Formononetin Antagonizes the Interleukin-1β-Induced Catabolic Effects Through Suppressing Inflammation in Primary Rat Chondrocytes

Cho, In‐A; Kim, Tae-Hyeon; Lim, HyangI; Park, Jong‐Hyun; Kang, Kyeong‐Rok; Lee, Sook-Young; Kim, Chun Sung; Kim, Do Kyung; Kim, Heung-Joong; Yu, Sun‐Kyoung; Kim, Su-Gwan; Kim, Jae-Sung

doi:10.1007/s10753-019-01005-1

Cited by 29 publications

(21 citation statements)

References 39 publications

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“…Fractalkine also known as chemokine CX3CL1 is exuberantly expressed in both adult human and rat articular chondrocytes treated with IL-1β [41,42]. Recent studies have reported that fractalkine promotes the expression of MMP-3 through the CX3CR1, c-Raf, MEK, ERK, and NFκB cellular signaling pathways in the synovial tissue obtained from the patients with OA [43].…”

Section: Discussionmentioning

confidence: 99%

Acteoside Counteracts Interleukin‐1β‐Induced Catabolic Processes through the Modulation of Mitogen‐Activated Protein Kinases and the NFκB Cellular Signaling Pathway

Lim

Kim

et al. 2021

Oxidative Medicine and Cellular Longevity

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Osteoarthritis (OA) is the most common degenerative joint disease with chronic joint pain caused by progressive degeneration of articular cartilage at synovial joints. Acteoside, a caffeoylphenylethanoid glycoside, has various biological activities such as antimicrobial, anti-inflammatory, anticancer, antioxidative, cytoprotective, and neuroprotective effect. Further, oral administration of acteoside at high dosage does not cause genotoxicity. Therefore, the aim of present study is to verify the anticatabolic effects of acteoside against osteoarthritis and its anticatabolic signaling pathway. Acteoside did not decrease the viabilities of mouse fibroblast L929 cells used as normal cells and primary rat chondrocytes. Acteoside counteracted the IL-1β-induced proteoglycan loss in the chondrocytes and articular cartilage through suppressing the expression and activation of cartilage-degrading enzyme such as matrix metalloproteinase- (MMP-) 13, MMP-1, and MMP-3. Furthermore, acteoside suppressed the expression of inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in the primary rat chondrocytes treated with IL-1β. Subsequently, the expression of proinflammatory cytokines was decreased by acteoside in the primary rat chondrocytes treated with IL-1β. Moreover, acteoside suppressed not only the phosphorylation of mitogen-activated protein kinases in primary rat chondrocytes treated with IL-1β but also the translocation of NFκB from the cytosol to the nucleus through suppression of its phosphorylation. Oral administration of 5 and 10 mg/kg acteoside attenuated the progressive degeneration of articular cartilage in the osteoarthritic mouse model generated by destabilization of the medial meniscus. Our findings indicate that acteoside is a promising potential anticatabolic agent or supplement to attenuate or prevent progressive degeneration of articular cartilage.

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Section: Discussionmentioning

confidence: 99%

Acteoside Counteracts Interleukin‐1β‐Induced Catabolic Processes through the Modulation of Mitogen‐Activated Protein Kinases and the NFκB Cellular Signaling Pathway

Lim

Kim

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…As a plant natural product, FMN has antioxidant properties and shows neuroprotective effects against traumatic brain injury through activation of Nrf2dependent antioxidant pathways [41]. Further, FMN showed anti-in ammatory capacity by suppressing IL-6 and TNF-α in neuroin ammatory rats [16] and effectively antagonized proteoglycan loss through decreasing the expression MMP-3, MMP-13 and attenuating oxidative stress [7]. Further, with the studying of the repression of OA-marked factors, such as IL-1, MMP-3 and MMP-13, and the promotion of cartilage-speci c marker (collagen II α1), anti-in ammatory and chondro-protective characters of PCFMN were exhibited ( Figure.…”

Section: Discussionmentioning

confidence: 99%

“…It was reported to have series of pharmacological effects including anti-in ammatory [7,8], anti-angiogenic [9], antioxidant [10], cardioprotective [11], neuroprotective [12] and other effects [13], which has been extensively applicated in treatment of various human diseases, such as diabetic retinopathy, Alzheimer's disease and other diseases [14][15][16]. In recent years, it is found that FMN can effectively decrease proteoglycan loss and improve pericellular matrix formation of chondrocytes [7], which may be developed as potential agents for OA treatment. However, bioavailability of FMN is low because it has poor water solubility and can hardly penetrate through the dense matrix of cartilage [17].…”

Section: Introductionmentioning

confidence: 99%

Cartilage-targeting Poly(Ethyleneglycol) (PEG)-formononetin (FMN) Nanodrug for Treating Osteoarthritis

