Protective Effects and Mechanisms of Polyethylene Glycol Loxenatide Against Hyperglycemia and Liver Injury in db/db diabetic Mice

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder with insulin resistance and impaired insulin secretion that can cause complications, including liver injury. Polyethylene glycol loxenatide (PEG-Loxe), a glucagon-like peptide-1 (GLP-1) analog, is widely used to treat T2DM. However, its specific glucose-lowering and hepatoprotective mechanisms of action have not been established yet.METHODS: Using a high glucose-induced hepatocyte injury model and a type 2 diabetic db/db mouse model, we assessed PEG-Loxe’s impact on reducing blood glucose and improving liver injury in T2DM and revealed its mechanism.RESULTS: PEG-Loxe treatment significantly reduced body weight and fasting glucose, increased glucose tolerance, improved serum and liver biochemical parameters (glycated hemoglobin, serum insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate aminotransferase), and attenuated hepatic steatosis and liver and pancreatic tissue damages in db/db mice. Additionally, PEG-Loxe considerably inhibited oxidative stress, decreased pro-inflammatory factor (TNF-α, IL-6, and MCP-1) levels, and increased anti-inflammatory factor IL-10 levels. PEG-Loxe possibly inhibits hepatic lipid synthesis, oxidative stress, and inflammatory response by upregulating Sirt1, p-AMPK, and p-ACC expressions in the Sirt1/AMPK/ACC pathway of lipid metabolism, thereby improving T2DM liver injury. PEG-Loxe most likely also promotes GLP-1R expression by inhibiting β-cell apoptosis, which in turn activates the insulin PI3K/AKT pathway to promote insulin synthesis and secretion, thereby exerting hypoglycemic effects. In vitro cellular experiments further confirmed that PEG-Loxe possibly exerts hypoglycemic effects by activating the insulin PI3K/AKT pathway.Conclusion: PEG-Loxe improved liver injury in T2DM probably by activating Sirt1/AMPK/ACC lipid metabolism pathway, and exerted hypoglycemic effects through activation of insulin PI3K/AKT pathway.

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The effect of a fibre extract from the red seaweed, Palmaria palmata, on lipid metabolism and inflammation in healthy adults

Proceedings of The Nutrition Society ◽

10.1017/s0029665120006400 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Zoe Irwin ◽

Emeir M. McSorley ◽

Mary M. Slevin ◽

Lisa Rowan ◽

Paul McMillen ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Metabolism ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Palmaria Palmata ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Markers Of Inflammation ◽

And Oxidative Stress

AbstractEvidence from observational studies indicates that seaweed consumption may reduce the risk of non-communicable diseases such as cardiovascular disease, type two diabetes, and obesity. Accumulating evidence from in vitro and animal studies suggest seaweed have antihyperlipidemic, anti-inflammatory and antioxidant properties which may in part be attributed to the high content of soluble dietary fibre in seaweeds. The viscosity of seaweed fibres is suggested to mediate antihyperlipdiemic effects via the alteration of lipid/bile acid absorption kinetics to decrease low-density lipoprotein cholesterol (LDL). Thus, there is a need to evaluate the efficacy of seaweed derived dietary fibre in the management of dyslipidemia. Therefore, the aim of this study was to determine the effect of a fibre rich extract from Palmaria palmata on the lipid profile as well as markers of inflammation and oxidative stress in healthy adults. A total of 60 healthy participants (30 male and 30 female) aged 20 to 58 years, were assigned to consume the Palmaria palmata fibre extract (5g/day), Synergy-1 and the placebo (maltodextrin) for a duration of 4 weeks with a minimum 4 week washout between each treatment in a double blind, randomised crossover study conducted over 5 months. Fasting concentrations of cholesterol, triglycerides and high-density lipoprotein cholesterol (HDL) were analysed and low-density lipoprotein cholesterol (LDL) and LDL: HDL ratio was calculated. C-reactive protein (CRP) and Ferric Reducing Ability of Plasma (FRAP) were analysed as markers of inflammation and oxidative stress, respectively. Supplementation for 4 weeks with Palmaria palmata resulted in favourable changes to lipid profiles with a reduced LDL:HDL ratio; however intention-to-treat univariate ANCOVA identified no significant difference between the treatment groups over time on any of the lipid profile markers. A non-significant increase in CRP and triglyceride concentration along with lower FRAP was also observed with Palmaria palmata supplementation. Evidence from this study suggests that Palmaria palmata may have effects on lipid metabolism and appears to mobilise triglycerides. More research is needed in individuals with dyslipidaemia to fully elucidate these effects.

