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QCT inhibits IL-1β-induced ferroptosis in chondrocytes by activating <t>AMPK/Nrf2/Gpx4</t> signaling. CHON-001 cells were treated with QCT (50 or 100 µM) for 24 h, and then exposed to IL-1β for 24 h. (A) Lipid ROS and (B) Fe 2+ levels in CHON-001 cells were evaluated using ELISAs. (C) Western blotting was used to detect p-AMPK, AMPK, Nrf2 and Gpx4 levels in CHON-001 cells. The level of p-AMPK was normalized to that of AMPK. **P<0.01 vs. control group; ## P<0.01 vs. IL-1β group. AMPK, 5′ AMP-activated protein kinase; Gpx4, glutathione peroxidase 4; Nrf2, nuclear factor erythroid 2-related factor 2; p-, phosphorylated; QCT, quercetin; ROS, reactive oxygen species.
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QCT inhibits IL-1β-induced ferroptosis in chondrocytes by activating AMPK/Nrf2/Gpx4 signaling. CHON-001 cells were treated with QCT (50 or 100 µM) for 24 h, and then exposed to IL-1β for 24 h. (A) Lipid ROS and (B) Fe 2+ levels in CHON-001 cells were evaluated using ELISAs. (C) Western blotting was used to detect p-AMPK, AMPK, Nrf2 and Gpx4 levels in CHON-001 cells. The level of p-AMPK was normalized to that of AMPK. **P<0.01 vs. control group; ## P<0.01 vs. IL-1β group. AMPK, 5′ AMP-activated protein kinase; Gpx4, glutathione peroxidase 4; Nrf2, nuclear factor erythroid 2-related factor 2; p-, phosphorylated; QCT, quercetin; ROS, reactive oxygen species.

Journal: Molecular Medicine Reports

Article Title: Quercetin attenuates the symptoms of osteoarthritis in vitro and in vivo by suppressing ferroptosis via activation of AMPK/Nrf2/Gpx4 signaling

doi: 10.3892/mmr.2024.13425

Figure Lengend Snippet: QCT inhibits IL-1β-induced ferroptosis in chondrocytes by activating AMPK/Nrf2/Gpx4 signaling. CHON-001 cells were treated with QCT (50 or 100 µM) for 24 h, and then exposed to IL-1β for 24 h. (A) Lipid ROS and (B) Fe 2+ levels in CHON-001 cells were evaluated using ELISAs. (C) Western blotting was used to detect p-AMPK, AMPK, Nrf2 and Gpx4 levels in CHON-001 cells. The level of p-AMPK was normalized to that of AMPK. **P<0.01 vs. control group; ## P<0.01 vs. IL-1β group. AMPK, 5′ AMP-activated protein kinase; Gpx4, glutathione peroxidase 4; Nrf2, nuclear factor erythroid 2-related factor 2; p-, phosphorylated; QCT, quercetin; ROS, reactive oxygen species.

Article Snippet: The 5′ AMP-activated protein kinase (AMPK) inhibitor compound C, QCT and erastin were purchased from MedChemExpress, and the cells were treated with QCT (100 µM), QCT and erastin (5 µM) or QCT and compound C (5 µM) for 24 h at 37°C, and then exposed to IL-1β for 24 h at 37°C.

Techniques: Western Blot, Control

QCT protects against IL-1β-induced chondrocyte injury in vitro by suppressing ferroptosis via the activation of AMPK/Nrf2/Gpx4 signaling. CHON-001 cells were treated with QCT (100 µM) or QCT and compound C (5 µM) for 24 h at 37°C, and then exposed to IL-1β for 24 h at 37°C. (A) Western blotting was used to detect p-AMPK, AMPK, Nrf2 and Gpx4 levels in CHON-001 cells. The level of p-AMPK was normalized to that of AMPK. (B) Western blotting was used to detect aggrecan, collagen II, MMP13 and ADAMTS5 levels in CHON-001 cells. **P<0.01 vs. control group; ## P<0.01 vs. IL-1β group; ^ P<0.05 ^^ P<0.01 vs. IL-1β + QCT group. ADAMTS5, ADAM metallopeptidase with thrombospondin type 1 motif 5; AMPK, 5′ AMP-activated protein kinase; collagen II, type II collagen; Gpx4, glutathione peroxidase 4; Nrf2, nuclear factor erythroid 2-related factor 2; p-, phosphorylated; QCT, quercetin.

