A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice

Numerous studies have identified mitochondria as critical players in the pathophysiology of sickle cell disease (SCD). Here, we investigated the bioenergetic impairment in cardiac mitochondria as well as the putative benefits of a transdermal (TD) curcumin (VAS-101) treatment in a Berkeley SCD (BERK-SS) mouse model. Low oxygen consumption rate observed in cardiac mitochondria was indicative of impaired electron transport chain (ETC) activities in these animals. Furthermore, there was a loss of enzymatic activity primarily in complex I (reduced NAD dehydrogenase) and to a lesser degree in complex V (ATP synthase) observed in BERK-SS cardiac mitochondrial fractions. Proteomic analysis of cardiac mitochondria revealed changes in the relative abundance of proteins related to ETC complexes, especially in multiple subunits of complex I and complex V. Changes were also seen in proteins involved in several other pathways (eg, β-oxidation, glycolysis, mitochondrial protein transport, cytoskeleton, Ca⁺² regulation, and mitophagy). Moreover, TD curcumin treatment caused improvements in various oxidative stress parameters in heart tissues of BERK-SS mice. Together, our results suggest that novel TD curcumin may affect oxygen homeostasis at cellular and subcellular levels by improving mitochondrial respiration in the heart muscle of BERK-SS mice.