Antioxidant and free radical scavenging potential of yakuchinone B derivatives in reduction of lipofuscin formation using H2O2-treated neuroblastoma cells

Background: The progressive accumulation of misfolded and aggregated proteins in neurons is an accepted mechanism in aging. Overproduction of reactive oxygen species (ROS), referred to as oxidative stress, is currently believed to play a pivotal role in this process. Lipofuscin as a histological index of aging results from cross-links between oxidized proteins and lipids. Therefore, to attenuate lipofuscin formation, it would be logical to use exogenous natural or synthetic antioxidants. Yakuchinone B (1-4''-hydroxy-3''-methoxyphenyl]-7-phenylhept-1-en-3-one) is a component of Alpinia oxyphylla seeds with established antioxidant activity. Methods: To evaluate the neuroprotective roles of yakuchinone B (JC6) and its structural analogues (JC1-JC5), the free radical scavenging capabilities of yakuchinone B derivatives were studied in terms of cell viability, apoptosis, cells ROS content, catalase (CAT) and superoxide dismutase (SOD) activity and the intracellular lipofuscin content in SK-N-MC cells exposed to H₂O₂. The level of MDA (malondialdehyde), as an index of lipid peroxidation and acid phosphatase activity were also measured. Results: Our results indicated that derivatives especially JC4, JC5 and JC6 decreased the extent of apoptosis and ROS level, while they increased the activities of SOD and CAT in drug-pretreated cells as compared to H₂O₂-treated cells. A clear relationship between the structure and antioxidant activities of these compounds was established. In addition, JC4, JC5 and JC6 were capable of down-regulating the formation of MDA and lipofuscin. Conclusion: Our results indicated that free radicals play significant roles in lipofuscin formation and cellular aging which can be attenuated by yakuchinone B derivatives.Key Words: Aging, Lipofuscin, Reactive oxygen species (ROS), Yakuchinone B