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. 2023 Mar 24;10:1020950. doi: 10.3389/fnut.2023.1020950

Table 4.

Protective effects of carotenoids against diabetic complications—animal study evidence.

Carotenoid name Administration Experimental design Treatment Duration Results References
Upregulation Downregulation
Lutein and zeaxanthin Oral, diet Transgenic db/db type-2 diabetic mice Formulated diet containing 1% (kCal) of wolfberry 8 weeks 1. Improved the thickness of the whole retina 2. Restored the inner nuclear layer and photoreceptor layer, the integrity of RPE, and the ganglion cell number (81)
Lutein Gastric tube Alloxan-induced mice 0.2 mg/kg/day 14 days Restored retinal and hippocampal levels of GSH and GPx activity compared to control group 1. Reduced serum, retinal and hippocampal levels of MDA 2. Prevention of increase in NFκB activity in the diabetic retina and hippocampus (82)
Zeaxanthin Oral, dietary supplement STZ-induced diabetic rats 0.02% or 0.1% (w/w) zeaxanthin 8 weeks 1. Increased GSH/GPx activity 2. Elevated mitochondrial SOD 1. Inhibited diabetes-induced retinal oxidative damage 2. Prevented diabetes-induced elevation in retinal VEGF and ICAM-1 3. Decreased NFkB activity (83)
Lycopene Oral, solution STZ-induced diabetic rats 20 mg/kg/day 8 weeks 1. Increased level of HDL-C 2. Increased Akt/PKB phosphorylation and SOD activity in diabetic renal tissues 1. Decreased levels of blood urea nitrogen, 24 h urea protein and creatinine. 2. Reduction in serum TC, TG, and LDL-C 3. Decreased levels of MDA content and expression of CTGF (84)
Lycopene Oral, solution STZ-induced diabetic rats 5, 10, and 15 mg/kg/day 10 weeks Increased otal antioxidative capacity and the activities of antioxidants including CAT, SOD, and GPx 1. Decreased FBG 2. Decreased oxidative stress biomarkers incl. GHb, ox-LDL, and MDA 3. Decreased TNF-α and CRP (85)
Astaxanthin Oral, dietary supplement Diabetic db/db mice 0.02% (w/w) astaxanthin 12 weeks 1. Lowered blood glucose level 2. Inhibition of increases in urinary albumin and 8-OHdG 3. Reduced the mesangial area/total glomerular area ratio (86)
Astaxanthin Oral, dietary supplement Diabetic db/db mice with diabetic retinopathy 25 or 50 mg/kg/day 8 weeks 1. Inhibited apoptosis of RGCs 2. Decreased levels of oxidative stress markers, including superoxide anion, MDA, 8-OHdG and MnSOD activity in the retinal tissue (87)
Astaxanthin or lutein Oral, solution STZ-induced diabetic rats 0.6 mg/kg or 3 mg astaxanthin, or 0.5 mg/kg lutein daily 6 weeks Increased levels of antioxidant enzymes (heme oxygenase-1 and peroxiredoxin) 1. Reduced levels of oxidative stress mediators (8-hydroxy-2′-deoxyguanosine, nitrotyrosine, and acrolein) in ocular tissues 2. Reduced levels of inflammatory mediators (ICAM-1, MCP-1, and fractalkine) 3. Reduced activity of the NF-κB (88)

RPE, retinal pigment epithelia; GSH, glutathione; GPx, glutathione peroxidase; MDA, malondialdehyde; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; STZ, streptozotocin; HDL-C, high-density lipoprotein cholesterol; PKB, protein kinase B; SOD, superoxide dismutase; TC, total cholesterol; TG, triglycerides; LDL-C, low-density lipoprotein cholesterol; MDA, malondialdehyde; CTGF, connective tissue growth factor; CAT, catalase; FBG, fasting blood glucose; GHb, glycosylated hemoglobin; ox-LDL, oxidized-LDL; TNF-α, tumor necrosis factor alpha; CRP, C-reactive protein; 8-OHdG, 8-hydroxydeoxyguanosine; RGCs, retinal ganglion cells; MnSOD, manganese superoxide dismutase; ICAM-1, intercellular adhesion molecule-1; MCP-1, monocyte chemoattractant protein-1.