Han Luyang, Han Peng, Zhu Yanbo, Dong Jiawei, Guan Zhenyang, Xu Yuekang, Li Jinyao, Liu Xiaoying
Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830017, China.
Int J Mol Sci. 2025 Apr 11;26(8):3626. doi: 10.3390/ijms26083626.
Rheumatoid arthritis (RA) is a highly prevalent systemic autoimmune disease. Recently, natural small molecules have been explored as alternative therapeutic agents. is the traditional herbal medicine, and it is rich in active ingredients with anti-inflammatory and immunomodulatory effects. In our previous study, LC-MS analysis revealed that piceatannol (PIC) is one of the primary active ingredients in the root of Iris tectorum. The purpose of this study was to explore the immunomodulatory effects of PIC on the maturation and function of dendritic cells, as well as on experimental arthritis induced by complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA). Additionally, we aimed to probe into the potential mechanisms underlying the effects of PIC. We first verified the immunosuppressive effect of PIC using flow cytometry and an ELISA. The immunosuppressive mechanism of PIC on dendritic cells (DCs) was investigated through a joint analysis of network pharmacology and Western blotting. Our findings revealed that under Lipopolysaccharide (LPS)-induced inflammatory conditions, PIC could restrain the maturation and function of DCs ( < 0.001) and decrease the secretion of inflammatory cytokines ( < 0.001) compared to the LPS group. Furthermore, PIC suppressed the activation and polarization of CD4 T cells, resulting in a decreased proportion of Th1 and Th17 cells ( < 0.001), ultimately improving the symptoms of CFA-induced arthritis in comparison to the model group. The PIC-induced shift in the T helper cell differentiation correlated with the secretion of polarizing cytokines from DCs in the AIA model. Mechanistically, PIC exerted its immunosuppressive function mainly by down-regulating the Mitogen-Activated Protein Kinase (MAPK) and Nuclear Factor kappa-B (NF-κB) signaling pathways. Collectively, these data unveil the anti-inflammatory mechanisms of a traditional medicine via the inhibition of the immune activation function of DCs in vivo and open up a therapeutic approach for autoinflammatory diseases.
类风湿性关节炎（RA）是一种高度流行的全身性自身免疫性疾病。近年来，天然小分子已被探索作为替代治疗药物。鸢尾是一种传统草药，富含具有抗炎和免疫调节作用的活性成分。在我们之前的研究中，液相色谱-质谱联用（LC-MS）分析显示，白皮杉醇（PIC）是鸢尾根中的主要活性成分之一。本研究的目的是探讨PIC对树突状细胞成熟和功能的免疫调节作用，以及对完全弗氏佐剂（CFA）和不完全弗氏佐剂（IFA）诱导的实验性关节炎的影响。此外，我们旨在探究PIC作用的潜在机制。我们首先使用流式细胞术和酶联免疫吸附测定（ELISA）验证了PIC的免疫抑制作用。通过网络药理学和蛋白质免疫印迹法的联合分析，研究了PIC对树突状细胞（DCs）的免疫抑制机制。我们的研究结果表明，在脂多糖（LPS）诱导的炎症条件下，与LPS组相比，PIC可以抑制DCs的成熟和功能（<0.001），并减少炎性细胞因子的分泌（<0.001）。此外，PIC抑制CD4 T细胞的激活和极化，导致Th1和Th17细胞比例降低（<0.001），最终与模型组相比改善了CFA诱导的关节炎症状。在佐剂性关节炎（AIA）模型中，PIC诱导的辅助性T细胞分化转变与DCs分泌的极化细胞因子相关。从机制上讲，PIC主要通过下调丝裂原活化蛋白激酶（MAPK）和核因子κB（NF-κB）信号通路发挥其免疫抑制功能。总的来说，这些数据揭示了一种传统药物通过抑制体内DCs的免疫激活功能的抗炎机制，并为自身炎症性疾病开辟了一种治疗方法。
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