Nano guar gum triphenyl phosphonium conjugated rutin complex ameliorates hypertrophy in H9c2 cells via...

Mitochondria-targeted antioxidants have emerged as a promising frontier in drug discovery, offering advantages over conventional antioxidants owing to recent technological advances. As the primary intracellular source of reactive oxygen species (ROS) mitochondria play a critical role in cellular health. Consequently, excessive mitochondrial ROS generation is heavily implicated in the pathogenesis of cardiovascular, neurodegenerative, and metabolic disorders. The etiopathogenesis of cardiovascular disease is mainly due to the dysfunction of mitochondria. Therefore, mitochondrial dysfunction is a novel curious target for developing new drug therapies. In this study, mitochondrial antioxidant (Ru-TPP-GGN) was prepared by incorporating triphenylphosphonium (TPP) conjugated rutin into guar gum nanoparticles (GGN) and was evaluated against angiotensin II (Ang II) induced hypertrophy in the H9c2 cell lines. The size of the synthesized Ru-TPP-GGN was about ≈ 15 nm, and it was subjected to detailed characterization to confirm its nano-characteristics. The cytoxicity analysis showed that the Ru-TPP-GGN was nontoxic to the cells. The cells treated with Ang II showed abnormalities in mitochondria with surplus superoxide generation, an increase in atrial natriuretic peptide (ANP) (125.75%↑) and brain natriuretic peptide (BNP) (82.75%↑) level, dissipation of mitochondrial transmembrane potential (ΔΨm), mitochondrial permeability transition pore (mPTP) opening, upregulation of transforming growth factor-β (TGF-β) protein expression, and alterations in the expression of proteins (OPA1, MFN1/2, FIS1, DRP1, and MFF) involved in mitochondrial biogenesis. Ru-TPP-GGN was found to avert the progression of hypertrophy via safeguarding mitochondrial integrity and dynamics. It is found to be a potential nanomaterial for further exploration for the development of mitochondrial antioxidant-based therapies against cardiac hypertrophy.