Icariin inhibits chondrocyte apoptosis and angiogenesis by regulating the <scp>TDP</scp>‐43 signaling pathway

Huang, He; Zhang, Zhao‐Fei; Qin, Feng-Wei; Tang, Wang; Liu, Donghua; Wu, Pei; Jiao, Feng

doi:10.1002/mgg3.586

Cited by 22 publications

(17 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ICA was reported to inhibit osteoarthritis via suppressing pyroptosis mediated by NLRP3 (19). ICA repressed the death and angiogenesis of chondrocytes in a rat osteoarthritis model via the modulation of the TDP-43 signaling pathway (20), enhanced chondrocyte viability via promoting anaerobic glycolysis and the expression of hypoxia-inducible factor-1α (21), exerted an immune-suppressive role in rheumatoid arthritis (22) Icariin enhances cell survival in lipopolysaccharide-induced synoviocytes by suppressing ferroptosis via the Xc-/GPX4 axis and ameliorated rheumatoid arthritis in in a murine model of rheumatoid arthritis (23). However, the mechanism of ICA in rheumatoid arthritis and osteoarthritis is not fully elucidated, and clarifying the concrete mechanism is beneficial for developing more therapeutic drugs based on this compound.…”

Section: Introductionmentioning

confidence: 99%

Icariin enhances cell survival in lipopolysaccharide‑induced synoviocytes by suppressing ferroptosis via the Xc‑/GPX4 axis

Luo

Zhang

2020

Exp Ther Med

View full text Add to dashboard Cite

The mechanism of action of synovitis, as the vital pathological process of rheumatoid arthritis and osteoarthritis, remains to be elucidated. The effects and the mechanism of icariin (ICA), which is a promising therapeutic agent in synovitis, was investigated in the present study. In addition, ferroptosis, a vital cell process involved in several diseases, was also studied in synovitis for the first time. Lipopolysacc haride (LPS)-induced synoviocytes served as a synovitis cell model. The cells were divided into control, LPS and experimental groups and were treated with different concentrations of ICA. Cell viability was determined by Cell Counting Kit-8 assay and cell death was determined by flow cytometry. The expression levels of proteins (GPX4, SLC7A11, SLC3A2L, TRF, Nrf2 and NCOA4) were measured by western blotting. Quantification of malondialdehyde (MDA), iron and glutathione peroxidase 4 (GPX4) activity levels were performed via using corresponding assay kits. Cell death was increased, and cell viability was decreased in LPS-induced synoviocytes. Furthermore, MDA levels and iron content were elevated and GPX levels was reduced in LPS-induced synoviocytes. Transferrin receptor protein 1 and nuclear receptor coactivator 4 were upregulated and proteins of the Xc-/GPX4 axis, as well as nuclear factor erythroid 2-related factor 2, were decreased by LPS treatment. All aforementioned LPS affects were alleviated by ICA via a concentration-dependent manner. ICA counteracted the effects of RSL3, a ferroptosis activator, on cell viability, lipid peroxidation, iron content and relative protein expression of ferroptosis in synoviocytes. ICA protects the cells from death in synoviocytes induced by LPS, via the inhibition of ferroptosis by activating the Xc-/GPX4 axis, which can be exploited as a new therapeutic strategy for synovitis.

show abstract

Section: Introductionmentioning

confidence: 99%

Icariin enhances cell survival in lipopolysaccharide‑induced synoviocytes by suppressing ferroptosis via the Xc‑/GPX4 axis

Luo

Zhang

2020

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…in serum. Icariin reduces VEGF and hypoxia-inducible factor-lα levels in the peripheral blood, which may help to inhibit the formation of new blood vessels in the synovial tissue of joints [9]. Resveratrol effectively improves the blood rheology, which facilitates to prevent and delay the degenerative changes in the articular cartilage of OA model [109].…”

Section: The Effects Of Bioactive Components On Circulatory System In Oamentioning

confidence: 99%

“…Paeonol alleviates chondrocyte apoptosis by regulating the levels of ROS, bcl-2, and bax [ 56 , 71 ]. Some components (icariin [ 9 ], sinomenine [ 72 ], astragaloside IV [ 73 ], quercetin [ 21 ], shikonin [ 35 ], tectorigenin [ 48 ], gastrodin [ 51 ], and ginsenoside Rg5 [ 74 ]) also exert anti-apoptotic effects on chondrocytes through various mechanisms. The promoting effects of puerarin [ 53 ], psoralen [ 75 ], magnoflorine [ 23 ], and emodin [ 38 ] on proliferation may be also beneficial to reverse cartilage apoptosis.…”

