Zhao, M.; Wang, X.; Yang, W.; Qiu, D.; Li, S.; Tang, J.; Chen, H.; Ruan, H.; Miao, X.; Cheng, X.; Sui, X.; Jiang, J.; Wei, C.; Li, H.; Xiao, J. Usnic Acid Reduces Cartilage Matrix Degradation in Osteoarthritis Rats Through the Nrf2/NFκB Pathway. Preprints2024, 2024010408. https://doi.org/10.20944/preprints202401.0408.v1
APA Style
Zhao, M., Wang, X., Yang, W., Qiu, D., Li, S., Tang, J., Chen, H., Ruan, H., Miao, X., Cheng, X., Sui, X., Jiang, J., Wei, C., Li, H., & Xiao, J. (2024). Usnic Acid Reduces Cartilage Matrix Degradation in Osteoarthritis Rats Through the Nrf2/NFκB Pathway. Preprints. https://doi.org/10.20944/preprints202401.0408.v1
Chicago/Turabian Style
Zhao, M., Hai Li and Jianhua Xiao. 2024 "Usnic Acid Reduces Cartilage Matrix Degradation in Osteoarthritis Rats Through the Nrf2/NFκB Pathway" Preprints. https://doi.org/10.20944/preprints202401.0408.v1
Abstract
Chondrocytes maintain the normal morphological structure and physiological function of articular cartilage. However, the increased expression of inflammatory mediators and matrix-degrading enzymes in chondrocytes can promote ECM degradation, consequently disrupting the physiological function of articular cartilage and ultimately leading to the onset of osteoarthritis (OA). Usnic acid (UA), an extract derived from plants, possesses multiple bioactive properties including anti-inflammatory and antioxidant effects. Hence, this study aims to explore the molecular mechanisms underlying its protective effects in an in vitro simulated model of OA in rat chondrocytes.
In vivo experiments encompassed three groups: Control, Model, and Usnic acid (50 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via ELISA assays. In this study, primary rat chondrocytes were employed as the experimental subject. After a 24-hour treatment period, culture supernatants, total RNA, total protein, and nuclear protein were extracted from the different chondrocyte groups. ELISA and qPCR methods were used to measure levels of IL-6, TNF-α, and PGE2. WB and qPCR were employed to assess levels of p65, p-p65, IκBα, p-IκBα, Nrf2, HO-1, NQO1 ADAMTS-4, MMP-1, MMP-3, MMP-13, INOS, COX-2, and COL2A1. IF analysis was performed to examine Nrf2, p-p65 and COL2A1.
Results: (1) In vivo, intraperitoneal injection of usnic acid (50mg/kg) can alleviate pathological changes in articular cartilage and the levels of inflammatory and oxidative-related matrix in the serum. (2) UA reduced the level of inflammatory cytokines in IL-1β-induced chondrocytes supernatant. (3) UA can produce anti-inflammatory and antioxidant effects and inhibit chondrocytes matrix degradation through the Nrf2 and NF-κB pathways. (3) The mechanism by which UA exerts a protective role in chondrocytes is mediated by Nrf2
Conclusion: UA inhibits the expression of chondrocyte matrix degradation-related components through Nrf2 mediated Nrf2 pathway and NF-κB pathway, promotes the production of protective substances, and ultimately exerts a protective effect on chondrocytes.
Biology and Life Sciences, Animal Science, Veterinary Science and Zoology
Copyright:
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