Rosacea is a chronic inflammatory disease affecting facial skin. It is associated with immune and vascular dysfunction mediated via increased expression and activity of cathelicidin and kallikrein 5 (KLK5), a serine protease of stratum corneum. Therefore, KLK5 inhibitors are considered as therapeutic agents for improving the underlying pathophysiology and clinical manifestation of rosacea. Here, we isolated the active constituents of Artemisia lavandulaefolia (A. lavandulaefolia) and investigated their inhibitory effect on KLK5 protease activity. Using bioassay-guided isolation, two bioactive compounds including chlorogenic acid isomers, 3,5-dicaffeoylquinic acid (isochlorogenic acid A) (1), and 4,5-dicaffeoylquinic acid (isochlorogenic acid C) (2) were isolated from A. lavandulaefolia. In this study, we evaluated the effects of isochlorogenic acids A and C on dysregulation of vascular and immune responses to rosacea, and elucidated their molecular mechanisms of action. The two chlorogenic acid isomers inhibit KLK5 protease activity, leading to reduced conversion of inactive cathelicidin into active LL-37. This inhibition of LL-37 production by isochlorogenic acids A and C reveals the efficacy of suppressing the expression of inflammatory mediators induced by LL-37 in immune cells such as macrophages and mast cells. In addition, both isomers of chlorogenic acid directly inhibited the proliferation and migration of vascular endothelial cells induced by LL-37.

The activation of hair follicle dermal papilla cells (HFDPCs), a critical target of hair loss relief, can be achieved through the upregulation of proliferation, the stimulation of hair inducibility, and the inhibition of cellular senescence. Veratric acid (VA) is a major benzoic acid found in fruits and vegetables. The biological activity of VA on HFDPCs remains to be elucidated. In this study, we investigated the capacity of VA for hair loss mitigation. An MTT assay, Ki67 staining, quantitative RT-PCR (qRT-PCR), and a Western blot analysis were performed to confirm the proliferative effect of VA. Hair inductivity was determined through a cell aggregation assay and ALP staining. Annexin V/PI staining was performed to confirm the anti-apoptotic effect of VA. The inhibitory effect of VA on cellular senescence was confirmed by a β-galactosidase (β-gal) assay and qRT-PCR using replicative senescence and oxidative stress-induced senescence models. As a result, VA dose-dependently upregulated the proliferation of HFDPCs, the expression of growth factors, and β-catenin protein levels. VA also dose-dependently increased ALP activity and cell aggregation and decreased apoptotic cells through the regulation of BCL2 and BAX expression. Moreover, VA reduced β-gal activity and the senescence-associated secretory phenotype (SASP) in a dose-dependent manner in senescent HFDPCs. These findings suggest that VA may serve as a potential therapeutic agent for alleviating hair loss by targeting multiple pathways involved in HFDPC activation.

Skin aging is characterized by fibroblast senescence, extracellular matrix (ECM) degradation, and impaired wound healing, driven by oxidative stress and telomere dysfunction. Here, we investigated the anti-aging effects of a standardized microwave-assisted propolis extract (MAPE) in both H₂O₂-induced and replicative senescence models of human dermal fibroblasts (HDFs). MAPE significantly reduced reactive oxygen species (ROS) accumulation and enhanced antioxidant gene expression (NQO1, GCLM), indicating activation of NRF2-dependent defense pathways. It suppressed senescence markers (CDKN2A, CDKN1A, IL6), decreased SA-β-gal activity, and attenuated inflammaging. Moreover, MAPE inhibited MMP1 expression, restored COL1A1, and improved fibroblast wound closure, thereby maintaining ECM homeostasis. Importantly, MAPE modulated Wnt/β-catenin signaling by upregulating WNT3A and LEF1 while suppressing DKK1, and increased TERT expression, suggesting involvement of telomerase-related regulatory pathways. These effects resembled those of CHIR99021, a canonical Wnt activator, while providing additional antioxidant protection. Together, our findings suggest that MAPE is a propolis-derived bioactive ingredient that counteracts fibroblast senescence through coordinated modulation of NRF2 and Wnt/β-catenin–TERT signaling pathways, supporting its potential as a cosmeceutical ingredient for mitigating skin aging.

The aim of this study was to investigate the effect of Sargassum fusiforme extract (SFE) on melanogenesis and its mechanism both in vitro and ex vivo. The melanogenic-inducing effect of SFE was evaluated using a melanin contents assay and a cellular tyrosinase activity assay. To investigate whether SFE could protect melanocytes against oxidative stress, hydrogen peroxidase was used. The molecular mechanism underlying the effect of SFE on melanogenesis was determined via Western blot analysis of tyrosinase, a microphthalmia-associated transcription factor (MITF), and a phosphorylated cAMP response element-binding protein (p-CREB) expression. The degree of pigmentation in a 3D skin model was determined by measuring the L* values. Contents of melanin in ex vivo human hair follicles were evaluated via Fontana–Masson staining. SFE significantly increased melanin contents and cellular tyrosinase activity in human epidermal melanocytes. SFE also increased the phosphorylation of CREB and the protein levels of tyrosinase and MITF. Moreover, SFE attenuated oxidative stress-induced cytotoxicity and depigmentation. Finally, the melanogenesis promoting effect of SFE was confirmed in both a 3D skin model and ex vivo human hair follicles. These findings suggest that SFE can induce melanogenesis via the cAMP/PKA/CREB signaling pathway in human epidermal melanocytes through its hyperpigmentation activity.

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.