Design and synthesis of new curcumin analogues as hepatoprotectives and antioxidants in liver dysfunction through caspase-3 regulation

BACKGROUND: Chronic liver disease is a progressive, worldwide health crisis, with its incidence and prevalence increasing annually. It causes progressive liver injury and ultimately fibrosis. Globally, it is responsible for approximately 2 million deaths annually. Despite its growing prevalence, there is currently no approved, highly effective targeted therapy for managing liver dysfunction. OBJECTIVE: Targeting caspase-3 activity may attenuate hepatocellular injury, reduce inflammation and oxidative stress, and thereby improve liver functional integrity. METHODOLOGY: significantly improved biochemical and molecular markers associated with liver dysfunction, including reductions in inflammation, oxidative stress, caspase-3 activity, TNF-α, p53, and Bax levels, alongside modulation of Bcl-2 expression. CONCLUSION: demonstrate promising hepatoprotective activity and may represent stable lead compounds for potential therapeutic management of liver dysfunction.