Introduction: The mulberry tree (Morus alba L.) is a prolific source of biologically active compounds. There is considerable growing interest in probing M. alba twigs as a source of disruptive antioxidant lead candidates for cosmetic skin care product development.Objective: An integrated approach using high‐performance liquid chromatography (HPLC) coupled with either chemical detection (CD) or high‐resolution mass spectrometry (HRMS) was applied to the hydroalcoholic extract of M. alba to detect and identify lead antioxidant compounds, respectively.Material and methods: The twigs were weighed, powdered and homogenized using a mill and the extract was prepared using 70% aqueous ethanol. The antioxidant metabolites were detected with HPLC coupled with CD (based on the ORAC assay) and their structural identification was carried out using a Q‐Exactive Orbitrap MS instrument.Results: Using this approach, 13 peaks were detected as overall contributors to the antioxidant activity of M. alba, i.e. mulberrosides (A & E), oxyresveratrol & its derivatives, moracin & its derivatives and a dihydroxy‐octadecadienoic acid, which together accounted for >90% of the antioxidant activity, highlighting the effectiveness of the integrated approach based on HPLC‐CD and HPLC‐HRMS. Additionally, a (3,4‐dimethoxyphenyl‐1‐O‐β‐D‐apiofuranosyl‐(1″ → 6′)‐O‐β‐D‐glucopyranoside was also discovered for the first time from the twig extract and is presented here.Conclusion: To our knowledge, this is the first report from M. alba twigs using HPLC‐CD and HPLC‐HRMS that identifies key compounds responsible for the antioxidant property of this native Chinese medicinal plant.

Cosmetics legislation in Europe has driven the validation and acceptance of non-animal alternatives, most recently in the area of skin sensitization. Despite use of these methods to meet regulatory needs, it is also essential that they allow evaluation regarding human safety. For cosmetic product safety, it is necessary to understand how they can be used and with what limitations, and thereby reveal what remains to be addressed. A dataset of 165 ingredients (137 cosmetic ingredients +28 reference substances) has been identified, curated, and subjected to testing using accepted in vitro methods, with additional information, including physicochemical data and in silico results. The inputs from multiple determinants of skin sensitizing activity have been used in five individual supervised classification models (or machine learning approaches), which were then collated in a robust statistical manner, a stacking meta-model, to deliver a prediction with an optimized level of confidence. For the training set, with the probability cutoffs at 70% and 30%, predictive sensitivity was 97%, specificity was 88%, the overall accuracy was 93%, and kappa was 85%. A further 52 substances were used to test the effectiveness of the model: the predictive sensitivity was 89%, specificity was 95%, overall accuracy was 91%, and kappa was 82%. In conclusion, this stacking meta-model delivers improved performance and therefore enhanced confidence in the discrimination of skin sensitizers from nonsensitizers. The key remaining gap, prediction of skin sensitization potency, may benefit from a similar approach, maximizing use of evidence from individual strands of prediction, while minimizing the impact of the limitations from any particular one.

Filipendula ulmaria, commonly known as meadowsweet, is a wild herbaceous flowering plant that is widely distributed in Europe. A range of salicylic acid derivatives and flavonol glycosides have been previously associated with the antirheumatic and diuretic properties of F. ulmaria. In the present work, a hydroalcoholic extract from F. ulmaria aerial parts was extensively profiled using an efficient NMR-based dereplication strategy. The approach involves the fractionation of the crude extract by centrifugal partition chromatography (CPC), ¹³C NMR analysis of the fractions, 2D-cluster mapping of the entire NMR dataset, and, finally, structure elucidation using a natural metabolite database, validated by 2D NMR data interpretation and liquid chromatography coupled with mass spectrometry. The chemodiversity of the aerial parts was extensive, with 28 compounds unambiguously identified, spanning various biosynthetic classes. The F. ulmaria extract and CPC fractions were screened for their potential to enhance skin epidermal barrier function and skin renewal properties using in vitro assays performed on Normal Human Epidermal Keratinocytes. Fractions containing quercetin, kaempferol glycosides, ursolic acid, pomolic acid, naringenin, β-sitosterol, and Tellimagrandins I and II were found to upregulate genes related to skin barrier function, epidermal renewal, and stress responses. This research is significant as it could provide a natural solution for improving hydration and skin renewal properties.

