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  3. Isoliquiritigenin inhibits apoptosis and ameliorates oxidative stress in rheumatoid arthritis chondrocytes through the Nrf2/HO-1-mediated pathway

Isoliquiritigenin inhibits apoptosis and ameliorates oxidative stress in rheumatoid arthritis chondrocytes through the Nrf2/HO-1-mediated pathway

  • Biomed Pharmacother. 2023 Dec 12:170:116006. doi: 10.1016/j.biopha.2023.116006.
Shih-Ya Hung 1,  Jen-Lung Chen 2,  Yuan-Kun Tu 3,  Hsin-Yi Tsai 4,  Pin-Hsuan Lu 4,  I-Ming Jou 5,  Lulekiwe Mbuyisa 6,  Ming-Wei Lin 7
Affiliations

Affiliations

  • 1 Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan; Division of Surgery, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan.
  • 2 Department of Surgery, E-Da Hospital, Kaohsiung 82445, Taiwan.
  • 3 Department of Orthopaedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
  • 4 Department of Medical Research, E-Da Hospital/ E-Da Cancer Hospital, Kaohsiung 82445, Taiwan.
  • 5 Department of Orthopaedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
  • 6 School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan.
  • 7 Department of Medical Research, E-Da Hospital/ E-Da Cancer Hospital, Kaohsiung 82445, Taiwan; Department of Nursing, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan; Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: [email protected].
PMID: 38091640 DOI: 10.1016/j.biopha.2023.116006
Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory condition known for its irreversible destructive impact on the joints. Chondrocytes play a pivotal role in the production and maintenance of the cartilage matrix. However, the presence of inflammatory cytokines can hinder chondrocyte proliferation and promote Apoptosis. Isoliquiritigenin (ISL), a flavonoid, potentially exerts protective effects against various inflammatory diseases. However, its specific role in regulating the nuclear factor E2-associated factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in chondrocytes in RA remains unclear. To investigate this, this study used human chondrocytes and Sprague-Dawley rats to construct in vitro and in vivo RA models, respectively. The study findings reveal that cytokines markedly induced oxidative stress, the activation of Matrix Metalloproteinases, and Apoptosis both in vitro and in vivo. Notably, ISL treatment significantly mitigated these effects. Moreover, Nrf2 or HO-1 inhibitors reversed the protective effects of ISL, attenuated the expression of Nrf2/HO-1 and Peroxisome Proliferator-activated Receptor gamma-coactivator-1α, and promoted chondrocyte Apoptosis. This finding indicates that ISL primarily targets the Nrf2/HO-1 pathway in RA chondrocytes. Moreover, ISL treatment led to improved behavior scores, reduced paw thickness, and mitigated joint damage as well as ameliorated oxidative stress in skeletal muscles in an RA rat model. In conclusion, this study highlights the pivotal role of the Nrf2/HO-1 pathway in the protective effects of ISL and demonstrates the potential of ISL as a treatment option for RA.

Keywords

Chondrocytes; HO-1; Isoliquiritigenin; Nrf2; Oxidative stress; Rheumatoid arthritis; Skeletal muscles.

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