Purified Vitexin Compound 1 Inhibits UVA-Induced Cellular Senescence in Human Dermal Fibroblasts by Binding Mitogen-Activated Protein Kinase 1
Purified Vitexin Compound 1 Inhibits UVA-Induced Cellular Senescence in Human Dermal Fibroblasts by Binding Mitogen-Activated Protein Kinase 1
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纯化的牡荆素化合物 1 通过结合丝裂原激活的蛋白激酶 1 抑制人真皮成纤维细胞中 UVA 诱导的细胞衰老
DOI：
10.3389/fcell.2020.00691
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发表时间：
2020-07-31
影响因子：
5.5
通讯作者：
Li, Ji
中科院分区：
文献类型：
--
作者：
Wang, Ben;Yan, Sha;Li, Ji
纯化的牡荆素化合物1（VB 1）是从中药黄荆种子中分离得到的一种新木脂素类化合物，具有较强的抗氧化能力和广泛的抗肿瘤活性。然而，关于其对皮肤的抗光老化作用及其潜在机制知之甚少。在这里，我们证明，VB 1显着减弱紫外线A（UVA）诱导的人皮肤成纤维细胞（HDF）的衰老，证明了衰老相关的β-半乳糖染色，MTT法，蛋白质印迹分析的p16和基质金属蛋白酶-1（MMP-1）的表达。此外，质谱分析表明，VB 1可以直接结合有丝分裂原活化蛋白激酶1（MAPK 1）。分子对接和分子动力学模拟的方法证实了质谱的结果，并预测了6个可能的结合氨基酸的MAPK 1，最有可能与VB 1相互作用。随后的免疫沉淀分析，包括不同的MAPK 1突变体，揭示了VB 1直接与残基，谷氨酸58（E58）和精氨酸65（R65）的MAPK 1，导致部分逆转UVA诱导的衰老HEK 293 T细胞。最后，我们证明了小鼠皮肤局部应用VB 1可显着降低体内光老化表型。总的来说，这些数据表明，VB 1通过靶向MAPK 1减少UVA诱导的衰老，并减轻小鼠皮肤光老化，这表明VB 1可能适用于预防和治疗皮肤光老化。
Purified vitexin compound 1 (VB1), a novel lignanoid isolated from the seeds of the Chinese herb Vitex negundo, has strong antioxidant abilities and broad antitumor activities. However, little is known about its anti-photoaging effect on the skin and the underlying mechanism. Here, we demonstrated that VB1 significantly attenuates ultraviolet A (UVA)-induced senescence in human dermal fibroblasts (HDFs), as evidenced by senescence-associated beta-gal staining, MTT assays, and western blot analysis of the expression of p16 and matrix metalloproteinase-1 (MMP-1). Furthermore, mass spectrometry revealed that VB1 could directly bind to Mitogen-Activated Protein Kinase 1 (MAPK1). Molecular docking and molecular dynamics simulation methods confirmed the mass spectroscopy results and predicted six possible binding amino acids of MAPK1 that most likely interacted with VB1. Subsequent immunoprecipitation analysis, including different MAPK1 mutants, revealed that VB1 directly interacted with the residues, glutamic acid 58 (E58) and arginine 65 (R65) of MAPK1, leading to the partial reversal of UVA-induced senescence in HEK293T cells. Finally, we demonstrated that the topical application of VB1 to the skin of mice significantly reduced photoaging phenotypesin vivo. Collectively, these data demonstrated that VB1 reduces UVA-induced senescence by targeting MAPK1 and alleviates skin photoaging in mice, suggesting that VB1 may be applicable for the prevention and treatment of skin photoaging.