Table 2. An Overview of Studies Involved in Antidiabetic Effect of Acylated Anthocyanins and Comparison of Potential Antidiabetic Effects between Nonacylated and Acylated Anthocyaninsa,b.
| Source of anthocyanins | Main anthocyanin(s) | Model | Effects |
|---|---|---|---|
| The potential antidiabetic effects of acylated anthocyanins | |||
| Acylated anthocyanins extract from purple sweet potato (Ipomoea batatas)79 | Cya-3-(6″-caf-6′′′-hba-sop)-5-glc, peo-3-(6″,6′′′-dicaf-sop)-5-glc, peo-3-(6″-caf-6′′′-p-hba-sop)-5-glc, peo-3-(6″-caf-6′′′-fer-sop)-5-glc | Enzyme inhibition study; human liver cell line HepG2 cells | Inhibited α-amylase, α-glucosidase, and xanthine oxidase; phenolic compound but not anthocyanin faction induced the transcription factor Nrf2 and Nrf2 target gene Gclc |
| Acylated anthocyanins extract from purple sweet potato (Ipomoea batatas)118 | Not available | 3T3-L1 adipocytes | Suppressed leptin secretion. Exerted anti-inflammatory, lipolytic effects on adipocytes and radical scavenging and reducing activity |
| Diacylated anthocyanin extracts from purple sweet potatoes (Ipomoea batatas L. cultivar Eshu No. 8)39 | Peo-3-(6′-caf-6′′-hba-sop)-5-glc, peo-3-(6′-caffeoyl-6′′-fer-sop)-5-glc | SD rats. 80 and 160 mg/kg. One dose | Decreased postprandial blood glucose |
| Purple sweet potato (cultivar ‘NingZi No. 2’) anthocyanin extract119 | Peo-3-caf-sop-5-glc, peo-3- (6′′,6′′′-dicaf-sop)-5-glc, peo-3-caf-hba-sop-5-glc, peo-3-(6′′-caf-6′′′-fer-sop)-5-glc, cya3-(6′′-caf-6′′′-fersop)-5-glc | HFD-indued obese SD rat; 100–400 mg/kg bodyweight; 6 weeks | Decreased adipocyte number and size of adipose tissue |
| Decreased glucose, triglyceride, and total cholesterol levels | |||
| Reduced the level of ROS and inhibited the receptor of AGE products and thioredoxin interacting protein in the hypothalamus | |||
| Preserved the leptin signaling capability, decreased in hypothalamic AMPK activity | |||
| Anthocyanin extract from purple sweet potato (Ipomoea batatas)74 | Peo-3-(6-caf-glc-β-glc)-5-glc, peo-3 -(2-(6-caf-glc)-6-caf-glc)-5-glc, peo-3-(2-(6-fer-glc)-6-caf-glcp)-5-glc, cya-3-(6-cou)-glc | HFD-induced obese C57BL/6 mice; 700 mg/kg/day; 20 weeks | Ameliorated obesity and liver injuries. Blocked hepatic oxidative stress. Restored NAD+ level in liver |
| Suppressed the NF-κBp65 nuclear translocation, NOD1/2 signaling, the NLRP3 inflammasome activation and inflammation-related genes (TNF-α, MCP-1, and IL-1) in liver | |||
| Anthocyanin extract from purple sweet potato (Ipomoea batatas)120 | Peo-3-(6-caf-glc-β-glc)-5-glc, peo-3 -(2-(6-caf-glc)-6-caf-glc)-5-glc, peo-3-(2-(6-fer-glc)-6-caf-glc)-5-glc, cya-3-(6-cou)-glc | HFD-induced obese C57BL/6 mice; 500 mg/kg/day; 32 weeks | Alleviated the cognitive impairment |
| Decreased the expression of Iba1, TNF-α, IL-1β, SOCS3, galectin-3 in hippocampus | |||
| Increased insulin signaling molecules including the p-IRS1 (Tyr608), PI3K p110α and p-AKT (Ser473) | |||
| Increased Bcl-2 expression and diminished the Bak and the cleaved-caspase 3 expressions in hippocampus | |||
| Anthocyanin extract from purple sweet potato (Ipomoea batatas)50 | Peo-3-(6-caf-glc-β-glc)-5-glc, peo-3 -(2-(6-caf-glc-6-caf-glc)-5-glc, peo-3-(2-(6-fer-glc)-6-caf-glc)-5-glc, cya-3-(6-cou)-glc | HFD-induced obese ICR mice; 200 mg/kg per day;4 weeks | Reduced weight gain and hepatic triglyceride accumulation and improved serum lipid parameters |
| Increased the phosphorylation of AMPK and ACC in the liver | |||
| Anthocyanin extract from purple sweet potato (Ipomoea batatas)45 | Cya- and peo-derived acylated anthocyanins | HFD-induced obese ICR mice; 700 mg/kg/day; 20 weeks | Improved the fasting blood glucose level, glucose, insulin tolerance and oxidative-stress-mediated endoplasmic reticulum stress |