Background: Within the solar ultraviolet (UV) spectrum, ultraviolet A rays (UVA, 320–400 nm), although less energetic than ultraviolet B rays (UVB, 280–320 nm), constitute at least 95% of solar UV radiation that penetrates deep into the skin The UV rays are associated with both epidermal and dermal damage resulting from the generation of reactive oxygen species (ROS). Among them, the longest UVA wavelengths (UVA1, 340–400 nm) can represent up to 75% of the total UV energy. Therefore, UVA radiation is linked to various acute and chronic conditions, including increased skin pigmentation and photoaging. Despite many advances in the skin photoprotection category, there is still a growing demand for natural daily photoprotection active ingredients that offer broad protection against skin damage caused by UVA exposure. In our quest to discover new, disruptive, next generation of photoprotective ingredients, we were drawn to pomegranate, based on its diverse polyphenolic profile. We investigated the pericarp of the fruit, so far considered as byproducts of the pomegranate supply chain, to design a novel patented extract “POMAOX” with a desired spectrum of phenolic components comprising of αβ-punicalagins, αβ-punicalins and ellagic acid. Methods: Antioxidant properties of POMAOX were measured using in-tubo standard tests capable of revealing a battery of radical oxygen species (ROS): peroxyl radical (ORAC), singlet oxygen (SOAC), superoxide anion (SORAC), peroxynitrite (NORAC), and hydroxyl radical (HORAC). In vitro, confirmation of antioxidant properties was first performed by evaluating protection against UVA-induced lipid peroxidation in human dermal fibroblasts (HDF), via the release of 8 iso-prostanes. The protection offered by POMAOX was further validated in a 3D in vitro reconstructed T-Skin^TM model, by analyzing tissue viability/morphology and measuring the release of Matrix Metallopeptidase 1 (MMP-1) & pro-inflammatory mediators (IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNF-α) after UVA1 exposure. Results: POMAOX displayed strong antioxidant activity against peroxynitrite (NORAC) at 1.0–3.0 ppm, comparable to the reference vitaminC, as well as singlet oxygen (SOAC) at 220 ppm, and superoxide radicals with a SORAC value of 500 ppm. Additionally, POMAOX demonstrated strong photoprotection benefit at 0.001% concentration, offering up to 74% protection against UVA-induced lipid peroxidation on HDF, in a similar range as the positive reference, Vitamin E at 0.002% (50 µM), and with higher efficacy than ellagic acid alone at 5 µM. Moreover, our pomegranate-derived extract delivered photoprotection at 0.001%, mitigating dermal damages induced by UVA1, through inhibition of MMP-1 and significant inhibition of pro-inflammatory mediators release (including IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNFα) on an in vitro reconstructed full-thickness human skin model with a similar level of protection to that of Vitamin C tested at 0.035% (200 µM). Conclusions: Overall, the novel pomegranate-derived extract “POMAOX” significantly reduced the impact of UVA on human skin, due to its broad-spectrum antioxidant profile. These findings suggest that POMAOX could offer enhanced protection against the detrimental effects of UV exposure, addressing the growing consumer demand for strong photoprotection with skincare benefits.

The skin hydration level is a key factor that influences the physical and mechanical properties of the skin. The stratum corneum (SC), the outermost layer of the epidermis, is responsible for the skin’s barrier function. In this study, we investigated the role of a unique composition of Viola yedoensis extract for its ability to activate CD44, a cell-surface receptor of hyaluronic acid, and aquaporin-3, a water-transporting protein, in human keratinocytes (HaCaT). An ELISA assay evaluating the protein expression levels of CD44, aquaporin-3 (AQP3), filaggrin, and keratin-10 revealed that V. yedoensis extract upregulated the levels of CD44 and AQP3 by 15% and 78%, respectively. Additionally, V. yedoensis extract demonstrated a comparative effect on water vapor flux in TEWL and lipid perturbation in DSC versus the reference, glycerin. In light of this new biological efficacy, a detailed phytochemical characterization was undertaken using an integrated LC-HRMS/MS-based metabolomics approach, which provided further insights on the chemistry of V. yedoensis. This led to the identification of 29 secondary metabolites, 14 of which are reported here for the first time, including esculetin, aesculin, apigenin and kaempferol C-glycosides, megastigmane glycosides, roseoside, platanionoside B, and an eriojaposide B isomer, along with the rare, calenduloside F and esculetin diglucoside, which are reported for the first time from the genus, Viola. Notably, two active components identified in the V. yedoensis extract, namely, aesculin and schaftoside, showed an upregulation of the protein expression of CD44 in HaCaT cells by 123% and 193% within 24 h of treatment, respectively, while aesculin increased AQP3 levels by 46%. Aesculin and schaftoside also significantly upregulated the expression of K-10 levels by 299% and 116%, which was considerably higher than sodium hyaluronate, the positive control. The rationale used to characterize the new structures is outlined along with the related biosynthetic pathways envisioned to generate roseoside and Eriojaposide B. These findings provide new molecular insights to deepen the understanding of how V. yedoensis extract, along with the biomarkers aesculin and schaftoside, restores the skin barrier and skin hydration benefits.