Modulatory effects of cinnamomi cortex and its components epicatechin and linalool on skin circadian rhythms

Circadian rhythms, intrinsic 24-h cycles regulating physiological processes, are crucial for skin homeostasis. Disruptions in these rhythms are linked to various skin disorders and impaired barrier function. Circadian rhythms can be modulated by botanical compounds, which hold therapeutic potential. However, the effect of cinnamomi cortex (CC), an anti-inflammatory, antioxidant, and antimicrobial agent, on the circadian rhythm of keratinocytes remains unclear. This study aimed to examine the effects of CC extract and its 18 individual components on the circadian rhythm of HaCaT, an immortalized human keratinocyte line. CC extract and its bioactive components epicatechin (EC) and linalool (LO) significantly enhanced the circadian amplitude without altering the period. Gene expression analysis revealed that CC extract, EC, and LO altered the mRNA and protein levels of clock genes in a time-dependent manner. During molecular docking simulations, both EC and LO exhibited strong binding affinities for RORA, a key nuclear receptor involved in circadian regulation. Enhanced BMAL1 promoter activity following EC and LO treatments corroborated these findings. Furthermore, EC and LO demonstrated significant antioxidant activities, as evidenced by reduced reactive oxygen species levels and increased expression of antioxidant enzymes. EC and LO also upregulated skin barrier-related and ceramide synthesis genes and modulated the expression of cellular longevity-promoting genes. In conclusion, CC extract, particularly the components EC and LO, modulated circadian rhythms, reduced oxidative stress, and enhanced skin barrier function in keratinocytes. These findings highlight the potential of CC extract and its components as novel dermatological treatments to improve skin health and combat aging.