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<p>Rheumatoid arthritis (RA) is a highly prevalent autoimmune syndrome characterised by consecutive inflammation, synovial hyperplasia, and chondrocyte apoptosis. Carvocal (CAR) is a monoterpenes phenol that commonly occurs in <i>Thymus vulgaris</i> and <i>Origanum vulgare</i>, which exhibits antioxidative, anti-inflammatory, and antitumor activity. Hence, this work has to assess the anti-arthritic and anti-apoptotic activities of CAR in both in vivo and in vitro models. IL-1β-induced chondrocytes reduced (<i>p</i> &lt; 0.05) cell viability, antioxidants, and PTEN, while enhancing (<i>p</i> &lt; 0.05) the levels of ROS, MDA, nitrite, cytokines, inflammatory enzymes, MMPs, and PI3K/Akt versus control. These levels were reversed by the administration of CAR (25, 50, and 100 µM/ml) in a quantity-related manner. An in vivo RA rat model was induced using collagen (CIA), and the anti-arthritic and anti-apoptotic effects of CAR were compared with Diclofenac (DCF, 2.5&#xa0;mg/kg bw). Treatment with CAR (20 and 40&#xa0;mg/kg bw) reduced (<i>p</i> &lt; 0.05) loss of body weight, organ weight, inflammatory enzymes, cytokines, chemokines, and histopathological alterations in a dosage-related way when compared to RA rats. Molecular docking analyses were performed to confirm the compound’s multi-targeting potency that CAR could prevent proliferation and inflammation by triggering apoptosis in arthritis. By validating the CAR multi-targeting effectiveness against arthritis, as suggested by the results of docking analysis and MD simulation of COX-2 and iNOS. Furthermore, CAR could attenuate (<i>p</i> &lt; 0.05) the levels of caspase-3, -9, PGE2, Ang-1, MMP-9, and JAK/STAT while elevating SOCS signalling. Thus, CAR has potential as an anti-arthritic and anti-apoptotic component in both types of models.</p>

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Carvocal Suppresses IL-1β-Induced Chondrocytes and in Type II Collagen-Induced Arthritis in Rats by Regulation of PI3K/AKT/PTEN and JAK/STAT/SOCS Signalling Pathways - In Vitro, In Vivo and In Silico Approach

  • 期刊论文

  • 发表日期：

    2026年4月22日

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  • Chao Ban,
  • Jun Liu,
  • Jiazhao Pan,
  • Yang Liu,
  • Jie Liu

摘要

Rheumatoid arthritis (RA) is a highly prevalent autoimmune syndrome characterised by consecutive inflammation, synovial hyperplasia, and chondrocyte apoptosis. Carvocal (CAR) is a monoterpenes phenol that commonly occurs in Thymus vulgaris and Origanum vulgare, which exhibits antioxidative, anti-inflammatory, and antitumor activity. Hence, this work has to assess the anti-arthritic and anti-apoptotic activities of CAR in both in vivo and in vitro models. IL-1β-induced chondrocytes reduced (p < 0.05) cell viability, antioxidants, and PTEN, while enhancing (p < 0.05) the levels of ROS, MDA, nitrite, cytokines, inflammatory enzymes, MMPs, and PI3K/Akt versus control. These levels were reversed by the administration of CAR (25, 50, and 100 µM/ml) in a quantity-related manner. An in vivo RA rat model was induced using collagen (CIA), and the anti-arthritic and anti-apoptotic effects of CAR were compared with Diclofenac (DCF, 2.5 mg/kg bw). Treatment with CAR (20 and 40 mg/kg bw) reduced (p < 0.05) loss of body weight, organ weight, inflammatory enzymes, cytokines, chemokines, and histopathological alterations in a dosage-related way when compared to RA rats. Molecular docking analyses were performed to confirm the compound’s multi-targeting potency that CAR could prevent proliferation and inflammation by triggering apoptosis in arthritis. By validating the CAR multi-targeting effectiveness against arthritis, as suggested by the results of docking analysis and MD simulation of COX-2 and iNOS. Furthermore, CAR could attenuate (p < 0.05) the levels of caspase-3, -9, PGE2, Ang-1, MMP-9, and JAK/STAT while elevating SOCS signalling. Thus, CAR has potential as an anti-arthritic and anti-apoptotic component in both types of models.