Wang Rou-Jun, Ma Guang-Chao, Yu Shun, Zhang Mei, Pu Shi-Biao
Nanjing University of Chinese Mdicine, 282 Hanzhong Road, Nanjing City, Jiangsu Province, Nanjing 210029, China.
Department of Diabetes and Endocrinology, Kunming Municipal Hospital of Traditional Chinese Medicine, No. 2628 Xiangyuan Road, Chenggong District, Kunming 650500, China.
Toxicol Res (Camb). 2024 Mar 31;13(2):tfae052. doi: 10.1093/toxres/tfae052. eCollection 2024 Apr.
Storke is a leading cause of death and disability affecting million people worldwide, 80% of which is ischemic stroke (IS). Recently, traditional Chinese medicines (TCMs) have received great attentions in treating IS due to their low poisonous effects and high safety. Buyang Huanwu Decoction (BHD), a famous and classical Chinese prescription, has been used for treating stroke-induced disability for centuries. Yet, its underlying mechanism is still in fancy.
We first constructed an IS model by middle cerebral artery occlusion (MCAO). Then, a metabonomics study on serum samples was performed using UHPLC-QTOF/MS, followed by multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA).
Metabolic profiling of PCA indicated metabolic perturbation caused by MCAO was regulated by BHD back to normal levels, which is in agreement with the neurobehavioral evaluations. In the OPLS-DA, 12 metabolites were screened as potential biomarkers involved in MCAO-induced IS. Three metabolic pathways were recognized as the most relevant pathways, involving one carbon pool by folate, sphingolipid metabolism and inositol phosphate metabolism. BHD significantly reversed the abnormality of 7 metabolites to normal levels.
This is the first study to investigate the effect of BHD on IS at the metabolite level and to reveal the underlying mechanisms of BHD, which is complementary to neurobehavioral evaluation. In a broad sense, the current study brings novel and valuable insights to evaluate efficacy of TCMs, to interpret the action mechanisms, and to provide the theoretical basis for further research on the therapeutic mechanisms in clinical practice.
中风是全球影响数百万人的主要死亡和致残原因,其中80%为缺血性中风(IS)。近年来,中药因其低毒、高安全性在治疗缺血性中风方面受到广泛关注。补阳还五汤(BHD)作为一个著名的经典中药方剂,数百年以来一直用于治疗中风所致的残疾。然而,其潜在机制仍不清楚。
首先通过大脑中动脉闭塞(MCAO)构建缺血性中风模型。然后,采用超高效液相色谱-四极杆飞行时间质谱(UHPLC-QTOF/MS)对血清样本进行代谢组学研究,随后进行包括主成分分析(PCA)和正交偏最小二乘法判别分析(OPLS-DA)在内的多变量数据分析。
PCA代谢图谱表明,MCAO引起的代谢紊乱被BHD调节至正常水平,这与神经行为学评估结果一致。在OPLS-DA中,筛选出12种代谢物作为与MCAO诱导的IS相关的潜在生物标志物。确定了三条最相关的代谢途径,涉及叶酸一碳池、鞘脂代谢和肌醇磷酸代谢。BHD显著将7种代谢物的异常逆转至正常水平。
本研究首次在代谢物水平上研究BHD对缺血性中风的影响,并揭示其潜在机制,这是对神经行为学评估的补充。从广义上讲,本研究为评估中药疗效、解释作用机制以及为临床实践中治疗机制的进一步研究提供理论依据带来了新的有价值的见解。