Anti-Inflammatory Activity of APPA (Apocynin and Paeonol) in Human Articular Chondrocytes

Author:

Fernández-Moreno Mercedes12ORCID,Hermida-Gómez Tamara123,Larkins Nicholas4,Reynolds Alan4ORCID,Blanco Francisco J.15ORCID

Affiliation:

1. Grupo de Investigación en Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade de A Coruña (UDC), 15071 A Coruña, Spain

2. Grupo de Investigación en Reumatología y Salud (GIR-S), Centro Interdisciplinar de Química y Biología (CICA), Universidade de A Coruña (UDC), Campus de Elviña, 15071 A Coruña, Spain

3. Centro de Investigación Biomédica en Red, Bioingenieria, Biomatereial y Nanomedicina (CIBER-BBN), 50018 Zaragoza, Spain

4. AKL Therapeutics Ltd., Stevenage Bioscience, Gunnels Wood Rd, Stevenage SG1 2FX, UK

5. Grupo de Investigación en Reumatología y Salud (GIR-S), Departamento de Fisioterapia, Medicina y Ciencias Biomédicas, Facultad de Fisioterapia, Centro Interdisciplinar de Química y Biología (CICA), INIBIC-Sergas, Universidade de A Coruña (UDC), Campus de Oza, 15008 A Coruña, Spain

Abstract

Osteoarthritis (OA) is a chronic joint disease leading to cartilage loss and reduction in the joint space which results in pain. The current pharmacological treatment of OA is inadequate and pharmacological interventions focus on symptom management. APPA, a combination of apocynin (AP) and paeonol (PA), is a potential drug for treating OA. The aim of this study was to analyze the effects of APPA on the modulation of the inflammatory response in chondrocytes. Samples were incubated with IL-1β and APPA, and their responses to proinflammatory cytokines, catabolic mediators and redox responses were then measured. The effect of APPA on mitogenesis was also evaluated. Results show that APPA attenuated the expression of IL-8, TNF-α, MMP-3, MMP-13, SOD-2 and iNOS, resulting in the protection of human articular cartilage. APPA decreased PGC-1α gene expression induced by IL-1β. APPA did not modulate the gene expression of Mfn2, Sirt-1 or Sirt-3. The overall findings indicate that APPA may be an effective treatment for OA by targeting several of the pathways involved in OA pathogenesis.

Funder

AKL Therapeutics, Ltd.

Publisher

MDPI AG

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