A new phthalide derivative from the mushroom Cyclocybe cf. erebia culture filtrate affects the phase of circadian rhythms in mouse fibroblasts.

Abstract

Circadian rhythms are biological systems that provide approximately 24-hour cycles for the behavior and physiological functions of organisms. As diverse modern lifestyles often cause disturbances in circadian rhythms, new approaches to their regulation are required. Therefore, new compounds that affect circadian rhythms have been explored in edible mushrooms. The extract from the culture filtrate of Cyclocybe cf. erebia showed activity that advanced the circadian rhythm in a bioassay with mouse fibroblasts expressing the LUCIFERASE protein under the control of the Period2 promoter. Bioassay-guided fractionation of the extract resulted in the isolation of the compound. Spectroscopic analyses identified the compound as a phthalide derivative, and the compound was named cyclocybelide. Treatment of mouse fibroblasts with the compound shifted the circadian rhythm forward, irrespective of the timing of treatment. In addition, some phthalide derivatives with hydroxy and methoxy groups showed similar effects on circadian rhythms.