用阿魏酸（一种膳食多酚）靶向炎症介质，以抑制大鼠体内尿酸钠晶体诱导的炎症。

Targeting inflammatory mediators with ferulic acid, a dietary polyphenol, for the suppression of monosodium urate crystal-induced inflammation in rats.

作者信息

Doss Hari Madhuri, Dey Chandrima, Sudandiradoss C, Rasool Mahaboob Khan

机构信息

Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore 632 014, India.

Division of Bio-informatics, School of Bio Sciences and Technology, VIT University, Vellore 632014, India.

出版信息

Life Sci. 2016 Mar 1;148:201-10. doi: 10.1016/j.lfs.2016.02.004. Epub 2016 Feb 4.

DOI:10.1016/j.lfs.2016.02.004

PMID:26851531

Abstract

AIMS

The aim of this study was to investigate the anti-inflammatory effect of ferulic acid, a dietary phenol, on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. For the purpose of comparison, colchicine was used as a reference drug.

MAIN METHODS

Paw edema, levels/activities of elastase, lysosomal enzymes (acid phosphatase and β-galactosidase), nitric oxide, lipid peroxidation, antioxidant status and pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β), and histology of ankle joints were evaluated in rats with MSU crystal-induced inflammation. The messenger RNA (mRNA) expression of pro-inflammatory cytokines (TNF-α and IL-1β), NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasomes, caspase-1, and the transcription factor nuclear factor kappa B p65 (NF-κB p65) was determined by real-time polymerase chain reaction (PCR) analysis. The protein expression of NF-κB p65 and TNF-α was detected by immunohistochemical analysis. Further, a molecular docking analysis was conducted to determine the ligand efficiency of ferulic acid towards NF-κB, apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC), NLRP3, and pro-caspase-1.

KEY FINDINGS

In the joint homogenate of rats with MSU crystal-induced inflammation, treatment with ferulic acid (30mg/kg body weight (b.wt)) decreased paw edema; the level/activity of elastase, lysosomal enzymes, nitric oxide, lipid peroxidation, and pro-inflammatory cytokines (TNF-α and IL-1β); and the mRNA expression of NLRP3 inflammasomes, caspase-1, pro-inflammatory cytokines, and NF-κB p65. In addition, the protein expression of NF-κB p65 and TNF-α was also found to be significantly decreased. However, the antioxidant status (superoxide dismutase (SOD) and catalase (CAT)) were found to be increased. The molecular docking analysis showed that ferulic acid exhibited significant ligand efficiency towards pro-caspase-1, NF-κB, PYCARD/ASC, and NLRP3.

SIGNIFICANCE

Our findings demonstrate the potential anti-inflammatory effect of ferulic acid on MSU crystal-induced inflammation in rats.

摘要

目的

本研究旨在探讨膳食酚类阿魏酸对大鼠尿酸钠（MSU）晶体诱导的炎症的抗炎作用，该炎症是急性痛风性关节炎的实验模型。为作比较，秋水仙碱用作参比药物。

主要方法

对MSU晶体诱导炎症的大鼠，评估其爪部水肿、弹性蛋白酶水平/活性、溶酶体酶（酸性磷酸酶和β-半乳糖苷酶）、一氧化氮、脂质过氧化、抗氧化状态及促炎细胞因子（肿瘤坏死因子α（TNF-α）和白细胞介素（IL）-1β），并对踝关节进行组织学检查。通过实时聚合酶链反应（PCR）分析测定促炎细胞因子（TNF-α和IL-1β）、NLRP3（含pyrin结构域的NOD样受体家族3）炎性小体、半胱天冬酶-1及转录因子核因子κB p65（NF-κB p65）的信使核糖核酸（mRNA）表达。通过免疫组织化学分析检测NF-κB p65和TNF-α的蛋白表达。此外，进行分子对接分析以确定阿魏酸对NF-κB、含CARD的凋亡相关斑点样蛋白（PYCARD/ASC）、NLRP3和前半胱天冬酶-1的配体效率。

主要发现

在MSU晶体诱导炎症的大鼠关节匀浆中，阿魏酸（30mg/kg体重（b.wt））治疗可减轻爪部水肿；降低弹性蛋白酶水平/活性、溶酶体酶、一氧化氮、脂质过氧化及促炎细胞因子（TNF-α和IL-1β）；降低NLRP3炎性小体、半胱天冬酶-1、促炎细胞因子及NF-κB p65的mRNA表达。此外，还发现NF-κB p65和TNF-α的蛋白表达显著降低。然而，抗氧化状态（超氧化物歧化酶（SOD）和过氧化氢酶（CAT））升高。分子对接分析表明，阿魏酸对前半胱天冬酶-1、NF-κB、PYCARD/ASC和NLRP3表现出显著的配体效率。