astaxanthine and Diabetes-Mellitus

The complex pathophysiological mechanisms behind destructive chronic conditions, including cancer, neurodegenerative diseases, diabetes mellitus, cardiovascular diseases, and hepatic failure urge the need for finding related pivotal dysregulated signaling mediators, as well as multi-target therapeutic agents. In the current study, critical roles of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, as potential therapeutic targets in the pathogenesis of various diseases has been described. This pathway is also interconnected with several downstream inflammatory, oxidative stress, and apoptotic mediators, as dysregulated pathways in chronic diseases. Therefore, identifying novel multi-target agents to attenuate PI3K/Akt, thereby related downstream pathways, is of great importance. Astaxanthin (AST) is a multi-target lipid-soluble keto-carotenoid derived from the varieties of marine organisms, with potential anti-inflammatory, antioxidant and antiapoptotic properties through PI3K/Akt pathway. Nowadays, due to its high nutritional and medicinal value, research on AST is increasing. This review aimed to address PI3K/Akt targeted by AST in several diseases toward clinical applications.

Topics: Animals; Diabetes Mellitus; Humans; Neoplasms; Neurodegenerative Diseases; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Signal Transduction; Xanthophylls

The pathophysiology of diabetic retinopathy (DR) is thought to be influenced by oxidative stress. Astaxanthin (ASX) is a natural product with antioxidant effect, but it is not clear whether its mechanism of inhibiting the development of DR is related to anti-oxidation.. Rats were intraperitoneally injected with streptozotocin (60 mg/kg) to create DR rat models followed by ASX (20 mg/kg) for 45 days. Retinal tissue was examined by Hematoxylin and Eosin staining. By using Enzyme-linked immunosorbent assay (ELISA), 2,7-Dichlorodrhydrofluorescein diace (DCFH-DA) probes, immunohistochemistry and western blot, it was feasible to evaluate the contents of inflammation-related factors (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and macrophage inhibitory cytokine-1 (MIC-1)), oxidative stress-related indicators (glutathione (GSH), malonic dialdehyde (MDA), glutathione peroxidase (GPx), reactive oxygen species (ROS) and Total antioxidant capacity (T-AOC)), antioxidant enzymes (hemoxgenase-1(HO-1) and Quinone Oxidoreductase 1 (NQO1)), and apoptosis-related proteins (Bcl-2, Bcl2 Associated X Protein (BAX), and cleaved-caspase-3). Additionally, antioxidant proteins downstream of the nuclear factor E2 related factors (Nrf-2) pathway, expression levels of Nrf2/ Kelch-like ECH-associated protein 1(Keap 1) pathway-associated proteins, and nuclear and cytoplasmic levels of Nrf2 were assessed using immunohistochemistry, western blot, or quantitative real-time polymerase chain reaction (qRT-PCR).. ASX alleviated retinal tissue damage by increasing overall retina thickness and ganglion cell layer (GCL) cell numbers and exerted the anti-inflammatory, anti-oxidative stress, and anti-apoptosis effects in DR rats. Additionally, ASX could inhibit the expression of Keap1, promote the transport of Nrf2 from cytoplasm to nucleus and facilitate the expressions of HO-1, NQO1, γ-glutamylcysteine synthetase, (γ-GCS) and GPx.. ASX exerted antioxidant effects through Nrf2/keap1 pathway, thereby alleviating apoptosis, inflammation, and oxidative stress in retinal tissues of DR rats.

Topics: Animals; Antioxidants; Diabetes Mellitus; Diabetic Retinopathy; Glutathione; Inflammation; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Oxidative Stress; Rats

Diabetes remains a major health emergency in our entire world, affecting hundreds of millions of people worldwide. In conjunction with its much-dreaded complications (e.g., nephropathy, neuropathy, retinopathy, cardiovascular diseases, etc.) it substantially reduces the quality of life, increases mortality as well as economic burden among patients. Over the years, oxidative stress and inflammation have been highlighted as key players in the development and progression of diabetes and its associated complications. Much research has been devoted, as such, to the role of antioxidants in diabetes. Astaxanthin is a powerful antioxidant found mostly in marine organisms. Over the past years, several studies have demonstrated that astaxanthin could be useful in the treatment and management of diabetes. It has been shown to protect β-cells, neurons as well as several organs including the eyes, kidney, liver, etc. against oxidative injuries experienced during diabetes. Furthermore, it improves glucose and lipid metabolism along with cardiovascular health. Its beneficial effects are exerted through multiple actions on cellular functions. Considering these and the fact that foods and natural products with biological and pharmacological activities are of much interest in the 21st-century food and drug industry, astaxanthin has a bright prospect in the management of diabetes and its complications.

