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| Andrographolide reduces cartilage damage in rats with knee osteoarthritis by activating the NRF2/HO-1 signaling pathway |
| Hits 194 Download times 101 Received:September 22, 2025 |
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| DOI
10.11656/j.issn.1672-1519.2025.12.13 |
| Key Words
Andrographolide;knee osteoarthritis;cartilage injury;NRF2/HO-1 signaling pathway;oxidative stress;inflammation;apoptosis |
| Author Name | Affiliation | E-mail | | MA Xin | Handan Central Hospital, Handan 056001, China | | | JIANG Nan | Handan Central Hospital, Handan 056001, China | cwzh2015@163.com | | WANG Haiye | Handan Central Hospital, Handan 056001, China | | | ZHANG Hongfeng | Handan Central Hospital, Handan 056001, China | | | GAO Guangran | Handan Second Hospital, Handan 056001, China | | | YIN Jiang | Handan Second Hospital, Handan 056001, China | | | WAN Yongjian | Handan Second Hospital, Handan 056001, China | |
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| Abstract
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| [Objective] To investigate the effect of Andrographolide on cartilage injury and nuclear factor E2 related factor 2/heme oxygenase-1（NRF2/HO-1） signaling pathway in rats with knee osteoarthritis（KOA）. [Methods] The KOA rat models were established by injecting a mixture of papain and L-cysteine into the knee joint cavity twice with a 3 days interval. The rats were randomly assigned to the following groups：normal，model，glucosamine（130 mg/kg），Andrographolide low dose group（30 mg/kg），Andrographolide high dose group（60 mg/kg） and Andrographolide high dose+NRF2 inhibitor Brusatol group（60 mg/kg + 2 mg/kg），with 8 rats in each group. After 4 weeks of treatment once a day，the behavioral performance of rats was evaluated by Lequesne MG score. The paw withdrawal mechanical threshold（PWMT） and paw withdraw thermal latency（PWTL） were determined by Von Frey experiment or hot plate experiment. The activity of antioxidant enzyme [total superoxide dismutase（T-SOD），glutathione peroxidase（GSH-Px），catalase（CAT）] and the content of malondialdehyde（MDA），tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β），monocyte chemoattractant protein-1（MCP-1） in knee joint fluid were detected by enzyme-linked immunosorbent assay（ELISA）. The pathological changes of cartilage tissue were examined by hematoxylin-eosin（HE） staining and safranin O-green staining，the Mankin’s score was used to evaluate the degree of cartilage degeneration；cell apoptosis was investigated by TUNEL staining. The expression of NRF2/HO-1 signaling pathway related proteins in cartilage tissue were detected by Western blot. [Results] Compared with the normal group，the Lequesne MG score of the rats in model group was increased，while the PWMT and PWTL were decreased（P＜0.05）. The activities of T-SOD，GSH-Px，and CAT in knee joint fluid were decreased，while the level of MDA，TNF-α，IL-1β，MCP-1 were increased（P＜0.05）. The cartilage tissue showed pathological changes such as thinning，division，surface defects，cell number decreased and disordered，inflammatory cell infiltration；the number of apoptotic chondrocytes was significantly increased；the Mankin’s score and apoptosis index（AI） were increased（P＜0.05）. The expression of NRF2，HO-1，B-cell lymphoma-2（Bcl-2） proteins were decreased，the expression of nuclear factor-κB p65（NF-κB p65），Bcl-2 related X protein（Bax），Cleaved Caspase-3 proteins and the Bax/Bcl-2 were increased（P＜0.05）. Compared with the model group，the Lequesne MG score of the rats in Glucosamine group and Andrographolide low，high dose groups was decreased，the PWMT and PWTL were increased（P＜0.05）. The activity of T-SOD，GSH-Px，CAT were increased，and the level of MDA，TNF-α，IL-1β，MCP-1 were decreased（P＜0.05）. The pathological changes of cartilage tissue and the apoptosis of chondrocytes were improved to varying degrees，the Mankin's score and AI were decreased（P＜0.05）. The expression of NRF2，HO-1，Bcl-2 proteins were increased，the expression of NF-κB p65，Bax，Cleaved Caspase-3 proteins and the Bax/Bcl-2 were decreased（P＜0.05）. The regulating effect of Andrographolide high dose group on various indexes were better than those of Andrographolide low dose group and Glucosamine group，the regulating effect of Andrographolide high dose+Brusatol group on various indexes were weaker than those of Andrographolide high dose group（P＜0.05）. [Conclusion] Andrographolide may alleviate oxidative stress，inflammatory response and cell apoptosis by activating the NRF2/HO-1 signaling pathway，and thereby protect against cartilage damage in rats with KOA. |
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