Astragaloside prevents UV-induced keratinocyte injury by regulating TLR4/NF-κB pathway

Background: Ultraviolet (UV) radiation is a key risk factor of environment to contribute photoaging and skin Cancer through production of Reactive Oxygen Species (ROS) and inflammatory responses. Astragaloside IV (AS-IV) is an active component from Astragalus membranaceus, and shows various pharmacological effects on inflammation, oxidative stress and Apoptosis. However, whether AS-IV shows protective effect on UVB-induced injury in epidermal keratinocytes remain unknown.

Aims: To explored the effects of AS-IV on UVB-induced oxidative injury and inflammatory response in human epidermal keratinocytes.

Methods: HaCaT keratinocytes were exposed to UVB irradiation, followed by AS-IV incubation. The cell viability, intracellular ROS level, oxidative stress, and Apoptosis were determined. The regulatory effects of AS-IV on Toll-like Receptor 4 (TLR4) pathway in UVB-exposed HaCaT cells were also investigated.

Results: Astragaloside IV pretreatment (10, 25, 50, 100 and 150 μM) increased cell viability in UVB-exposed HaCaT cells. AS-IV (50 μM) significantly reduced intracellular ROS level and lipid oxidation product malondialdehyde (MDA) content, and increased a ROS-scavenging Enzyme superoxide dismutase (SOD) in HaCaT cells with UVB irradiation. In addition, AS-IV pretreatment suppressed Apoptosis, increased Bax protein, Caspase-3 and 9, and decreased Bcl-2 protein in contrast to HaCaT cells with UVB-irradiation. AS-IV suppressed proinflammatory cytokine production, inhibited TLR4 and its downstream signaling molecules NF-κB, iNOS and cyclooxygenase-2 (COX-2) protein expression. We also found that the effects of AS-IV on cell viability and TLR4 expression was reversed by NAC. The protective of AS-IV on UVB-induced damage and TLR4 expression was dependent on ROS, as the increase in viability and decrease in TLR4 protein by AS-IV was significantly attenuated by ROS scavenger NAC (1 mM).

Conclusion: Astragaloside IV prevent UVB-induced oxidative damage and inflammation by inhibiting TLR4 expression.