Non‐Pulmonary Mechanisms of Action of Ambroxol in In Vivo Experimental Models: a Systematic Review

ABSTRACT Background Repositioning offers a cost‐effective approach to discovering new therapeutic applications for existing medications. Ambroxol, primarily used as a mucolytic for respiratory diseases, has demonstrated anti‐inflammatory, analgesic, and antioxidant properties, suggesting potential benefits in non‐pulmonary conditions. This study conducted a systematic review to evaluate the efficacy of ambroxol in experimental disease models unrelated to the respiratory system. Methods Following registration in the Open Science Framework and adherence to the PICO strategy for formulating the guiding question, searches were performed in PUBMED/MEDLINE, EMBASE, and SCOPUS using the keywords: (Ambroxol) AND (Anti‐Inflammatory Agents OR Analgesics OR Antioxidants) AND (Animals OR in vivo). The SYRCLE tool assessed methodological quality. Among 353 identified records, eight articles met eligibility criteria. Results These studies investigated ambroxol's effects in models of gastric lesions, neuropathic pain, psoriasis‐like skin inflammation, hemorrhagic cystitis, and ischemia/reperfusion injuries in the liver and kidneys. Ambroxol doses ranged from 5 to 1000 mg/kg, predominantly administered orally. Its antioxidant properties were demonstrated by reducing free radicals and increasing enzymatic activity (SOD, CAT, GSH). Anti‐inflammatory effects included a decrease in pro‐inflammatory cytokines (TNF‐α, IL‐1β) and histological improvements. Antinociceptive action was observed through inhibition of voltage‐gated sodium channels and reduction of oxidative stress, alleviating neuropathic pain. Conclusions Despite ambroxol's widespread clinical use, limited research has explored its non‐respiratory applications. Existing studies suggest its promising therapeutic potential, reinforcing the need for further investigation into its role as an alternative treatment for various inflammatory and oxidative stress–related conditions beyond pulmonary diseases.