Reactive oxygen species (ROS) produced in the mitochondria of skin cells play a significant role in the degradation of the extracellular matrix and induction of inflammatory responses, both of which are major contributors to skin aging. Antioxidants that reduce ROS production and inhibit inflammatory skin lesions are considered beneficial for the treatment of inflammatory skin diseases and prevention of skin aging. In this study, we evaluated the potential of Nypa fruticans (NF), which is known for its antioxidant properties, to mitigate tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-induced damage in normal human epidermal keratinocytes. The major active constituents identified in NF include protocatechuic acid, hydroxybenzoic acid, procyanidin B, catechin, and epicatechin. NF significantly suppressed the production of ROS, nitric oxide (NO), and prostaglandin E2 (PGE2), while also reducing the levels of inflammatory cytokines interleukin-6 (IL-6) and interleukin-1 beta (IL-1β), which were elevated by TNF-α/IFN-γ stimulation. Furthermore, NF restored the expression of key skin barrier-related proteins such as serine peptidase inhibitor kazal type 5 (SPINK5), collagen type I alpha 1 chain (COLIA1), loricrin (LOR), aquaporin-3 (AQP3), and filaggrin (FLG). Additionally, NF significantly upregulated the expression of hyaluronan synthase (HAS) -1 and − 2 and human β-defensin (HBD) -2 and − 3, which are important for skin hydration and innate immune defense. These findings underscore the potential therapeutic applications of Nypa fruticans (NF) in mitigating oxidative stress, inflammation, skin barrier dysfunction, dehydration, and microbial imbalances. By targeting multiple pathways implicated in skin aging, NF represents a promising comprehensive approach for preserving skin health and addressing age-related dermatological conditions. Moreover, NF holds significant potential not only to alleviate the manifestations of skin aging but also to provide a basis for the development of innovative dermatological therapies. Future investigations should aim to further elucidate the clinical applications of NF in dermatology to maximize its therapeutic benefits.
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