| Suppressed ROS production and GSH and antioxidant enzymes’ activities. Suppressed the JNK1and Ikb kinase β activation and NF-κB p65 nuclear translocation | |||
| Restored the impairment of the insulin receptor substrate-1/phosphoinositide 3 kinase/protein kinase B (AKT) insulin signaling in the livers | |||
| Anthocyanin extract from purple sweet potato (Ipomoea batatas)48 | Cya-3-sop-5-glc, peo-3-sop-5-glc, cya-3-hba-sop-5-glc, peo-3-hba-sop-5-glc, cya-3-(6″-fer- sop)-5-glc, peo-3-(6″-fer-sop)-5-glc, cya-3-caff-hba-sop-5-glc, cya-3-(6″-caff-sop)-5-glc, cya-3-(6″-caf-6″′-fer-sop)-5-glc, peo-3-caf-hba-sop-5-glc, peo-3-caf-sop-5-glc, peo-3-(6″-caf-6″′-fer-sop)-5-glc, Peo-3-(6″-hba-6″′-fer-sop)-5-glc | HFD and streptozotocin- induced obese ICR mice; 500 mg/kg body weight; 12 weeks | Activated AMPK in liver |
| Increased GLUT4, glucokinase, and insulin receptor α in liver | |||
| Upregulated glycolysis key genes (Pfk and Pkm) | |||
| Downregulated gluconeogenic genes (G6pase and Pepck). | |||
| Anthocyanin extract from Blue Congo potatoes121 | Acylated anthocyanins dominant by pet-3-cou-rut-5-glc | Streptozotocin- induced diabetic Wistar rats; 165 mg/kg bodyweight; 2 weeks | Lowered blood glucose, glycated hemoglobin, malondialdehyde levels in plasma |
| Restored antioxidant enzyme activities | |||
| Improved glucose tolerance | |||
| Inhibited oxidative modified proteins OMP, AGE, and advanced oxidation protein products formation in plasma | |||
| Acylated anthocyanin extract from purple potato (Solanum tuberosum L. var. “Synkeä Sakari”)122 | Acylated anthocyanins dominated by pet-cou-rut-glc and peo-cou-rut-glc | 17 healthy volunteers; postprandial study; a meal containing acylated anthocyanins (152 mg) | Acylated anthocyanin extract alleviates postprandial glycemia and insulinemia and affects postprandial inflammation |
| Anthocyanin extract from black goji berry (Lycium ruthenicum)75 | Pet-3-rut-cou-5-glc as the main anthocyanin | HFD and vitamin-D3- induced atherosclerosis rat, 50–200 mg/kg body weight; 8 weeks | Decreased total glyceride, total cholesterol, low density lipoprotein, TNF-α, IL-6 levels, and atherogenic index and increased HDL-C concentrations |
| Upregulated NF-κB, VCAM-1, and CYP7A1, and downregulated SREBP-2 | |||
| Anthocyanin extract from black goji berry (Lycium ruthenicum)53 | Del-3–6″-rha-glc-5-glc, pet-3-rut-cou-5-glc, pet-3-rut-caf-5-glc, pet-3–6-cou-rha-pyr)-glc-5-glc | HFD-induced insulin resistance C57BL/6J mice; 50–200 mg/kg body weight; 12 weeks | Decreased the weight gain, hepatic lipid, dyslipidemia, inflammation, and oxidative stress |
| Inactivated TLR4/NF-κB/JNK in the liver tissues and ameliorated oxidative stress and insulin resistance by activating the Nrf2/HO-1/NQO1 and IRS-1/AKT pathways | |||
| Comparison of potential antidiabetic effects between nonacylated and acylated anthocyanins | |||
| Pure nonacylated anthocyanins and diacylated anthocyanins38 | Cya-3-(2-(6-fer-glc)-6-caf-glc)-5-glc, cya and peo-3-(2-(6-fer-glc)-6-caf-glc)-5-glc, pg-3-(2-(6–3-glc-caf)-glc)-6-caf-glc)-5-glc, pg-3-(2-(6-caf-glc)-6-caf-glc)-5-glc, pg, cya, and peo-3-(2-glc-glc)-5-glc-3-sop-5-glc | Enzyme inhibition study | Diacylated anthocyanin showed the best ability to inhibit α-glucosidase |
| Nonacylated anthocyanin extracts from (V. corymbosum L. × V. angustifolium Aiton.; V. ashei Reade) berries; Monoacylated and diacylated extracts from purple sweet potatoes (Ipomoea batatas cultivar Eshu No. 8)39 | Del-, cya-, pet-, peo-, and mal-3-gal, glc, ara; cy-, pet-, and peo-3-hba-sop-5-glc; cy and peo-3-(6′′-caf-sop)-5-glc; cya and peo-fer-sop-5-glc; cya-3-caf-sop-5-glc; peo-3-(6′-caf-6′′-hba-sop)-5-glc; peo-3-(6′-caffeoyl-6′′-fer-sop)-5-glc | Enzyme inhibition study | Diacylated anthocyanin extracts showed the highest inhibition ability of α-amylase and α-glucosidase than monoacylated anthocyanin extracts and deacylated anthocyanin extract |
