Study Of Astaxanthin Esters On Improving Chronic Inflammation Effects And Mechanism Of Insulin Resistance Mice

Chronic inflammation is an significant induction of insulin resistance, as well as the pathological of metabolic diseases. Astaxanthin has been widely known due to its antioxidant and anti-inflammation. Astaxanthin esters is the conjugates of astanxanthin and fatty acide. Currently, reports of Astaxanthin esters were only introduced its antioxidant. Then, This study investigated the improvement and mechanism of astaxanthin esters on chronic inflammation of insulin resistant mice. Results are as follows:Firstly, a series of tests were conducted by the toxiclogical safety evaluation procedures to study food safety of astaxanthin esters. In acute toxicity test, different doses of astaxanthin esters were given to mice by Gavaging. Results showed that the maximum tolerated dose was 21.5 g/kg’bw and it belonged to a nontoxic level according to toxicity criteria. Genitic toxicity studies and 30 d-feeding test were conducted on the basis of acute toxicity test. Genitic toxicity studies included Ames test, mouse bone marrow cells micronucleus test and mouse sperm malformation tests. Ames tests results were negative indicating that astaxanthin esters had no mutagenic activity to the gene of prokaryotic cells in vitro. Furthermore, based on the observation of bone marrow smear in bone marrow cells, the result showed that no genotoxic effects on micronucleus rate, which indicated that astaxanthin esters had no distortion effect on chromosome of somatic cells. In sperm teratogenicity test, the result showed no significant deformity changes were observed on sperm deformity rate, which indicates that astaxanthin esters has no mutations in germ cells in vivo.30 d-feeding tests showed that no obvious changes in body weight, blood cell content and biochemical index compared with the normal group. It indicated that astaxanthin esters have no toxicity effects on growth, peripheral hemogram and function of liver, kidney and myocardial.This paper further verified the anti-inflammation effects of astaxanthin esters.The insulin resistance model was established by feeding high-fat high-fructose diet using male C57BL/6J mice. After 60 days, we found that astaxanthin esters can effectively reduce fat accumulation and fasting glucose levels, alleviate glucose tolerance damage, decrease insulin level and HOMA-IR and increase QUICKI score. It shows that astaxanthin esters can significantly improve insulin resistance of model mice. Insulin resistance and chronic inflammation have closely relationship. Insulin resistance would occur due to the influence of chronic inflammation. Results showed that astaxanthin esters can ameliorate chronic inflammation of insulin resistant mice by improving inflammatory infiltration in adipose tissue, decreasing serum pro-inflammatory cytokines FFA, NO, ROS, TNF-α, IL-6, IL-1β and CRP, and increasing serum anti-inflammatory cytokines including adiponectin and IL-10. Furthermore, astaxanthin esters can also increase anti-inflammation cytokines PPAR-Y, adiponectin and IL-10 mRNA expression, while decrease mRNA expression of pro-inflammation cytokines TNF-a and IL-6. These indicated that astaxanthin esters could improve chronic inflammation by regulating the section of inflammation cytokines.NF-κB pathway is the key pathway of inflammation, this paper used qRT-PCR method to study the key genes mRNA expression in NF-κB pathway in order to investigate the mechanism of improving chronic inflammation by astaxanthin esters. Results showed that astaxanthin esters could remarkably decrease the mRNA expression of IKK β andNF-κB, increase I κB a mRNA expression. These indicated that astaxanthin esters could improve chronic inflammation by inhibiting NF-κB pathway.Chronic innflammation plays an important role in the emergence and development of insulin resistance. Chronic inflammation can activated insulin resistance by IKK/NF-κB, JNK, iNOS/NO and SOCS signaling pathway for inhibiting IRS-1 tyrosine phosphorylation in PI3K-PKB insulin signal transduction pathway. To research the relationship of chronic inflammation and insulin resistance mechanism, key genes expression of those inflammation and PI3K-PKB pathways were detected by qRT-PCR method. Results showed that astaxanthin esters can decrease the key genes expression including IKK β, JNK, iNOS and SOCS3 of inflammation signaling pathway, and improve IRS-1, PI3K, PKB and GLUT4 mRNA impression. It indicated that astaxanthin esters would improve insulin resistance by ameliorate chronic inflammation.Firstly, this paper studied effects and mechanism of astaxanthin esters on chronic inflammation by established insulin resistant model mice, providing theoretical and experimental basis for anti-inflammation of astaxanthin esters. For the first time, this paper also researched food safety of astaxanthin esters refered to toxicological safety evaluation prucedures, the result provide a scientific basis for development and utilization of astaxanthin esters.