Specnuezhenide ameliorates ultraviolet‐induced skin photoaging in mice by regulating the Sirtuin 3/8‐Oxoguanine DNA glycosylase signal

Abstract Purpose Ultraviolet‐induced skin photoaging was involved in DNA oxidative damage. Specnuezhenide, one of the secoiridoids extracted from Ligustri Lucidi Fructus , possesses antioxidant and anti‐inflammatory effects. Whether specnuezhenide ameliorates skin photoaging remains unclear. This study aimed to investigate the effect of specnuezhenide on skin photoaging induced by ultraviolet and explore the underlying mechanism. Methods Mice were employed to treat with ultraviolet to induce skin photoaging, then administrated 10 and 20 mg/kg of specnuezhenide. Histological analysis, protein expression, network pharmacology, and autodock analysis were conducted. Results Specnuezhenide ameliorated ultraviolet‐induced skin photoaging in mice via the increase in collagen contents, and decrease in epidermal thickness, malondialdehyde content, and β‐galactosidase expression in the skin. Specnuezhenide reduced cutaneous apoptosis and inflammation in mice with skin photoaging. In addition, network pharmacology data indicated that specnuezhenide possessed potential targets on the NOD‐like receptor signaling pathway. Validation experiment found that specnuezhenide inhibited the expression of NOD‐like receptor family pyrin domain‐containing 3, gasdermin D‐C1, and Caspase 1. Furthermore, the expression of 8‐Oxoguanine DNA glycosylase (OGG1), sirtuin 3 (SIRT3), and superoxide dismutase 2 was increased in specnuezhenide‐treated mice with photoaging. Conclusion Specnuezhenide protected against ultraviolet‐induced skin photoaging in mice via a probable activation of SIRT3/OGG1 signal.