A novel transdermal curcumin shows potential in improving cardiac bioenergetic functions in Berkeley sickle mouse. Open Access

Berkeley sickle mice show impaired heart mitochondrial bioenergetics along with oxidative changes and alterations in mitochondrial proteome.

Transdermal curcumin-gel can protect mitochondrial proteome and bioenergetic functions from oxidative stress in Berkeley sickle mice heart.

Numerous studies have identified mitochondria as critical players in the pathophysiology of sickle cell disease (SCD). Here, we investigated the bioenergetic impairment in cardiac muscle mitochondria as well as the putative benefits of a transdermal (TD) curcumin (VAS-101) treatment in a BERK-SS mouse model. Low oxygen consumption rate in cardiac mitochondria indicative of impaired electron transport chain (ETC) activities was observed in these animals. Further, there was a loss in enzymatic activity primarily in complex I (NADH 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 various other pathways (e.g., 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 impact oxygen homeostasis at cellular and subcellular level by improving mitochondrial respiration in the heart muscle of BERK SS mice.