Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

Lu, Rui; Yu, Xiaojun; Liang, Shuang; Peng, Cheng; Wang, Zhenggang; He, Zhiyi; Lv, Zheng‐tao; Wan, Junlai; Mo, Haokun; Zhu, Wentao; Chen, Anmin

doi:10.3389/fphar.2021.761922

Cited by 17 publications

(16 citation statements)

References 68 publications

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“…Proinflammatory cytokines such as IL-1β, tumor necrosis factor (TNF)-α, and IL-6 are critical mediators of articular cartilage degeneration and synovium inflammation [ 9 , 10 , 11 ]. In other studies, the nuclear factor-kappaB (NF-κB) and the mitogen-activated protein kinase (MAPK) have been suggested as alternative treatments for OA [ 9 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Dietary Polyphenols on Osteoarthritis—Molecular Mechanisms

Sirše

2022

Life

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Osteoarthritis is a common crippling and degenerative disease resulting in irreversible functional changes due to damage of the cartilage and other tissues of the joint. With limited safe and effective pharmaceutical treatments, the demand and use for alternative therapeutic approaches with symptomatic relief for OA patients have increased. Clinical, pre-clinical, and in vitro studies have demonstrated that polyphenols can exert pain-relieving symptoms coupled with increased functional capacity in OA models. This review will highlight studies carried out in the last five years to define the efficacies and underlying mechanisms in polyphenols such as quercetin, resveratrol, curcumin, epigallocatechin-3-gallate, rosmarinic acid, genistein, ginger, berries, silver fir, pine bark, and Boswellia. Most of these studies indicate that polyphenols exhibit their beneficial roles through regulating changes at the biochemical and molecular levels, inducing or inhibiting various signaling pathways related to inflammation and oxidative stress. Polyphenols have also been implicated in modulating microRNA at the posttranscriptional level to counteract OA pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Effect of Dietary Polyphenols on Osteoarthritis—Molecular Mechanisms

Sirše

2022

Life

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“…The viability of chondrocytes treated with IL-1β or OB or 3-MA for 24 h was determined by a CCK-8 kit. The selection of time duration of the above reagent on chondrocytes is based on previous studies by us and others ( 5 , 14 – 17 ). The chemical structure of OB was showed in Figures 1A, B demonstrated that the viability of chondrocytes was not significantly affected when cells were administration with 5 ng/ml IL-1β or 160 μM OB or 5 mM 3-MA for 24 h ( p > 0.05).…”

Section: Resultsmentioning

confidence: 99%

“…Studies illustrated that IL-1β can induce the decreased expression of anabolic-related proteins, such as Aggrecan and type II collagen (Collagen II), also trigger the overexpression of catabolic-related proteins, such as matrix metallopeptidase 3 (MMP3), matrix metallopeptidase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). Then an imbalance of cellular anabolism and catabolism will arise, triggering the degradation of the extracellular matrix (ECM) of the cartilage and the occurrence of OA ( 5 ). Besides, IL-1β can promote the release of a large number of pro-inflammatory cytokines, which also contribute to the degradation of cartilage.…”

Section: Introductionmentioning

confidence: 99%

Oroxin B alleviates osteoarthritis through anti-inflammation and inhibition of PI3K/AKT/mTOR signaling pathway and enhancement of autophagy

Zhang

et al. 2022

Front. Endocrinol.

