College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming, China.
Beijing Entry-Exit Inspection and Quarantine Bureau, Beijing, China.
J Pharm Pharmacol. 2021 Apr 27;73(6):796-807. doi: 10.1093/jpp/rgab012.
Glucolipid metabolic disorders (GLMD) promote a series of major chronic diseases. Polygoni Multilori Radix Preparata (PMRP) has been widely acknowledged in the prevention and treatment of GLMD. We previously reported that water extract (WE) of PMRP and its major bioactive constituents such as polysaccharides (POL) and 2,3,5,4´-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) could alleviate GLMD. The mitochondrial dysfunction is an important mechanism of GLMD, but the underlying mechanisms behind the regulation of mitochondria to alleviate GLMD by WE, POL from PMRP and TSG are still unknown.
In this study, we elucidated the effects of WE, POL, and TSG towards regulating the mitochondrial dysfunction and alleviating GLMD using mitochondrial metabonomics. A rat model of GLMD was established by high-sugar and high-fat (HS-HF) diet. Rats were intragastrically given WE, POL, and TSG for 12 weeks. The liver mitochondrial metabolites were analyzed by ultra-high-performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to identify the differential metabolites and metabolic pathways.
The WE, POL, and TSG could significantly restore the level of endogenous metabolites in liver mitochondria toward normal status. In total, sixteen, seven, and fourteen differential metabolites were identified in the liver mitochondrial samples obtained from the WE, GOL, and TSG groups, respectively. These metabolites were found to be mainly involved in glycerol phospholipid, histidine, alanine, aspartic acid, glutamate metabolism, and arginine biosynthesis.
PMRP could improve the liver mitochondrial function by regulating the mitochondrial metabolic pathways to alleviate GLMD. Therefore, the application of PMRP might be a promising mitochondrial regulator/nutrient for alleviating GLMD-associated diseases and the mitochondrial metabonomics might provide insights into the evaluation of the efficacies and mechanisms of action of drugs.
糖脂代谢紊乱（GLMD）可促进一系列重大慢性疾病的发生。制何首乌已被广泛用于 GLMD 的预防和治疗。我们之前的研究报道，制何首乌水提物（WE）及其主要生物活性成分，如多糖（POL）和 2,3,5,4´-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（TSG），可缓解 GLMD。线粒体功能障碍是 GLMD 的一个重要机制，但 WE、POL 和 TSG 通过调节线粒体缓解 GLMD 的潜在机制尚不清楚。
在这项研究中，我们使用线粒体代谢组学阐明了 WE、POL 和 TSG 调节线粒体功能障碍和缓解 GLMD 的作用。采用高糖高脂（HS-HF）饮食建立 GLMD 大鼠模型。大鼠连续灌胃 WE、POL 和 TSG 12 周。采用超高效液相色谱/质谱联用技术结合多变量统计分析方法分析肝线粒体代谢产物，以鉴定差异代谢物和代谢途径。
WE、POL 和 TSG 可显著恢复肝线粒体中内源性代谢物的水平至正常状态。在 WE、POL 和 TSG 组的肝线粒体样本中，共鉴定出 16、7 和 14 个差异代谢物。这些代谢物主要参与甘油磷脂、组氨酸、丙氨酸、天冬氨酸、谷氨酸代谢和精氨酸生物合成。
制何首乌可通过调节线粒体代谢途径改善肝脏线粒体功能，从而缓解 GLMD。因此，制何首乌的应用可能是一种有前途的缓解 GLMD 相关疾病的线粒体调节剂/营养物质，线粒体代谢组学可能为评价药物的疗效和作用机制提供新的思路。
