Targeting NLRP3 Inflammasomes in Myocarditis: Potential Therapeutic Strategies and Clinical Translation

Myocarditis can be caused by viral infections, systematic autoimmune diseases, and as a reaction to prescribed medications, and the nucleotide-binding domain leucine-rich repeat pyrin domain-containing 3 (NLRP3) inflammasome is implicated in its pathophysiology. Here, we explore pharmaceutical and other therapies that modulate NLRP3 activation and may therefore be useful for treating myocarditis. Pharmaceutical agents such as colchicine, SGLT2 inhibitors (empagliflozin and canagliflozin), calpain inhibitors, and sacubitril/valsartan have shown promise in reducing inflammation and preserving cardiac function. Natural compounds, including morroniside and crocin, exhibit anti-inflammatory and cardioprotective effects by targeting the NLRP3 inflammasome. While these treatments have shown preclinical potential, successful clinical translation of inflammasome-targeting drugs will require efforts to overcome recruitment challenges, flawed trial designs, high dropout rates, safety and toxicity concerns, and a lack of biomarkers. Natural products may offer a practical solution to these issues, providing safer therapeutic options and providing innovative approaches for managing myocarditis and preventing long-term complications. Trial Registration: ClinicalTrials.gov identifier: NCT05855746.