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Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis

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Title: Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis
Authors: Zhenyuan Ma, Zhengquan Huang, Li Zhang, Xiaochen Li, Bo Xu, Yancheng Xiao, Xiaoqing Shi, Haosheng Zhang, Taiyang Liao, Peimin Wang
Source: Frontiers in Pharmacology, Vol 11 (2021)
Publisher Information: Frontiers Media S.A., 2021.
Publication Year: 2021
Collection: LCC:Therapeutics. Pharmacology
Subject Terms: vanillic acid, knee osteoarthritis, synovial inflammation, NLRP3 inflammasome, pain 3, Therapeutics. Pharmacology, RM1-950
More Details: Objectives: Synovitis plays an important role in knee osteoarthritis (KOA) pain. The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in fibroblast-like synoviocytes (FLSs) promotes KOA development. In this study, we aimed to investigate whether vanillic acid (VA), a monomer derived from Chinese herbal medicines, could target NLRP3 inflammasome-related synovitis to reduce pain.Methods: Rats in the KOA and KOA + VA groups were injected with monosodium iodoacetate (MIA) in the knee to induce KOA. From day 14, the KOA + VA group was given VA at 30 mg/kg every day via gastric intubation. FLSs were collected from the synovial tissues. We examined both the protein and gene expression of caspase-1, apoptosis-associated speck-like protein with a caspase recruitment domain (ASC), NLRP3, components of the NLRP3 inflammasome, and interleukin-1β (IL-1β) and IL-18 in vivo and in vitro.Results: The upregulation of caspase-1, ASC, and NLRP3 in the KOA model were reduced by VA. VA also lowered the level of IL-1β and IL-18 in the KOA model. In addition, VA relieved pain-related behavior of KOA model rats and downregulated the pain mediators CGRP, NGF, and TrkA in FLSs. Interestingly, we also observed reduced synovial fibrosis in the animal experiments.Conclusion: Our research showed that VA reduces synovitis and pain-related behaviors in a rat model of KOA, which provides the basis for further investigations into the potential therapeutic impact of VA in KOA.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1663-9812
Relation: https://www.frontiersin.org/articles/10.3389/fphar.2020.599022/full; https://doaj.org/toc/1663-9812
DOI: 10.3389/fphar.2020.599022
Access URL: https://doaj.org/article/1bd3d57b19834c98baa4e3bd388426b7
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  Data: Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis
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  Data: <searchLink fieldCode="AR" term="%22Zhenyuan+Ma%22">Zhenyuan Ma</searchLink><br /><searchLink fieldCode="AR" term="%22Zhengquan+Huang%22">Zhengquan Huang</searchLink><br /><searchLink fieldCode="AR" term="%22Li+Zhang%22">Li Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Xiaochen+Li%22">Xiaochen Li</searchLink><br /><searchLink fieldCode="AR" term="%22Bo+Xu%22">Bo Xu</searchLink><br /><searchLink fieldCode="AR" term="%22Yancheng+Xiao%22">Yancheng Xiao</searchLink><br /><searchLink fieldCode="AR" term="%22Xiaoqing+Shi%22">Xiaoqing Shi</searchLink><br /><searchLink fieldCode="AR" term="%22Haosheng+Zhang%22">Haosheng Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Taiyang+Liao%22">Taiyang Liao</searchLink><br /><searchLink fieldCode="AR" term="%22Peimin+Wang%22">Peimin Wang</searchLink>
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  Data: Frontiers in Pharmacology, Vol 11 (2021)
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  Data: LCC:Therapeutics. Pharmacology
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  Data: <searchLink fieldCode="DE" term="%22vanillic+acid%22">vanillic acid</searchLink><br /><searchLink fieldCode="DE" term="%22knee+osteoarthritis%22">knee osteoarthritis</searchLink><br /><searchLink fieldCode="DE" term="%22synovial+inflammation%22">synovial inflammation</searchLink><br /><searchLink fieldCode="DE" term="%22NLRP3+inflammasome%22">NLRP3 inflammasome</searchLink><br /><searchLink fieldCode="DE" term="%22pain+3%22">pain 3</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%2E+Pharmacology%22">Therapeutics. Pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22RM1-950%22">RM1-950</searchLink>
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  Data: Objectives: Synovitis plays an important role in knee osteoarthritis (KOA) pain. The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in fibroblast-like synoviocytes (FLSs) promotes KOA development. In this study, we aimed to investigate whether vanillic acid (VA), a monomer derived from Chinese herbal medicines, could target NLRP3 inflammasome-related synovitis to reduce pain.Methods: Rats in the KOA and KOA + VA groups were injected with monosodium iodoacetate (MIA) in the knee to induce KOA. From day 14, the KOA + VA group was given VA at 30 mg/kg every day via gastric intubation. FLSs were collected from the synovial tissues. We examined both the protein and gene expression of caspase-1, apoptosis-associated speck-like protein with a caspase recruitment domain (ASC), NLRP3, components of the NLRP3 inflammasome, and interleukin-1β (IL-1β) and IL-18 in vivo and in vitro.Results: The upregulation of caspase-1, ASC, and NLRP3 in the KOA model were reduced by VA. VA also lowered the level of IL-1β and IL-18 in the KOA model. In addition, VA relieved pain-related behavior of KOA model rats and downregulated the pain mediators CGRP, NGF, and TrkA in FLSs. Interestingly, we also observed reduced synovial fibrosis in the animal experiments.Conclusion: Our research showed that VA reduces synovitis and pain-related behaviors in a rat model of KOA, which provides the basis for further investigations into the potential therapeutic impact of VA in KOA.
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