Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jul 15;1178:122805. doi: 10.1016/j.jchromb.2021.122805. Epub 2021 May 27.
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.
基于气相色谱-质谱联用（GC-MS）的代谢组学方法被采用，以探索中国著名草药丹参（RSM）抗疲劳作用的潜在机制，RSM 具有多种生物学功能，在大鼠负重游泳试验中结合生化参数评估。结果表明，代谢组学研究结合正交偏最小二乘法（OPLS）分析可以区分对照组和力竭运动组的代谢谱，表明大鼠经历了明显的代谢扰动，而 RSM 处理使得分图接近正常，并显示对肌肉代谢谱的调节作用。对 RSM 处理力竭运动大鼠潜在生物标志物的代谢途径变化包括葡萄糖代谢（葡萄糖、乳酸、丙氨酸）、谷胱甘肽代谢（甘氨酸、谷氨酸、5-氧脯氨酸）、TCA 循环（琥珀酸）、精氨酸生物合成（谷氨酰胺、鸟氨酸、尿素）、乙醛酸和二羧酸代谢（丝氨酸、甘氨酸）、氧化应激（牛磺酸）和嘌呤代谢（肌苷）。此外，RSM 干预增加了肝糖原、肌肉糖原和血清葡萄糖，降低了甘油三酯和血尿素氮水平，表明 RSM 治疗可能通过增加脂肪利用率来调节能量代谢，减少蛋白质和碳水化合物的利用。此外，RSM 减少了力竭运动引起的脂质过氧化产物丙二醛的积累，并提高了抗氧化剂的水平，包括还原型谷胱甘肽和超氧化物歧化酶，这可能是氧化还原平衡改善的积极反映。此外，RSM 可以通过减少肌酸激酶的释放来防止运动引起的肌肉损伤。总之，RSM 通过调节能量代谢、氧化还原平衡和运动肌肉中的内源性代谢物提供了良好的抗疲劳效果。本研究表明，代谢组学是评估 RSM 潜在抗疲劳作用及其药理学机制的有效工具。
