Therapeutic Potential of Ambroxol in Osteoarthritis: A Drug Repurposing Study

Background/Objectives: Ambroxol is a mucolytic agent widely used in the treatment of respiratory diseases; however, evidence in the literature indicates anti-inflammatory, analgesic, and immunomodulatory properties, suggesting potential for therapeutic repositioning. This study aimed to evaluate the analgesic and anti-inflammatory effects of ambroxol in an experimental model of osteoarthritis (OA). Methods: Adult male Wistar rats underwent OA induction on day zero (D0) by sodium monoiodoacetate (MIA) injection and were allocated into the following groups: Healthy, negative control (CTRL−), and groups treated with meloxicam (2 mg/kg) or ambroxol (10, 50, and 100 mg/kg). Treatments were administered orally (gavage) once daily for 28 days. Behavioral tests were performed, including rotarod, walkway gait analysis, weight-bearing, Von Frey, and Rat Grimace Scale assessments, along with radiographic and histopathological analyses and quantification of pro- and anti-inflammatory cytokines (IL-1β, IL-6, and IL-10). Results: Ambroxol treatment improved nociceptive parameters and motor function, reduced radiographic and histopathological scores, and showed performance comparable to meloxicam in several tests. There was a marked reduction in IL-1β and IL-6 levels, while IL-10 levels were lower in ambroxol-treated groups, suggesting early control of the inflammatory response. Conclusions: The results indicate that ambroxol exhibits antinociceptive and anti-inflammatory actions and suggest a potential chondroprotective effect, reinforcing its viability as a candidate for therapeutic repositioning in osteoarthritis. Further studies are required to more precisely elucidate its mechanisms of action, define optimal dosing and treatment duration, and support translation to clinical models.