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Lactobacillus rhamnosus NCDC17 ameliorates type-2 diabetes by improving gut function, oxidative stress and inflammation in high-fat-diet fed and streptozotocintreated rats

Beneficial Microbes ◽

10.3920/bm2016.0090 ◽

2017 ◽

Vol 8 (2) ◽

pp. 243-255 ◽

Cited By ~ 28

Author(s):

S. Singh ◽

R.K. Sharma ◽

S. Malhotra ◽

R. Pothuraju ◽

U.K. Shandilya

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

High Fat Diet ◽

Lactobacillus Rhamnosus ◽

Density Lipoprotein ◽

Diabetic Rats ◽

Lipoprotein Cholesterol ◽

High Fat ◽

Epididymal Fat

Restoration of dysbiosed gut microbiota through probiotic may have profound effect on type 2 diabetes. In the present study, rats were fed high fat diet (HFD) for 3 weeks and injected with low dose streptozotocin to induce type 2 diabetes. Diabetic rats were then fed Lactobacillus rhamnosus NCDC 17 and L. rhamnosus GG with HFD for six weeks. L. rhamnosus NCDC 17 improved oral glucose tolerance test, biochemical parameters (fasting blood glucose, plasma insulin, glycosylated haemoglobin, free fatty acids, triglycerides, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol), oxidative stress (thiobarbituric acid reactive substance and activities of catalase, superoxide dismutase and glutathione peroxidase in blood and liver), bifidobacteria and lactobacilli in cecum, expression of glucagon like peptide-1 producing genes in cecum, and adiponection in epididymal fat, while decreased propionate proportions (%) in caecum, and expression of tumour necrosis factor-α and interlukin-6 in epididymal fat of diabetic rats as compared to diabetes control group. These findings offered a base for the use of L. rhamnosus NCDC 17 for the improvement and early treatment of type 2 diabetes.

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Protective Effects of Honey-Processed Astragalus on Liver Injury and Gut Microbiota in Mice Induced by Chronic Alcohol Intake

Journal of Food Quality ◽

10.1155/2022/5333691 ◽

2022 ◽

Vol 2022 ◽

pp. 1-12

Author(s):

Jingxuan Zhou ◽

Nanhai Zhang ◽

Liang Zhao ◽

Mohamed Mohamed Soliman ◽

Wei Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Liver Function ◽

Low Density Lipoprotein ◽

Intestinal Flora ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Protective Effects ◽

Factor Α ◽

Antioxidant Markers

Honey-processed Astragalus (HPA) is a mixture of Astragalus and honey, which is a processed product of Chinese medicine. It has the active ingredients of Astragalus and the unique effects of honey. However, the mechanism of HPA for improving alcoholic liver disease (ALD) is not clear. The purpose of this study is to explore the ameliorating effect and mechanism of HPA (4 and 8 g/kg bw) on alcoholic liver injury. Two doses of HPA were orally administered to alcohol-treated mice for four weeks. The results showed that HPA could effectively reduce triglycerides (TG) by 59% and free fat acid (FFA) and total cholesterol (TC) in serum and hepatic were reduced by least 25.9%. HPA could cause a decrease in serum low-density lipoprotein cholesterol (LDL-C) from 0.145 mM to 0.117 mM, and the serum high-density lipoprotein cholesterol (HDL-C) was increased. After alcohol-treated mice were supplemented with HPA, antioxidant markers (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and Glutathione peroxidase (GSH-Px)), liver function index (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)), proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)), and liver tissue were all significantly improved. This is related to the fact that HPA can promote the expression of oxidative stress-related genes and inhibit the expression of inflammation-related genes. In addition, HPA could also regulate the disturbance of the intestinal microflora. In general, HPA could significantly improve the accumulation of serum and liver lipids caused by alcohol and the imbalance of intestinal flora in mice. It could also improve liver function, oxidative stress, and inflammation.