| Acylated anthocyanin extract from purple carrot and pure cya-3-glc and del-3-rut54 | Cya-3-(2″-xyl-6-glc-gal), cya-3-(2′′-xyl-gal), cya-3-(2′′-xylose-6′′-sin-glc-gal, cya-3-(2′′-xyl-6′′-fer-glc-gal, cya-3-(2′′-xyl-6′′(4-cou)-glc-gal | Wistar rats; Single intragastric doses | Acylated anthocyanin induced highest level of AKT phosphorylation in aorta than cya-3-glc and del-3-rut |
| Nonacylated anthocyanin extract from bilberry (Vaccinium myrtillus) and acylated anthocyanin extract from purple potato (Solanum tuberosum var. “Synkeä Sakari”)58 | Nonacylated anthocyanins dominated by del-3-gal, del-3-glc, cya-3-gal, del-3-ara, cya-3-glc; | Zucker diabetic fatty rats; daily doses of 25–50 mg/kg body weight; 8 weeks | Both anthocyanin extracts decreased the levels of plasma glucose, branched-chain amino acids, and improved lipid profiles. Acylated anthocyanin extract increased the glutamine/glutamate ratio and decreased the levels of glycerol and metabolites involved in glycolysis. Acylated anthocyanin extract decreased the hepatic TBC1D1 and G6PC mRNA levels |
| Acylated anthocyanins dominated by pet-cou-rut-glc and peo-cou-rut-glc | |||
| Nonacylated anthocyanin extract from bilberry (Vaccinium myrtillus) and acylated anthocyanin extract from purple potato (Solanum tuberosum var. “Synkeä Sakari”)57 | Nonacylated anthocyanins dominated by del-3-gal, del-3-glc, cya-3-gal, del-3-ara, cya-3-glc; | Zucker diabetic fatty rats; daily doses of 25–50 mg/kg body weight; 8 weeks | Both anthocyanin extracts restored the levels of metabolites (glucose, lactate, alanine, and pyruvate) and expression of genes (G6pac, Pck1, Pklr, and Gck) involved in glycolysis and gluconeogenesis. Acylated anthocyanin extract decreased the hepatic glutamine level. Nonacylated anthocyanin extract regulated the expression of Mgat4a, Gstm6, and Lpl, whereas acylated anthocyanin extract modified the expression of Mgat4a, Jun, Fos, and Egr1 |
| Acylated anthocyanins dominated by pet-cou-rut-glc and peo-cou-rut-glc | |||
a
Note: Anthocyanidins: cya, cyanidin; del, delphinidin; mv, malvidin; pg, pelargonidin; peo, peonidin; pet, petunidin. Acyl moieties: ace, acetyl; caf, caffeoyl; cou, coumaroyl; hba, hydroxybenzoyl; mal, malonyl; oxa, oxaloyl; sin, sinapoyl; suc, succinyl; pyr, pyranosyl. Sugar moieties: glc, glucopyranoside; gal, galactoside; rut, rutinoside; sop, sophoroside; xyl, xyloside.
b
Abbreviations: ACC, acetyl-CoA carboxylase; AKT, protein kinase B; AMPK, AMP-activating protein kinase; Bcl-2, B-cell lymphoma 2; CPT, carnitine palmitoyltransferase; CYP7A1, cytochrome P450 family 7 subfamily A member 1; C/EBPα, CCAAT enhancer binding protein α; FAS, fatty acid synthase; FOXO1, forkhead box protein O1; Gclc, glutamate–cysteine ligase catalytic subunit; GSK3, Glycogen synthase kinase-3; GLUT, glucose transporter; G6pase, Glucose 6-phosphatase; HbA1c, hemoglobin A1c; HFD, high-fat diet; HMG-CoA, 3-hydroxy-3-methylglutaryl-CoA; HO-1, Heme oxygenase 1; IL, interleukin; IRS-1, Insulin receptor substrate 1; mtGPAT1, mitochondria glycerol-3-phosphate acyltransferase 1; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-κB; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; Nrf2, nuclear factor-erythroid factor 2-related factor 2; NOD, nucleotide-binding oligomerization domain; NQO1, NAD(P)H quinone dehydrogenase 1; SOCS3, suppressor of cytokine signaling 3; SREBP-2, sterol regulatory element-binding protein 2; TNF, tumor necrosis factor; PEPCK, Phosphoenolpyruvate carboxykinase; PPARγ, peroxisome proliferator-activated receptor γ; VCAM-1, vascular cell adhesion protein 1.