Binaphthoquinone attenuates myofibroblast transition of human ventricular cardiac fibroblasts in vitro via mitochondrial modulation under diabetic conditions.

Binaphthoquinone (BiNQ), a dimeric compound composed of juglone (5-hydroxy-1,4-naphthoquinone) and naphthazarin (5,8-dihydroxy-1,4-naphthoquinone), was originally isolated from the sea urchin Spatangus purpureus O.F. Müller. In this study, we examined the anti-fibrotic effects of BiNQ in a diabetic context, focusing on its potential to enhance mitochondrial function. Human cardiac fibroblasts (NHCF-V) were cultured under control 5 mM glucose or exposed to 33 mM glucose plus palmitic acid (100 μM). Fibroblast-to-myofibroblast transition was evaluated by measuring the expression level of the myofibroblast marker α-smooth muscle actin (α-SMA), and functional changes were further assessed using a contraction assay. BiNQ was applied at two concentrations (10 nM and 1 μM) and was found to reduce α-SMA expression, indicating inhibition of myofibroblast differentiation. Concurrently, BiNQ enhanced the expression of mitochondrial respiratory chain complexes, resulting in increased ATP production. To elucidate the underlying molecular mechanisms, targeted proteomic analysis was performed using LC-MS/MS, enabling identification and quantification of proteins involved in mitochondrial bioenergetics and fibrotic regulation. Collectively, these findings suggest that BiNQ attenuates fibroblast activation in a diabetic context by improving mitochondrial function and modulating key pro-fibrotic pathways.