Ardisia silvestris is a traditional medicinal herb used in Vietnam and several other countries. However, the skin-protective properties of A. silvestris ethanol extract (As-EE) have not been evaluated. Human keratinocytes form the outermost barrier of the skin and are the main target of ultraviolet (UV) radiation. UV exposure causes skin photoaging via the production of reactive oxygen species. Protection from photoaging is thus a key component of dermatological and cosmetic products. In this research, we found that As-EE can prevent UV-induced skin aging and cell death as well as enhance the barrier effect of the skin. First, the radical-scavenging ability of As-EE was checked using DPPH, ABTS, TPC, CUPRAC, and FRAP assays, and a 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay was used to examine cytotoxicity. Reporter gene assays were used to determine the doses that affect skin-barrier-related genes. A luciferase assay was used to identify possible transcription factors. The anti-photoaging mechanism of As-EE was investigated by determining correlated signaling pathways using immunoblotting analyses. As-EE had no harmful effects on HaCaT cells, according to our findings, and As-EE revealed moderate radical-scavenging ability. With high-performance liquid chromatography (HPLC) analysis, rutin was found to be one of the major components. In addition, As-EE enhanced the expression levels of hyaluronic acid synthase-1 and occludin in HaCaT cells. Moreover, As-EE dose-dependently up-regulated the production of occludin and transglutaminase-1 after suppression caused by UVB blocking the activator protein-1 signaling pathway, in particular, the extracellular response kinase and c-Jun N-terminal kinase. Our findings suggest that As-EE may have anti-photoaging effects by regulating mitogen-activated protein kinase, which is good news for the cosmetics and dermatology sectors.

This study introduces the concept of MDRN, referring to monomeric deoxyribonucleoside, and evaluates cordycepin (251.24 Da) as a low-molecular-weight alternative to polydeoxyribonucleotide (PDRN). Cordycepin (1–20 μM) was compared with PDRN (100 μg/mL) in human keratinocytes and dermal fibroblasts. Molecular simulations and cellular thermal-shift assays supported a potential interaction with the adenosine A₂A receptor, while 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine receptor antagonist, attenuated selected signaling responses. Cordycepin reduced UVA-induced oxidative and inflammatory responses in keratinocytes, altered autophagy-related reporter signals in HEK293T cells, and selectively modulated barrier- and tight-junction-related gene expression. In fibroblasts, it decreased MMP-1 expression and increased COL1A1 expression. Cordycepin also increased scratch-wound closure in both cell types at selected concentrations. Selected cordycepin treatments significantly increased fibroblast scratch-wound closure and the expression of specific keratinocyte barrier-associated genes compared with PDRN. These comparative responses depended on the endpoint and concentration. Notably, 20 μM cordycepin corresponds to approximately 5.02 μg/mL, one-twentieth of the tested PDRN mass concentration. These findings support cordycepin as an MDRN candidate that elicits skin-repair-related cellular responses at substantially lower mass concentrations than PDRN. Further studies are required to establish relative potency and topical applicability.