Carotenoids have a polyene chain and long conjugated double bonds. The structure of these compounds is responsible for antioxidant activity, such as the hardening of singlet oxygen and the removal of radicals to complete the chain reactions. The structure of astaxanthin consists of a conjugated polyene chain in the center and hydroxyl and ketone moieties on each ion ring.
Astaxanthin is characterized by higher biological activity than other antioxidants because it can bind to the cell membrane from the inside to the outside. The astaxanthin end ring captures radicals on the surface and inside the cell membrane, while the polyene chain does so only in the cell membrane.
After the quenching of singlet oxygen, astaxanthin dissipates energy through interaction with the solvent; then, the carotenoid structure returns to its original state. Astaxanthin exhibits higher antioxidant activity than various carotenoids, which include α-carotene, β-carotene, lycopene, and lutein. Additionally, it induces peroxidase, an enzyme with antioxidant activity.
- Anti-Lipid Peroxidation
Lipid peroxidation involves the oxidation of lipids and, in consequence, the formation of lipid peroxides. The reaction consists of three stages: initiation, propagation, and termination.
Lipid peroxidation yields aldehydes, hydroxy aldehydes, and hydrocarbons. These compounds can modify the physical properties of cell membranes, including a reduction in the hydrophobicity of the lipid interior of the membranes, disturbance in the lipid asymmetry of the membranes, inhibition of the activity of transporting proteins, depolarization of membranes, and inhibition of the activity of membrane enzymes.
These changes may result in the loss of intracellular membrane and plasma membrane integrity. The antioxidant activity of astaxanthin is pH-dependent. Studies showed that astaxanthin strongly inhibits the formation of by-products of lipid peroxidation in zwitterionic phosphatidylcholine liposomes at pH 7.4 (80%) and pH 8 (65%). Furthermore, it also slightly inhibits the process of lipid peroxidation at pH 6.2 (20%) and 6.8 (30%).
Interestingly, astaxanthin is more effective than β-carotene in preventing lipid peroxidation. Studies showed that astaxanthin was twice as effective as β-carotene in inhibiting ADP and Fe2+ induced liposomal peroxidation. This supposed mechanism of astaxanthin activity in preventing lipid peroxidation.
The effect of astaxanthin on lipid peroxidation was assessed in LDL studies in ex vivo conditions. For two weeks, volunteers were given different doses of astaxanthin (1.8, 3.6, 14.4, and 21.6 mg/day). Samples of LDL from the group of people who received astaxanthin were characterized by lower susceptibility to oxidation when compared to the control group (LDL from the group not consuming astaxanthin).
- Anti-Inflammation
Chronic inflammation is the main pathophysiological factor in many diseases, such as diabetes or many neurodegenerative diseases. Due to the high percentage of polyunsaturated fatty acids in the plasma membranes, immune cells are particularly sensitive to oxidative stress, overproduction of reactive oxygen species disturbs the antioxidant balance. Astaxanthin is a powerful antioxidant that inhibits inflammation in biological systems. This carotenoid can regulate the immune response or reduce inflammation associated with peripheral diseases. Studies have shown that astaxanthin can regulate microglial cells, non-neuronal cells of the central nervous system.
Microglial cells are tissue-specific resident macrophages that control homeostasis and are involved in the immune response. These cells release proinflammatory cytokines such as IL-1β, TNF-α, IL-6, and NO.
In the initial phase, this response is effective in danger neutralization.
However, due to the toxic nature of proinflammatory molecules, prolonged action of microglia can destroy the central nervous system. In several studies, the use of astaxanthin resulted in decreased secretion of IL-6, Cox-2, and iNos/nitric oxide in microglia during the presence of bacteria. A reduction of κB and neurodegeneration was reported in the frontal cortex and hippocampus. This research described the performance of mice treated with astaxanthin in the Morris water maze. Astaxanthin plays an important role in ameliorating inflammatory diseases, including arteriosclerosis, inflammatory bowel disease, sepsis, rheumatoid arthritis, gastric inflammation, and brain inflammatory diseases.
- Anti–Diabetic Activity
Insulin resistance is a severe disorder of glucose homeostasis characterized by decreased insulin sensitivity of various tissues, such as skeletal muscle, adipose tissue, or liver. Insulin resistance is one of the causes of type 2 diabetes and gestational diabetes; usually, it is also a factor in type 1 diabetes. Insulin resistance is often accompanied by hyperinsulinemia. Astaxanthin improves the whole body’s insulin sensitivity, and insulin stimulates glucose uptake in the muscle of insulin-resistant animals.
Astaxanthin reduces oxidative stress caused by hyperglycemia in pancreatic β cells and has a positive effect on serum glucose and insulin. Studies in astaxanthin-fed mice have reported increased insulin sensitivity in hypertensive rats and mice fed with high fat and fructose diets. In contrast, the level of albumin in the urine of diabetic mice was significantly lower than in the control group (without astaxanthin in diet). Astaxanthin stimulates the insulin receptor substrate (IRS) -PI3K-AKT signaling pathway due to the reduction of the serine phosphorylation of IRS proteins and increases glucose metabolism by regulating metabolic enzymes.
