AdapalenevsResveratrol

Adapalene selectively binds RAR-beta and RAR-gamma (minimal RAR-alpha affinity), reducing inflammatory signaling compared to pan-RAR agonists. It normalizes follicular epithelial differentiation and reduces corneocyte cohesion in the pilosebaceous unit, preventing microcomedo formation. Adapalene inhibits AP-1 transcription factor (c-Fos/c-Jun dimerization), suppressing IL-6, TNF-alpha, and neutrophil chemotaxis. It promotes comedolysis by accelerating desquamation of existing comedones. For anti-aging, it stimulates fibroblast collagen I and III via RAR-beta/gamma, with comparable efficacy to tretinoin. Its lipophilic naphthoic acid structure confers superior follicular penetration and light stability.

Resveratrol activates SIRT1 (sirtuin 1), a NAD+-dependent deacetylase that deacetylates histones and non-histone targets including p53, FOXO transcription factors, and NF-κB, regulating cellular stress response, DNA repair, autophagy, and inflammatory pathways in keratinocytes and fibroblasts. It scavenges superoxide anion, hydroxyl radical, and metal-induced free radicals through its phenolic hydroxyl groups. Resveratrol inhibits NF-κB nuclear translocation and downstream cytokine production (TNF-α, IL-1β, IL-6), reducing UV-induced inflammation. It inhibits tyrosinase (mild brightening), matrix metalloproteinase-9 (MMP-9, gelatinase B) to prevent collagen and elastin breakdown, and AP-1 (c-Fos/c-Jun) to reduce photoaging-related gene expression. It may also activate Nrf2, upregulating antioxidant enzymes (HO-1, NQO1). Topical application achieves higher skin tissue concentrations than oral supplementation due to first-pass metabolism. Stability is improved in anhydrous or encapsulated formulations.