Na Li, Kun Zhang, Xin Mu, Qiong Tian, Wenli Liu, Tianyuan Gao, Xiaona Ma and Jian Zhang* Pages 1001 - 1008 ( 8 )
Background: Actinic keratosis (AK), is the most common precancerous skin lesion induced by the excessive ultraviolet B (UVB) and is a significant threat to the public health. UVB exposure causes oxidative DNA damage and is considered to be a significant contributor to AK and subsequent development of skin cancer. Besides, activation of p38 MAPK also plays a significant role in the development of AK.
Objective: This study aimed at the development of a nature compound which can inhibit UVB-induced AK.
Method: MTS Cell Proliferation Assay Kit was used to detect the toxicity of astragalin. HE-staining, Immunohistochemical, Western blot and Enzyme Linked Immunosorbent Assay were applied to examine the clinicopathologic feature of AK and the change of p38 MAPK signal pathway treated with astraglin under the condition of UVB in vitro and in vivo.
Results：In our clinical findings revealed that p38 MAPK, phospho-MSK1, and γ-H2AX were significantly highly expressed in human AK tissue than the normal healthy skin tissue. Moreover, in vitro studies showed that UVB induced the phospho-MSK1 and γ-H2AX in a time- and dose-dependent manner in HaCaT cells. Further, in vitro kinase assay demonstrated that astragalin could directly bind to p38 MAPK and suppress p38 MAPK activity. Furthermore, astragalin exhibited no toxicity and suppressed the UVB-induced expression of phospho- MSK1 and γ-H2AX by suppressing p38 MAPK activity in a time-dependent and dose-dependent manner in HaCaT cells. The in vivo studies with animal UV model demonstrated that astragalin inhibited UVB-induced expression of phospho-MSK1 and γ-H2AX in Babl/c mice.
Conclusion: These results suggested that p38 MAPK is a direct valid molecular target of astragalin for the attenuation of UVB-induced AK. Furthermore, astragalin could be a potential promising novel natural therapeutic agent for the prevention and management of UVB-induced AK with high target specificity and low toxicity.
Actinic keratosis, UVB, astragalin, p38 MAPK, phosphorylation, H2AX
the Second Affiliated Hospital of Xi'an Medical University Xi'an, Nuclear Industry 215 Plastic Surgery Hospital Xian yang, First Affiliated Hospital of Xi'an Jiaotong University Xi'an, First Affiliated Hospital of Xi'an Jiaotong University Xi'an, First Affiliated Hospital of Xi'an Jiaotong University Xi'an, First Affiliated Hospital of Xi'an Jiaotong University Xi'an, Department of Dematology, Affiliated Hospital of Yan'an University, Yan'an 716000 Shaanxi, first affiliated hospital of Xi 'an jiaotong university