Purpose: Dihydromyricetin (DHM) is the major bioactive constituent of Rattan Tea. Our aim was to investigate the effect of DHM, in counteracting hypobaric hypoxia (HH)-induced exercise intolerance and the possible mechanism.
Methods: Male Sprague-Dawley rats were pretreated with three doses of DHM (50, 75, and 100 mg/kg) for 7 days and subjected to simulated high altitude conditions (5,000 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 (TEM). Proteins expression was detected by western blotting. The activity of mitochondrial electron transport chain was analyzed by enzyme-linked immuno-sorbent assay.
Results: 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 50mg/kg, 75mg/kg, 100mg/kg 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 mtDNA 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-[gamma] coactivator 1[alpha], sirtuin1, nuclear respiratory factor 1, mitochondrial transcription factor A, AMP-activated protein kinase, and AMPK phosphorylation, were significantly down-regulated in HH, while DHM pretreatment significantly restored expression levels. DHM also modulated mitochondrial dynamics of fusion and fission by increasing mitofusin-1 and 2, meanwhile decreasing fission-related dynamin-related protein 1 and mitochondrial fission 1.
Conclusions: DHM improves physical performance under simulated high altitude conditions via protecting mitochondrial biogenesis and modulating mitochondrial dynamics in skeletal muscle cells.
(C) 2014 American College of Sports Medicine