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Differences in lipid metabolism between anagliptin and sitagliptin in patients with type 2 diabetes on statin therapy: a secondary analysis of the REASON trial

Cardiovascular Diabetology ◽

10.1186/s12933-019-0965-3 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 2

Author(s):

Atsuko Chihara ◽

Atsushi Tanaka ◽

Takeshi Morimoto ◽

Mio Sakuma ◽

Michio Shimabukuro ◽

...

Keyword(s):

Type 2 Diabetes ◽

Lipid Metabolism ◽

Statin Therapy ◽

Low Density Lipoprotein ◽

Secondary Analysis ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol

Abstract Background Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain. Aim and methods We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared with those of sitagliptin. The study was a secondary analysis using data obtained from the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. This trial in patients with type 2 diabetes at a high risk of cardiovascular events and on statin therapy showed that anagliptin reduced LDL-C levels to a greater extent than sitagliptin. Cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) markers were measured at baseline and 52 weeks in the study cohort (n = 353). Results There was no significant difference in the changes of campesterol or sitosterol between the two treatment groups (p = 0.85 and 0.55, respectively). Lathosterol concentration was increased significantly at 52 weeks with sitagliptin treatment (baseline, 1.2 ± 0.7 μg/mL vs. 52 weeks, 1.4 ± 1.0 μg/mL, p = 0.02), whereas it did not change in the anagliptin group (baseline, 1.3 ± 0.8 μg/mL vs. 52 weeks, 1.3 ± 0.7 μg/mL, p = 0.99). The difference in absolute change between the two groups showed a borderline significance (p = 0.06). Conclusion These findings suggest that anagliptin reduces LDL-C level by suppressing excess cholesterol synthesis, even in combination with statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. https://clinicaltrials.gov/ct2/show/NCT02330406; registered January 5, 2015.

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Hypoglycemic Agents and Changes in Oxidative Stress Indices, Electrolytes, and Cardiovascular Risk Factors in Type 2 Diabetes

International Journal of Diabetes and Metabolism ◽

10.1159/000500912 ◽

2019 ◽

Vol 25 (3-4) ◽

pp. 118-126

Author(s):

Augusta Chinyere Nsonwu-Anyanwu ◽

Magnus Chinonye Nsonwu ◽

Chinyere Adanna Opara Usoro

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Lipid Peroxidation ◽

Glycemic Control ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Hypoglycemic Agents ◽

Stress Indices ◽

And Oxidative Stress

Background: Metabolic complications of type 2 diabetes (T2DM), including dyslipidemia, electrolyte imbalance, and oxidative stress, have been shown to be modulated by hypoglycemic agents. Objective: The lipid profile, electrolytes, and oxidative stress indices were evaluated in T2DM. Methods: Fifty T2DM patients on metformin (n = 23), insulin (n = 17), and insulin/metformin (n = 10) and 40 controls were studied. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), total antioxidant capacity (TAC), total plasma peroxide (TPP), and total calcium (Ca) values were determined colorimetrically, sodium (Na+) and potassium (K+) levels were determined by flame photometry, chloride (Cl–) and bicarbonate (HCO3–) levels were determined by titration, and low-density lipoprotein cholesterol (LDL-C) levels, the atherogenic index of plasma (AIP), and the oxidative stress index (OSI) were determined by calculation. Data were analyzed using t test, analysis of variance, and Pearson’s correlation at p < 0.05. Results: T2DM patients had higher lipid peroxidation (TPP and OSI), atherogenic lipids (higher LDL-C and AIP and lower HDL-C), and lower antioxidants compared to controls (p < 0.05). T2DM patients with poor glycemic control had higher lipid peroxidation (higher TPP) and atherogenic lipids (TG and AIP) compared to those with good control (p < 0.05). Patients with T2DM for >5 years had higher protein glycosylation (higher HBA1c) and TC compared to those with T2DM for <5 years (p < 0.05). The class of hypoglycemic agent has no effect on the levels of all of the biochemical indices studied (p > 0.05). HDL-C correlated negatively with TG (r = –0.347, p = 0.013), LDL-C (r = –0.322, p = 0.018), and AIP (r = –0.714, p = 0.000) in T2DM. Conclusion: Chronic T2DM and poor glycemic control are associated with reduced antioxidants, lipid peroxidation, and atherogenic dyslipidemia. Different hypoglycemic agents exert no differential effects on the metabolic indices of T2DM studied.

