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叶提取物及其主要成分杨梅素通过抑制小胶质细胞炎症和小胶质细胞介导的星形胶质细胞激活来抑制与瘙痒相关的白细胞介素 6 和白细胞介素 31。

leaf extract and its main component myricitrin inhibit itch‑related IL‑6 and IL‑31 by suppressing microglial inflammation and microglial‑mediated astrocyte activation.

机构信息

Institute of Health and Science, Jeonju University, Jeonju‑si, Jeollabuk‑do 55069, Republic of Korea.

Department of Pharmaceutical Science and Engineering, Seowon University, Cheongju‑si, Chungcheongbuk‑do 28674, Republic of Korea.

出版信息

Mol Med Rep. 2024 Oct;30(4). doi: 10.3892/mmr.2024.13303. Epub 2024 Aug 12.

Abstract

has been traditionally used in Asia for medicinal purposes, exhibiting a broad spectrum of pharmacological effects including antioxidant, neuroprotective and anti‑inflammatory properties. While the anti‑itch effect of leaves has been reported, studies on the detailed mechanism of action in microglia and astrocytes, which are members of the central nervous system, have yet to be revealed. The present study aimed to investigate effects of leaf extract (DLE) and its main component myricitrin (MC) on itch‑related cytokines and signaling pathways in lipopolysaccharide (LPS)‑stimulated microglia. The effect of DLE and MC on activation of astrocyte stimulated by microglia was also examined. Cytokine production was evaluated through reverse transcription PCR and western blot analysis. Signaling pathway was analyzed by performing western blotting and immunofluorescence staining. The effect of microglia on astrocytes activation was evaluated via western blotting for receptors, signaling molecules and itch mediators and confirmed through gene silencing using short interfering RNA. DLE and MC suppressed the production of itch‑related cytokine IL‑6 and IL‑31 in LPS‑stimulated microglia. These inhibitory effects were mediated through the blockade of NF‑κB, MAPK and JAK/STAT pathways. In astrocytes, stimulation by microglia promoted the expression of itch‑related molecules such as oncostatin M receptor, interleukin 31 receptor a, inositol 1,4,5‑trisphosphate receptor 1, lipocalin‑2 (LCN2), STAT3 and glial fibrillary acidic protein. However, DLE and MC significantly inhibited these receptors. Additionally, astrocytes stimulated by microglia with IL‑6, IL‑31, or both genes silenced did not show activation of LCN2 or STAT3. The findings of the present study demonstrated that DLE and MC could suppress pruritic activity in astrocytes induced by microglia‑derived IL‑6 and IL‑31. This suggested the potential of DLE and MC as functional materials capable of alleviating pruritus.

摘要

在亚洲,它一直被用于医学用途,具有广泛的药理作用,包括抗氧化、神经保护和抗炎特性。虽然已经报道了 的止痒作用,但关于其在小胶质细胞和星形胶质细胞(中枢神经系统的成员)中的详细作用机制的研究尚未揭示。本研究旨在探讨 叶提取物(DLE)及其主要成分杨梅素(MC)对脂多糖(LPS)刺激的小胶质细胞中与瘙痒相关的细胞因子和信号通路的影响。还研究了 DLE 和 MC 对小胶质细胞刺激的星形胶质细胞激活的影响。通过逆转录 PCR 和 Western blot 分析评估细胞因子的产生。通过 Western blot 和免疫荧光染色分析信号通路。通过 Western blot 检测小胶质细胞对星形胶质细胞激活的影响,用于检测受体、信号分子和瘙痒介质,并通过使用短发夹 RNA 进行基因沉默进行确认。DLE 和 MC 抑制了 LPS 刺激的小胶质细胞中与瘙痒相关的细胞因子 IL-6 和 IL-31 的产生。这些抑制作用是通过阻断 NF-κB、MAPK 和 JAK/STAT 通路介导的。在星形胶质细胞中,小胶质细胞的刺激促进了与瘙痒相关的分子的表达,如孤啡肽受体、白细胞介素 31 受体 a、三磷酸肌醇受体 1、脂联素-2(LCN2)、STAT3 和胶质纤维酸性蛋白。然而,DLE 和 MC 显著抑制了这些受体。此外,用小胶质细胞来源的 IL-6、IL-31 或两者的基因沉默刺激的星形胶质细胞不会激活 LCN2 或 STAT3。本研究的结果表明,DLE 和 MC 可以抑制小胶质细胞衍生的 IL-6 和 IL-31 诱导的星形胶质细胞的瘙痒活性。这表明 DLE 和 MC 作为能够缓解瘙痒的功能材料具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aba/11338241/ed9825942ef2/mmr-30-04-13303-g00.jpg

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