|Year : 2018 | Volume
| Issue : 10 | Page : 471-477
Beneficial effects of anthocyanins against diabetes mellitus associated consequences-A mini review
Bhagavathi Sundaram Sivamaruthi1, Periyanaina Kesika1, Kumaresan Subasankari2, Chaiyavat Chaiyasut1
1 Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
2 Centre of Advanced Study in Marine Biology, Annamalai University, Parangipettai 608 502 Tamilnadu, India
|Date of Submission||04-Sep-2018|
|Date of Decision||20-Sep-2018|
|Date of Acceptance||11-Oct-2018|
|Date of Web Publication||29-Oct-2018|
Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200
Source of Support: None, Conflict of Interest: None
Anthocyanins (ACN) are water-soluble pigments, belonging to flavonoids, and are present in almost all fruits, and vegetables at varying concentration. About 635 ACN were distinguished based on the position and number of methoxyl and hydroxyl moieties in the basic structure of ACN. Pelargonidin, cyanidin, delphinidin, malvidin, peonidin, and petunidin are extensively studied anthocyanidins. The absorption, bioavailability, metabolism, pharmacokinetics, molecular mechanism, and analytical techniques of several phytochemicals were described. The biological benefits (antidiabetic, anti-neuro-disorder, anti-cardiovascular diseases, antigastrointestinal diseases, and disorders) of flavonoids and ACN have been reported. Several in vitro, and in vivo reports demonstrated that ACN-rich plant extracts ameliorate the diabetes-associated consequences by reducing the glucose absorption, ROS production, oxidative stress, glomerular angiogenesis, lipid synthesis, and FoxO1 and adipose triglyceride lipase expressions, and improve the insulin secretion, insulin sensitivity, glucose tolerance, glucose uptake, glucose consumption, antioxidant activity. The literature search was made in Scopus, Google Scholar, PubMed using the keywords “anthocyanin” and “diabetes”. The documents were carefully checked for the relevance to the current manuscript and the selection was made without any chronological restriction. The present manuscript summarizes the updated reports on antihyperglycemic properties of ACN.
Keywords: Anthocyanins, Flavonoids, Diabetes, Cyanidin 3-O-β-D-glucoside, Insulin sensitivity
|How to cite this article:|
Sivamaruthi BS, Kesika P, Subasankari K, Chaiyasut C. Beneficial effects of anthocyanins against diabetes mellitus associated consequences-A mini review. Asian Pac J Trop Biomed 2018;8:471-7
|How to cite this URL:|
Sivamaruthi BS, Kesika P, Subasankari K, Chaiyasut C. Beneficial effects of anthocyanins against diabetes mellitus associated consequences-A mini review. Asian Pac J Trop Biomed [serial online] 2018 [cited 2018 Nov 12];8:471-7. Available from: http://www.apjtb.org/text.asp?2018/8/10/471/244137
Foundation project: This work is supported by the Chiang Mai University Grant (CMU grant)
| 1. Introduction|| |
Anthocyanins (ACN) are water-soluble flavonoids and are responsible for the pigmentation in plant tissues. ACN are present in almost all plants at varying concentration, and are widely present in fruits, and vegetables. The distribution of ACN varies based on plant species, cultivars, cultivation area, and climate. The delivery of ACN in Thai rice varieties has been reported. ACN have a heterocyclic, and two benzyl rings, and are connected by a carbon bridge (3n of C). Anthocyanidins are aglycon forms of ACN, architecturally based on the 2-phenylbenzopyrilium or flavylium ion, and consist of methoxyl and hydroxyl groups in different positions. About 635 ACN were identified based on the position and number of methoxyl and hydroxyl moieties. Pelargonidin, cyanidin, delphinidin, malvidin, peonidin, and petunidin are commonly found and most described anthocyanidins in plants,.
ACN are easily susceptible to deprivation, and biological (enzymes), and physical (pH, temperature and light) factors, which can trigger the degradation of ACN. The pH is responsible for color of the ACN and also prompts the degradation. It is known that ACN are more stable in acidic pH compared to alkaline condition. The temperature and oxygen also play a crucial role in ACN stability, and the anaerobic condition comparatively protects the ACN from degradation. Studies on the factors affecting the stability of ACN suggested that heat facilitates the deformation of ACN quickly compared to other physical factors like sonication and microwave,.