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Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2011/924851 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 34

Author(s):

Qian Zhang ◽

Xinhua Xiao ◽

Kai Feng ◽

Tong Wang ◽

Wenhui Li ◽

...

Keyword(s):

Lipid Metabolism ◽

Protein Kinase ◽

Serum Insulin ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Control Group ◽

Pcr Array ◽

Fasting Serum ◽

Glucose And Lipid Metabolism ◽

Kkay Mice

Berberine is known to improve glucose and lipid metabolism disorders, but the mechanism is still under investigation. In this paper, we explored the effects of berberine on the weight, glucose levels, lipid metabolism, and serum insulin of KKAy mice and investigated its possible glucose and lipid-regulating mechanism. We randomly divided KKAy mice into two groups: berberine group (treated with 250 mg/kg/d berberine) and control group. Fasting blood glucose (FBG), weight, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), and fasting serum insulin were measured in both groups. The oral glucose tolerance test (OGTT) was performed.RT2PCR array gene expression analysis was performed using skeletal muscle of KKAy mice. Our data demonstrated that berberine significantly decreased FBG, area under the curve (AUC), fasting serum insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR) index, TC, and TG, compared with those of control group.RT2profiler PCR array analysis showed that berberine upregulated the expression of glucose transporter 4 (GLUT4), mitogen-activated protein kinase 14 (MAPK14), MAPK8(c-jun N-terminal kinase, JNK), peroxisome proliferator-activated receptorα(PPARα), uncoupling protein 2 (UCP2), and hepatic nuclear factor 4α(HNF4α), whereas it downregulated the expression of PPARγ, CCAAT/enhancer-binding protein (CEBP), PPARγcoactivator 1α(PGC 1α), and resistin. These results suggest that berberine moderates glucose and lipid metabolism through a multipathway mechanism that includes AMP-activated protein kinase-(AMPK-) p38 MAPK-GLUT4, JNK pathway, and PPARαpathway.

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Administration of Lactobacillus paracasei ameliorates type 2 diabetes in mice

Food & Function ◽

10.1039/c8fo00081f ◽

2018 ◽

Vol 9 (7) ◽

pp. 3630-3639 ◽

Cited By ~ 22

Author(s):

Fangfang Dang ◽

Yujun Jiang ◽

Ruili Pan ◽

Yanhong Zhou ◽

Shuang Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Lipid Metabolism ◽

Glucose Metabolism ◽

Lactobacillus Paracasei ◽

Akt Pathway ◽

Diabetic Mice ◽

Diabetes In Mice ◽

Dose Dependent

Lactobacillus paracasei TD062 with high inhibitory activity ameliorated lipid metabolism, oxidative stress, glucose metabolism and the PI3K/Akt pathway in diabetic mice, and the effects were dose-dependent to some extent.

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ESRα Promoter Methylation May Modify the Association Between Lipid Metabolism and Type 2 Diabetes in Chinese Farmers

Frontiers in Public Health ◽

10.3389/fpubh.2021.578134 ◽

2021 ◽

Vol 9 ◽

Author(s):

Guoyu Zhou ◽

Lihua Liu ◽

Xing Li ◽

Xiangbo Hou ◽

Ling Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Lipid Metabolism ◽

Promoter Methylation ◽

Estrogen Receptor Alpha ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Potential Association ◽

