Lv Yaping, Xu Yingsheng, Liu Songchun, Zeng Xianjing, Yang Bin
Department of Dermatology and Venereology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, Shanxi, 030032, China.
Department of Clinical Nutrition, Ezhou Central Hospital, Ezhou, Hubei, 436000, China.
Cell Biochem Biophys. 2025 Jun;83(2):1879-1895. doi: 10.1007/s12013-024-01595-0. Epub 2024 Nov 5.
Psoriasis is a long-term inflammatory skin condition marked by an overabundance of keratinocytes and the release of pro-inflammatory cytokines in the outer layer of skin. For the comprehensive management of intermediate to advanced psoriasis, innovative biological treatments have been developed. Products for the superficial therapy of mild to moderate psoriasis are still necessary, though. Trifolium pratense contains the isoflavone biochanin A (BCA), which exhibits antiviral, antioxidant, anti-carcinogenic, and anti-inflammatory properties, and helps protect the integrity and function of the endothelium. Although investigations have not shown that BCA is effective in treating psoriasis, it has been shown to slow down the breakdown of the skin barrier by regulating keratinocyte growth. We sought to clarify the basic mechanisms behind BCA's impact on psoriasis in vitro and in vivo using experimental research via regulating Nrf2/HO-1 signaling pathway. By subjecting human primary keratinocytes to psoriasis-related cytokines, psoriasis-like keratinocytes were produced. The CCK8 test was used in this investigation to assess cell viability. BCA reduced keratinocyte growth and inflammatory cascade stimulation produced by TNF-α and IL-6, according to in vitro investigations conducted on HaCaT cells. The in vivo findings showed that six days of BCA therapy significantly decreased the skin, hematological indicators, levels of NO, TBARS, histopathological, and pro-inflammatory factors of COX-2, iNOS, NF-κB pathway. It additionally influenced the protein content of pro-inflammatory cytokines such as IL-17, IL-23, IL-1β in the epidermis along with IL-6, TNF-α among the epidermis and serum. In addition, in contrast to the IMQ group, BCA improved the skin's level of Nrf2/HO-1 protein, anti-inflammatory cytokine IL-10, and antioxidant indicators like SOD, CAT, GST, GSH, GR, and Vit-C. Ultimately, our research shows that BCA was effective in treating psoriasis in pre-clinical animal models by activating the Nrf2/HO-1 pathway, leading to an increase in antioxidant and anti-inflammatory markers.
银屑病是一种长期的炎症性皮肤病，其特征是角质形成细胞过多以及皮肤外层促炎细胞因子的释放。对于中重度银屑病的综合管理，已经开发出了创新的生物治疗方法。不过，轻度至中度银屑病的浅表治疗产品仍然是必要的。红车轴草含有异黄酮染料木黄酮A（BCA），它具有抗病毒、抗氧化、抗癌和抗炎特性，并有助于保护内皮的完整性和功能。尽管研究尚未表明BCA对治疗银屑病有效，但已证明它可通过调节角质形成细胞生长来减缓皮肤屏障的破坏。我们试图通过调节Nrf2/HO-1信号通路的实验研究，阐明BCA在体外和体内对银屑病影响的基本机制。通过将人原代角质形成细胞暴露于银屑病相关细胞因子，产生了银屑病样角质形成细胞。本研究使用CCK8试验评估细胞活力。对HaCaT细胞进行的体外研究表明，BCA可减少角质形成细胞生长以及由TNF-α和IL-6产生的炎症级联刺激。体内研究结果表明，BCA治疗6天可显著降低皮肤、血液学指标、NO、TBARS水平、组织病理学以及COX-2、iNOS、NF-κB途径的促炎因子。它还影响表皮中IL-17、IL-23、IL-1β等促炎细胞因子以及表皮和血清中的IL-6、TNF-α的蛋白质含量。此外，与IMQ组相比，BCA提高了皮肤中Nrf2/HO-1蛋白、抗炎细胞因子IL-10以及抗氧化指标如SOD、CAT、GST、GSH、GR和Vit-C的水平。最终，我们的研究表明，BCA通过激活Nrf2/HO-1途径在临床前动物模型中有效治疗银屑病，导致抗氧化和抗炎标志物增加。
