleen (traditional Chinese medicine, ie, TCM, refers to the spleen channel) and dissipating excessive fluid based on TCM theory. BBTD is particularly effective in the treatment of excessive phlegm-dampness hypertension. However, the precise pharmacological effect of each herb of BBTD on hypertension treatment is not yet fully understood.
OBJECTIVE: To investigate the pharmacological effects of each herb in BBTD on hypertension treatment and to explore the mechanisms behind them.
METHODS: A high-fat-diet fed animal model was developed to evaluate the efficacy of different groups of drugs in BBTD for the treatment of hypertension. Untargeted metabolism was used to detect the metabolic changes after modeling and drug intervention. Then, Stigmasterol (STI) and gastrodin (GAS), major components of Pinellia Ternate Makino and Gastrodia elata Blume, were selected for treatment on HepG2 cell steatosis model. Real-time quantitative polymerase chain reaction and Western blotting were used to detect changes of corresponding gene and protein after drug intervention to explore the exam anti-hyperlipidemia mechanism of STI and GAS combination.
RESULTS: The weight gain, elevated blood pressure and increased blood lipids induced by high-fat-diet were significantly decreased (p < 0.05) after each prescription medicine intervention in a dose-dependent manner. In addition, 28 differential metabolites (DMs) were detected after modeling and were regulated to normal at varying degrees after each drug group treatment. In addition, eight of the 28 DMs were significantly different from the model group after the full prescription drug intervention, primarily related to four metabolic pathways, while only two metabolites were significantly different from the model group after the unprincipled drug intervention, related to one metabolic pathway. In HepG2 hyperlipidemia cell model, STI, GAS and their combination significantly decreased TC, TG levels and lipid accumulation (p < 0.05), and decreased sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1) and their protein expressions (p < 0.05), increased adenosine monophosphate-activated protein kinase (AMPK) and it\'s protein expression (p < 0.05). The two drugs work better in combination than alone.
CONCLUSIONS: BBTD has been shown to be effective in reducing lipid accumulation in a high-fat rat model, as well as in restoring the model-induced abnormal metabolites to normal levels in a dose-dependent manner. Pinellia ternata Makino and Gastrodia elata Blume, the main components of BBTD, may regulate lipid metabolism through fatty acid biosynthesis, arginine and proline metabolism. Their main active agents, STI and GAS, effectively reduce lipid accumulation and lipid content in cells and regulate the expression levels of genes and proteins associated with lipid metabolism. These results suggest that BBTD may regulate lipid metabolism via AMPK/SREBP-1c pathway.