Topics: Antioxidants; Diabetes Mellitus; Humans; Oxidative Stress; Quality of Life; Xanthophylls

To develop hydrophilic astaxanthin with significantly enhanced solubility and stability, astaxanthin polyethylene glycol succinate (APGS) was synthesized by esterification of an astaxanthin succinate diester with polyethylene glycol 1000. The chemical structure of the hydrophilic derivative was confirmed by

Topics: Animals; Diabetes Mellitus; Mice; Polyethylene Glycols; Solubility; Xanthophylls

Obesity and diabetes, risk factors for metabolic syndrome, are characterized by oxidative stress and inflammatory responses. Marine biofunctionals, astaxanthin (Ax) and squalene (SQ), were evaluated for their combined effect. Groups of male KK-A (y) mice were fed high fat/sucrose diet for 4 weeks, supplemented with either 0.1 %Ax, 2 %SQ or 0.1 %Ax + 2 %SQ. In comparison to control, Sod was elevated in only Ax + SQ. However, Gpx was highest in Ax + SQ, indicating the combined antioxidant effect of Ax and SQ. This was supported by elevated mRNA expression of Sod1 and Gpx1. Except adiponectin (elevated in Ax and Ax + SQ), expression of other inflammatory markers was not altered. Blood glucose levels were decreased in SQ and Ax + SQ while liver triglycerides decreased in SQ group. This is the first in vivo study demonstrating combined effects of Ax and SQ resulting in antioxidant effects and modulation of glucose/triglyceride levels. This study highlights the benefit of utilizing Ax and SQ together for management of obesity/diabetes.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Liver; Male; Mice; Mice, Obese; Obesity; Oxidative Stress; Squalene; Triglycerides; Xanthophylls

Diabetes mellitus is a syndrome of impaired insulin secretion/sensitivity and frequently diagnosed by hyperglycemia, lipid abnormalities, and vascular complications. The diabetic 'glucolipotoxicity' also induces immunodepression in patients by redox impairment of immune cells. Astaxanthin (ASTA) is a pinkish-orange carotenoid found in many marine foods (e.g. shrimp, crabs, salmon), which has powerful antioxidant, photoprotective, antitumor, and cardioprotective properties. Aiming for an antioxidant therapy against diabetic immunodepression, we here tested the ability of prophylactic ASTA supplementation (30 days, 20 mg ASTA/kg BW) to oppose the redox impairment observed in isolated lymphocytes from alloxan-induced diabetic Wistar rats. The redox status of lymphocytes were thoroughly screened by measuring: (i) production of superoxide (O(2)(-)), nitric oxide (NO), and hydrogen peroxide (H(2)O(2)); (ii) cytosolic Ca(2+); (iii) indexes of oxidative injury; and (iv) activities of major antioxidant enzymes. Hypolipidemic and antioxidant effects of ASTA in plasma of ASTA-fed/diabetic rats were apparently reflected in the circulating lymphocytes, since lower activities of catalase, restored ratio between glutathione peroxidase and glutathione reductase activities and lower scores of lipid oxidation were concomitantly measured in those immune cells. Noteworthy, lower production of NO and O(2)(-) (precursors of peroxynitrite), and lower cytosolic Ca(2+) indicate a hypothetical antiapoptotic effect of ASTA in diabetic lymphocytes. However, questions are still open regarding the proper ASTA supplementation dose needed to balance efficient antioxidant protection and essential NO/H(2)O(2)-mediated proliferative capacities of diabetic lymphocytes.

Topics: Animals; Antioxidants; Calcium; Cell Proliferation; Diabetes Mellitus; Hydrogen Peroxide; Lymphocytes; Male; Nitric Oxide; Oxidation-Reduction; Rats; Rats, Wistar; Reactive Oxygen Species; Xanthophylls