Abstract

Hypoxia-induced cardiomyocyte death plays a critical role in the deterioration of many heart diseases. Danshen (Salvia miltorrhiza), a famous traditional Chinese medicine, has shown a cardio-protective effect in both clinical and animal studies. Nevertheless, the mechanism underlying its cardioprotective effects, particularly the improvement of energy metabolism, is rarely known. Hence, the purposes of this study were to determine the active glucose metabolism involved in cardio-protection of Danshen and its possible mechanisms. Cardiomyocytes from neonatal rat were pretreated with Danshen or vehicle for 24 h, and then exposed to 1% O₂ for 12 h. Cellular viability, lactate dehydrogenase release, glucose uptaking, lactate leakage, pH, cell death, and the mRNA levels of hypoxia inducible factor-1α (HIF-1α) and glucose transporter 1 (Glut 1) were investigated. After pretreating with Danshen, the hypoxia-induced cellular damages in cardiomyocytes were significantly attenuated. Besides, the mRNA levels of HIF-1α and Glut 1 were up-regulated in parallel with the enhancement of glucose uptake and metabolism in Danshen-treated cardiomyocytes. 2-Methoxyestradiol (2-ME), a HIF inhibitor, obviously reduced these protections. Our results indicate that Danshen prevents hypoxia-induced cardiomyocyte death by enhanced glucose uptaking in a HIF-1α dependent manner.

Key words: Danshen, hypoxia, hypoxia inducible factor (HIF).

Abbreviation

HIF-1, Hypoxia inducible factor-1; TCM, traditional Chinese medicine; Glut 1, glucose transporter 1; 2-ME, 2-methoxyestradiol.