Metabolomics study on the intervention effect of Radix Salviae Miltiorrhizae extract in exercise-induced exhaustion rat using gas chromatography coupled to mass spectrometry

The metabolomics approach based on the gas chromatography coupled to mass spectrometry (GC-MS) was adopted to explore the underlying mechanism of the anti-fatigue effect of Radix Salviae Miltiorrhizae (RSM), a famous herbal medicine in China used for multiple biological functions, in load-weighted swimming test in rat, combined with biochemical parameters evaluations. As a result, the metabolomics study followed by orthogonal partial least-square (OPLS) analysis could differentiate metabolic profiling between the control and exhaustive exercise group, showing the rats underwent an obvious metabolic perturbation, whereas RSM treatment restored scores plot close to normal and showed regulatory effects on the muscle metabolic profiles. The changed metabolic pathways of the potential biomarkers in response to the effect of RSM treatment for exhaustive exercise rats included in glucose metabolism (glucose, lactic acid, alanine), glutathione metabolism (glycine, glutamate, 5-oxo-proline), TCA cycle (succinic acid), arginine biosynthesis (glutamine, ornithine, urea), glyoxylate and dicarboxylate metabolism (serine, glycine), oxidative stress (taurine) and purine metabolism (inosine). In addition, intervention of RSM increased hepatic glycogen, muscle glycogen and serum glucose, and decreased triglyceride and blood urea nitrogen levels, indicating RSM treatment may regulate energy metabolism by increasing the rate of fat utilization, decrease the protein and carbohydrate utilization. Furthermore, RSM reduced exhaustive exercise-induced accumulation of the lipid peroxidation byproduct malonaldehyde and elevated antioxidants' levels, including reduced glutathione and superoxide dismutase, which might be a positive reflection of improved oxidant-antioxidant balance. Moreover, RSM could protect against exercise-induced muscle damage by attenuating creatine kinase release. In summary, RSM provided a good anti-fatigue effect by regulating energy metabolism, oxidant-antioxidant balance, and the endogenous metabolites in the exercising muscle. This study demonstrates that metabolomics is an effective tool for the estimation of the potential anti-fatigue effect of RSM and for the illustration of its pharmacological mechanism.