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

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.