Section: The Anti-oa Activities Of Bioactive Components From Herbal Mmentioning

confidence: 99%

See 1 more Smart Citation

Recent advance in treatment of osteoarthritis by bioactive components from herbal medicine

Zhang

2020

Chin Med

View full text Add to dashboard Cite

Osteoarthritis (OA) is a common chronic articular degenerative disease, and characterized by articular cartilage degradation, synovial inflammation/immunity, and subchondral bone lesion, etc. The disease affects 2-6% of the population around the world, and its prevalence rises with age and exceeds 40% in people over 70. Recently, increasing interest has been devoted to the treatment or prevention of OA by herbal medicines. In this paper, the herbal compounds with anti-OA activities were reviewed, and the cheminformatics tools were used to predict their drug-likeness properties and pharmacokinetic parameters. A total of 43 herbal compounds were analyzed, which mainly target the damaged joints (e.g. cartilage, subchondral bone, and synovium, etc.) and circulatory system to improve the pathogenesis of OA. Through cheminformatics analysis, over half of these compounds have good drug-likeness properties, and the pharmacokinetic behavior of these components still needs to be further optimized, which is conducive to the enhancement in their drug-likeness properties. Most of the compounds can be an alternative and valuable source for anti-OA drug discovery, which may be worthy of further investigation and development.

show abstract

“…In recent years, more and more researchers have turned their attention to the traditional Chinese medicine extracts for cartilage damage and OA treatment. Icariin (ICA) is a typical flavonoid compound originated from Epimedii Folium with anti-inflammation, anticancer and bone-protective effects [17]. Our previous studies demonstrate that ICA up-regulates the expressions of HIF-1α and glycolysis key enzymes in chondrocytes, promotes ECM secretion and glycolysis, and maintains the chondrocyte phenotype.…”

Section: Introductionmentioning

confidence: 99%

Icariin inhibits the inflammation through down-regulating NF-κB/HIF-2α signal pathways in chondrocytes

et al. 2020

View full text Add to dashboard Cite

Articular cartilage injury or defect is a common disease and is mainly characterized by cartilage degradation because of chondrocyte inflammation. By now, there are no effective drugs and methods to protect articular cartilage from degradation. Icariin (ICA) is a typical flavonoid compound extracted from Epimedii Folium with anti-inflammatory and bone-protective effects. Our previous studies demonstrate that ICA up-regulates HIF-1α expression and glycolysis in chondrocytes and maintains chondrocyte phenotype. As another member of HIFs family, HIF-2α always plays a key role in inflammation. The effect of ICA on HIF-2α is unclear by now. In this study, we not only confirmed the findings in our previous study that ICA promoted chondrocyte vitality and extracellular matrix (ECM) synthesis, but also the anti-inflammatory effect of ICA. In bone defect mice, ICA inhibited the expressions of NF-κB and HIF-2α. In TNF-α-treated ADTC5 chondrocytes, ICA neutralized the activation of IKK (IKK phosphorylation), the phosphorylation of IkB and NF-κB and the expression of HIF-2α. Furthermore, ICA inhibited the nucleus transfer of NF-κB and the expressions of MMP9 and ADAMTS5, two key targets of NF-κB/HIF-2α signal pathway. Taken together, this study demonstrated that ICA may increase the vitality of chondrocytes by suppressing the inflammatory injury through the inhibition on NF-κB/HIF-2α signaling pathway. ICA is one effective candidate drug for the treatment of articular cartilage injury.

show abstract

Icariin inhibits chondrocyte apoptosis and angiogenesis by regulating the TDP‐43 signaling pathway

Cited by 22 publications

References 19 publications

Icariin enhances cell survival in lipopolysaccharide‑induced synoviocytes by suppressing ferroptosis via the Xc‑/GPX4 axis

Icariin enhances cell survival in lipopolysaccharide‑induced synoviocytes by suppressing ferroptosis via the Xc‑/GPX4 axis

Recent advance in treatment of osteoarthritis by bioactive components from herbal medicine

Icariin inhibits the inflammation through down-regulating NF-κB/HIF-2α signal pathways in chondrocytes

Contact Info

Product

Resources

About