Modulatory Effects of Procyanidin B1 on Inflammation-Induced Oxidative Stress and ECM-Related Responses in Human Dermal Fibroblasts and Epidermal Keratinocytes

Oxidative stress and inflammation are central environmental contributors to skin aging, accelerating extracellular matrix (ECM) breakdown and loss of dermal structure. Although Nypa fruticans is recognized for its antioxidant properties, the constituents responsible for these effects remain undefined. To address this, we screened five major polyphenols—protocatechuic acid (PA), hydroxybenzoic acid (HA), procyanidin B1 (PB), catechin (CA), and epicatechin (EC)—for protective activity in two inflammatory skin cell models: human dermal fibroblasts (HDFs) stimulated with tumor necrosis factor-α (TNF-α), and human epidermal keratinocytes (HEKs) co-stimulated with TNF-α and interferon-γ (IFN-γ). PB emerged as the most consistently active compound. In fibroblasts, it suppressed intracellular reactive oxygen species, limited matrix metalloproteinase-1 (MMP-1) release, and restored pro-collagen I α1 output. In keratinocytes, it reduced both pro-inflammatory cytokines—interleukin (IL)-6, IL-8, and IL-1β and inflammatory mediators, including prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), and nitric oxide (NO). At the transcriptional level, PB shifted the ECM balance by lowering MMP expression while elevating collagen- and hyaluronan-associated genes. Collectively, these results position PB as a principal driver of the protective activity of Nypa fruticans (N. fruticans) leaves under inflammatory conditions. Mechanistically, PB suppressed nuclear factor kappa B (NF-κB) activation and promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation in keratinocytes, supporting its dual anti-inflammatory and antioxidant activities.