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提取物可抑制脂多糖触发的炎症标志物,并抑制RAW264.7细胞中核因子κB受体活化因子配体诱导的破骨细胞生成。

Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses RANKL-Induced Osteoclastogenesis in RAW264.7.

作者信息

Orecchini Elena, Mondanelli Giada, Orabona Ciriana, Volpi Claudia, Adorisio Sabrina, Calvitti Mario, Thuy Trinh Thi, Delfino Domenico V, Belladonna Maria Laura

机构信息

Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

Department of Medicine and Surgery, Foligno Nursing School, University of Perugia, Perugia, Italy.

出版信息

Front Pharmacol. 2021 Jan 22;11:593829. doi: 10.3389/fphar.2020.593829. eCollection 2020.

Abstract

() leaf decoction, a traditional remedy prepared in North by the Hmong ethnic group, is a tea extract rich in bioactive compounds that may have therapeutic effects in arthritis and backache. Indeed, it has been demonstrated that is able to inhibit Th17 lymphocytes development and to protect mice in an experimental model of collagen-induced arthritis. By resorting to macrophage models of inflammation and osteoclastogenesis, we showed that extract significantly reduced nitric oxide synthase 2 (NOS2) activity and IL-6 production by RAW 264.7 murine cells. Moreover, demonstrated an anti-osteoclastogenic effect, as revealed by complete inhibition of TRAP-positive osteoclast formation and decreased expression of key osteoclast-related genes. This activity likely relies on the inhibition of RANK downstream signaling pathway, as the activation of non-receptor tyrosine kinase Src is reduced upon RANKL- exposure. Protective effect of against bone loss was also enlightened by collagen-induced arthritis (CIA) experiment demonstrating that, although paw edema was only weakly opposed by drinking decoction, bone and cartilage were well preserved in CIA+ mice and joint tissue expressed decreased levels of osteoclast marker genes respect to CIA control group. Maesopsin 4-O-β-D-glucoside (i.e., TAT-2, one of the main decoction bioactive components) was capable to contrast NOS2 activity, IL-6 expression and osteoclast formation, too, albeit to a lesser extent when compared to decoction. Overall, this study enlightens another cell target, macrophages, beside Th17 lymphocytes, and suggests that the anti-arthritic beneficial effects of decoction largely derives from its ability to counteract not only inflammation, but also osteoclastogenesis.

摘要

()叶煎剂是苗族在北方制备的一种传统药物,是一种富含生物活性化合物的茶提取物,可能对关节炎和背痛有治疗作用。事实上,已经证明()能够抑制Th17淋巴细胞的发育,并在胶原诱导的关节炎实验模型中保护小鼠。通过采用巨噬细胞炎症和破骨细胞形成模型,我们发现()提取物显著降低了RAW 264.7小鼠细胞中一氧化氮合酶2(NOS2)的活性和IL-6的产生。此外,()表现出抗破骨细胞形成的作用,这通过TRAP阳性破骨细胞形成的完全抑制和关键破骨细胞相关基因表达的降低得以体现。这种()活性可能依赖于对RANK下游信号通路的抑制,因为在RANKL暴露后非受体酪氨酸激酶Src的激活减少。胶原诱导的关节炎(CIA)实验也揭示了()对骨质流失的保护作用,表明虽然饮用()煎剂对爪肿胀的抑制作用较弱,但在CIA +小鼠中骨骼和软骨保存良好,并且与CIA对照组相比,关节组织中破骨细胞标记基因的表达水平降低。毛茛黄素4-O-β-D-葡萄糖苷(即TAT-2,煎剂的主要生物活性成分之一)也能够抑制NOS2活性、IL-6表达和破骨细胞形成,尽管与()煎剂相比程度较小。总体而言,这项研究揭示了除Th17淋巴细胞外的另一个()细胞靶点,即巨噬细胞,并表明()煎剂的抗关节炎有益作用很大程度上源于其不仅能够对抗炎症,还能对抗破骨细胞形成的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1d2/7862131/09c46a90bf23/fphar-11-593829-g001.jpg

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