Lee Yu Jeong, Li Zijun, Jang Hyun Hee, Kim Moon-Ju, Saravanakumar Kandasamy, Shim Seung Cheol, Cho Namki, Won Eun Jeong, Kim Tae-Jong
Department of Biomedical Sciences, Graduate School of Chonnam National University, Jeollanam-do, Republic of Korea.
Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Front Pharmacol. 2024 Dec 3;15:1456216. doi: 10.3389/fphar.2024.1456216. eCollection 2024.
Usenamine A (UA) is a natural compound isolated from the lichen , and its therapeutic effects on rheumatic diseases are not well understood. This study aimed to evaluate the potential anti-inflammatory effects of UA and its therapeutic effects on rheumatoid arthritis (RA) and ankylosing spondylitis (AS).
Molecular docking was performed between the 3D structure of UA and the TNF-TNFR2 complex. Peripheral blood mononuclear cells (PBMCs) from RA and AS patients were treated with UA, and cell viability was measured using the MTS assay and flow cytometry. The in vitro effects of co-culture with UA were determined by measuring inflammatory cytokines, including IFN-γ, IL-17A, and GM-CSF, using flow cytometry and enzyme-linked immunosorbent assay (ELISA). The in vivo effects of UA were evaluated using an arthritis mouse model.
The docking complex of UA bound to the TNF-TNFR2 complex exhibited docking scores of -5.251 kcal/mol and -6.274 kcal/mol, confirming their active sites. UA did not affect cell viability and suppressed the production of inflammatory cytokines in the PBMCs of RA (IFN-γ, IL-17A, and GM-CSF) and AS (GM-CSF) patients. The ELISA also confirmed reduced cytokine levels in the co-culture of UA and PBMCs from RA or AS patients. In the arthritis mouse model, significantly reduced clinical and histological scores were observed in the UA treatment group.
Our findings suggest that UA has potential as a binding target for TNF, suppresses inflammatory cytokines in PBMCs, and exhibits anti-inflammatory effects on arthritis in a mouse model.
乌斯那明A（UA）是从地衣中分离出的一种天然化合物，其对风湿性疾病的治疗作用尚未完全明确。本研究旨在评估UA的潜在抗炎作用及其对类风湿关节炎（RA）和强直性脊柱炎（AS）的治疗效果。
对UA的三维结构与肿瘤坏死因子 - 肿瘤坏死因子受体2（TNF - TNFR2）复合物进行分子对接。用UA处理RA和AS患者的外周血单个核细胞（PBMC），采用MTS法和流式细胞术检测细胞活力。通过流式细胞术和酶联免疫吸附测定（ELISA）测量包括干扰素 - γ（IFN - γ）、白细胞介素 - 17A（IL - 17A）和粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）在内的炎性细胞因子，以确定与UA共培养的体外效果。使用关节炎小鼠模型评估UA的体内效果。
UA与TNF - TNFR2复合物的对接复合物显示对接分数分别为 - 5.251千卡/摩尔和 - 6.274千卡/摩尔，证实了它们的活性位点。UA不影响细胞活力，并抑制RA患者（IFN - γ、IL - 17A和GM - CSF）和AS患者（GM - CSF）PBMC中炎性细胞因子的产生。ELISA也证实了UA与RA或AS患者PBMC共培养中细胞因子水平降低。在关节炎小鼠模型中，UA治疗组的临床和组织学评分显著降低。
我们的研究结果表明，UA有潜力作为TNF的结合靶点，抑制PBMC中的炎性细胞因子，并在小鼠模型中对关节炎表现出抗炎作用。
