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 PPARα and suppresses that of PPARβ/δ and PPARγ, 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 PPARγ activation, which induces the expression of pro-inflammatory cytokines in macrophages and gastric epithelial cells. The PPARγ-agonistic effect of ASX treatment results in the inhibition of cellular growth and apoptosis in tumor cells. Simultaneous and differential regulation of PPARα and PPARγ 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.

Astaxanthin Inhibits p70 S6 Kinase 1 Activity to Sensitize Insulin Signaling

“…AST offers a broad spectrum of other benefits to diabetic patients, including the suppression of inflammation and oxidative stress as well as the control of nonalcoholic fatty liver and diabetic complications [ 22 , 26 , 31 , 36 ]. AST functions as an antagonist of peroxisome proliferator-activated receptor (PPARγ) to exert its anti-inflammatory activity [ 37 ]. Our present study, focusing on the mechanisms of action of AST-mediated anti-hyperglycemic activity, has led to the identification of S6K1 as its molecular target.…”

Effect of Astaxanthin on the Inhibition of Lipid Accumulation in 3T3-L1 Adipocytes via Modulation of Lipogenesis and Fatty Acid Transport Pathways

“…Astaxanthin is the most common carotenoid in marine organisms, such as algae and aquatic animals. Previous studies indicated that astaxanthin has multiple pharmacological properties including antioxidant, anti-inflammatory, anti-cancer activities, and anti-adiposity action [22]. Therefore, adipose tissue mass represents an attractive concept for combating obesity and associated metabolic diseases [23].…”

Trends in use, pharmacology, and clinical applications of emerging herbal nutraceuticals

“…However, it has opposing effects on some PPARs, depending on the cell context. Regulation of PPARα and PPARγ activity by AX prevented hepatic injury by maintaining lipid homoeostasis, the cardio‐, neuro‐ and retino‐protective effects may be related to PPAR modulation (Choi, ).…”

“…The underlying mechanisms for the effects of AX include its high antioxidant capacity, its role as a modulator of the peroxisome proliferator-activated receptors (PPAR; Choi, 2019) and its complex effects on signalling pathways associated with inflammation and apoptosis (see review by Fakhri et al, 2018). AX enhances the effect of the usual reservations about quality and independence of many nutraceutical studies, Andrew & Izzo, 2017).…”