Gynostemma pentaphyllum Hydrodistillate and Damulin B Prevent UVB‐Induced Photoaging In Vitro and In Vivo via ROS Suppression and Restoration of MAPK/AP‐1 and TGF‐β/Smad Signaling

ABSTRACT Photoaging of the skin, driven by ultraviolet B (UVB) radiation, is characterized by the upregulation of matrix metalloproteinases (MMPs), accelerated collagen degradation, diminished hyaluronic acid (HA) content, and disruption of extracellular matrix (ECM) integrity, culminating in wrinkle formation, and structural damage. Nutritional and plant‐derived compounds have garnered increasing attention as promising therapeutic agents for skin aging. In this study, we explored the anti‐photoaging effects of Gynostemma pentaphyllum hydrodistillate (GPHD) and its bioactive constituent, Damulin B, in UVB‐irradiated in vivo and in vitro models. In HR‐1 hairless mice, GPHD treatment significantly ameliorated UVB‐induced wrinkle formation, collagen degradation, epidermal hyperplasia, and transepidermal water loss, while improving hydration and elasticity. It also modulated hyaluronic acid metabolism by upregulating hyaluronic acid synthases (HAS1 and HAS2) and downregulating hyaluronidases (HYAL1 and HYAL2). In UVB‐irradiated Hs68 fibroblasts, GPHD and Damulin B attenuated reactive oxygen species (ROS) generation, thereby inhibiting mitogen‐activated protein kinase/activator protein‐1 (MAPK/AP‐1) signaling and restoring transforming growth factor‐beta/Smad (TGF‐β/Smad) activity, ultimately contributing to ECM stability. Collectively, our findings demonstrate that GPHD and Damulin B exert potent anti‐photoaging effects by mitigating oxidative stress and orchestrating downstream signaling pathways essential for ECM remodeling and skin homeostasis.