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BackgroundOsteoarthritis (OA) is a common aging-related degenerative joint disease with chronic inflammation as its possible pathogenesis. Oroxin B (OB), a flavonoid isolated from traditional Chinese herbal medicine, possesses anti-inflammation properties which may be involved in regulating the pathogenesis of OA, but its mechanism has not been elucidated. Our study was the first to explore the potential chondroprotective effect and elucidate the underlying mechanism of OB in OA.MethodsIn vitro, primary mice chondrocytes were stimulated with IL-1β along with or without the administration of OB or autophagy inhibitor 3-methyladenine (3-MA). Cell viability assay was measured with a cell counting kit-8 (CCK-8). The phenotypes of anabolic-related (Aggrecan and Collagen II), catabolic-related (MMP3, MMP13, and ADAMTS5), inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1β), and markers of related signaling pathways in chondrocytes with different treatment were detected through western blot, RT-qPCR, and immunofluorescent staining. In vivo, the destabilized medial meniscus (DMM) operation was performed to establish the OA mice model. After knee intra-articular injection with OB for 8 weeks, the mice’s knee joints were obtained for subsequent histological staining and analysis.ResultsOB reversed the expression level of anabolic-related proteins (Aggrecan and Collagen II) and catabolic-related (MMP3, MMP13, and ADAMTS5) in IL-1β-induced chondrocytes. Mechanistically, OB suppressed the inflammatory response stimulated by IL-1β, as the inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1β) markers were downregulated after the administration of OB in IL-1β-induced chondrocytes. Besides, the activation of PI3K/AKT/mTOR signaling pathway induced by IL-1β could be inhibited by OB. Additionally, the autophagy process impaired by IL-1β could be rescued by OB. What’s more, the introduction of 3-MA to specifically inhibit the autophagic process impairs the protective effect of OB on cartilage. In vivo, histological staining revealed that intra-articular injection of OB attenuated the cartilage degradation, as well as reversed the expression level of anabolic and catabolic-related proteins such as Aggrecan, Collagen II, and MMP13 induced in DMM-induced OA models.ConclusionsThe study verified that OB exhibited the chondroprotective effect by anti-inflammatory, inhibiting the PI3K/AKT/mTOR signaling pathway, and enhancing the autophagy process, indicating that OB might be a promising agent for the treatment of OA.

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“…Eighteen specific pathogen-free C57BL/6J male mice were acquired from the Experimental Animal Center of Tongji Hospital. Mouse DMM OA model was established as previously described ( Lu et al, 2021 ). The mouse were anesthetized by intraperitoneal injection of pentobarbital (100 μl/10g body weight).…”

Section: Methodsmentioning

confidence: 99%

Flavokawain A alleviates the progression of mouse osteoarthritis: An in vitro and in vivo study

Jing

Wan²,

Wang³

et al. 2022

Front. Bioeng. Biotechnol.

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Osteoarthritis (OA) is one of the most prevalent chronic degenerative joint diseases affecting adults in their middle or later years. It is characterized by symptoms such as joint pain, difficulty in movement, disability, and even loss of motion. Moreover, the onset and progression of inflammation are directly associated with OA. In this research, we evaluated the impact of Flavokawain A (FKA) on osteoarthritis. In-vitro effects of FKA on murine chondrocytes have been examined using cell counting kit-8 (CCK-8), safranin o staining, western blot, immunofluorescence staining, senescence β-galactosidase staining, flow cytometry analysis, and mRFP-GFP-LC3 adenovirus infection. An in-vivo model of destabilization of the medial meniscus (DMM) was employed to investigate FKA’s effect on OA mouse. An analysis of bioinformatics was performed on FKA and its potential role in OA. It was observed that FKA blocked interleukin (IL)-1β-induced expression of inflammatory factors, i.e., cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) in chondrocytes. In addition, FKA also downregulated the catabolic enzyme expression, i.e., aggrecanase-2 (ADAMTS5) and matrix metalloproteinases (MMPs), and helped in the upregulation of the anabolic protein expression, i.e., type II collagen (Col2), Aggrecan, and sry-box transcription factor 9 (SOX9). Moreover, FKA ameliorated IL-1β-triggered autophagy in chondrocytes, and it was observed that the FKA causes anti-inflammatory effects by the mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathways inhibition. The results of immunohistochemical analysis and microcomputed tomography from the in vivo OA mouse model confirmed the therapeutic effect of FKA. Finally, we assessed the anti-arthritic impacts of FKA by conducting in vivo and in vitro analyses. We concluded that FKA can be employed as a useful therapeutic agent for OA therapy, but the findings require needs further clinical investigation.

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Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

Cited by 17 publications

References 68 publications

Effect of Dietary Polyphenols on Osteoarthritis—Molecular Mechanisms

Effect of Dietary Polyphenols on Osteoarthritis—Molecular Mechanisms

Oroxin B alleviates osteoarthritis through anti-inflammation and inhibition of PI3K/AKT/mTOR signaling pathway and enhancement of autophagy

Flavokawain A alleviates the progression of mouse osteoarthritis: An in vitro and in vivo study

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