Astaxanthin as a Peroxisome Proliferator-Activated Receptor (PPAR) Modulator: Its Therapeutic Implications

Abstract

Peroxisome proliferator-activated receptors (PPARs) are part of the nuclear hormone receptors superfamily that plays a pivotal role in functions such as glucose and lipid homeostasis. Astaxanthin (ASX) is a lipid-soluble xanthophyll carotenoid synthesized by many microorganisms and various types of marine life that is known to possess antioxidant, anti-inflammatory, antidiabetic, anti-atherosclerotic, and anticancer activities. As such, it is a promising nutraceutical resource. ASX-mediated modulation of PPARs and its therapeutic implications in various pathophysiological conditions are described in this review. ASX primarily enhances the action of PPAR and suppresses that of PPAR/ and PPAR, but it has also been confirmed that ASX displays the opposite effects on PPARs, depending on the cell context. Anti-inflammatory effects of ASX are mediated by PPAR activation, which induces the expression of pro-inflammatory cytokines in macrophages and gastric epithelial cells. The PPAR-agonistic effect of ASX treatment results in the inhibition of cellular growth and apoptosis in tumor cells. Simultaneous and differential regulation of PPAR and PPAR activity by ASX has demonstrated a hepatoprotective effect, maintaining hepatic lipid homeostasis and preventing related hepatic problems. Considering additional therapeutic benefits of ASX such as anti-gastric, cardioprotective, immuno-modulatory, neuroprotective, retinoprotective, and osteogenic effects, more studies on the association between ASX-mediated PPAR regulation and its therapeutic outcomes in various pathophysiological conditions are needed to further elucidate the role of ASX as a novel nutraceutical PPAR modulator.