astaxanthine and Colitis

Smart delivery systems with stimuli-responsive capability are able to improve the bioaccessibility through increasing the solubility, physicochemical stability and biocompatibility of bioactive compounds. In this study, the astaxanthin nanoparticles with reactive oxygen species (ROS) and pH dual-response function were design and constructed using poly (propylene sulfide) covalently modified sodium alginate as carriers based on ultrasonic assisted self-assembly strategy. Atomic force microscope and scanning electron microscope analysis showed that the nanoparticles were spherical in shape with a size of around 260 nm. Meanwhile, the astaxanthin nanoparticles showed both pH and ROS stimuli-responsive release characteristics. In vitro cell experiments showed that astaxanthin nanoparticles significantly inhibited the production of ROS and mitochondrial depolarization induced by oxidative stress. In vivo colitis experiment of mice revealed that astaxanthin nanoparticles could significantly relieve colitis, protect the integrity of colon tissue and restore the expression of tight junction proteins ZO-1 and occludin. The abundance of Lactobacillus and Lachnospiraceae, and the ratio of Firmicutes/Bacteroidota of gut microbiota were significantly improved after intervention of the stimuli-responsive astaxanthin nanoparticles. This work provided a simple strategy for constructing ROS/pH dual response delivery system, which provided an experimental basis for improving the oral bioavailability of hydrophobic active compounds.

Topics: Animals; Colitis; Hydrogen-Ion Concentration; Mice; Nanoparticles; Reactive Oxygen Species

Orally targeted strategy of anti-inflammatory agents has attracted tremendous attention for reducing highly health-care costs and enhancing the intervention efficiency of ulcerative colitis (UC). Herein, we developed a new kind of sequence-targeted astaxanthin nanoparticles for UC treatment. Astaxanthin nanoparticles were firstly designed by self-assembly method using (3-carboxypentyl) (triphenyl) phosphonium bromide (TPP)-modified whey protein isolate (WPI)-dextran (DX) conjugates. Subsequently, lipoic acid (LA) modified hyaluronic acid (HA) was coated on the surface of the nanoparticles by double emulsion evaporation method. Exhilaratingly, the constructed sequence-targeted astaxanthin nanoparticle exhibited excellent macrophages and mitochondria targeting ability, with a Pearson's correlation coefficient of 0.84 adstnd 0.92, respectively. In vivo imaging elucidated an obvious accumulation of the sequence-targeted nanoparticles in colon tissues in UC mice. Meanwhile, the reduction stimulus release features of astaxanthin were observed in the presence of 10 mM of glutathione (GSH) at pH 7.4. Most importantly, in vivo experiments indicated that sequence-targeted astaxanthin nanoparticles could markedly alleviate inflammation by moderating the TLR4/MyD88/NF-κB signaling pathway. What's more, the composition of gut microbiota and the production of short chain fatty acid were also improved upon the uptake of sequence-targeted astaxanthin nanoparticles. Our results suggested this novel astaxanthin nanoparticles, which showed sequence-targeted ability and reduction response feature, could be exploited as a promising strategy for effective UC treatment.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Colon; Disease Models, Animal; Mice; Nanoparticles; NF-kappa B

This study aimed to develop a novel astaxanthin nanoparticle using gum arabic (GA) and whey protein powder enriched with milk fat globule membranes (MFGM-WPI) as carriers and to investigate its effect and alleviation mechanism on colitis in mice. We demonstrated that MFGM-GA-astaxanthin could improve the bioaccessibility of astaxanthin and cope with oxidative stress more effectively in a Caco-2 cell model.

