Distinct metabonomic signatures of Polygoni Multiflori Radix Praeparata against glucolipid metabolic disorders

Objectives 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-beta-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. Methods In this study, we elucidated the effects of WE, POL, andTSG towards regulating the mitochondria' 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. Key findingsThe WE, POL, andTSG 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, andTSG groups, respectively. These metabolites were found to be mainly involved in glycerol phospholipid, histidine, alanine, aspartic acid, glutamate metabolism, and arginine biosynthesis. Conclusions PMRP could improve the liver mitochondrial function by regulating the mitochondria' 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.

Automated summary

This study elucidated the effects of Polygoni Multilori Radix Preparata (PMRP) in regulating mitochondria dysfunction and alleviating glucolipid metabolic disorders (GLMD) using mitochondrial metabonomics. The results showed that PMRP could improve liver mitochondrial function by regulating metabolic pathways, indicating its potential as a promising nutrient for alleviating GLMD-associated diseases.