基于网络药理学、分子对接和实验验证探究蝉花核苷提取物治疗日光性皮炎的作用机制

In order to explore the new application and mechanism of action of Cordyceps chanhua nucleoside extracts on solar dermatitis, the targets of C. chanhua nucleoside components treating solar dermatitis were screened by network pharmacology and molecular docking. The results of network pharmacology analysis were verified by mouse animal experiments. The results showed that thymine, adenine, N6-(2 hydroxyethyl) adenosine, inosine and adenosine were the main active nucleoside components of C. chanhua in the treatment of solar dermatitis, and TNF, IL1β, AKT1, IL6, INS, IFNG, EGFR, PTGS2, CTNNB1, and MAPK1 were the core targets of C. chanhua nucleoside components. Enrichment analysis showed that PI3K-Akt, TNF, MAPK and IL-17 signaling pathways were the major biomechanistic pathways of C. chanhua nucleoside components for the treatment of solar dermatitis. Molecular docking analysis showed that there was a strong binding affinity between the main active components of C. chanhua nucleoside components and the core targets. Animal experiments verified that dermal administration of C. chanhua increased collagen content and SOD antioxidant enzyme activity, and decreased PTGS2 content and levels of TNF-ɑ, IL-1β, and IL-17 inflammatory factors in mouse skin tissues. The results of Western blotting showed that C. chanhua nucleoside extracts inhibited the release of p38 MAPK and MMP9, and the molecular mechanism might be related to the MAPK signaling pathway. This study provides a new basis for the development of natural drugs against solar dermatitis.

为探索蝉花虫草（Cordyceps chanhua）核苷提取物在日光性皮炎中的新应用与作用机制，本研究通过网络药理学（network pharmacology）与分子对接（molecular docking）技术，筛选蝉花虫草核苷类成分治疗日光性皮炎的作用靶点，并通过小鼠动物实验对网络药理学分析结果进行验证。研究结果显示，胸腺嘧啶、腺嘌呤、N6-(2-羟乙基)腺苷、肌苷与腺苷为蝉花虫草治疗日光性皮炎的主要活性核苷类成分；肿瘤坏死因子（TNF）、IL1β、AKT1、IL6、胰岛素（INS）、干扰素γ（IFNG）、表皮生长因子受体（EGFR）、PTGS2、CTNNB1及MAPK1为蝉花虫草核苷类成分的核心作用靶点。富集分析结果表明，PI3K-Akt、TNF、MAPK及IL-17信号通路是蝉花虫草核苷类成分治疗日光性皮炎的主要生物作用通路。分子对接分析显示，蝉花虫草核苷类主要活性成分与核心靶点之间具有较强的结合亲和力。动物实验验证表明，经皮肤给药的蝉花虫草可提升小鼠皮肤组织中的胶原蛋白含量与超氧化物歧化酶（SOD）抗氧化酶活性，同时降低PTGS2含量及肿瘤坏死因子-α（TNF-α）、IL-1β、IL-17炎症因子水平。蛋白质印迹法（Western blotting）结果显示，蝉花虫草核苷提取物可抑制p38丝裂原活化蛋白激酶（p38 MAPK）与基质金属蛋白酶9（MMP9）的释放，其分子机制可能与MAPK信号通路相关。本研究为开发抗日光性皮炎的天然药物提供了全新依据。