Butanolic Extract of Noni Inhibits Proliferation, Inflammation, and Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Expression in Cultured Smooth Muscle Cells

Abstract

Platelet-derived growth factor-BB (PDGF-BB) plays a central role in smooth muscle cell (SMC) proliferation and inflammation, being involved in atherosclerotic cardiovascular disease. We have previously found that butanolic extract of noni, a tropical plant belonging to the family Rubiaceae, exerts anti-inflammatory effects on endothelial cells exposed to advanced glycation end products (AGEs). Here, we examined the effects of noni extract on oxidative stress production, growth, and inflammatory reactions in PDGF-BB or AGE-exposed SMCs. Reactive oxygen species (ROS) generation, cell proliferation, and adhesion were measured by a fluorescent dye, a colorimetric agent, and labeled THP-1 cells, respectively. Gene and protein expression was evaluated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. Butanolic extract of noni reduced ROS production, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and proprotein convertase subtilisin kexin type 9 (PCSK9) expression, and proliferation in, and THP-1 cell adhesion to, PDGF-BB-exposed SMCs. Gene expression and protein level of receptor for AGEs (RAGE) were significantly decreased by noni extract in SMCs. Furthermore, AGEs significantly increased PCSK9 mRNA and protein levels in SMCs, which were inhibited by noni extract or an antioxidant N-acetylcysteine. Our present study suggests that butanolic extract of noni not only inhibits the PDGF-BB-induced proliferation and inflammatory reactions in SMCs through its antioxidative properties but also reduces PCSK9 levels in AGE-exposed SMCs via suppression of RAGE expression. Butanolic extract of noni may play a protective role against atherosclerosis.