Mijiti Nuerbiyemu, Someya Akimasa, Nagaoka Isao
Department of Host Defense and Biochemical Research, Juntendo University, Graduate School of Medicine, Tokyo 113-8421, Japan.
Department of Physical Therapy, Faculty of Health Science, Juntendo University, Tokyo 113-0033, Japan.
Exp Ther Med. 2021 Nov;22(5):1300. doi: 10.3892/etm.2021.10735. Epub 2021 Sep 16.
The present study investigated the effects of isoflavone derivatives (daidzein, genistein and glycitein) on the production of inflammatory cytokines (IL-6 and IL-8) by IL-1β-stimulated synovial cells. Synovial MH7A cells were stimulated with IL-1β in the absence or presence of isoflavone derivatives, and IL-6 and IL-8 production was measured by ELISA. The results of the present study indicated that daidzein significantly inhibited the production of IL-6, but not IL-8. Conversely, neither genistein nor glycitein exerted any inhibitory effects on the production of IL-6 or IL-8 by IL-1β-stimulated synovial cells. To elucidate the molecular mechanisms underlying the daidzein-mediated inhibition of IL-6 production, the present study examined the effects of daidzein on the phosphorylation (activation) of NF-κB p65, ERK1/2 and p38 MAPK. Daidzein significantly inhibited the phosphorylation of NF-κB p65 and ERK1/2, but not p38 MAPK in IL-1β-stimulated MH7A cells. The present study revealed that among the isoflavone derivatives examined (daidzein, genistein and glycitein), daidzein inhibited the production of IL-6, but not IL-8, by IL-1β-stimulated synovial MH7A cells via the suppression of NF-κB p65 and ERK1/2 activation. Collectively, these results suggested that daidzein may have potential as a therapeutic agent for the treatment of arthritic disorders through its anti-inflammatory effects via the inhibition of IL-6 production.
本研究调查了异黄酮衍生物（大豆苷元、染料木黄酮和黄豆黄素）对白细胞介素-1β刺激的滑膜细胞产生炎性细胞因子（白细胞介素-6和白细胞介素-8）的影响。在不存在或存在异黄酮衍生物的情况下，用白细胞介素-1β刺激滑膜MH7A细胞，并通过酶联免疫吸附测定法测量白细胞介素-6和白细胞介素-8的产生。本研究结果表明，大豆苷元显著抑制白细胞介素-6的产生，但不抑制白细胞介素-8的产生。相反，染料木黄酮和黄豆黄素对白细胞介素-1β刺激的滑膜细胞产生白细胞介素-6或白细胞介素-8均未发挥任何抑制作用。为了阐明大豆苷元介导的白细胞介素-6产生抑制作用的分子机制，本研究检测了大豆苷元对核因子-κB p65、细胞外信号调节激酶1/2和p38丝裂原活化蛋白激酶磷酸化（激活）的影响。在白细胞介素-1β刺激的MH7A细胞中，大豆苷元显著抑制核因子-κB p65和细胞外信号调节激酶1/2的磷酸化，但不抑制p38丝裂原活化蛋白激酶的磷酸化。本研究表明，在所检测的异黄酮衍生物（大豆苷元、染料木黄酮和黄豆黄素）中，大豆苷元通过抑制核因子-κB p65和细胞外信号调节激酶1/2的激活，抑制白细胞介素-1β刺激的滑膜MH7A细胞产生白细胞介素-6，但不抑制白细胞介素-8。总体而言，这些结果表明，大豆苷元可能因其通过抑制白细胞介素-6产生而具有的抗炎作用，具有作为治疗关节炎疾病的治疗剂的潜力。
