A Novel Traditional Chinese Medicine ameliorates fatigue-induced cardiac hypertrophy and dysfunction via regulation of energy metabolism

Aims：Prolonged exercise and exercise training can adversely affect cardiac function in some individuals. QiShenYiQi Pills® (QSYQ), a compound Chinese medicine，has been previously shown to improve pressure overload-induced cardiac hypertrophy. We hypothesized that QSYQ can ameliorate as well the fatigue-induced cardiac hypertrophy. This study was to test this hypothesis and underlying mechanism with focusing on its role in energy regulation. Methods：Male Sprague-Dawley rats were used to establish exercise adaption and fatigue model on a motorized rodent treadmill. Echocardiographic analysis and heart function test were performed to assess heart systolic function. Food-Intake Weight/Body Weight, Heart Weight/Body Weightwere assessed, hematoxylin and eosin staining, and immunofluorescence staining of myocardium sections were performed. ATP synthase expression and activity, ATP, ADP and AMP levels were assessed using Western blotand ELISA. Expression of proteins related to energy metabolism and IGF-1R signaling was determined using Western blot. Results:QSYQ attenuated Food-Intake Weight/Body Weight decrease, improved myocardial structure and heart function, restored the expression and distribution of myocardial cx43 after fatigue, concomitant with an increased ATP production and a restoration of metabolism-related proteins expression. QSYQ upgraded the expression of IGF-1R, P-AMPK/AMPK, PGC-1α, Nrf1, P-PI3K/PI3K and P-Akt/Akt thereby attenuated the dysregulation of IGF-1R signaling after fatigue. Conclusion：QSYQ relieved fatigue-induced cardiac hypertrophy and enhanced heart function, which is correlated to its potential to improve energy metabolism by regulating IGF-1R signaling.