Walvekar Komal Paresh, Tirunavalli Satya Krishna, Eedara Abhisheik Chowdary, Chandra Yogesh, Kuncha Madhusudhana, B R Kumar Ashwin, Sistla Ramakrishna, Andugulapati Sai Balaji, Chilaka Sabarinadh
Division of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, Telangana, India.
Academy of Scientific and Innovative Research (AcSIR), 201 002, Ghaziabad, Uttar Pradesh, India.
Inflammation. 2024 Jul 17. doi: 10.1007/s10753-024-02103-5.
Psoriasis is a chronic skin inflammatory disorder characterized by the hyper-activation of the immune system and the over-proliferation of epidermal keratinocytes. This study aimed to investigate the anti-psoriatic activity of Biochanin A (BCA), a phytomolecule with known anti-inflammatory and anti-cancer properties, using the IMQ-induced psoriasis-like mouse model. Network pharmacology analysis was performed to investigate the targetability of Biochanin A (BCA) against psoriasis. Psoriasis-like skin inflammation was established using BALB/c mice by topical application of IMQ (5%). BCA cream (0.3%, 1%, 3%) was applied on the skin regions every day for 6 days. The skin phenotypes-erythema and scaling were scored every day. On the 7th day, skin tissues were collected for gene expression analysis, histopathological analysis, cytokine levels determination, and western blot analysis for signaling mechanisms. The network pharmacology analysis has identified 57 common targets between psoriasis and BCA. The topical application of IMQ induced a typical psoriasis-like skin phenotype including redness, skin thickening, and plaque formation. Upon BCA treatment, the psoriasis-like symptoms were significantly reduced in a dose-dependent manner. The targets identified by the network pharmacology (MMP9, EGFR, and PTGS2) and the pro-inflammatory cytokine gene expression were found to be significantly elevated in IMQ controls, and upon BCA treatment they were found significantly reduced. The release of cytokines linked to psoriasis (IL-17A and IL-23) were significantly reduced upon BCA treatment. Furthermore, our findings demonstrated that BCA treatment alleviated the psoriasis-like symptoms via modulating NF-κB and MAPK signaling pathways. Our results demonstrate the therapeutic potential of BCA against IMQ-induced psoriasis-like skin inflammation.
银屑病是一种慢性皮肤炎症性疾病，其特征是免疫系统过度激活和表皮角质形成细胞过度增殖。本研究旨在使用咪喹莫特（IMQ）诱导的银屑病样小鼠模型，研究具有已知抗炎和抗癌特性的植物分子大豆黄素A（BCA）的抗银屑病活性。进行网络药理学分析以研究大豆黄素A（BCA）对银屑病的靶向性。通过局部应用IMQ（5%）在BALB/c小鼠中建立银屑病样皮肤炎症。每天在皮肤区域涂抹BCA乳膏（0.3%、1%、3%），持续6天。每天对皮肤表型——红斑和脱屑进行评分。在第7天，收集皮肤组织进行基因表达分析、组织病理学分析、细胞因子水平测定以及信号传导机制的蛋白质印迹分析。网络药理学分析确定了银屑病和BCA之间的57个共同靶点。局部应用IMQ诱导出典型的银屑病样皮肤表型，包括发红、皮肤增厚和斑块形成。经BCA治疗后，银屑病样症状以剂量依赖性方式显著减轻。发现网络药理学确定的靶点（基质金属蛋白酶9、表皮生长因子受体和环氧化酶-2）以及促炎细胞因子基因表达在IMQ对照组中显著升高，而在BCA治疗后显著降低。经BCA治疗后，与银屑病相关的细胞因子（白细胞介素-17A和白细胞介素-23）的释放显著减少。此外，我们的研究结果表明，BCA治疗通过调节核因子κB和丝裂原活化蛋白激酶信号通路减轻了银屑病样症状。我们的结果证明了BCA对IMQ诱导的银屑病样皮肤炎症的治疗潜力。
