Z‐ligustilide ameliorated ultraviolet B‐induced oxidative stress and inflammatory cytokine production in human keratinocytes through upregulation of Nrf2/HO‐1 and suppression of NF‐κB pathway

Abstract

Ultraviolet B (UVB), a harmful environmental factor, is responsible for a variety of skin disorders including skin inflammation through reactive oxygen species (ROS) and inflammatory mediator production. Here, we investigated the effect of Z-ligustilide (Z-lig), an active ingredient isolated from the medicinal plants Cnidium officinale and Angelica acutiloba, on UVB-induced ROS generation and inflammatory mediator production in normal human epidermal keratinocytes (NHEKs) as well as its underlying mechanisms. Z-lig significantly rescued UVB-induced NHEKs damage in a dosage-dependent manner. Pretreatment of NHEKs with Z-lig inhibited UVB-induced ROS production in NHEKs. Both silencing the nuclear factor E2-related factor 2 (Nrf2) and the supplement of tin protoporphyrin IX (SnPP), a haeme oxygenase-1 (HO-1) inhibitor, cancelled the inhibitory effect of Z-lig on UVB-induced ROS upregulation in NHEKs. Moreover, pretreatment of NHEKs with Z-lig reduced UVB-induced nuclear factor kappa B (NF-κB)-dependent inflammatory mediators (IL-6, IL-8 and MCP-1) production at both mRNA and protein level. In the presence of Z-lig, UVB-induced NF-κB subunit p65 nuclear translocation was abolished, and the IκBα degradation was suppressed. Taken together, these findings suggest that Z-lig can suppress UVB-induced ROS generation through Nrf2/HO-1 upregulation and inflammation by suppressing the NF-κB pathway, suggesting that Z-lig may be beneficial in protecting skin from UVB exposure.

Schisandra chinensis Protects the Skin from Global Pollution by Inflammatory and Redox Balance Pathway Modulations: An In Vitro Study

“…Data in the literature shows that most of the phytochemicals upregulate Nrf2 signaling in association with AhR activation [32][33][34]. Besides having an effect on Nrf2, we also noted that S.C. extract has an effect on the AhR pathway.…”

Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2

“…Z-Ligustilide is the major bioactive phthalide of Cnidium officinale and Angelica acutiloba , which are widely used in folk medicine in East Asia [60,61]. Z-Ligustilide ameliorates UVB-induced oxidative stress and inflammatory cytokine production through upregulation of the NRF2/HO-1 pathway and the suppression of NF-κB signaling [61].…”

“…Z-Ligustilide ameliorates UVB-induced oxidative stress and inflammatory cytokine production through upregulation of the NRF2/HO-1 pathway and the suppression of NF-κB signaling [61]. Z-Ligustilide is not an AHR ligand, but it significantly inhibits benzo[a]pyrene-induced CYP1A1 expression via NRF2 activation [60]. …”

Ginsenoside Rg1 attenuates ultraviolet B-induced glucocortisides resistance in keratinocytes via Nrf2/HDAC2 signalling

“…A number of reports have demonstrated that oxidative stress plays an important role in glucocorticoid insensitivity by inhibiting the expression and activity of histone deacetylase 2 (HDAC2)34. Ultraviolet B (UVB) irradiation is responsible for a variety of skin disorders by triggering the overproduction of reactive oxygen species (ROS)5678; exposure to UVB (290–320 nm) typically aggravates skin inflammation9. In addition, some reports have suggested that enhanced cortisol production10111213 and reduced epidermal glucocorticoid receptor (GR) expression caused by UVB exposure might contribute to decreased GCs efficacy in chronic inflammatory diseases of the skin13.…”