ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
This article is part of the Research TopicPromising Photosensitive Agents for Photodynamic TherapyView all 21 articles
The mechanism of Vicenin-2 in ameliorating skin photoaging: involvement of m6A-modified macrophage polarization
Provisionally accepted
- 1Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- 2North Sichuan Medical College, Nanchong, China
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Skin photoaging is primarily induced by ultraviolet radiation and is closely associated with chronic inflammation and degradation of the extracellular matrix, with an imbalance in macrophage polarization (elevated M1/M2 ratio) being a key factor. This study first conducted single-cell sequencing analysis to investigate the correlation between macrophage subtypes and photoaging. It was found that in the photodamage model, the infiltration of pro-inflammatory M1 macrophages significantly increased, and the key regulatory factor KIAA1429 was positively correlated with the level of anti-inflammatory M2 macrophages. At the same time, we investigated the effects and mechanisms of the natural flavonoid Vicenin-2 on photoaging through both in vivo and in vitro experiments. In vitro, Vicenin-2 was applied to LPS-induced RAW264.7 macrophages; in vivo, a mouse model of photoaging was established using UVA/UVB irradiation, followed by topical treatment with different concentrations of Vicenin-2 cream. The results showed that Vicenin-2 significantly alleviated skin damage, improved hydration and collagen organization, and promoted the shift of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Mechanistically, Vicenin-2 upregulated the m6A modification regulator KIAA1429, enhanced overall m6A RNA methylation, and inhibited NF-κB pathway activation by suppressing p65 phosphorylation. The findings indicate that Vicenin-2 may mitigate skin photoaging by modulating macrophage polarization toward the M2 phenotype through m6A-dependent regulation of the NF-κB signaling pathway, supporting its potential as a novel topical agent for photoaging intervention.
Keywords: M6A, Macrophage polarization, NF-κB pathway, Photoaging, Vicenin-2
Received: 31 Dec 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Zhou, Shuai, Peng, Li, Chen, Tan, Mu and Duan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xi Duan
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