The absorption, bioavailability, metabolism, pharmacokinetics, molecular mechanism, and analytical techniques of several phytochemicals were described previously,,,. The biological benefits (antidiabetic, neuroprotective activity, anti-cardiovascular diseases, antioxidant, antimicrobial, anti-gastrointestinal diseases and disorders) of flavonoids, and ACN have been reported,,,,,.
Diabetes mellitus (DM) is a disorder characterized by hyperglycemia due to the fault in insulin secretion and action, and untreated DM condition causes organ damage, and dysfunction. As per the International Diabetes Federation, the prevalence of DM may raise up to 552 million by 2030. The plasma glucose level, glucose tolerance, and HbA1c testing were used to determine the DM. The intravenous insulin infusion is the current eventual treatment for management of the hyperglycemic condition. Several alternative and complementary treatment strategies have been reported to manage and treat the DM condition,. The plant based alternative formulas, treatment methods, and clinical outcomes have been reported to manage the DM,,,,,. The current manuscript summarizes the reported anti-hyperglycemic properties of ACN. The literature search was made in Scopus, Google Scholar, PubMed using the keywords “anthocyanin” and “diabetes”. The documents were carefully checked for the relevance to the current manuscript and the selection was made without any chronological restriction.
| 2. Anti-diabetic properties of ACN|| |
2.1. In vitro studies
Cyanidin-3-O-β-glucoside (C3G) treatment introverted the glycerol and free fatty acid release in mouse embryo 3T3-L1 cells in a dose-dependent manner during hyperglycemic condition, which also increased the adenosine monophosphate (AMP)-activated protein kinase, as well as suppressed the hexosamine biosynthesis and FoxO1 activation and adipose triglyceride lipase expression. The results suggested that ACN controls FoxO1-mediated adipocyte lipolysis, which helps to manage or reduce the diabetes-associated hyperlipidemia. The short-term exposure of 0.125%, w/v ACN-rich berry extract (ARBE) decreased the glucose uptake via both in sodium-dependent and independent manner in human intestinal Caco-2 cells. The ARBE exposure further reduced the transcriptional expression of SGLT1 and GLUT2. The results suggested that the ARBE modified post-prandial glycemia via reducing the glucose transporter expression.
ACN-rich purple corn extract (APCE) treatment reduced the expression of vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1a, and also inhibited the integrin β 3 and platelet endothelial cell adhesion molecule. The study also proved that the APCE exposure interrupted the endothelial tube formation in high glucose condition. The results suggested that APCE supplementation may protect from diabetic nephropathy. Delphinidin inhibits the glucose absorption in a free fatty acid receptor-1 (FFAR-1) dependent way, which also distresses the function of sodium-glucose cotransporter 1. The study revealed that the mechanism behind the ACN delphinidin mediated anti-hyperglycemic effect is associated with FFAR-1.
Recently, Luna-Vital and Gonzalez de Mejia demonstrated that APCE and pure ACN compounds improved the glucose-stimulated insulin secretion and glucose absorption in INS-1E, and HepG2 cells, respectively. Delphinidin-3-O-glucoside and APCE effectively activated the FFAR-1 and stimulated the FFAR1-dependent insulin secretory pathway. APCE significantly reduced the gluconeogenesis by suppressing the PEPCK expression and AMPK phosphorylation in HepG2 cells. The study proved that APCE supplementation could protect the DM associated consequences.
Protocatechuic acid (PCA) exposure normalized the insulin-induced phosphorylation in obese visceral adipose tissue. PCA exposure reduced the activity of protein-tyrosine phosphatase 1B, and phospho-p65 NF-κB and IL-6 in obese visceral adipose tissue. Moreover, it also increased the secretion of adiponectin in normal visceral adipose tissue. The results suggested that ACN treatment reduced the inflammation and insulin resistance in obesity.
3T3-Ll cells exposed to black soybean seed coat extract (BSSCE) showed adipocytes differentiation, which is associated with amplified expression of PPARγ and C/EBPα genes, increased secretion of adiponectin, insulin signaling, and glucose uptake, and reduced TNF-α secretion. The study also found that BSSCE treatment increased the SIRT1, PGC-1α , and UCP-3 genes expressions. It has been proved that BSSCE has potent antidiabetic activity. C3G-rich blood orange variety Moro juice activated the AMP-activated protein kinase and suppressed the mTOR/S6K kinase, which increased the expression of glut 1 and glut 4, as well as glucose tolerance, thereby exhibiting antidiabetic property in BNL CL.2 murine hepatocytes and Hela cells.
