Dihydromyricetin Improves Physical Performance under Simulated High Altitude

Abstract

Dihydromyricetin (DHM) is the major bioactive constituent of rattan tea. Our aim was to investigate the possible mechanism and the effect of DHM in counteracting hypobaric hypoxia (HH)-induced exercise intolerance. Male Sprague-Dawley rats were pretreated with three doses of DHM (50, 75, and 100 mg · kg(-1)) for 7 d and subjected to simulated high-altitude conditions (5000 m with 10.9% oxygen). Physical performance was assessed with the run-to-fatigue model. Mitochondrial morphology in the gastrocnemius muscle was observed by transmission electron microscopy. Protein expression was detected by western blotting. The activity of mitochondrial electron transport chain was analyzed by enzyme-linked immunosorbent assay. DHM administration prolonged the run-to-fatigue time in a dose-dependent manner compared with the control (22.9 ± 2.2, 46.1 ± 4.4, 61.3 ± 3.1 vs 18.4 ± 1.7 min, which represented 50, 75, 100 mg · kg(-1), and the control groups, respectively). DHM also reduced serum blood urea nitrogen, lactate dehydrogenase, and creatine kinase activity levels. HH-induced mitochondrial injuries, including morphological changes, reduction in mitochondrial density and mitochondrial DNA content, and decrease in respiratory chain complex (I, II, IV, and V) activities were effectively attenuated by DHM. Protein expression of mitochondrial biogenesis markers, including peroxisome proliferator-activated receptor-γ coactivator 1α, sirtuin 1, nuclear respiratory factor 1, mitochondrial transcription factor A, AMP-activated protein kinase, and AMP-activated protein kinase phosphorylation, was significantly downregulated in HH, whereas DHM pretreatment significantly restored expression levels. DHM also modulated mitochondrial dynamics of fusion and fission by increasing mitofusins 1 and 2, while decreasing fission-related, dynamin-related protein 1 and mitochondrial fission 1. DHM improves physical performance under simulated high-altitude conditions via protecting mitochondrial biogenesis and modulating mitochondrial dynamics in skeletal muscle cells.