Wang

Lan

Liang

et al. 2021

Preprint

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Intra-articular (IA) injection is an efficient treatment for osteoarthritis. Such a treatment will minimize systemic side effects and avoid the inconvenience of frequent injections. However, the joint has poor bioavailability for systemically administered drugs and experiences rapid clearance of therapeutics after intra-articular injection. Delivering system modified through active targeting strategies to facilitate localization within specific joint tissues such as cartilage is hopeful to increase the therapeutic effects. In this study, we designed a nanoscaled amphiphilic and cartilage-targeting polymer-drug delivery system by using formononetin (FMN)-poly(ethylene glycol) (PEG) (denoted as PCFMN), which was prepared by PEGylation of FMN followed by coupling with cartilage-targeting peptide (CollBP). Our results showed that PCFMN was approximately regular spherical with the average diameter about 218 nm. The in vitro test using IL-1β stimulated chondrocytes indicated that PCFMN were biocompatible and upregulated anabolic genes while simultaneously downregulated catabolic genes of the articular cartilage. The therapeutic effects in vivo indicated that PCFMN could effectively attenuate the progression of OA as evidenced by immunohistochemical staining and histological analysis. In addition, PCFMN showed higher intention time in joints and better anti-inflammatory effects than FMN, indicating the efficacy of cartilage targeting nanodrug on OA. This study may provide reference for clinical OA therapy.

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“…27,28 What's more, paeoniflorin has been reported as protective effects against OAwith anti-apoptosis and anti-inflammation effects on chondrocyte. 29,30 As for other key active ingredients, formononetin existing in HL and RG has been proved the anti-catabolic effects on rat chondrocytes and articular cartilage, 31 and it dose-dependently decreased IL-6 in OA subchondral osteoblasts. 32 Stigmasterol existing in HL and RAS, was demonstrated to block cartilage degradation in the rabbit model of OA, showing potential anti-osteoarthritic properties.…”

Section: Discussionmentioning

confidence: 99%

<p>Validation of the Key Active Ingredients and Anti-Inflammatory and Analgesic Effects of Shenjin Huoxue Mixture Against Osteoarthritis by Integrating Network Pharmacology Approach and Thin-Layer Chromatography Analysis</p>

Yu¹,

Ma²,

Song³

et al. 2020

DDDT

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Background: Shenjin Huoxue Mixture (SHM), a classic traditional herb mixture has shown significant clinical efficacy against osteoarthritis (OA). Our previous experimental study has confirmed its anti-inflammatory and analgesic effect on acute soft tissue injury in rats, with the compound of glycyrrhizinate in SHM identified and the content of paeoniflorin in SHM determined by high-performance liquid chromatography (HPLC). However, the components and its pharmacological mechanisms of SHM against OA have not been systematically elucidated yet. Thus this study aimed to predict the key active ingredients and potential pharmacological mechanisms of SHM in the treatment of OA by network pharmacology approach and thin-layer chromatography (TLC) validation. Methods: The active ingredients of SHM and their targets, as well as OA-related targets, were identified from databases. The key active ingredients were defined and ranked by the number of articles retrieved in PubMed using the keyword "(the active ingredients [Title/Abstract]) AND Osteoarthritis[Title/Abstract] ", and validated partially by TLC. The pharmacological mechanisms of SHM against OA were displayed by GO term and Reactome pathway enrichment analysis with Discovery Studio 3.0 software docking to testing the reliability. Results: Finally, 16 key active ingredients were identified and ranked, including quercetin validated through TLC. Inflammatory response, IL-6 signaling pathway and toll-like receptor (TLR) cascades pathway were predicted as the main pharmacological mechanisms of SHM against OA. Especially, 12 out of 16 key active ingredients, including validated quercetin, were well docked to IL-6 proteins. Conclusion: Our results confirmed the anti-inflammatory and analgesic effect of SHM against OA through multiple components, multiple targets and multiple pathways, which revealed the theoretical basis of SHM against OA and may provide a new drug option for treating OA.

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Formononetin Antagonizes the Interleukin-1β-Induced Catabolic Effects Through Suppressing Inflammation in Primary Rat Chondrocytes

Cited by 29 publications

References 39 publications

Acteoside Counteracts Interleukin‐1β‐Induced Catabolic Processes through the Modulation of Mitogen‐Activated Protein Kinases and the NFκB Cellular Signaling Pathway

Acteoside Counteracts Interleukin‐1β‐Induced Catabolic Processes through the Modulation of Mitogen‐Activated Protein Kinases and the NFκB Cellular Signaling Pathway

Cartilage-targeting Poly(Ethyleneglycol) (PEG)-formononetin (FMN) Nanodrug for Treating Osteoarthritis

<p>Validation of the Key Active Ingredients and Anti-Inflammatory and Analgesic Effects of Shenjin Huoxue Mixture Against Osteoarthritis by Integrating Network Pharmacology Approach and Thin-Layer Chromatography Analysis</p>

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