Cedrol mitigates hepatic lipid accumulation and adipocyte hypertrophy induced by corticosteroids through the inhibition of glucocorticoid receptor activity.

Cedrol is a sesquiterpene alcohol derived from ginger and cedar oil. Cedrol has multiple pharmacological effects such as sedation, promoting hair growth, decreasing blood pressure and reducing obesity. But its pharmacological mechanisms are not fully understood and its direct targets remain unknown. Glucocorticoids, particularly dexamethasone, are stress hormones in the body and interact with glucocorticoid receptors (GRs) to regulate physiological functions such as metabolism. In this study, we find that cedrol effectively mitigates the lipid accumulation in liver and adipose tissues induced by dexamethasone in adult male mice. Cedrol treatment also inhibits the dexamethasone-induced expression of genes involved in lipid metabolism, including Cd36, C/ebpβ, Srebp1, Fas and Scd1 in the liver. In addition, cedrol binds to GR in the cellular thermal shift assay and shows antagonistic activity in luciferase reporter assays. These results indicate that cedrol has GR antagonist activity, which may be responsible for its effect on lipid metabolism, and suggest that cedrol could also be potentially used in the treatment of lipid metabolism disorders induced by high glucocorticoids.