Journal: Molecular Medicine Reports

Article Title: Quercetin attenuates the symptoms of osteoarthritis in vitro and in vivo by suppressing ferroptosis via activation of AMPK/Nrf2/Gpx4 signaling

doi: 10.3892/mmr.2024.13425

Figure Lengend Snippet: QCT protects against IL-1β-induced chondrocyte injury in vitro by suppressing ferroptosis via the activation of AMPK/Nrf2/Gpx4 signaling. CHON-001 cells were treated with QCT (100 µM) or QCT and compound C (5 µM) for 24 h at 37°C, and then exposed to IL-1β for 24 h at 37°C. (A) Western blotting was used to detect p-AMPK, AMPK, Nrf2 and Gpx4 levels in CHON-001 cells. The level of p-AMPK was normalized to that of AMPK. (B) Western blotting was used to detect aggrecan, collagen II, MMP13 and ADAMTS5 levels in CHON-001 cells. **P<0.01 vs. control group; ## P<0.01 vs. IL-1β group; ^ P<0.05 ^^ P<0.01 vs. IL-1β + QCT group. ADAMTS5, ADAM metallopeptidase with thrombospondin type 1 motif 5; AMPK, 5′ AMP-activated protein kinase; collagen II, type II collagen; Gpx4, glutathione peroxidase 4; Nrf2, nuclear factor erythroid 2-related factor 2; p-, phosphorylated; QCT, quercetin.

Article Snippet: The 5′ AMP-activated protein kinase (AMPK) inhibitor compound C, QCT and erastin were purchased from MedChemExpress, and the cells were treated with QCT (100 µM), QCT and erastin (5 µM) or QCT and compound C (5 µM) for 24 h at 37°C, and then exposed to IL-1β for 24 h at 37°C.

Techniques: In Vitro, Activation Assay, Western Blot, Control

QCT ameliorates OA in mice in vivo via activation of AMPK/Nrf2/Gpx4 signaling. (A) Pathologic changes of mouse cartilage tissue were evaluated using H&E staining and safranin O/fast green assays. Immunohistochemistry was used to assess aggrecan, collagen II, MMP13 and ADAMTS5 levels in mouse cartilage tissues. Magnification, ×200. Scale bar, 100 µm. (B) Western blotting was used to detect p-AMPK, AMPK, Nrf2 and Gpx4 levels in mouse cartilage tissues. (C) The level of p-AMPK was normalized to that of AMPK and the other proteins were normalized to β-actin. (D) OARSI score in each group. **P<0.01 vs. sham group; # P<0.05, ## P<0.01 vs. OA group. ADAMTS5, ADAM metallopeptidase with thrombospondin type 1 motif 5; AMPK, 5′ AMP-activated protein kinase; collagen II, type II collagen; Gpx4, glutathione peroxidase 4; Nrf2, nuclear factor erythroid 2-related factor 2; OA, osteoarthritis; OARSI, Osteoarthritis Research Society International; p-, phosphorylated; QCT, quercetin.

Journal: Molecular Medicine Reports

Article Title: Quercetin attenuates the symptoms of osteoarthritis in vitro and in vivo by suppressing ferroptosis via activation of AMPK/Nrf2/Gpx4 signaling

doi: 10.3892/mmr.2024.13425

Figure Lengend Snippet: QCT ameliorates OA in mice in vivo via activation of AMPK/Nrf2/Gpx4 signaling. (A) Pathologic changes of mouse cartilage tissue were evaluated using H&E staining and safranin O/fast green assays. Immunohistochemistry was used to assess aggrecan, collagen II, MMP13 and ADAMTS5 levels in mouse cartilage tissues. Magnification, ×200. Scale bar, 100 µm. (B) Western blotting was used to detect p-AMPK, AMPK, Nrf2 and Gpx4 levels in mouse cartilage tissues. (C) The level of p-AMPK was normalized to that of AMPK and the other proteins were normalized to β-actin. (D) OARSI score in each group. **P<0.01 vs. sham group; # P<0.05, ## P<0.01 vs. OA group. ADAMTS5, ADAM metallopeptidase with thrombospondin type 1 motif 5; AMPK, 5′ AMP-activated protein kinase; collagen II, type II collagen; Gpx4, glutathione peroxidase 4; Nrf2, nuclear factor erythroid 2-related factor 2; OA, osteoarthritis; OARSI, Osteoarthritis Research Society International; p-, phosphorylated; QCT, quercetin.

Article Snippet: The 5′ AMP-activated protein kinase (AMPK) inhibitor compound C, QCT and erastin were purchased from MedChemExpress, and the cells were treated with QCT (100 µM), QCT and erastin (5 µM) or QCT and compound C (5 µM) for 24 h at 37°C, and then exposed to IL-1β for 24 h at 37°C.

Techniques: In Vivo, Activation Assay, Staining, Immunohistochemistry, Western Blot