背景:四妙永安汤(SMYAD)是一种著名的中药配方,在中国古代已经使用了几个世纪,用于治疗血栓闭塞性脉管炎。由于其悠久的使用历史,它在中国已经被用于治疗患者数千年了。近年来,SMYAD已广泛用于治疗心血管和内分泌疾病。显示出显着增加血清中高密度脂蛋白胆固醇水平并降低总胆固醇和低密度脂蛋白胆固醇水平。
目的:在此,采用基于HPLC-MS/MS方法的血清代谢组学方法评价SMYAD对高脂饮食诱导的高脂血症的治疗效果,探讨高脂血症的治疗机制。
方法:首先,体重的变化,肝脏组织病理学,和血清生物化学,包括肝毒性相关酶的水平,氧化应激指标,并监测大鼠的炎症因子,评价SMYAD对高脂饮食诱导的高脂血症的治疗作用。然后,应用了血清代谢组学方法,使用主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)对不同的组进行聚类,以及筛选出敏感和可靠的生物标志物。最后,分析了与特定生物标志物相关的代谢途径,了解SMYAD作用的可能机制。
结果:结果表明SMYAD具有明显的抗高脂血症作用,抗氧化剂,和抗炎作用。根据血清代谢组学分析结果,与对照大鼠相比,高脂血症大鼠显示出完全不同的结果;SMYAD治疗组大鼠的代谢物谱以剂量依赖性方式显示出与正常对照组相当的趋势。此外,与丙酮酸代谢相关的12种生物标志物,牛磺酸和下牛磺酸代谢,TCA循环,胆汁酸代谢,和葡萄糖代谢被识别和确认,阐明SMYAD的作用机制。
结论:使用代谢组学技术,据预测,SMYAD的治疗作用与其抗氧化、抗炎活性和丙酮酸盐的调节有关,高血脂状态下的牛磺酸和下牛磺酸代谢途径。这项研究为SMYAD的临床应用提供了证据,并彻底探索了该中药的作用机制。
BACKGROUND: The Si-miao-yong-an decoction (SMYAD) is a famous traditional Chinese medicinal formula that has been used for centuries in ancient China for treating thromboangiitis obliterans. Because of its long history of use, it has been used to treat patients in China for thousands of years. In recent years, SMYAD has been widely used for treating cardiovascular and endocrine diseases. It was shown to significantly increase high-density lipoprotein-cholesterol levels and reduce total cholesterol and low-density lipoprotein-cholesterol levels in the serum.
OBJECTIVE: Herein, a serum metabonomics approach based on the HPLC-MS/MS method was adopted to evaluate the therapeutic effect of SMYAD on high-fat diet-induced hyperlipidemia, and investigate the mechanisms for treating hyperlipidemia.
METHODS: Firstly, the change in body weight, liver histopathology, and serum biochemistry, including that in the levels of hepatotoxicity-related enzymes, oxidative stress indexes, and inflammatory factors were monitored in rats, to evaluate the therapeutic effect of SMYAD on high-fat diet-induced hyperlipidemia. Then, a serum metabolomics approach was applied, to cluster different groups using principle component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), as well as to screen out sensitive and reliable biomarkers. Finally, the metabolic pathways associated with specific biomarkers were analyzed, to understand the possible mechanism underlying the action of SMYAD.
RESULTS: The results indicated that SMYAD had significant anti-hyperlipidemic, anti-oxidant, and anti-inflammatory effects. Based on the results of serum metabolomics analysis, the hyperlipidemic rats showed completely different results compared to the control rats; metabolite profiles of rats from the SMYAD treatment groups showed a trend comparable to those of the normal control group in a dose-dependent manner. Besides, twelve biomarkers associated with pyruvate metabolism, taurine and hypotaurine metabolism, TCA cycle, bile acid metabolism, and glucose metabolism were identified and confirmed, to clarify the mechanism of action of SMYAD.
CONCLUSIONS: Using metabonomics technology, it was predicted that the therapeutic effects of SMYAD were associated with its anti-oxidation as well as anti-inflammatory activities and the adjustment of the pyruvate, taurine as well as hypotaurine metabolism pathways in the hyperlipidemic state. This study provided evidence regarding the clinical application of SMYAD and thoroughly explored the mechanism underlying the action of this traditional Chinese medicine.