Contribution of Nrf2 modulation to the mechanism of action of analgesic and anti-inflammatory drugs in pre-clinical and clinical stages

Abstract

Despite the progress that has occurred in recent years in the development of therapies to treat painful and inflammatory diseases, there is still a need for effective and potent analgesics and antiinflammatory drugs. It has long been known that several types of antioxidants also possess analgesic and anti-inflammatory properties, indicating a strong relationship between inflammation and oxidative stress. Understanding the underlying mechanisms of action of antiinflammatory and analgesic drugs, as well as essential targets in disease physiopathology, is essential to the development of novel therapeutic strategies. The Nuclear factor-2 erythroid related factor-2 (Nrf2) is a transcription factor that regulates cellular redox status through endogenous antioxidant systems with simultaneous anti-inflammatory activity. This review summarizes the molecular mechanisms and pharmacological actions screened that link analgesic, antiinflammatory, natural products, and other therapies to Nrf2 as a regulatory system based on emerging evidences from experimental disease models and new clinical trial data.