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紫鹃茶水提物通过调节 Akt/GSK3β 和 Blimp1-Irf8 通路阻断 RANKL 诱导的破骨细胞生成。

Purple tea water extract blocks RANKL-induced osteoclastogenesis through modulation of Akt/GSK3β and Blimp1-Irf8 pathways.

机构信息

Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin Province, PR China.

Department of Neurology, Ruikang Hospital of Guangxi TCM University, Nanning, Guangxi Province, PR China.

出版信息

Food Funct. 2022 Aug 30;13(17):8850-8859. doi: 10.1039/d2fo00780k.

Abstract

A number of studies demonstrated that some tea extracts exert inhibitory effects on osteoclastogenesis induced by receptor activator of nuclear factor κB ligand (RANKL). However, the effect of purple tea, a famous tea in China, on osteoclastogenesis remains unclear. In this study, a water-based purple tea extract (PTE) was found to suppress osteoclast formation, osteoclastic resorption pit area formation, and F-actin ring formation within RANKL-stimulated bone marrow macrophages (BMMs). Furthermore, our results demonstrated that PTE could inhibit expression of master transcription factors NFATc1 and c-Fos and their target genes , , and . Western blot analysis revealed that PTE treatment led to reduced RANKL-induced phosphorylation of Akt and GSK3β without altering transient activation of NF-κB and MAPKs (p38, JNK, ERK1/2) signaling. In addition, the results demonstrated that PTE treatment of RANKL-stimulated BMMs could down-regulate Blimp1 expression and up-regulate Irf8 expression. In summary, these results suggest that PTE treatment of RANKL-stimulated BMMs inhibited osteoclast differentiation modulation of Blimp1-Irf8 and Akt/GSK3β signaling pathways. Aligning with our results, PTE administration ameliorated bone loss in LPS-treated mice. Taken together, the results presented in this work suggest that PTE treatment possesses anti-osteolytic activity.

摘要

一些研究表明,一些茶提取物对核因子κB 受体激活剂配体(RANKL)诱导的破骨细胞形成具有抑制作用。然而,中国著名茶叶——紫茶对破骨细胞形成的影响尚不清楚。在这项研究中,发现一种基于水的紫茶提取物(PTE)可抑制 RANKL 刺激的骨髓巨噬细胞(BMM)中的破骨细胞形成、破骨细胞吸收陷窝形成和 F-肌动蛋白环形成。此外,我们的结果表明,PTE 可以抑制主转录因子 NFATc1 和 c-Fos 及其靶基因 、 、 和 的表达。Western blot 分析显示,PTE 处理导致 Akt 和 GSK3β 的磷酸化减少,而不改变 NF-κB 和 MAPKs(p38、JNK、ERK1/2)信号的瞬时激活。此外,结果表明,PTE 处理 RANKL 刺激的 BMM 可以下调 Blimp1 表达并上调 Irf8 表达。总之,这些结果表明,PTE 处理 RANKL 刺激的 BMM 抑制破骨细胞分化——调节 Blimp1-Irf8 和 Akt/GSK3β 信号通路。与我们的结果一致,PTE 给药改善了 LPS 处理小鼠的骨丢失。总之,本工作的结果表明,PTE 处理具有抗溶骨活性。

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