Citrulluside H and citrulluside T from young watermelon fruit attenuate ultraviolet B radiation-induced matrix metalloproteinase expression through the scavenging of generated reactive oxygen species in human dermal fibroblasts

Abstract

Background: Prolonged exposure to UV radiation disrupts the oxidative stress defense systems; in the absence of adequate reactive oxygen species (ROS)-scavenging mechanisms, the ROS produced cause oxidative damage to DNA, proteins, carbohydrates, and lipids. Thus, ROS elimination can protect against photoaging and possibly skin cancer. We recently isolated two novel phenolic glycosides (citrulluside H and citrulluside T) with antioxidative activity from young watermelon (Citrullus lanatus) fruits. In the present study, we evaluated the protective effect of these compounds against UV-B-induced photodamage in normal human dermal fibroblasts (NHDFs).

Methods: NHDFs were exposed to UV-B irradiation at 25 mJ/cm² . Matrix metalloproteinase (MMP)-1 and MMP-3 mRNA levels were measured by quantitative real-time PCR. MMP protein expression, as well as MAPK and NF-κB signaling, was investigated by Western blot analysis. Activation protein-1 (AP-1) transcriptional activity was determined using a luciferase reporter assay. Intracellular ROS levels were measured using the CellROX™ Deep Red Reagent.

Results: Citrulluside H and citrulluside T significantly downregulated the protein and mRNA expression of MMP-1 and MMP-3, which are associated with the onset of skin wrinkle formation. Importantly, inhibition of UV-B-induced MMP expression in NHDFs by citrulluside H and citrulluside T was primarily due to the attenuation of MAPK/AP-1 and NF-κB signaling via scavenging of the generated ROS.

Conclusion: Our findings delineated both citrulluside H and citrulluside T as potential agents for alleviating UV-induced skin photoaging.

Keywords: UV radiation; anti-collagenase; phenolic glycosides; protein oxidation; skin photoaging.