Endophytic fungal metabolite fumigaclavine C causes relaxation of isolated rat aortic rings

Two indole alkaloids were isolated from the culture of Aspergillus fumigatus (strain No. CY018), an endophytic fungus harboring inside the elder leaf of Cynodon dactylon. These two chemicals were identified as fumigaclavine C and fumitremorgin C. In screening the bioactivity of these two indole alkaloids, their vasorelaxant effects on isolated rat thoracic aortic rings were observed. The results showed that fumigaclavine C exhibited potent concentration-dependent vasorelaxant actions in isolated rat aortic rings pre-contracted by high K+ or phenylephrine (with EC50 values of 5.62 mu mol/L and 1.58 mu mol/L, respectively) whereas fumitremorgin C displayed a weaker vasorelaxation. A detailed investigation was therefore performed with fumigaclavine C. The vasorelaxing action of fumigaclavine C is independent of the presence of endothelium, suggesting its effect of vasorelaxation was not related to endothelial mediators. Blockage of L-type voltage-dependent calcium channels, activation of ATP-sensitive potassium channels and inhibition of Ca2+ release from intracellular Ca2+ stores may be involved in fumigaclavine C induced relaxation of rat isolated aortic rings. These results demonstrate that fumigaclavine C from the endophytic fungus has a potential capacity in vascular protection and thus may have therapeutic use in protection against cardiovascular disease.