Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice

Zheng, Wenhao; Feng, Zhenhua; You, Shengban; Zhang, Hui; Tao, Zhenyu; Wang, Quan; Chen, Hua; Wu, Yaosen

doi:10.1016/j.intimp.2017.02.009

Cited by 128 publications

(106 citation statements)

References 45 publications

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“…1, 2, and 3). Other natural CRMs, such as butein and fisetin (11,21,27,38,48,53,58,59), also inhibited T-cell activation (IC 50 = 2.8 μM and 5.2 μM, respectively) ( Figs. 1 and 3).…”

Section: Resultsmentioning

confidence: 94%

T-cell activation-inhibitory assay: a proposed novel method for screening caloric restriction mimetics

et al. 2019

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Caloric restriction (CR) is a major contributor to good health and longevity. CR mimetics (CRMs) are a group of plant-derived compounds capable of inducing the benefits of CR. Since a longevity gene, SIRT1, inhibits T-cell activation and SIRT1 loss results in increased T-cell activation, we hypothesized that compounds capable of activating SIRT1 signaling can inhibit T-cell activation and function as CRMs. Thus we propose, in the present study, the application of a T-cell activation-inhibitory assay to screen candidate CRMs. Well-known CRMs, such as resveratrol, butein, and fisetin, suppressed the anti-CD3/CD28 antibody-induced activation of mouse spleen T-cells. We next randomly assessed 68 plant-derived compounds for screening novel candidate CRMs using this bioassay and found that all four compounds showing IC 50 values <5 μM, such as curcumin, α-mangostin, nobiletin, and heptamethoxyflavone, have beneficial functions for health such as anti-inflammatory effect. These results suggest that the T-cell activation-inhibitory assay can be used to screen candidate CRMs.

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“…1, 2, and 3). Other natural CRMs, such as butein and fisetin (11,21,27,38,48,53,58,59), also inhibited T-cell activation (IC 50 = 2.8 μM and 5.2 μM, respectively) ( Figs. 1 and 3).…”

Section: Resultsmentioning

confidence: 94%

T-cell activation-inhibitory assay: a proposed novel method for screening caloric restriction mimetics

et al. 2019

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“…In addition, intra-articular injections of glucocorticoids and hyaluronic acid, used to relieve OA symptoms, have only temporary effects and are not capable of reversing the pathophysiological progression of OA [Hochberg et al, 2012;McAlindon et al, 2014]. Therefore, the number of studies investigating the mitigation of OA with medicinal plant extracts with relatively few side effects has increased, along with the use of nutraceuticals in the management of OA [Akhtar and Haqqi, 2012;Zheng et al, 2017;Lee et al, 2018a].…”

Section: Discussionmentioning

confidence: 99%

“…These catabolic factors continuously induce the inflammatory response of chondrocytes and degrade the extracellular matrix (ECM) of cartilage, thereby providing an environment suitable for OA development [Goldring and Goldring, 2004;Kobayashi et al, 2005;Blom et al, 2007]. In addition, IL-1β-induced increase in expression is found in the synovial fluid and cartilage tissue of patients with OA [Dieppe et al, 1999;Zheng et al, 2017]. Thus, a reduction in the activity of cartilage-degrading enzymes and inflammatory mediators is expected to have beneficial effects, such as chondroprotection, against pathological conditions like OA [Jeoun et al, 2016].…”

Section: Introductionmentioning

confidence: 99%

The Effect of the Prethanol Extract of <b><i>Trifolium pratense</i></b> Leaves on Interleukin-1β-Induced Cartilage Matrix Degradation in Primary Rat Chondrocytes

Lee

Moon²,

Han³

et al. 2018

Cells Tissues Organs

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Background: Osteoarthritis (OA) is a degenerative joint disease, characterized by cartilage degradation and inflammation. The proinflammatory cytokine, interleukin (IL)-1β, plays a crucial role in the pathogenesis of OA by inducing the release of other catabolic factors that contribute to cartilage degradation. Trifolium pratense L. (red clover) has been used as a medicinal plant in many countries and as a source of nutraceuticals to alleviate the symptoms of menopause. Objectives: In this study, we aimed to evaluate the anticatabolic effect of 40% prethanol extract of T. pratense (40% PeTP) on IL-1β-stimulated chondrocytes. Methods: Primary rat chondrocytes were pretreated with 40% PeTP for 1 h before stimulation with IL-1β (20 ng/mL). The production of nitrite, prostaglandin E₂ (PGE₂), and aggrecan was measured by using Griess reagent and ELISA. Protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, A disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-4, mitogen-activated protein kinase (MAPK), and the nuclear factor (NF)-κB p65 subunit was measured by using Western blotting. Results: PeTP (40%) significantly inhibited the IL-1β-induced expression of nitrite, iNOS, PGE₂, COX-2, MMP-1, MMP-3, MMP-13, and ADAMTS-4 in isolated primary rat chondrocytes. Furthermore, 40% PeTP decreased the IL-1β-induced degradation of aggrecan, the phosphorylation of MAPKs, and the nuclear translocation of the NF-κB p65 subunit. Conclusion: These results suggested that 40% PeTP has a chondroprotective effect on inflammation and may be a potential preventative agent for OA progression.

