Concurrent Changes in Facial Skin Parameters, Sleep, and the Salivary Melatonin Day–Night Difference During Topical Use of a Clock-Oriented Six-Botanical Formulation: An Exploratory 4-Week, Single-Arm Pilot Study

Insufficient sleep can disrupt circadian organization and adversely affect skin condition. Perturbation of the cutaneous clock, which governs skin homeostasis, may contribute to this deterioration. In our study, a six-botanical mixture extract increased PER2 promoter-driven luciferase output in HaCaT keratinocytes, and reduced IL6 and CXCL10 expression, two PER2-associated inflammatory mediators. Separately, a 4-week single-arm pilot study evaluated a cream containing 2.00% (w/w) of a liquid preparation of this extract, applied nightly by 22 women aged 40–70 years with poor sleep quality. Skin indicators, sleep, mood, and salivary melatonin and cortisol were assessed as changes from baseline at week 4. The 13 skin indicators changed from baseline across the anti-aging, barrier, complexion, and dark-circle categories (Cohen’s d 0.47–4.81). Sleep duration increased, whereas PSQI-K and PHQ-9 scores decreased; the melatonin day–night difference increased (d = 0.75); cortisol measures did not change significantly. No adverse skin reactions were reported. These exploratory findings do not establish product-attributable efficacy or a causal PER2-mediated mechanism; placebo, vehicle, expectancy, seasonal, behavioral, and regression-to-the-mean effects cannot be excluded. A randomized, vehicle-controlled study is required, with prespecified primary outcomes, denser circadian sampling, and clock activity measured directly in treated skin.