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

Yusei Kobayashi; Yuanyuan Lu; Nan Li; Naoki Endo; Kozue Sotome; Kotomi Ueno; Yu Tahara; Atsushi Ishihara

doi:10.1093/bbb/zbae187

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

Biosci Biotechnol Biochem. 2024 Dec 5:zbae187. doi: 10.1093/bbb/zbae187. Online ahead of print.

Authors

Yusei Kobayashi¹, Yuanyuan Lu², Nan Li², Naoki Endo³, Kozue Sotome³, Kotomi Ueno⁴, Yu Tahara², Atsushi Ishihara^{3

4}

Affiliations

¹ The United Graduate School of Agricultural Sciences, Tottori University, Tottori, 680-8553, Japan.
² Department of Public Health and Health Policy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-0037, Japan.
³ Fungus/Mushroom Resource and Research Center, Faculty of Agriculture, Tottori University, Minami 4-101, Koyama, Tottori, Tottori 680-8553, Japan.
⁴ Faculty of Agriculture, Tottori University, 4-101, Koyama-cho Minami, Tottori, 680-8553, Japan.

PMID: 39657072
DOI: 10.1093/bbb/zbae187

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.

Keywords: Cyclocybe cf. erebia, lactone; Period2; circadian rhythm; mushroom.