ACN-rich mulberry extract (AME) exposure improved the glucose uptake, consumption, glycogen content and diminished the insulin resistance in HepG2 cells. AME exposure inhibited the forkhead box protein O1 (FOXO1), and PPARγ coactivator 1 α (PGC-1α) followed by reducing the glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase activities. AME treatment also improved the protein kinase B (AKT) and glycogen synthase kinase-3β activation. The results suggested that AME exhibited strong anti-hyperglycemic property.
The grape seed procyanidin and C3G inhibited the ROS production, apoptosis, and expression of cleaved caspase-3 and the Bax/Bcl-2 ratio, and enhanced cytochrome c expression. C3G treatment activated the p38 MAPK, thioredoxin 2 and ERK1/2 oxidase in HK-2 cells under high glucose condition. The results revealed that intervention of grape seed procyanidin and C3G protects diabetic nephropathy via antioxidant system [Table 1].
2.2. In vivo studies
ACN-rich grape-bilberry juice (AGBJ) was supplemented to male Fischer rats for ten weeks and assessed for the several risk factors related to obesity-associated diseases. The study proved that AGBJ intervention effectively reduced the serum cholesterol, triglycerides, leptin, and resistin levels while glucose, insulin, adiponectin, adipokines secretion and non-esterified fatty acids were not affected. Moreover, AGBJ improved the polyunsaturated fatty acids content and reduced the saturated fatty acids content in plasma. Collectively, the results revealed that AGBJ could be active against obesity-associated metabolic diseases.
Male Sprague-Dawley rats were fed with a fructose-enriched diet for four weeks and ensured the fructose-induced insulin resistance. ACN-rich black rice extract (ABRE) was supplemented to rats fed with a fructose-enriched diet. ABRE supplementation improved the glucose intolerance and hyperlipidemia but hyperinsulinemia was not reverted. ABRE supplemented rats displayed less oxidative stress, plasma thiobarbituric acid reactive substances and blood oxidized glutathione.
C3G treatment enhanced the secretion of leptin and adiponectin in rat adipocytes and increased the expression of adipocyte-specific gene. The mice fed with C3G showed the increased expression of adiponectin in white adipose tissue. The authors claimed that the changes in activation of AMP-activated protein kinase and decreased AMP: ATP ratio are greatly associated with ACN supplementation, and ACN could be a potent therapeutic agent to prevent the obesity and diabetes.
C3G treatment reduced the glycerol-3-phosphate acyltransferase 1 activity by preventing the translocation of mitochondrial acyl-CoA: glycerol-sn-3-phosphate acyltransferase 1 (mtGPAT1) activity and suppressed the lipid synthesis in hepatoma cell lines. C3G exposure increased the protein kinase C ζ phosphorylation by which prevents the mtGPAT1 activation. C3G supplementation suppressed the hepatic mtGPAT1 activity and reduced the hepatic steatosis in diabetic KKAy mice model.
The supplementation of APCE (10 mg/kg) for eight weeks inhibits the glomerular angiogenesis in mice via VEGF and hypoxia-inducible factor-1 α attenuation. APCE intervention condensed the endothelial proliferation and activation of VEGF receptor 2. The suppression of glomerular angiogenesis in mice by APCE intervention was associated with renal VEGF receptor 2 signaling pathway.
Wistar rats were fed with an ACN-rich extract from Kamchatka honeysuckle berry extract (AKHBE) (2 g/kg) for four weeks along with control and high-fructose diet. AKHBE supplementation increased the mucosal lactase activity, and bacterial α and β glucosidase activity when compared to control. The dietary AKHBE interventions stabilized the plasma triglyceride concentration and atherogenicity, while insulin concentration and resistance, and plasma non-HDL cholesterol were amended when compared to control. AKHBE supplementation improved the glucose metabolic status and gut enzymatic activities in rats fed on a high-fructose diet.
The supplementation of C3G improved the free radical scavenging status and inhibited the mitochondria-mediated apoptotic pathway via inactivation of c-Jun N-terminal kinase pathway and activation of phosphatidylinositol 3-kinase/Akt pathway, which prevented the high glucose-induced hepatic damages in C57BL/J mice.
The supplementation of 30 mg/kg of BSSCE for 30 d reduced the adipose tissue mass in BKS.Cg-Dock7m+/+ Leprdb/J male mice. The study proved that BSSCE have antidiabetic activity by encouraging adipocyte differentiation. The supplementation of ACN-rich blood orange juice (ABOJ), especially rich in C3G, and PCA, activated the AMP-activated protein kinase and suppressed mTOR/S6K. ABOJ intervention improved the glucose tolerance, augmented the glut 1 and glut 4 expressions, and increased the insulin sensitivity in mice. The results suggest that the ABOJ could be used to improve the health status of DM patients.
