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姜黄二甲亚砜提取物和姜黄素对人椎间盘细胞具有抗炎和抗分解代谢作用,可能通过影响 TLR2 表达和 JNK 活性。

Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity.

机构信息

Spine Research Group, Competence Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland.

出版信息

J Inflamm (Lond). 2012 Aug 21;9(1):29. doi: 10.1186/1476-9255-9-29.

Abstract

BACKGROUND

As proinflammatory cytokines seem to play a role in discogenic back pain, substances exhibiting anti-inflammatory effects on intervertebral disc cells may be used as minimal-invasive therapeutics for intradiscal/epidural injection. The purpose of this study was to investigate the anti-inflammatory and anti-catabolic potential of curcuma, which has been used in the Indian Ayurvedic medicine to treat multiple ailments for a long time.

METHODS

Human disc cells were treated with IL-1β to induce an inflammatory/catabolic cascade. Different extracts of curcuma as well as curcumin (= a component selected based on results with curcuma extracts and HPLC/MS analysis) were tested for their ability to reduce mRNA expression of proinflammatory cytokines and matrix degrading enzymes after 6 hours (real-time RT-PCR), followed by analysis of typical inflammatory signaling mechanisms such as NF-κB (Western Blot, Transcription Factor Assay), MAP kinases (Western Blot) and Toll-like receptors (real-time RT-PCR). Quantitative data was statistically analyzed using a Mann Whitney U test with a significance level of p < 0.05 (two-tailed).

RESULTS

Results indicate that the curcuma DMSO extract significantly reduced levels of IL-6, MMP1, MMP3 and MMP13. The DMSO-soluble component curcumin, whose occurrence within the DMSO extract was verified by HPLC/MS, reduced levels of IL-1β, IL-6, IL-8, MMP1, MMP3 and MMP13 and both caused an up-regulation of TNF-α. Pathway analysis indicated that curcumin did not show involvement of NF-κB, but down-regulated TLR2 expression and inhibited the MAP kinase JNK while activating p38 and ERK.

CONCLUSIONS

Based on its anti-inflammatory and anti-catabolic effects, intradiscal injection of curcumin may be an attractive treatment alternative. However, whether the anti-inflammatory properties in vitro lead to analgesia in vivo will need to be confirmed in an appropriate animal model.

摘要

背景

由于促炎细胞因子似乎在椎间盘源性腰痛中发挥作用,因此具有抗椎间盘细胞炎症作用的物质可能被用作椎间盘内/硬膜外注射的微创治疗方法。本研究的目的是研究姜黄的抗炎和抗分解代谢作用,姜黄长期以来一直被用于印度阿育吠陀医学来治疗多种疾病。

方法

用白细胞介素-1β(IL-1β)处理人椎间盘细胞,以诱导炎症/分解代谢级联反应。测试了姜黄的不同提取物以及姜黄素(=根据姜黄提取物和 HPLC/MS 分析的结果选择的一种成分),以检测它们在 6 小时后降低促炎细胞因子和基质降解酶的 mRNA 表达的能力(实时 RT-PCR),然后分析典型的炎症信号机制,如 NF-κB(Western Blot、转录因子测定)、MAP 激酶(Western Blot)和 Toll 样受体(实时 RT-PCR)。使用具有双侧检验的 Mann-Whitney U 检验对定量数据进行统计分析,显著性水平为 p<0.05。

结果

结果表明,姜黄 DMSO 提取物显著降低了 IL-6、MMP1、MMP3 和 MMP13 的水平。DMSO 可溶性成分姜黄素,其在 DMSO 提取物中的存在通过 HPLC/MS 得到证实,降低了 IL-1β、IL-6、IL-8、MMP1、MMP3 和 MMP13 的水平,同时导致 TNF-α 的上调。通路分析表明,姜黄素不参与 NF-κB,但下调 TLR2 表达并抑制 MAP 激酶 JNK,同时激活 p38 和 ERK。

结论

基于其抗炎和抗分解代谢作用,姜黄素的椎间盘内注射可能是一种有吸引力的治疗选择。然而,体外的抗炎特性是否会导致体内的镇痛作用,需要在适当的动物模型中得到证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/3506446/59741f466495/1476-9255-9-29-1.jpg

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