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Astaxanthin (AST) is a potent lipid-soluble keto-carotenoid with auspicious effects on human health. It protects organisms against a wide range of diseases with excellent safety and tolerability. Various imperative biological activities in in vitro and in vivo models have been suggested for AST. This review article is focused on the therapeutic potentials, biological activities, and beneficial health effects of AST. The pharmacological mechanisms of action of AST in the treatment and prevention of peripheral and central nervous system diseases are also reviewed to provide new insights to researchers. Finally, we suggest a novel hypothesis for the mechanism of action of AST in neuropathic pain following spinal cord injury.

Introduction

Astaxanthin (AST) is a lipid-soluble and red-orange oxycarotenoid pigment. It is an important colorant in crustacean and salmonid aquaculture feed industry. AST belongs to a group of carotenoids called xanthophylls, which primarily includes AST, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin. AST was discovered in 1938 in lobsters by Kuhn et al. and was initially employed only for pigmentation in aquaculture. In 1991, AST gained approval as a supplement for food when its biological activities, anti-oxidative features, and physiological performance as a precursor of vitamin A in rats and fish were reported. Today, research on AST is increasing due to the demand for natural AST in the promotion of human health worldwide.

AST can be extracted from various microorganisms, phytoplankton, marine animals, and seafood such as shrimp, lobster, asteroidean, algae, fish, crustacean, trout, krill, red sea bream, and salmon. Wild salmon obtains its AST from the food chain, but farmed salmon acquire the characteristic color of salmon flesh from AST feed supplements. The green microalga Haematococcus pluvialis is the major source of AST for human consumption and has the greatest potential to provide AST among suggested sources. The rich AST content of microalgae is produced under stress conditions including nitrogen deficiency, high salinity, and high temperature. AST is also found in the yeast Xanthophyllomyces dendrorhous (formerly known as Phaffia rhodozyma), in plants, a few fungi, Chlorococcum sp., Chlorella zofingiensis, and the marine bacterium Agrobacterium aurantiacum.

AST has a molecular structure similar to β-carotene. It is differentiated from other molecules of the carotene subclass by containing oxygen groups in its molecular structure. It has an extended structure with polar regions at either end of the molecule (ionone rings), which makes it capable of neutralizing free radicals. The nonpolar zone in the middle, composed of a series of carbon-carbon double bonds termed “conjugated,” gives AST its unique chemical properties, molecular structure, and light absorption characteristics. AST possesses 13 conjugated double polyunsaturated bonds, in contrast to 11 in β-carotene, which contributes to its unique properties. The hydroxyl in the 3,3′β position and moieties of keto on each ionone ring make AST molecules more polar and enhance its membrane function. This polar-nonpolar-polar structure allows AST to fit precisely into the polar-nonpolar-polar area of the cell membrane.

Due to its biological implications, it is necessary to develop effective methods for quantification of carotenoids including AST in cultivated, food, and biological samples. Various extraction methods and analytical techniques, such as UV and visible spectrophotometry and chromatographic methods like thin-layer (TLC), high-performance liquid (HPLC) with a photodiode array detector (HPLC-PDA), and supercritical fluid (SFC) chromatography, are used for determination of carotenoids. Gentili et al. described an efficient and novel analytical method to define the profile of carotenoids and fat-soluble vitamins using liquid chromatography-diode array detector–tandem mass spectrometry. HPLC, the most commonly used procedure for quantitative AST determination, is time-consuming and accurate analysis of esterified AST is difficult by this method. Chen et al. introduced a method using flow cytometry for in-vivo determination of AST in green microalga, which appears to be a highly efficient and feasible method for rapid estimation of AST.

Anti-oxidant Activity of AST

Excess oxidative molecules may react with proteins, lipids, and DNA through a chain reaction that induces protein and lipid oxidation and DNA damage. The impairment of these biomolecules is associated with various disorders. Oxidative stress (OS), as a key mediator in the pathology of diseases, is induced by the disturbance of the equilibrium status of pro-oxidant/anti-oxidant reactions in cells. It precipitates the production of reactive oxygen species (ROS) and free radicals.

Anti-cancer Activity

Aerobic metabolism is commonly associated with the production of superoxide, hydroxyl radical, and hydrogen peroxide. Singlet oxygen and peroxyl radicals are also produced during photochemical reactions and lipid peroxidation. These processes facilitate aging, carcinogenesis, mutagenesis, and the occurrence of degenerative diseases like cancer through the oxidation of proteins, DNA, and lipids. Anti-oxidants decrease carcinogenesis and mutagenesis via inhibition of oxidative processes.

Health Benefits, Clinical Applications, and Safety of AST in Humans

Several studies have shown the health-promoting effects of AST in the treatment and prevention of numerous diseases. Over 65 clinical studies and reports in over 300 peer-reviewed publications have provided proof of these effects and confirmed auspicious applications of AST in promoting human health and nutritional status. The most clinically demonstrated effects of AST include cardioprotection, immune modulation, and skin health.

Conclusion

Carotenoids available in supplementary forms provide health benefits by decreasing a wide range of diseases. The antioxidant and anti-inflammatory effects of these natural fat-soluble pigments allow them to protect against oxidative stress-associated and inflammatory diseases. AST, a keto-carotenoid, shows potential effects on various diseases, including inflammatory diseases, cancer, obesity, hypertriglyceridemia, and hypercholesterolemia.

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