Epigallocatechin‐3‐O‐gallate ameliorates oxidative stress‐induced chondrocyte dysfunction and exerts chondroprotective effects via the Keap1/Nrf2/ARE signaling pathway

Wenrun Zhu; Han Tang; Lu Cao; Juncheng Li; Duan Ma; Changan Guo

doi:10.1111/cbdd.14056

journal article May 06, 2022

Epigallocatechin‐3‐O‐gallate ameliorates oxidative stress‐induced chondrocyte dysfunction and exerts chondroprotective effects via the Keap1/Nrf2/ARE signaling pathway

Wenrun Zhu Han Tang

Lu Cao

Juncheng Li

Duan Ma

Changan Guo

Chemical Biology & Drug Design Vol. 100 No. 1 pp. 108-120 · Wiley

View at Publisher Save 10.1111/cbdd.14056

Abstract

AbstractOxidative stress‐induced degeneration and dysfunction of chondrocytes play a key role in the pathological progression of osteoarthritis (OA), a common degenerative joint disease in the elderly. Epigallocatechin‐3‐O‐gallate (EGCG) increases Nrf2‐mediated antioxidase expression levels. We aimed to determine the effects of EGCG on C28/I2 human chondrocytes subjected to interleukin‐1β (IL‐1β)‐induced oxidative stress. EGCG suppressed IL‐1β‐induced oxidative stress, as indicated by decreased malondialdehyde (MDA) and reactive oxygen species (ROS) generation. Additionally, EGCG attenuated the IL‐1β‐induced reduction in cartilage matrix generated by chondrocytes by upregulating collagen II, aggrecan, sulfated proteoglycans, and SRY‐box transcription factor 9 (SOX9). EGCG reversed the IL‐1β‐induced increased cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), collagen X, and matrix metalloproteinases (MMPs). Furthermore, EGCG inhibited apoptosis and senescence of IL‐1β‐treated chondrocytes, as indicated by the decrease in mitochondrial membrane potential and senescence‐associated β‐galactosidase‐positive cells, respectively. Mechanically, EGCG upregulated nuclear factor erythroid 2‐related factor 2 (Nrf2), oxygenase‐1 (HO‐1), and NADPH quinone oxidoreductase1 (NQO1). The antioxidant and chondroprotective effects of EGCG were blocked by ML385, a Keap1/Nrf2/ARE signaling pathway inhibitor. Thus, EGCG ameliorated oxidative stress‐induced chondrocyte dysfunction and exerted chondroprotective effects via Keap1/Nrf2/ARE signaling. This provides a novel perspective on the molecular mechanisms underlying the therapeutic effects of EGCG on OA.

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Details

Published: May 06, 2022
Vol/Issue: 100(1)
Pages: 108-120
License: View

Authors

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Wenrun Zhu