Kim Ju Hwan, Shin Chang Yell, Jang Sun Woo, Kim Dong-Seok, Lee Wonae, Kim Hyung-Gun, Kim Hak Rim
Department of Pharmacology, College of Medicine, Dankook University, Cheonan 31116, Korea.
Research Institute of Dong-A ST Co., Ltd., Yongin 17073, Korea.
Korean J Physiol Pharmacol. 2021 Sep 1;25(5):439-448. doi: 10.4196/kjpp.2021.25.5.439.
DA-9601 is an extract obtained from , which has been reported to have anti-inflammatory effects on gastrointestinal lesions; however, its possible anti-inflammatory effects on the small intestine have not been studied yet. Therefore, in this study, we investigated the protective effects of DA-9601 against the ACF-induced small intestinal inflammation. Inflammation of the small intestine was confirmed by histological studies and the changes in the CD4 T cell fraction induced by the inflammation-related cytokines, and the inflammatory reactions were analyzed. Multifocal discrete small necrotic ulcers with intervening normal mucosa were frequently observed after treatment with ACF. The expression of -6 , -17, and -α genes was increased in the ACF group; however, it was found to have been significantly decreased in the DA-9601 treated group. In addition, DA-9601 significantly decreased the levels of proinflammatory mediators such as IL-1β, GMCSF, IFN-γ, and TNF-α; the anti-inflammatory cytokine IL-10, on the other hand, was observed to have increased. It is known that inflammatory mediators related to T cell imbalance and dysfunction continuously activate the inflammatory response, causing chronic tissue damage. The fractions of IFN-γ Th1 cells, IL-4 Th2 cells, IL-9 Th9 cells, IL-17 Th17 cells, and Foxp3 Treg cells were significantly decreased upon DA-9601 treatment. These data suggest that the inflammatory response induced by ACF is reduced by DA-9601 via lowering of the expression of genes encoding the inflammatory cytokines and the concentration of inflammatory mediators. Furthermore, DA-9601 inhibited the acute inflammatory response mediated by T cells, resulting in an improvement in ACF-induced enteritis.
DA-9601是从[具体来源未提及]中提取的一种提取物，据报道它对胃肠道损伤具有抗炎作用；然而，其对小肠可能的抗炎作用尚未得到研究。因此，在本研究中，我们研究了DA-9601对ACF诱导的小肠炎症的保护作用。通过组织学研究以及炎症相关细胞因子诱导的CD4 T细胞分数变化来确认小肠炎症，并对炎症反应进行分析。用ACF处理后，经常观察到多灶性离散的小坏死性溃疡，其间有正常黏膜。ACF组中-6、-17和-α基因的表达增加；然而，在DA-9601处理组中发现其显著降低。此外，DA-9601显著降低了促炎介质如IL-1β、GMCSF、IFN-γ和TNF-α的水平；另一方面，抗炎细胞因子IL-10则有所增加。已知与T细胞失衡和功能障碍相关的炎症介质会持续激活炎症反应，导致慢性组织损伤。DA-9601处理后，IFN-γ Th1细胞、IL-4 Th2细胞、IL-9 Th9细胞、IL-17 Th17细胞和Foxp3 Treg细胞的比例显著降低。这些数据表明，DA-9601通过降低炎症细胞因子编码基因的表达和炎症介质的浓度，减轻了ACF诱导的炎症反应。此外，DA-9601抑制了由T细胞介导的急性炎症反应，从而改善了ACF诱导的肠炎。