Topics: Animals; Caco-2 Cells; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Nanoparticles; Oxidative Stress

As a fat-soluble carotenoid, astaxanthin has excellent antioxidant and anti-inflammation biological activities, but its poor biocompatibility and low stability limit application of astaxanthin in the food industry. In this study, cauliflower-like carriers (CCs) were constructed based on caseinate, chitosan-triphenylphosphonium (TPP) and sodium alginate through an electrostatic self-assembly method to improve the biocompatibility, stability and targeting transport properties of astaxanthin. The smart CCs showed pH-response release and mitochondrial targeted characteristics. In vitro studies demonstrated that the CCs could improve the internalization of astaxanthin, and significantly inhibited the excessive production of reactive oxygen species and the depolarization of mitochondrial membrane potential caused by oxidative stress. In vivo studies revealed that the astaxanthin-loaded CCs could effectively relieve the colitis induced by dextran sodium sulfate and protect the integrity of the colon tissue structure. The astaxanthin-loaded CCs could significantly inhibit the expression of inflammation factors such as interleukin-1β, interleukin-6, tumor necrosis factor alpha, cyclooxygenase-2, myeloperoxidase, inducible nitric oxide synthase, and nitric oxide. Moreover, the astaxanthin-loaded CCs could maintain the expression of zonula occludens-1, increase the abundance of Firmicutes and Lactobacillaceae in the intestine. In a word, the constructed astaxanthin delivery system provided a potential application for the oral uptake hydrophobic bio-activator in intervention of ulcerative colitis.

Topics: Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Humans; Inflammation; Xanthophylls

Astaxanthin (Ax) with a strong antioxidant activity is beneficial to human health, but its application is limited by its highly unsaturated structure and poor water-solubility. Ax-enriched colon targeted alginate particles (Ax-Alg) was prepared by high-pressure spraying and ionic gelation, and most of particles was in the range of 0.5-3.2 μm in a diameter. The in vitro models showed that Ax-Alg can maintain the structural integrity in the different conditions (pH, heat and ion). In addition, Ax-Alg can well tolerate the conditions in the mouth, stomach and small intestine and reach the colon where Ax was released due to fermentation of gut microbiota. Mice experiment showed that Ax-Alg reduced dextran sulfate sodium-induced colitis, involving weight loss, disease activity index, colonic mucosal integrity and inflammation, and oxidative damage. On the other hand, Ax-Alg regulated the gut microbiota composition and reduced the abundances of Bacteroidetes members that had positive correlation with ulcerative colitis. Ax-Alg had better effect on the treatment of ulcerative colitis than oil-in-water emulsion, which can be attributed to the synergistic effect of Ax and alginate. This study can be helpful for the application of colon-targeted delivery system in the foods and treatment of colon diseases.

Topics: Alginates; Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Mice; Microspheres; Xanthophylls

Astaxanthin (AX) is one of the marine carotenoid pigments, which possess powerful biological antioxidant, anti-inflammatory and anti-cancer properties. The purpose of this study is to investigate possible inhibitory effect of AX against inflammation-related mouse colon carcinogenesis and dextran sulfate sodium (DSS)-induced colitis in male ICR mice. We conducted two different experiments. In the first experiment, we evaluated the effects of AX at three dose levels, 50, 100 and 200 ppm in diet, on colitis-associated colon carcinogenesis induced by azoxymethane (AOM)/DSS in mice. In the second, the effects of the AX (100 and 200 ppm) in diet on DSS-induced colitis were determined. We found that dietary AX significantly inhibited the occurrence of colonic mucosal ulcers, dysplastic crypts, and colonic adenocarcinoma at week 20. AX-feeding suppressed expression of inflammatory cytokines, including nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α and interleukin (IL)-1β, inhibited proliferation, and induced apoptosis in the colonic adenocarcinomas. Feeding with 200 ppm AX, but not 100 ppm, significantly inhibited the development of DSS-induced colitis. AX feeding (200 ppm in diet) also lowered the protein expression of NF-κB, and the mRNA expression of inflammatory cytokines, including IL-1β, IL-6, and cyclooxygenase (COX)-2. Our results suggest that the dietary AX suppresses the colitis and colitis-related colon carcinogenesis in mice, partly through inhibition of the expression of inflammatory cytokine and proliferation. Our findings suggest that AX is one of the candidates for prevention of colitis and inflammation-associated colon carcinogenesis in humans.

Topics: Adenocarcinoma; Animals; Apoptosis; Azoxymethane; Colitis; Colonic Neoplasms; Cyclooxygenase 2; Cytokines; Dextran Sulfate; Dietary Supplements; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred ICR; NF-kappa B; Tumor Necrosis Factor-alpha; Xanthophylls