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“…Therefore, the mechanism of OA can be studied by focusing on signalling pathways. Studies have shown that the p38 mitogen‐activated protein kinase (MAPK) signalling pathway is activated and involved in progressive collagen type II degradation and destruction of cartilage matrix in the process of inflammation . In addition, studies by Joos et al have shown that p38 MAPK activation can cause pain in the patient's joints and lead to malignant circulation in the internal environment of articular cartilage .…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that the p38 mitogen-activated protein kinase (MAPK) signalling pathway is activated and involved in progressive collagen type II degradation and destruction of cartilage matrix in the process of inflammation. 7 In addition, studies by Joos et al have shown that p38 MAPK activation can cause pain in the patient's joints and lead to malignant circulation in the internal environment of articular cartilage. 8 Phosphorylated Jun N-terminal kinase (JNK) increases the expression of matrix metalloproteinase through its downstream transcription factors, leading to progressive degradation of the chondrocyte extracellular matrix.…”

Section: Introductionmentioning

confidence: 99%

The mechanism of TDP‐43 gene expression on inflammatory factors and the JNK and p38 MAPK signalling pathways in ischaemic hypoxic stress dependence

Huang¹,

Zhang²,

Qin³

et al. 2019

International Wound Journal

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In this study, the mechanism of TDP‐43 gene expression on inflammatory factors and Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase (MAPK) signalling pathways in ischaemic hypoxic stress dependence was investigated. Sixty SD rats were selected and divided into the control group, the osteoarthritis (OA) model group, and the TDP‐43‐mMSCs+OA group. In the OA model group and the TDP‐43‐mMSCs+OA group, OA was established by collagenase injection. Western blotting assays were used to detect the expression of TDP‐43 in cartilage tissues of each rat. The secretion of tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) in the serum of rats was determined by enzyme‐linked immunosorbent assay (ELISA). The formation of cytoplasmic stress granules (SGs) and the expression of receptor for activated c‐kinase 1 (RACK1) were detected by Western blotting assays in each group of rats. The expression of MTK1 and MAPKKK phosphorylation and changes in the JNK and p38 MAPK signalling pathways were detected by Western blotting assays. Compared with the control group, the expression of TDP‐43 in the cartilage tissue of rats in the OA model group was significantly decreased. The expression of TDP‐43 in the cartilage tissue of rats in the TDP‐43‐mMSCs+OA group was significantly higher than that of the control group and the OA model group, which indicates that TDP‐43‐mMSC transplantation was successful. Enzyme‐linked immunosorbent assay results showed that the plasma TNF‐α and IL‐1β levels in the OA model group were significantly increased (P < 0.01) when compared with the control group. However, the secretion of TNF‐α and IL‐1β in the serum of the TDP‐43‐mMSCs+OA group was significantly lower than that of the model group (P < 0.01) but still higher than the control group. This indicates that overexpression of TDP‐43 reduces the inflammatory response induced by OA. Western blotting assays showed that the amount of cytoplasmic SGs in the cartilage tissue of rats in the OA model group was significantly decreased when compared with the control group. The amount of SGs in the cartilage of rats in the TDP‐43‐mMSCs+OA group was significantly higher than that of the model group. The expression of RACK1 in the cartilage tissue of rats in the OA model group was significantly higher than that of the control group. Overexpression of the TDP‐43 gene can interfere with the secretion of inflammatory factors and inhibit the activation of the JNK and p38 MAPK signalling pathways by ischaemic hypoxia stress. Thus, the molecular mechanism of chondrocytopathic lesions was reversed, which provided a new theoretical basis for the treatment of OA.

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Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice

Cited by 128 publications

References 45 publications

T-cell activation-inhibitory assay: a proposed novel method for screening caloric restriction mimetics

T-cell activation-inhibitory assay: a proposed novel method for screening caloric restriction mimetics

The Effect of the Prethanol Extract of <b><i>Trifolium pratense</i></b> Leaves on Interleukin-1β-Induced Cartilage Matrix Degradation in Primary Rat Chondrocytes

The mechanism of TDP‐43 gene expression on inflammatory factors and the JNK and p38 MAPK signalling pathways in ischaemic hypoxic stress dependence

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