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.
Highlights
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptors superfamily and are ligand-activated transcription factors [1]
These include a blockade of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway [51,52,53,54,55,56], inhibition of c-Jun N-terminal kinase (JNK) in the mitogen-activated protein kinase (MAPK) signaling pathway [54,56], prevention of reactive oxygen species (ROS) accumulation by nuclear factor E2-related factor 2 (Nrf2) [55], positive modulation of Src homology region 2 domain-containing phosphatase-1 (SHP-1) protein expression [51], suppression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase [57], and induction of heme oxygenase-1 (HO-1) [58]
Rundblad et al [44] reported that the intake of ASX-added high-oleic sunflower oil (HOSO) supplementation downregulates the expression of PPARβ/δ, as well as other genes affecting lipid and glucose metabolism, in peripheral blood mononuclear cells (PBMCs) from healthy subjects
Summary
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptors superfamily and are ligand-activated transcription factors [1]. In addition to its major role in glucose and lipid homeostasis, PPARγ is associated with inflammatory responses, cardiovascular diseases, neurogenerative diseases, ocular diseases, and cancer [11] Since these various physiological functions of PPARs can serve as therapeutic targets for the treatment of chronic diseases, researchers have studied synthetic and. Mar. Drugs 2019, 17, x researchers have studied synthetic and naturally occurring substances, as well as marine organisms, to identify specific ligands that modulate PPAR activities [12,13,14,15,16,17,18,19,20,21]. Because synthetic which a morphological compound dissociates(Figure from the protein after thefrom association phase) of 197 μM It displays antioxidant, anti-inflammatory, antidiabetic, anti-atherosclerotic, and anticancer inferior effects on human health when compared with natural fluorescence algal-based ASX [27], many studies have.
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