And Gender

Objective: This study is aimed to explore the potential association among the estrogen receptor alpha (ESRα) promoter methylation, lipid metabolism and the risk of type 2 diabetes mellitus (T2DM).Methods: A total of 1143 rural residents were recruited randomly from Henan Province, China. The circulating methylation levels in ESRα promoter region were determined by quantitative methylation-specific polymerase chain reaction. Serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and fasting plasma-glucose (FPG) were measured.Results: The ESRα promoter methylation levels were negatively associated with HDL-C levels whether gender stratification was performed (P < 0.05) and positively correlated with LDL-C in men (P < 0.05). Each unit standard deviation (SD) increment in TG was associated with a 43% increase (95% CI: 1.25, 1.64) in the risks of T2DM in all participants, a 36% increase (95% CI: 1.13, 1.64) in the risks of T2DM in men and a 49% increase (95% CI: 1.21, 1.83) in the risks of T2DM in women. Furthermore, each SD increment in HDL-C was associated with a reduction of 25% (OR = 0.75, 95% CI: 0.58, 0.97) in the risks of T2DM in men, and the risk of T2DM in men may be more susceptible to HDL-C than that in women (P for interaction < 0.05). Additionally, we found that the risk of T2DM in participants with lower methylation levels (≤4.07%) were more susceptible to HDL-C (P for interaction < 0.05).Conclusions: These findings suggested that lipid metabolism was associated with ESRα promoter methylation levels and the risk of T2DM. Besides, the levels of ESRα promoter methylation and gender can modify the association of HDL-C and T2DM.

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Effect of Bushen Huoxue Prescription on Cognitive Dysfunction of KK-Ay Type 2 Diabetic Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6656362 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Shao-Yang Zhao ◽

Huan-Huan Zhao ◽

Ting-Ting Hao ◽

Wei-Wei Li ◽

Hao- Guo

Keyword(s):

Cognitive Impairment ◽

Blood Glucose ◽

Morphological Changes ◽

Neuroprotective Effect ◽

Serum Insulin ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Microvascular Damage

Diabetic cognitive impairment is one of the common complications of type 2 diabetes, which can cause neurological and microvascular damage in the brain. Bushen Huoxue prescription (BSHX), a compound Chinese medicine, has been used clinically to treat diabetes-induced cognitive impairment. However, its underlying mechanisms remain unclear. In this study, KK-Ay diabetic model mouse was administered BSHX daily for 12 weeks. Bodyweight, random blood glucose (RBG), and fasting blood glucose (FBG) were measured every 4 weeks. Triglycerides (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting serum insulin (FINS), and Morris water maze were tested after 12 weeks of administration. On the day of sacrifice, the hippocampus was collected for pathological staining and advanced glycation end products (AGEs) analysis to evaluate the neuroprotective effect of BSHX. Our results showed that BSHX treatment significantly ameliorated the T2DM related insults, including the increased bodyweight, blood glucose, TG, insulin levels, AGEs, the reduced HDL-C, the impaired spatial memory, and the neurological impairment. Moreover, Western blot analysis showed that increased expression of receptors of AGEs (RAGEs), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and activation of nuclear factor-κB (NF-κB) in the hippocampus were significantly inhibited by BSHX treatment. These results indicate that BSHX can significantly ameliorate glucose and lipid metabolism dysfunction, reduce the morphological changes in hippocampus tissues, and improve the cognitive function of KK-Ay mice. These protective effects of BSHX may involve regulation of the AGEs/RAGE/NF-κB signaling pathway.

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Differences in the Effects of Anthocyanin Supplementation on Glucose and Lipid Metabolism According to the Structure of the Main Anthocyanin: A Meta-Analysis of Randomized Controlled Trials

Nutrients ◽

10.3390/nu13062003 ◽

2021 ◽

Vol 13 (6) ◽

pp. 2003

Author(s):

Risa Araki ◽

Akira Yada ◽

Hirotsugu Ueda ◽

Kenichi Tominaga ◽

Hiroko Isoda

Keyword(s):

Lipid Metabolism ◽

Meta Analysis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Resistance Index ◽

Lipoprotein Cholesterol ◽

Controlled Trials ◽

Oh Groups ◽

Chemical Structures ◽

Glucose And Lipid Metabolism

The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): −0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: −0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins.

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