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Andrographolide protects chondrocytes from oxidative stress injury by activation of the Keap1–Nrf2–Are signaling pathway |
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| Authors: | Bo Li Tongmeng Jiang Hui Liu Zhikang Miao Depeng Fang Li Zheng Jinmin Zhao |
| Institution: | 1. Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China Bo Li and Tongmeng Jiang contributed equally to this study.;2. Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;3. Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;4. Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China |
| Abstract: | Recent studies have shown that andrographolide (AP) has the potential to be developed as a drug for therapy for osteoarthritis (OA). However, the role of AP in attenuating the progression of OA is still unknown. We hypothesized that its therapeutic effect may be associated with its antioxidant potential. In this study, we investigated the therapeutic effect of AP on chondrocytes injured by H2O2 and the association with the oxidation-related signaling pathways through the detection of cell proliferation, cell viability, the expression of oxidative stress-specific genes (Sod1, Cat, and malonaldehyde Mda]) and proteins (superoxide dismutase SOD], catalase CAT]) after a culture period of 3 and 5 days, respectively. Further exploration of the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) messenger RNA and protein was also performed. The results showed that 0.625 µg/ml and 2.5 µg/ml of AP decreased oxidative stress injury of chondrocytes by increasing cell proliferation reduced by H2O2 and antioxidant enzyme activity, including SOD and CAT. Inflammation factors, such as matrix metallopeptidase 13 (Mmp13), tissue inhibitor of metalloproteinase 1 (Timp1), and interleukin-6 (Il6), were downregulated in the H2O2 group with AP, demonstrating a decrease in the progression of OA. Pathway analyses identified that the kelch-like ECH-associated protein 1 (Keap1)–Nrf2–antioxidant response element (Are) pathway is an important mediator in AP therapy on H2O2-induced OA. This study indicates that AP exerts protection effects on oxidative stress via activation of the Keap1–Nrf2–Are pathway in chondrocytes injured by H2O2, which may be promising for the therapy of OA. |
| Keywords: | andrographolide (AP) chondrocytes kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2–antioxidant response element (Keap1–Nrf2–Are) osteoarthritis (OA) oxidative stress (OS) |