Pharmacology of apocynin: a natural acetophenone

Abstract

Apocynin is a naturally occurring acetophenone, found in the roots of Apocynum cannabinum and Picrorhiza kurroa. Various chemical and pharmaceutical modifications have been carried out to enhance the absorption and duration of action of apocynin, like, formulation of chitosan-based apocynin-loaded solid lipid nanoparticles, chitosan-oligosaccharide based nanoparticles, and biodegradable polyanhydride nanoparticles. Apocynin has been subjected to a wide range of experimental screening and has proved to be useful for amelioration of a variety of disorders, like diabetic complications, neurodegeneration, cardiovascular disorders, lung cancer, hepatocellular cancer, pancreatic cancer, and pheochromocytoma. Apocynin has been primarily reported as an NADPH oxidase (NOX) inhibitor and prevents translocation of its p47^phox subunit to the plasma membrane, observed in neurodegeneration and hypertension. However, recent studies highlight its off-target effects that it is able to function as a scavenger of non-radical oxidant species, which is relevant for its activity against NOX 4 mediated production of hydrogen peroxide. Additionally, apocynin has shown inhibition of eNOS-dependent superoxide production in diabetic cardiomyopathy, reduction of NLRP3 activation and TGFβ/Smad signaling in diabetic nephropathy, diminished VEGF expression and decreased retinal NF-κB activation in diabetic retinopathy, inhibition of P38/MAPK/Caspase3 pathway in pheochromocytoma, inhibition of AKT-GSK3β and ERK1/2 pathways in pancreatic cancer, and decreased FAK/PI3K/Akt signaling in hepatocellular cancer. This review aims to discuss the pharmacokinetics and mechanisms of the pharmacological actions of apocynin.

Keywords: Apocynin; NADPH oxidase; Parkinson’s disease; cancer; diabetic cardiomyopathy; diabetic nephropathy; diabetic retinopathy.