The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways

Gouty arthritis (GA) is a frequent inflammatory disease characterized by pain, swelling, and stiffness of joints. Neoastilbin is a flavonoid isolated from the rhizome of <i>Smilax glabra</i>, which possesses various anti-inflammatory effects. However, the mechanism of neoastilbin in trea...

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Main Authors: Wenjing Xu, Fenfen Li, Xiaoxi Zhang, Chenxi Wu, Yan Wang, Yanjing Yao, Daozong Xia
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/11/3477
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author Wenjing Xu
Fenfen Li
Xiaoxi Zhang
Chenxi Wu
Yan Wang
Yanjing Yao
Daozong Xia
author_facet Wenjing Xu
Fenfen Li
Xiaoxi Zhang
Chenxi Wu
Yan Wang
Yanjing Yao
Daozong Xia
author_sort Wenjing Xu
collection DOAJ
description Gouty arthritis (GA) is a frequent inflammatory disease characterized by pain, swelling, and stiffness of joints. Neoastilbin is a flavonoid isolated from the rhizome of <i>Smilax glabra</i>, which possesses various anti-inflammatory effects. However, the mechanism of neoastilbin in treating GA has not yet been clarified. Thus, this study was to investigate the protective effects of neoastilbin in both monosodium urate (MSU) stimulated THP-1-derived macrophages and the animal model of GA by injecting MSU into the ankle joints of mice. The levels of key inflammatory cytokines in MSU stimulated THP-1-derived macrophages were detected by enzyme-linked immunosorbent assay (ELISA) kits. Protein expressions of nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome pathways were further detected by Western blotting. In addition, swelling degree of ankle joints, the levels of inflammatory factors, infiltration of inflammatory cells and the expressions of related proteins were determined. Swelling degree and histopathological injury in ankle joints of MSU-injected mice were significantly decreased after being treated with neoastilbin. Moreover, neoastilbin significantly diminished the secretion of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), suppressing the activation of NF-κB and NLRP3 inflammasome pathways in both MSU stimulated THP-1-derived macrophages and the mouse model of GA. In summary, neoastilbin could alleviate GA by inhibiting the NF-κB and NLRP3 inflammasome pathways, which provided some evidence for neoastilbin as a promising therapeutic agent for GA treatment.
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spelling doaj.art-01e8b00a0e404292b5fad9c5a6665d652023-11-23T14:29:22ZengMDPI AGMolecules1420-30492022-05-012711347710.3390/molecules27113477The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome PathwaysWenjing Xu0Fenfen Li1Xiaoxi Zhang2Chenxi Wu3Yan Wang4Yanjing Yao5Daozong Xia6School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaAcademy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaGouty arthritis (GA) is a frequent inflammatory disease characterized by pain, swelling, and stiffness of joints. Neoastilbin is a flavonoid isolated from the rhizome of <i>Smilax glabra</i>, which possesses various anti-inflammatory effects. However, the mechanism of neoastilbin in treating GA has not yet been clarified. Thus, this study was to investigate the protective effects of neoastilbin in both monosodium urate (MSU) stimulated THP-1-derived macrophages and the animal model of GA by injecting MSU into the ankle joints of mice. The levels of key inflammatory cytokines in MSU stimulated THP-1-derived macrophages were detected by enzyme-linked immunosorbent assay (ELISA) kits. Protein expressions of nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome pathways were further detected by Western blotting. In addition, swelling degree of ankle joints, the levels of inflammatory factors, infiltration of inflammatory cells and the expressions of related proteins were determined. Swelling degree and histopathological injury in ankle joints of MSU-injected mice were significantly decreased after being treated with neoastilbin. Moreover, neoastilbin significantly diminished the secretion of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), suppressing the activation of NF-κB and NLRP3 inflammasome pathways in both MSU stimulated THP-1-derived macrophages and the mouse model of GA. In summary, neoastilbin could alleviate GA by inhibiting the NF-κB and NLRP3 inflammasome pathways, which provided some evidence for neoastilbin as a promising therapeutic agent for GA treatment.https://www.mdpi.com/1420-3049/27/11/3477gouty arthritisneoastilbinNLRP3 inflammasomeNF-κB pathway
spellingShingle Wenjing Xu
Fenfen Li
Xiaoxi Zhang
Chenxi Wu
Yan Wang
Yanjing Yao
Daozong Xia
The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways
Molecules
gouty arthritis
neoastilbin
NLRP3 inflammasome
NF-κB pathway
title The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways
title_full The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways
title_fullStr The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways
title_full_unstemmed The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways
title_short The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways
title_sort protective effects of neoastilbin on monosodium urate stimulated thp 1 derived macrophages and gouty arthritis in mice through nf κb and nlrp3 inflammasome pathways
topic gouty arthritis
neoastilbin
NLRP3 inflammasome
NF-κB pathway
url https://www.mdpi.com/1420-3049/27/11/3477
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