Background: The dermal extracellular matrix (ECM) is a dynamic scaffold composed mainly of proteins, with collagen as the key structural component providing resilience and support to the skin. Post‐menopause, declining estrogen levels lead to a significant reduction in skin health, notably a 30% decrease in collagen types I and III within 5 years. Aim: To discover natural extracts that stimulate collagen production. Methods: We utilized PathwayStudio to analyze protein–protein interactions and identify regulators of essential collagen types. Our study assessed Glycyrrhiza uralensis extract's ability to boost collagen production and enhance dermal density both in vitro and in vivo. Results: PathwayStudio analysis highlighted phytoestrogens including glycyrrhizin, isoliquiritigenin, liquiritigenin, liquiritin, and glabrol, as potential candidates. Liquorice rhizome ( G. uralensis ), used in traditional Chinese medicine, is rich in phytoestrogens like liquiritigenin. The G. uralensis extract increased collagen I and III gene expression and pro‐collagen I protein levels in human dermal fibroblasts and inhibited UVB and pollution‐induced matrix metalloproteinase‐1 (MMP1) production. In an in vivo study, a topical formulation containing the extract significantly improved dermal density after 56 days, measured by the DUB SkinScanner. Conclusions: These findings suggest G. uralensis extract as a promising agent for enhancing collagen production and skin health, particularly in postmenopausal women. Further research is needed to explore its mechanisms and long‐term effects.

The Scandinavian region is home to a unique biome with endemic plant species. The aim of this study was to explore this natural diversity and identify plant extracts providing positive skin barrier effects. Six plant extracts were identified as starting material. Following biochemical screening, two candidates outperformed the rest: Betula alba (BA) and Empetrum nigrum (EN). Quantitative PCR analysis showed that BA and EN upregulated barrier genes, when used individually and in combination. Betula alba increased AQP3 and OCLN protein expression, something niacinamide was incapable of. Additionally, the skin barrier was strengthened, evidenced by inhibition of KLK5 and hyaluronidase and showed strong antioxidant and anti-inflammatory activity through DPPH and COX2 inhibition, respectively. A first split-face clinical study was conducted using the combination of extracts versus placebo. There was a significantly better skin restructuring effect and corneocyte cohesion on the side treated with combined extracts. A second split-face clinical study assessed the combined extracts versus 3% niacinamide. Significant variations in skin hydration and TEWL were observed in favor of the extract treated side. In conclusion, we identified a natural alternative to niacinamide for improving skin barrier health, in Scandinavian plant extracts, which yield strong performance, but at a lower concentration.

Both UVB irradiation and air pollution are major extrinsic factors causing premature aging of the skin, including sagging, wrinkles, and pigmentation spots. Naringenin, a naturally occurring flavanone, found in citrus fruits, and known for its good antioxidant and anti-inflammatory effects, was investigated for protective effects in human skin cells and reconstructed epidermis. The results showed that naringenin inhibits UVB-induced inflammation markers MMP1, MMP3, IL6, and GM-CSF, as well as pollution-induced MMP1 in human skin fibroblasts. Furthermore, naringenin inhibited the pollution-induced expression of the CYP1A1 gene in human skin keratinocytes. In melanocytes and pigmented reconstructed epidermis, naringenin significantly downregulated several genes involved in melanogenesis, such as MITF, MLPH, and MYO5A. Additionally topical treatment with naringenin on pigmented reconstructed epidermis significantly decreased melanin production. In conclusion, this study demonstrates that naringenin could be a valuable ingredient in skincare products, protecting against the detrimental effects of both UVB and pollution on the skin.

Background/Objectives: Leucine-rich repeat kinase 2 (LRRK2) is an enzyme implicated in Parkinson’s disease (PD) and a potential therapeutic target. LRRK2 PET radioligands could therefore function as imaging biomarkers for PD and as tools to measure enzyme occupancy of novel therapeutic candidates. This study aimed at developing novel radioligands for imaging using positron emission tomography (PET). Specific objectives were to synthesize fluorine-18-labeled pyrrolopyridine 1 ([¹⁸F]1), pyrrolo-pyrimidine 2 ([¹⁸F]2), as well as carbon-11-labeled pyrrolo-pyrimidine 3 ([¹¹C]3), and examine their binding specificity, using in vitro autoradiography (ARG) and in vivo positron emission tomography (PET) imaging in non-human primates (NHPs). Methods: Radiolabeling was achieved either by classical one-step fluorine-18 nucleophilic substitution reaction or by methylation using carbon-11 methane. [¹⁸F]1 and [¹⁸F]2 were tested in NHP and human whole-hemisphere ARG experiments. PET imaging was performed in cynomolgus monkeys. Radiometabolites were measured in monkey plasma using gradient HPLC. Results: The results demonstrated successful radiolabeling of all three ligands. In ARG studies, both [¹⁸F]1 and [¹⁸F]2 displayed binding in brain slices from NHP and human samples. The binding of [¹⁸F]1 was blocked by cold Compound 1 and structurally distinct Compound 3, but not by the structurally distinct LRRK2 inhibitor PFE-360. On the other hand, the binding of [¹⁸F]2 was blocked by PFE-360 in certain regions of the brain, indicating some level of specific binding to LRRK2. All three ligands showed relevant brain uptake (>3%ID), with highest uptake being observed for [¹⁸F]1, particularly in the thalamus. In contrast, brain uptake of [¹⁸F]2 and [¹¹C]3 was evenly distributed across all brain regions. No blocking effect of [¹⁸F]1 was observed after pretreatment with the structurally distinct LRRK2 inhibitors PFE-360 (0.5 mg/kg, iv) and GEN-7915 (40 mg/kg). Conclusions: PET imaging indicated a low in vivo specific binding of the radioligands in the cynomolgus monkey brain, suggesting that the radioligands are not suitable for LRRK2 imaging in vivo with PET. This study emphasizes the challenges in the development of PET radioligands for imaging LRRK2 and the need for additional work to achieve this goal.