The Neuroprotective Effects and Therapeutic Potential of the Chalcone Cardamonin for Alzheimer's Disease

Neurodegenerative diseases (ND) include a wide range of conditions that result from progressive neuronal damage. Alzheimer's disease (AD) is one of the most common NDs, with neuroinflammation and oxidative stress (OS) as major contributors to its development and progression. Many phytochemicals exhibit antioxidant and anti-inflammatory activities with potential neuroprotective effects. Cardamonin (CD; 2′,4′-dihydroxy-6′-methoxychalcone), present in species such as Alpinia katsumadai and Alpinia conchigera, displays anticancer, anti-inflammatory, antioxidant, antiviral, and antibiotic activities. CD is a potent compound that can reduce OS and modulate inflammatory processes implicated in ND. It modulates signaling molecules involved in ND pathobiology, including transcription factors (NF-κB, STAT3), cytokines (TNF-α, IL-1, IL-6), enzymes (COX-2, MMP-9, ALDH1), and other proteins/genes (Bcl-2, XIAP, cyclin D1). CD also modulates miRNAs and autophagy-related pathways. This review provides mechanistic insights into CD’s ability to affect oxidative stress–antioxidant systems and Nrf2 signaling and to attenuate neuroinflammation, highlighting CD’s therapeutic potential and preventive utility in ND, particularly AD.

Lucian Hritcu, Kimberly Barber, Patricia Mendonca, F A Soliman, K M F A S