Astaxanthin is also responsible for lowering the level of cholesterol in the blood and the level of triglyceride in the liver and stimulating the expression of antioxidant genes. In addition, astaxanthin reduces the expression of CYP2E1 and, as a result, increases the sensitivity of cells to insulin and inhibits liver damage. In the early stages of diabetes, astaxanthin protects pancreatic β cells, increases insulin sensitivity, and improves glucose metabolism. As a consequence, insulin resistance and blood glucose levels decrease.
Supplementation with astaxanthin reduces oxidative stress, inflammation, and lipid peroxidation. Therefore it prevents such complications of diabetes as retinopathy, neuropathy, nephropathy, and cardiovascular complications. Mechanisms underlying antidiabetic effects of astaxanthin are as follows: (I) activation of IRS-PI3K-Akt signals and increased glucose metabolism in the liver; (II) normalization of hexokinase activity, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glycogen phosphorylase; (III) protection against oxidative stress and cytotoxicity in pancreatic cells; (IV) reduction of serine kinases activity; and (V) reduction of MDA.
- Anticancer Activity
Astaxanthin can inhibit cancer cell growth. Antioxidant compounds decrease mutagenesis and carcinogenesis by inhibiting oxidative damage to cells. Studies have reported that astaxanthin not only inhibits the proliferation of colon cancer cells but can also cause their apoptosis. An extract from H. pluvialis was used to inhibit the growth of human colon cancer cells. Astaxanthin was included in the extract and was responsible for stopping the progression of the cell cycle and promoting apoptosis. Astaxanthin showed higher antitumor activity than other carotenoids, including canthaxanthin and β-carotene.
After astaxanthin treatment, scientists proved increased immune cells, natural killer cells, and plasma γ interferon in mice. The oral administration of astaxanthin inhibited carcinogenesis in the urinary bladder of mice and in the colon and oral cavity of rats. This effect has been partially assigned to the suppression of cell proliferation. Recent research showed high anti-proliferative activity of astaxanthin against tumor cells like SHZ-88 breast cancer cells, hepatoma CBRH-7919 cells, and Lewis cells. A significant correlation was observed between astaxanthin concentrations and anti-proliferative activity. The most sensitive cell line to astaxanthin with half a maximal inhibitory concentration of 39 μM was the CBRH-7919 line.
According to the current publications, studies on the effects of astaxanthin on human health mainly cover such disorders as metabolic diseases, cancer, inflammatory diseases, and skin and eye conditions. Studies on the results of astaxanthin on animal organisms are promising, mainly due to the compound’s antioxidant properties. Research has demonstrated an astaxanthin-induced reduction in blood glucose and insulin levels; astaxanthin has also sensitized cellular receptors to insulin. The correlation between excess free radicals and the development of metabolic diseases, such as type 2 diabetes and insulin resistance, has been confirmed by many studies.
- Other Potential Benefits of Astaxanthin
Astaxanthin has a beneficial effect due to its high antioxidant and anti-inflammatory potential. As a result, more and more research is being conducted on the biological activities of astaxanthin in the context of the nervous, visual and cardiovascular systems.
Hypertension is a significant risk factor for cardiovascular disease. Overproduction of reactive oxygen and nitrogen species results in diseases like hypertension, atherosclerosis, endothelial dysfunction, or arrhythmias. Oral administration of astaxanthin to hypertensive rats decreased nitric oxide products and lowered blood pressure.
In vivo studies have shown that astaxanthin supplementation decreased TG, TC, LDL-C, IL-6, CRP, and LPO; as a result, this improved the antioxidant defense capacity and choroidal blood flow velocity. Astaxanthin also increased SOD activity and decreased PG-E2, LT-B4, NO, IL-8, and IFN- γ production. Astaxanthin has a cardiovascular protective effect in animals.
Astaxanthin has a beneficial effect in preventing and treating eye diseases, such as age-related macular degeneration, glaucoma, cataract, or keratopathy. Astaxanthin crosses the circulatory system’s barrier and the eye’s retina. It builds into the eye’s cell membrane as the only antioxidant, protecting it against damage and free radicals. Astaxanthin, due to antioxidant activity, inhibited ischemia-induced retinal cell death. Supplementation of rats with astaxanthin at a dose of 5 mg/kg/day for eight weeks resulted in decreased retinal apoptosis. It reduced the production of protein carbonyl and NOS-2, which increased renoprotective properties. Astaxanthin counteracts many eye diseases because of its anti-inflammatory, antioxidant properties, and regulation of metabolism.
Astaxanthin blocks neurodegenerative pathways, such as oxidative stress, inflammation, and apoptosis, and can pass through the blood-brain barrier. Supplementation lowers the expression of Bax and Cleaved-caspase-3, which inhibits and reduces neuronal apoptosis and pathological tissue damage. Oral supplementation with astaxanthin in rats after surgery decreased the expression of NF-KB and TNF-α, which resulted in a reduction of cerebral edema and neurological dysfunction. Astaxanthin is considered a multi-target pharmacological agent against neurological disorders, including Parkinson’s disease, Alzheimer’s disease, brain, and spinal cord injuries, neuropathic pain, aging, depression, and autism.
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