Icariin increases chondrocyte vitality by promoting hypoxia-inducible factor-1α expression and anaerobic glycolysis

Wang, Pengzhen; Xiong, Xuming; Zhang, Jinli; Qin, Shengnan; Wang, Wen; Liu, Zhihe

doi:10.1016/j.knee.2019.09.012

Cited by 29 publications

(33 citation statements)

References 28 publications

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“…According to the literature, ICA is expected to replace growth factors for the treatment of various cartilage injuries [24]. Our previous studies demonstrate that ICA protects cartilage chondrocyte vitality by promoting glycolysis and HIF-1α [25,26]. In the present study, we demonstrated that ICA protects cartilage chondrocyte vitality by neutralizing the inflammation induced by NF-κB/HIF-2α signal pathway.…”

Section: Discussionsupporting

confidence: 65%

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

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 65%

“…Our previous studies demonstrated that ICA increases the vitality of chondrocytes and ECM synthesis by promoting HIF-1α expression and anaerobic glycolysis [25,26]. It is reported that HIF-2α and HIF-1α has the opposite effect in chondrocytes and high HIF-2α expression may lead to the destruction and degradation of cartilage.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…The high expression of TDP-43 protein in transfected chondrocytes was confirmed, indicating the success of transfection of human chondrocytes with TDP-43 lentivirus vector. Icariin has been shown to increase chondrocyte viability by promoting hypoxia-inducible factor-1α expression and anaerobic glycolysis 16,17 and inhibits chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway 18 . Zuo et al demonstrated that icariin alleviated IL-1β-induced matrix degradation and eliminated reactive oxygen species by activating the Nrf2/ARE pathway in human chondrocytes in vitro 19 .…”

Section: Discussionmentioning

confidence: 99%

Icariin interferes with TDP43-induced inflammatory factor secretion and inhibits the JNK and p38 MAPK signaling pathway in vitro

Huang

Zhang

et al. 2021

Arch Med Sci

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IntroductionTo investigate the molecular mechanism of icariin (ICA) intervention in TDP-43 mediated chondrocyte lesions of osteoarthritis.Material and methodsHC-α chondrocytes were transfected with TDP-43 lentiviruses to generate TDP-43-overexpressing chondrocytes and treated with 5 μg/mL icariin. The level of TDP-43, JNK, p38 MAPK and relative factors were detected by Western blotting assays. TNF-α and IL-1β in the supernatant were determined by ELISA.ResultsCompared with the HC-α group, TDP-43 expression was significantly increased in the TDP-43-HC-α group and was not significantly different that of the HC-α+ICA group. However, TDP-43 expression in the TDP-43-HC-α+ICA group was significantly lower than that in the TDP-43-HC-α group. ELISA showed that the secretion of TNF-α and IL-1β in the supernatant of the TDP-43-HC-α group was significantly increased (P<0.01) compared with the HC-α group, but was significantly lower in the supernatant of the TDP-43-HC-α+ICA group than that of the TDP-43-HC-α group (P<0.01). ICA treatment reduced the expression of TDP-43 in chondrocytes and inhibited the elevation of inflammatory cytokines caused by TDP-43. ICA processing can also inhibit the activation of JNK/p38 MAPK related signaling pathways caused by TDP-43. Overexpression of TDP-43 reduced the formation of stress granules (SGs)in chondrocytes, and increased receptor for activated protein kinase C1 (RACK1) level. ICA could reverse these changes.ConclusionsIcariin could interfere with TDP-43-induced secretion of inflammatory factors, inhibit JNK/p38 MAPK signaling. Our findings provided a new theoretical basis for the treatment of osteoarthritis.

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“…According to the previous research results on the nutrition physiology of E. sinensis in our laboratory, icariin has the effects of antioxidation, enhancing immunity, promoting sex steroid hormone synthesis, vitellogenesis and ovarian nutrients deposition, suggesting that icariin has the potential to be used as a new functional feed additive in aquatic animals culturing (Zheng et al, 2019(Zheng et al, , 2020. Recent studies have shown that icariin has preventive and therapeutic effects on metabolic diseases such as diabetes, insulin resistance, obesity and dyslipidaemia (Li et al, 2020;Zheng et al, 2016;Aljehani et al, 2020;Wang, Gao, et al, 2020;Wang, Xiong, et al, 2020). Besides, scarce reports also showed that icariin affects anti-fatigue and regulating energy metabolism (Wang et al, 2014), but the mechanism therein is still not fully known.…”

Section: Introductionmentioning

confidence: 87%

Investigation of the regulatory effect of icariin on the hepatopancreas glycolipid metabolism and energy metabolism of female Eriocheir sinensis during exogenous vitellogenesis based on the transcriptomics and metabolomics

et al. 2021

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The Chinese mitten crab (Eriocheir sinensis) mainly depends on lipids and carbohydrates to meet the energy requirements for its growth and rapid ovarian development during the exogenous vitellogenesis. Therefore, this study aimed to explore the effects of dietary icariin supplement on the hepatopancreas' glycolipid metabolism and energy metabolism during this vital stage. Biochemical analysis revealed the apparent differential effects of icariin on the key indicators involving glycolipid metabolism.The functional mechanisms of icariin on glycolipid metabolism were systematically investigated using transcriptomic and metabolomic analysis. After 100 mg/kg icariin supplementation, fifty differential expression genes mainly involving in glycolysis, gluconeogenesis, fatty acid β-oxidation, tricarboxylic acid cycle and mitochondrial oxidative phosphorylation pathway were found. In addition, forty differential metabolites mainly involving the metabolism process of pyruvate metabolism, fatty acid metabolism, arachidonic acid metabolism and steroid hormone synthesis were identified.Besides, the results of RT-PCR and Western blot verified several key transcription factors related to glycolipid and energy metabolism; the results demonstrated that icariin could strengthen glycolipid metabolism and energy metabolism of E. sinensis by activating related genes. This would facilitate the further understanding of the metabolism and regulation mechanism of nutrition and energy during the exogenous vitellogenesis in crustaceans.

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Icariin increases chondrocyte vitality by promoting hypoxia-inducible factor-1α expression and anaerobic glycolysis

Cited by 29 publications

References 28 publications

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

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

Icariin interferes with TDP43-induced inflammatory factor secretion and inhibits the JNK and p38 MAPK signaling pathway in vitro

Investigation of the regulatory effect of icariin on the hepatopancreas glycolipid metabolism and energy metabolism of female Eriocheir sinensis during exogenous vitellogenesis based on the transcriptomics and metabolomics

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