The supplementation of 50 and 125 mg/kg body weight per day of AME reduced the blood glucose, serum insulin, triglyceride, cholesterol, and leptin level in experimental mice via AKT activation. The intervention of 20 mg/100g of body weight of purple sweet potato extract reduced the blood glucose level significantly and improved the histopathological parameters of pancreatic β cells in alloxan-induced diabetic Wistar rat model.
Pre-administration of blackcurrant polyphenol extract, rich in delphinidin 3-rutinoside, effectively improved the glucose tolerance in rats, which is associated with glucagon-like peptide-1 activation and insulin secretion. The study claimed that the delphinidin 3-rutinoside is responsible for the increased secretion of glucagon-like peptide-1, and blackcurrant polyphenol extract could be used as an adjuvant therapeutic agent to manage the hyperglycemic condition.
The intervention of C3G (20 mg/kg/day for 12 weeks) to db/db mice significantly reduced the body mass, glucose, HbA1c, C-peptide, serum insulin, blood pressure, and kidney related pathological biomarkers such as serum creatinine, urinary albumin, blood urea nitrogen, albumin/creatinine ratio, fibronectin, collagen IV, TGF β 1, matrix metalloprotein 9, TNF α, monocyte chemotactic protein-1, IL-1 α, and α-smooth muscle actin expressions. Further, C3G treatment improved the glutathione (GSH) level in db/db mice. The protective effect of C3G has been attributed to the elevation of GSH in db/db mice, which has been demonstrated using GSH inhibitors. The study suggested that the C3G supplementation could be an effective treatment strategy to prevent or protect diabetes associated nephropathy. Another study by Wei et al. also demonstrated that the supplementation of C3G and grape seed procyanidin protects the db/db mice from diabetic nephropathy by activating the antioxidant system [Table 2].
| 3. Conclusion and future perspectives|| |
Several in vitro and in vivo reports proved that ACN-rich plant extracts ameliorate the diabetes-associated consequences via suppressing the glucose absorption, hepatic steatosis, free fatty acids and glycerol discharge, oxidative stress, glomerular angiogenesis, ROS production, TNF-α secretion, phospho-p65 NF-κB, IL-6, IL-1 β expression, lipid synthesis, and FoxO1 and adipose triglyceride lipase expressions, and improve the insulin secretion, insulin sensitivity, glucose tolerance, glucose uptake, glucose consumption, antioxidant activity.
A cohort study conducted on more than 187 382 human subjects revealed that consumption of ACN-rich whole fruits, such as blueberries, grapes, raisins, prunes, reduced the risk of development of DM while the consumption of fruit juice increased the incidents of DM. Another study suggested that supplementation of protocatechuic acid significantly reduced the insulin resistance, and inflammation in the visceral adipose tissue of obese subjects. The clinical studies to explain the antidiabetic properties of ACN are very limited, and the direct evidence is inadequate. Further, extended clinical studies are required to explore the detailed health benefits of ACN, which helps to develop an effective and alternative treatment procedure to manage or to prevent the incidence of DM.
Conflict of interest statement
The authors declare that there is no conflict of interests.
Authors thankfully acknowledge the Chiang Mai University Grant (CMU grant) for the support and acknowledge the Faculty of Pharmacy, Chiang Mai University, Thailand, for the necessary provision. BSS and PK gratefully acknowledges the CMU Post-Doctoral Fellowship.
This work is supported by the Chiang Mai University Grant (CMU grant).
