Antagonizing Effects of Clematis apiifolia DC. Extract against Benzo[a]pyrene-Induced Damage to Human Keratinocytes

Abstract

Background. Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon present in the atmosphere, has cytotoxic and carcinogenic effects. There have been no reports to demonstrate involvement of Clematis apiifolia DC. extract (CAE) in B[a]P-induced effects. This study was conducted to investigate the effect of CAE on B[a]P-induced effects and to elucidate its mechanism of action in HaCaT human keratinocytes. CAE inhibited aryl hydrocarbon receptor (AhR) signaling by decreasing both XRE reporter activity and expression of cytochrome P450 1A1 (CYP1A1) induced by B[a]P treatment in HaCaT cells. We also found that B[a]P-induced nuclear translocation of AhR and production of reactive oxygen species (ROS) and proinflammatory cytokines were attenuated by CAE treatment. CAE treatment suppressed B[a]P-induced phosphorylation of Src (Tyr416). In addition, dasatinib, a Src inhibitor, also inhibited B[a]P-induced nuclear translocation of AhR, similar to CAE treatment. In addition, CAE activated antioxidant response element (ARE) signaling by increasing ARE luciferase reporter activity and expression of ARE-dependent genes such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2), NAD(P)H dehydrogenase [quinone] 1 (NQO1), and heme oxygenase-1 (HO-1). Nuclear translocation of Nrf2 by CAE was demonstrated by Western blot analysis and immunocytochemistry. The effects of CAE on ARE signaling were attenuated by knockdown of the Nrf2 gene. Inhibition of AhR signaling and activation of antioxidant activity by CAE operated in a reciprocally independent manner as evidenced by AhR and Nrf2 siRNA experiments. These findings indicate that CAE exerts protective effects against B[a]P by inhibiting AhR signaling and activating Nrf2-mediated signaling, suggesting its potential in protection from harmful B[a]P-containing pollutants.

Baicalein Inhibits Benzo[a]pyrene-Induced Toxic Response by Downregulating Src Phosphorylation and by Upregulating NRF2-HMOX1 System

“…Furthermore, the status of AHR nuclear translocation was assessed, since an Src inhibitor Dasatinib reportedly prevents BaP-induced AHR nuclear translocation and inhibits the effect of BaP [ 62 ]. Dasatinib was used as a positive control, which inhibits BaP-induced AHR nuclear translocation by inhibiting Src.…”

“…The phosphorylation of Src was upregulated by BaP in HaCaT cells, which was downregulated in the presence of BAI, as in NHEKs (Figure 7b, Supplementary Figure S8b). Furthermore, the status of AHR nuclear translocation was assessed, since an Src inhibitor Dasatinib reportedly prevents BaP-induced AHR nuclear translocation and inhibits the effect of BaP [62]. Dasatinib was used as a positive control, which inhibits BaP-induced AHR nuclear translocation by inhibiting Src.…”

Aspergillus oryzae-Fermented Wheat Peptone Enhances the Potential of Proliferation and Hydration of Human Keratinocytes through Activation of p44/42 MAPK

“…Cell proliferation or cellular senescence has been considered as one of the main hallmarks of skin aging [ 27 ]. Recent studies have reported the involvement of senescent cells in skin aging and aging-related diseases [ 28 , 29 ].…”

Protective Effects of Maclurin against Benzo[a]pyrene via Aryl Hydrocarbon Receptor and Nuclear Factor Erythroid 2-Related Factor 2 Targeting

“…MuLV reverse transcriptase was used to synthesize cDNA from the total RNA (1 μg) according to the manufacturer’s instructions. RT-PCR results was analyzed as previously reported [ 19 ]. The data were normalized to the expression level of three housekeeping genes such as GAPDH, 18S, and HPRT.…”

“…Various reports have demonstrated the cytotoxic, carcinogenic, oxidative stress, and mutagenic effects of B[a]P [ 17 , 18 , 19 , 20 ]. However, until now, there have been only a few reports regarding the development of compounds to reduce the toxicity of B[a]P [ 21 , 22 ].…”