Ginseng Berry Concentrate Promotes a Metabolic Shift From Anaerobic Glycolysis to Aerobic Mitochondrial Metabolism in C2C12 Myocytes

다국어 초록 (Multilingual Abstract)

Based on reports indicating that ginsenoside contents are higher in ginseng berries than in ginseng roots, this study aimed to investigate the muscle lactate accumulation-preventing potential of ginseng berry concentrate (GBC). To this end, mouse skeletal muscle C2C12 cells differentiated into myocytes were treated with cobalt chloride (CoCl2) to induce a hypoxic condition, and the effects of GBC on various metabolic parameters were examined. Treatment of C2C12 myocytes with CoCl2 activated hypoxic glycolytic metabolism while suppressing aerobic mitochondrial metabolism responsible for efficient adenosine triphosphate (ATP) production. These metabolic alterations were supported by the following experimental findings: elevated activity and expression of lactate dehydrogenase A, increased expression of glyceraldehyde-3-phosphate dehydrogenase and increased lactate levels in the reaction medium; decreased expression of enzymes involved in fatty acid catabolism, including acyl-CoA oxidase, carnitine palmitoyltransferase 1, and peroxisome proliferator-activated receptor (PPAR) α; reduced expression of proteins associated with mitochondrial biogenesis, such as PPARγ coactivator-1α, nuclear respiratory factor 1, and mitochondrial transcription factor A; a reduction in mitochondrial content; and increased CoCl2-induced cytotoxicity and oxidative stress. However, these CoCl2-induced alterations were dose-dependently attenuated by GBC. In addition, GBC dose-dependently prevented ammonium phosphate—induced enhancement of lactate metabolism, the downregulation of fatty-acid-catabolizing enzymes, and the reduction in mitochondrial electron transport chain component proteins, including cytochrome c oxidase subunit 4. Fenofibrate, which is known to shift cellular metabolism from an anaerobic to an aerobic state, also effectively blocked the aforementioned actions of CoCl2, thereby supporting the observed effects of GBC. Taken together, these results suggest that GBC improves energy metabolism by encouraging mitochondrial content and expression of lipid catabolism-related genes, whereas suppressing anaerobic glycolysis in myocytes.