Background/Objectives: With the rapid aging of the global population, the interest in therapies for age-related diseases has increased substantially. The skin is particularly important, as aging-related changes are visible and negatively impact quality of life. Therefore, the identification of senotherapeutic candidates that are effective against skin aging is of considerable importance. Given the cost and reproducibility limitations of existing senescence models, this study established three dermal fibroblast senescence models induced by etoposide, hydrogen peroxide, and ultraviolet A, representing intrinsic and extrinsic aging. Furthermore, considering the adverse effects of current photoaging treatments, such as tretinoin and methoxsalen, we investigated the senotherapeutic potential of araliadiol, a plant-derived compound, in these models. Methods: Senescence induction and validation were assessed using trypan blue-based cell counting, senescence-associated β-galactosidase (SA-β-gal) staining, and adenosine triphosphate content assays. The senotherapeutic potential of araliadiol was further evaluated using quantitative reverse transcriptase–polymerase chain reaction, Western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay. Results: Compared with non-senescent fibroblasts, senescent cells exhibited increased SA-β-gal positivity, elevated intracellular reactive oxygen species levels, and upregulated p16 and p21 expression. The senolytic agent ABT-737 selectively induced apoptosis in senescent fibroblasts but not in non-senescent fibroblasts, validating the models. Araliadiol showed no senolytic activity but demonstrated potential senomorphic effects, including reduced expression of senescence-associated secretory phenotype (SASP) genes (IL1β, IL6, IL8, CCL2, and CXCL1) and NF-κB p65 phosphorylation, suppression of MMP-1 (up to 2.35-fold reduction) and MMP-3 (up to 30.53-fold reduction) expression and AP-1 activation, and increased extracellular procollagen type I content (up to 18.35% increase). Conclusions: Araliadiol exerted senomorphic—but not senolytic—effects across three validated dermal fibroblast senescence models, supporting its potential as a natural topical therapeutic agent for mitigating skin aging.

Background/Objectives: Inflammatory disorders contribute to the pathogenesis of numerous diseases and are known to markedly reduce quality of life. Although anti-inflammatory drugs approved by the Food and Drug Administration are available, their prolonged use is frequently associated with adverse effects. In this study, we evaluated the pharmacological properties of araliadiol, a naturally occurring polyacetylene compound, as a novel anti-inflammatory agent. Methods: An in vitro hyperinflammatory model was established by stimulating RAW 264.7 cells with lipopolysaccharide (LPS). Dexamethasone (DEX) was used as a positive control to compare anti-inflammatory efficacy. The protective effects of araliadiol against LPS-induced cytotoxicity were assessed using adenosine triphosphate content and crystal violet staining assays. The anti-inflammatory activity was further examined by quantitative reverse transcriptase–polymerase chain reaction, Western blotting, cell fractionation, immunofluorescence staining, a nitric oxide assay, and an enzyme-linked immunosorbent assay. Results: Araliadiol significantly attenuated cytotoxicity and cell death in LPS-stimulated RAW 264.7 cells. It suppressed the expression of cell death markers Cleaved caspase-3 and Cleaved PARP-1. In addition, araliadiol downregulated key pro-inflammatory mediators, including inflammasome-related genes, cytokines, chemokines, and inducible nitric oxide synthase. It also reduced the expression of Cox-2 and PGE₂, indicating potential anti-hyperalgesic effects. Moreover, araliadiol inhibited the activation of Nfκb and Stat1 signaling pathways in LPS-stimulated macrophages. Conclusions: Araliadiol demonstrated robust anti-cytotoxic, anti-inflammatory, and anti-hyperalgesic activities in LPS-induced RAW 264.7 cells, with efficacy comparable to DEX. These findings support its potential as a plant-derived therapeutic candidate for the management of inflammatory conditions.

Chan Yoo, Do Yeong Son, Dae Sung Yoo, Eun Jin Sung, Ji Won Seo, Ji Yoon Park, Seong Rok Sim, and Dae Bang Seo. Journal of the Korean Society of Food Science and Nutrition 2025;54:526-34. https://doi.org/10.3746/jkfn.2025.54.6.526

Obesity is well-known as a major risk factor for metabolic disorders, and natural compounds are being explored as alternatives to conventional therapies. While Centella asiatica is well known for its medicinal and dietary benefits, the biological activities of Giant Centella asiatica (GCA), especially when extracted with mineral-rich lava seawater, remain poorly characterized. This study aimed to evaluate the anti-adipogenic and lipid-metabolism-regulating effects of a novel GCA extract (GCA-LS-90) and its ability to stimulate GLP-1 secretion in vitro. GCA-LS-90 significantly inhibited lipid accumulation in 3T3-L1 adipocytes by up to 24.3% at 200 µg/mL (p < 0.001). It downregulated adipogenic transcription factors (C/EBPβ, C/EBPα, PPARγ) and lipogenic regulators (SREBP1c, FAS, G6PD, ME), while upregulating KLF2 (all p < 0.001). Western blotting confirmed reduced SREBP1c and SREBP2 protein expression, increased phosphorylation of AMPKα/ACC, and enhanced HSL activity (p < 0.05–0.001). In STC-1 cells, GCA-LS-90 increased GLP-1 secretion (53.5 pmol/L at 90 µg/mL vs. 41.3 pmol/L in control, p < 0.001). The major compounds, 3,5- and 4,5-di-O-caffeoylquinic acids, reproduced these effects. In conclusion, GCA-LS-90 modulated adipogenesis-, lipid-metabolism-, and GLP-1 secretion-related pathways in vitro, suggesting its potential as a functional ingredient for obesity management. Further in vivo studies are needed to confirm efficacy and translational relevance.