| References|| |
Chaiyasut C, Sivamaruthi BS, Pengkumsri N, Sirilun S, Peerajan S, Chaiyasut K, et al
. Anthocyanin profile and its antioxidant activity of widely used fruits, vegetables, and flowers in Thailand. Asian J Pharm Clin Res
Sivamaruthi BS, Kesika P, Chaiyasut C. Anthocyanins in Thai rice varieties: Distribution and pharmacological significance. Int Food Res J
Li D, Wang P, Luo Y, Zhao M, Chen F. Health benefits of anthocyanins and molecular mechanisms: Update from recent decade. Crit Rev Food Sci Nutr
Sivamaruthi BS, Kesika P, Chaiyasut C. A comprehensive review on anti-diabetic property of rice bran. Asian Pac J Trop Biomed
Sivamaruthi BS, Pengkumsri N, Saelee M, Kesika P, Sirilun S, Peerajan S, et al
. Impact of physical treatments on stability and radical scavenging capacity of anthocyanidins. Int J Pharm Pharm Sci
McGhie TK, Walton MC. The bioavailability and absorption of anthocyanins: Towards a better understanding. Mol Nutr Food Res
He J, Giusti MM. Anthocyanins: Natural colorants with health-promoting properties. Annu Rev Food Sci Technol
Fernandes I, Faria A, Calhau C, de Freitas V, Mateus N. Bioavailability of anthocyanins and derivatives. J Funct Foods
Welch CR, Wu Q, Simon JE. Recent advances in anthocyanin analysis and characterization. Curr Anal Chem
Ghosh D, Konishi T. Anthocyanins and anthocyanin-rich extracts: Role in diabetes and eye function. Asia Pac J Clin Nutr
de Pascual-Teresa S. Molecular mechanisms involved in the cardiovascular and neuroprotective effects of anthocyanins. Arch Biochem Biophys
Murukan G, Murugan K. Composition of purified anthocyanin isolated from teak and its in vitro
antioxidant activity. Int J Pharm Pharm Sci
Kesika P, Sivamaruthi BS. Beneficial effects and molecular mechanisms of flavonoids against gastrointestinal diseases and disorders. In: Devi KP. (ed.) Recent advances in the molecular mechanism of flavonoids
. India: Studium Press; 2018, p.78-103.
Krishnan VGM, Murukan G, Aswathy JM, Lawarence B, Murugan K. Microbicidal potentiality of purified anthocyanin from in vitro
culture of Clerodendron infortunatum
L. against selected pathogens. Int J Pharm Pharm Sci
Shiyan S, Herlina, Sari LR. Nephroprotective of anthocyanin pigments extract from red cabbage (Brassica oleracea
L. var. Capitata F. rubra) against gentamicin-captopril-induced nephrotoxicity in rats. Asian J Pharm Clin Res
Alam U, Asghar O, Azmi S, Malik RA. General aspects of diabetes mellitus. Handb Clin Neurol
Birdee GS, Yeh G. Complementary and alternative medicine therapies for diabetes: A clinical review. Clin Diab
Pandey A, Tripathi P, Pandey R, Srivatava R, Goswami S. Alternative therapies useful in the management of diabetes: A systematic review. J Pharm Bioallied Sci
Li WL, Zheng HC, Bukuru J, De Kimpe N. Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus. J Ethnopharmacol
Malviya N, Jain S, Malviya S. Antidiabetic potential of medicinal plants. Acta Pol Pharm
Rupeshkumar M, Kavitha K, Haldar PK. Role of herbal plants in the diabetes mellitus therapy: An overview. Int J App Pharm
Chaiyasut C, Sivamaruthi BS, Pengkumsri N, Keapai W, Kesika P, Saelee M, et al
. Germinated Thai black rice extract protects the experimental diabetic rats from oxidative stress and other diabetic related consequences. Pharmaceuticals (Basel
) 2017; 10
(1): E3. Doi: 10.3390/ ph10010003.
Chaiyasut C, Woraharn S, Sivamaruthi BS, Kesika P, Lailerd N, Peerajan S. Lactobacillus fermentum
HP3 mediated fermented Hericium erinaceus
juice as a health promoting food supplement to manage diabetes mellitus. J Evid Based Integr Med
2515690X18765699. Doi: 10.1177/2515690X18765699.
Chaiyasut C, Sivamaruthi BS. Anti-hyperglycemic property of Hericium erinaceus-A
mini review. Asian Pac J Trop Biomed
Guo H, Guo J, Jiang X, Li Z, Ling W. Cyanidin-3-O
-b-glucoside, a typical anthocyanin, exhibits antilipolytic effects in 3T3-L1 adipocytes during hyperglycemia: Involvement of FoxO1-mediated transcription of adipose triglyceride lipase. Food Chem Toxicol
Alzaid F, Cheung H-M, Preedy VR, Sharp PA. Regulation of glucose transporter expression in human intestinal Caco-2 °Cells following exposure to an anthocyanin-rich berry extract. PLoS One
e78932. Doi: 10.1371/journal.pone.0078932.
Kang MK, Lim SS, Lee JY, Yeo KM, Kang YH. Anthocyanin-rich purple corn extract inhibit diabetes-associated glomerular angiogenesis. PLoS One
e79823. Doi: 10.1371/journal.pone.0079823.
