Melatonin is ubiquitously present in all animals and plants, where it exerts a variety of physiological activities thanks to its antioxidant properties and its key role as the first messenger of extracellular signaling functions. Most of the clinical studies on melatonin refer to its widespread oral use as a dietary supplement to improve sleep. A far smaller number of articles describe the clinical applications of topical melatonin to treat or prevent skin disorders by exploiting its antioxidant and anti-inflammatory activities. This review focuses on the clinical studies in which melatonin was applied on the skin as a photoprotective, anti-aging, or hair growth-promoting agent. The methodologies and results of such studies are discussed to provide an overall picture of the state of the art in this intriguing field of research. The clinical studies in which melatonin was applied on the skin before exposure to radiation (UV, sunlight, and high-energy beams) were all characterized by an appropriate design (randomized, double-blind, and placebo-controlled) and strongly support its clinical efficacy in preventing or reducing skin damage such as dermatitis, erythema, and sunburn. Most of the studies examined in this review do not provide a clear demonstration of the efficacy of topical melatonin as a skin anti-aging or as a hair growth-promoting agent owing to limitations in their design and/or to the use of melatonin combined with extra active ingredients, except for one trial that suggests a possible beneficial role of melatonin in treating some forms of alopecia in women. Further research efforts are required to reach definitive conclusions concerning the actual benefits of topical melatonin to counteract skin aging and hair loss.

Although edible flowers have been historically principally used due to their visual appeal and smell, the world is discovering their value as innovative and natural sources of bioactive compounds. Cucurbita pepo L. (CpL), a plant from the Cucurbitaceae family, is widely cultivated for its edible fruits and flowers, which are rich in polyphenols and carotenoids—compounds known for their potent antioxidant and anti-inflammatory properties. Despite their potential, the use of CpL flowers for skin-related applications remains underexplored. This study aimed to comprehensively analyze CpL flower extract (CpLfe), focusing on its polyphenolic and carotenoid content using, for the first time, advanced UHPLC-Q-Orbitrap HRMS and HPLC-DAD analysis. CpLfe highlighted remarkable antioxidant activity according to the DPPH, ABTS, and FRAP tests. CpLfe showed significantly reduced intracellular ROS in HaCaT (23%, p < 0.05) and protected against UVB-induced damage by lowering MMP-1 expression. CpLfe also upregulated genes crucial for skin hydration (AQP3) and barrier function (CerS2, CerS4, and CerS6). A placebo-controlled, randomized clinical trial further validated CpLfe efficacy, demonstrating marked improvements in moisture retention, wrinkle reduction, and collagen production in women aged 35–55. These findings suggested that CpL flowers could be a source of bioactive compounds recovered from edible flowers able to improve the major skin aging and photoaging features.

Metabolites resulting from the bacterial fermentation of dietary fibers, such as short-chain fatty acids, especially butyrate, play important roles in maintaining gut health and regulating various biological effects in the skin. However, butyrate is underutilized due to its unpleasant odor. To circumvent this organoleptic unfavorable property, phenylalanine butyramide (PBA), a butyrate precursor, has been synthesized and is currently available on the market. We evaluated the inhibition of mushroom tyrosinase by butyrate and PBA through in vitro assays, finding IC₅₀ values of 34.7 mM and 120.3 mM, respectively. Docking calculations using a homology model of human tyrosinase identified a putative binding mode of PBA into the catalytic site. The anti-aging and anti-spot efficacy of topical PBA was evaluated in a randomized, double-blind, parallel-arm, placebo-controlled clinical trial involving 43 women affected by photo-damage. The results of this study showed that PBA significantly improved skin conditions compared to the placebo and was well tolerated. Specifically, PBA demonstrated strong skin depigmenting activity on both UV and brown spots (UV: −12.7% and −9.9%, Bs: −20.8% and −17.7% after 15 and 30 days, respectively, p < 0.001). Moreover, PBA brightened and lightened the skin (ITA°: +12% and 13% after 15 and 30 days, respectively, p < 0.001). Finally, PBA significantly improved skin elasticity (Ua/Uf: +12.4% and +32.3% after 15 and 30 days, respectively, p < 0.001) and firmness (Uf: −3.2% and −14.9% after 15 and 30 days, respectively, p < 0.01).

Over the preceding five decades, there has been a noticeable surge in the pursuit of achieving voluminous and well-defined lips. This trend has prompted an escalating number of individuals to undergo lip augmentation procedures, aiming for a natural three-dimensional enhancement of lip volume and distinct vermilion borders. Despite the proliferation of lip augmentation techniques, there remains a dearth of comprehensive investigations into their precise effects on the three-dimensional structural integrity of the lips. This research endeavors to address this gap by employing stereophotogrammetry as a quantitative tool to scrutinize lip augmentation outcomes and to appraise the efficacy of lip plumpers. The study methodology involves a comparative analysis of lip dimensions among subjects treated with a commercial lip plumper using multi-spectral imaging for lip dimension assessment, coupled with markerless tracking technology and 3D interpolating surface methodology to analyze lip volume and shape. Additionally, the study evaluated lip youth state, including moisture level, softness, firmness, and tissue density. The demand for lip augmentation procedures is driven by perceived advantages such as quick recovery and minimal risk. Therefore, it is crucial to substantiate their efficacy with robust findings. The investigation suggests that both 3D and 2D stereophotogrammetry techniques are reliable for evaluating lip size before and after augmentation, whether through cosmetic or aesthetic approaches. Overall, the study provides a comprehensive analysis of a lip treatment aimed at enhancing volume and redesigning lip lines. It demonstrates that stereophotogrammetry is effective for assessing 3D lip dimensions and their correlation with internal lip structure. This research could be particularly valuable for evaluating the efficacy and duration of various lip enhancement techniques, including dermal fillers, implants, and topical cosmetic formulations, offering quantitative and reproducible assessments over time.

The skin barrier is essential for maintaining epidermal homeostasis and preventing transepidermal water loss (TEWL). This study investigated the ability of a Hyssopus officinalis cell culture hydroethanolic extract to support epidermal barrier function by modulating ceramide-related enzymes and structural proteins. Hydroethanolic extracts from cell cultures grown under light and dark conditions were characterized by high-resolution mass spectrometry. Dark-grown cultures accumulated higher levels of rosmarinic acid, hydroxytyrosol glycosides, and polymethoxyflavones than light-grown cultures and intact plants. In keratinocytes, the extract from dark-grown cells (HoEx) at 0.002% w/v exhibited significant antioxidant activity (20% ROS reduction) and increased β-glucocerebrosidase (GBA) activity (25%) as well as the expression of β-glucocerebrosidase (44%), serine palmitoyltransferase (34%), involucrin (17%), and filaggrin (44%) compared with control. In human skin explants, 0.5% w/w HoEx increased ceramide content (36%) and total epidermal lipid levels (99%) relative to control. In a clinical study involving 10 volunteers with mechanically stressed skin, 0.5% w/w HoEx increased GBA activity by 30% and reduced TEWL by 15%, whereas placebo treatment led to a 55% decrease in GBA activity and a 25% increase in TEWL. Collectively, these findings indicate that HoEx modulates multiple epidermal pathways involved in lipid processing and differentiation under in vitro, ex vivo, and stressed in vivo conditions. While the study was not designed to establish mechanistic causality, the coordinated modulation of ceramide-related enzymes, structural proteins, and TEWL suggests that HoEx may support epidermal barrier function within the limits of the tested models. HoEx therefore represents a standardized source of bioactive compounds with potential relevance for dermocosmetic applications.