Sarkar Debanjan, Pramanik Anik, Saha Jayasree, Das Dona, Mahanti Krishna, Mahato Maniprabha, Mondal Pallabi, Bhattacharyya Sankar
Immunobiology and Translational Medicine Laboratory, Department of Zoology, Sidho Kanho Birsha University, Purulia 723104, India.
Immunobiology and Translational Medicine Laboratory, Department of Zoology, Sidho Kanho Birsha University, Purulia 723104, India; Currently, DST-SERB NPDF, School of Bioscience, IIT Kharagpur, Paschim Medinipur, West Bengal 721302, India.
Int Immunopharmacol. 2025 Apr 24;153:114492. doi: 10.1016/j.intimp.2025.114492. Epub 2025 Mar 19.
Psoriasis is a chronic inflammatory skin disorder affecting approximately 125 million people. IL-17 A secreted from Th17 cells plays a major role in elucidating psoriasis. Dihydromyricetin (DHM) is plant derived flavonoid isolated from leaves and stems of Rattan tea (Ampelopsis grossedentata). Reports indicate anti-inflammatory property of DHM but no information is currently available on its mechanism of action or effect on IL17 producing Th17 cells and exact role in psoriasis.
DHM shows strong anti-inflammatory properties in vitro, DHM reduced LPS-induced ROS generation, and pro-inflammatory cytokines in macrophages. The efficacy of DHM against chronic inflammatory disorder in vivo was investigated in imiquimod-induced psoriasis established in male BALB/C mice as this model closely resembles human psoriasis. Immunophenotyping and cytokine production were observed by flow cytometry, the status of gene expression was determined by real-time PCR, and nuclear co-localization and immunofluorescence of skin tissue were studied using confocal microscopy.
We observed increased inflammatory parameters in imiquimod treated diseased animals and the application of DHM topically and orally reduced the inflammatory parameters and improved indicators of cardiac damage prominent in psoriatic conditions. In our study, we found that the application of DHM dose-dependently reduced the percentage of IL-17 A-producing T cell population and reduced the nuclear co-translocation of RORγt in psoriatic T cells and possibly also influenced upstream IL-6 signaling.
Our study suggests that DHM effectively alleviates psoriatic symptoms, and its mechanism of action involves the regulation of RORγt pathway in T cells.
银屑病是一种慢性炎症性皮肤病，影响着约1.25亿人。Th17细胞分泌的白细胞介素-17A（IL-17A）在银屑病的发病机制中起主要作用。二氢杨梅素（DHM）是从藤茶（显齿蛇葡萄）的叶和茎中分离出的一种植物源黄酮类化合物。有报道显示DHM具有抗炎特性，但目前尚无关于其作用机制、对产生IL-17的Th17细胞的影响以及在银屑病中的确切作用的相关信息。
DHM在体外显示出强大的抗炎特性，它能减少脂多糖（LPS）诱导的巨噬细胞中活性氧（ROS）的产生以及促炎细胞因子的分泌。由于雄性BALB/C小鼠建立的咪喹莫特诱导的银屑病模型与人类银屑病非常相似，因此在该模型中研究了DHM对体内慢性炎症性疾病的疗效。通过流式细胞术观察免疫表型和细胞因子产生情况，通过实时聚合酶链反应（PCR）确定基因表达状态，并使用共聚焦显微镜研究皮肤组织的核共定位和免疫荧光。
我们观察到咪喹莫特处理的患病动物炎症参数增加，而局部和口服应用DHM可降低炎症参数，并改善银屑病中突出的心脏损伤指标。在我们的研究中，我们发现应用DHM剂量依赖性地降低了产生IL-17A的T细胞群体的百分比，并减少了银屑病T细胞中维甲酸相关孤儿受体γt（RORγt）的核共转位，并且可能还影响了上游白细胞介素-6（IL-6）信号传导。
我们的研究表明，DHM能有效减轻银屑病症状，其作用机制涉及调节T细胞中的RORγt通路。