Hidalgo J, Teuber S, Morera FJ, Ojeda C, Flores CA, Hidalgo MA, et al
. Delphinidin reduces glucose uptake in mice jejunal tissue and human intestinal cells lines through FFA1/GPR40. Int J Mol Sci
(4): pii: E750. Doi: 10.3390/ijms18040750.
Luna-Vital DA, Gonzalez de Mejia E. Anthocyanins from purple corn activate free fatty acid-receptor 1 and glucokinase enhancing in vitro
insulin secretion and hepatic glucose uptake. PLoS One
e0200449. Doi: 10.1371/journal.pone.0200449.
Ormazabal P, Scazzocchio B, Varì R, Santangelo C, D’Archivio M, Silecchia G, et al
. Effect of protocatechuic acid on insulin responsiveness and inflammation in visceral adipose tissue from obese individuals: Possible role for PTP1B. Int J Obes (Lond
) 2018. In press. Doi: 10.1038/ s41366-018-0075-4.
Matsukawa T, Inaguma T, Han J, Villareal MO, Isoda H. Cyanidin-3-glucoside derived from black soybeans ameliorate type 2 diabetes through the induction of differentiation of preadipocytes into smaller and insulin-sensitive adipocytes. J Nutr Biochem
Talagavadi V, Rapisarda P, Galvano F, Pelicci P, Giorgio M. Cyanidin-3-O
-β-glucoside and protocatechuic acid activate AMPK/mTOR/S6K pathway and improve glucose homeostasis in mice. J Funct Foods
Yan F, Dai G, Zheng X. Mulberry anthocyanin extract ameliorates insulin resistance by regulating PI3K/AKT pathway in HepG2 cells and db/db mice. J Nutr Biochem
Wei J, Wu H, Zhang H, Li F, Chen S, Hou B, et al
. Anthocyanins inhibit high glucose-induced renal tubular cell apoptosis caused by oxidative stress in db/db mice. Int J Mol Med
Graf D, Seifert S, Jaudszus A, Bub A, Watzl B. Anthocyanin-rich juice lowers serum cholesterol, leptin, and resistin and improves plasma fatty acid composition in fischer rats. PLoS One
e66690. Doi: 10.1371/journal.pone.0066690.
Guo H, Ling W, Wang Q, Liu C, Hu Y, Xia M, et al
. Effect of anthocyanin-rich extract from black rice (Oryza sativa
L. indica) on hyperlipidemia and insulin resistance in fructose-fed rats. Plant Foods Hum Nutr
Tsuda T, Ueno Y, Aoki H, Koda T, Horio F, Takahashi N, et al
. Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes. Biochem Biophys Res Commun
Guo H, Li D, Ling W, Feng X, Xia M. Anthocyanin inhibits high glucose-induced hepatic mtGPAT1 activation and prevents fatty acid synthesis through PKCζ. J Lipid Res
Jurgoński A, Juśkiewicz J, Zdunczyk Z. An anthocyanin-rich extract from Kamchatka honeysuckle
increases enzymatic activity within the gut and ameliorates abnormal lipid and glucose metabolism in rats. Nutrition
Jiang X, Tang X, Zhang P, Liu G, Guo H. Cyanidin-3-O
-β-glucoside protects primary mouse hepatocytes against high glucose-induced apoptosis by modulating mitochondrial dysfunction and the PI3K/Akt pathway. Biochem Pharmacol
Wicaksono LA, Yunianta, Widyaningsih TD. Anthocyanin extraction from purple sweet potato cultivar antin-3 (Ipomoea batatas
L.) using maceration, microwave assisted extraction, ultrasonic assisted extraction and their application as anti-hyperglycemic agents in alloxan-induced Wistar rats. Int J Pharmtech Res
Tani T, Nishikawa S, Kato M, Tsuda T. Delphinidin 3-rutinoside-rich blackcurrant extract ameliorates glucose tolerance by increasing the release of glucagon-like peptide-1 secretion. Food Sci Nutr
Qin Y, Zhai Q, Li Y, Cao M, Xu Y, Zhao K, et al
-glucoside ameliorates diabetic nephropathy through regulation of glutathione pool. Biomed Pharmacother
Muraki I, Imamura F, Manson JE, Hu FB, Willett WC, van Dam RM, et al
. Fruit consumption and risk of type 2 diabetes: Results from three prospective longitudinal cohort studies. BMJ
f5001. Doi: 10.1136/bmj.f5001.
[Table 1], [Table 2]