Antidiabetic efficacy of Trifolium alexandrinum extracts hesperetin and quercetin in ameliorating carbohydrate metabolism and activating IR and AMPK signaling in the pancreatic tissues of diabetic rats

Abdou, Heba M.; Hamaad, Fatma A.; Ali, Esraa Y.; Ghoneum, Mamdooh

doi:10.1016/j.biopha.2022.112838

Cited by 22 publications

(22 citation statements)

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“…We performed a screen in PubMed with the key word naringin, chlorogenic acid, quercetin, STZ-induced diabetic rat and we found that in the majority of the papers, naringin was used at 25 to 50 mg/kg, quercetin at 25 to 100 mg/kg, and chlorogenic acid at 10 to 20 mg/kg. We decided then, based on this literature, to use the most cited concentration, meaning naringin (50 mg/kg), chlorogenic acid (10 mg/kg), and quercetin (50 mg/kg) [ 33 , 34 , 35 , 36 , 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

“…Phenolic compounds in foods such as naringin, quercetin, and chlorogenic acid has been found in a variety of herbs and fruits. These compounds were reported as having important antioxidant and anti-diabetic properties in several in vivo studies [ 33 , 34 , 35 , 36 , 37 , 38 ]. The aim of this study is to develop a new preventive and therapeutic possibility with polyphenols constituted by naringin, chlorogenic acid, and quercetin combination (NCQ) to prevent diabetic fibrosis using streptozotocin-induced diabetic aged rats.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of the Renal Protective Effect of Combined Dietary Polyphenols in Streptozotocin-Induced Diabetic Aged Rats

et al. 2022

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Natural polyphenols are widely reported to have a large range of pharmacological properties, especially antioxidant activities and free radical scavenging capacities. In this study, we investigate the effects of naringin, chlorogenic acid, and quercetin mixtures (NCQ) on renal fibrosis in streptozotocin (STZ)-induced diabetic aged rats and its underlying mechanisms for ten consecutive weeks. The oxidative defense system in the kidneys of treated rats was found to be improved. Several biomarkers were investigated including the blood urea nitrogen, creatinine, and uric acid. Moreover, antioxidant parameters were evaluated and we found that superoxide dismutase, catalase, glutathione peroxidase, Na+-K+-ATPase activities, the nitric oxide production, the protein carbonyl, the advanced oxidation protein products, lipid peroxidation, and reduced glutathione levels were all significantly balanced and close to control values. In addition, NCQ restored renal injuries and fibrosis as assessed by histological method and molecular biology investigation of the matrix metalloproteinase, the transforming growth factor-beta TGF-β, the tumor necrosis factor TNFα, and p53 expression. Our study proposes the NCQ combination as potential plant-derived bioactive compounds to prevent diabetic nephropathy.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Investigation of the Renal Protective Effect of Combined Dietary Polyphenols in Streptozotocin-Induced Diabetic Aged Rats

et al. 2022

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“…Quercetin, a major constituent of many traditional Chinese medicines, has certain anti-tumor and anti-platelet aggregation effects. It is a flavonol compound with multiple biological activities, which can exert antioxidant effects by activating the NrF-2-ARE pathway or by promoting the expressions of antioxidant proteins (CAT and SOD) to improve the symptoms of several diseases, including neurodegenerative diseases, tumors, inflammatory diseases, obesity and diabetes ( Wang et al, 2013 ; Kumar et al, 2016 ; Mukhopadhyay et al, 2018 ; Yarahmadi et al, 2018 ; Ebrahimpour et al, 2020 ; Abdou et al, 2022 ). Quercetin suppresses inflammation by reducing the expressions of pro-inflammatory factors, including IL-6 and IL-1β ( Cheng et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Quercetin targets VCAM1 to prevent diabetic cerebrovascular endothelial cell injury

Huang

Lin

Sun

et al. 2022

Front. Aging Neurosci.

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IntroductionEndothelial cells play important roles in neurodegenerative diseases caused by diabetes, therefore, we aimed at investigating the mechanisms through which endothelial cells are involved in diabetes development.MethodsSingle cell analysis was performed to identify the major endothelial cell subtypes in cardiovascular tissues that are involved in diabetes development. A cell-cell communication approach was then used to identify ligand-receptor interaction pairs between these cell types. Differential expression analysis between the two experimental groups [standard chow diet group and diabetogenic diet with cholesterol (DDC) group] was used to identify diabetes-related differentially expressed genes (DEGs). The upregulated genes were used to identify candidate ligands or receptors, as well as the corresponding cell types. Cell trajectory inference was performed to identify the stage of cell development and changes in expression of candidate ligands or receptors during cell development. Gene set enrichment analysis (GSEA) was conducted to investigate the biological functions of genes of purpose. Finally, molecular dynamics simulations (MDSs) were used to predict potential drugs with the ability to target the proteins of purpose.ResultsSeven cell types, including five endothelial cell subtypes (EC_1, EC_2, EC_3, EC_4, and EC_EndMT), were identified from endothelial cell-enriched single cell samples from the heart and aorta of mice. Cell-cell communication analysis revealed the potential ligand-receptor interactions between these cell types while five important ligand-receptor-associated genes, including Fn1, Vcam1, Fbn1, Col4a1, and Col4a2, were established by differential expression analysis. Among them, Vcam1 is mainly expressed in EC_EndMT and is involved in interactions between EC_EndMT and other cells. Cell trajectory extrapolation analysis revealed a shift from EC_2/EC_4 to EC_EndMT and a shift from EC_EndMT to EC_3/EC_1 during the progression of diabetes. GSEA analysis revealed that upregulation of VCAM1 may have inhibitory effects on cell growth and energy metabolism.ConclusionEC_EndMT subtypes have a complex role in neurodegenerative diseases caused by diabetes. Through mechanisms involved in cell-cell communication, Vcam1 may play an important role in dysregulation of biological functions of EC_ EndMT. Molecular docking results of the quercetin-VCAM1 complex suggest that quercetin may be an effective drug for targeting this protein.

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“…Hst also downregulated PI3 kinase activity whereas GLUT4, IRS, and AKT were upregulated in L6 myotubes pointing to the possible overlapping with the insulin signaling pathway. 39 Importantly, in a randomized, double-blind, placebo-controlled crossover study, the combination of trans-resveratrol and Hst reversed IR and improved dysglycemia and low-grade inflammation in obese subjects. 40 However, the prevention and reversal of early T2DM with this combination needs to be evaluated in further studies.…”

Section: L6 Cellmentioning

confidence: 99%

“…Oral intake of Hst (50 mg/kg/day) daily for 4 weeks considerably improved serum glucose, insulin, glucagon, liver function enzymes, hepatic glycogen, antioxidant enzymes, and oxidative stress indicators in diabetic rats. Furthermore, Hst treatments extract remedied IR by altering insulin receptors, phosphatidylinositol 3-kinase (PI3K), and AMP-activated protein kinase (AMPK) signaling pathways . Importantly, in a randomized, double-blind, placebo-controlled crossover study, the combination of trans-resveratrol and Hst reversed IR and improved dysglycemia and low-grade inflammation in obese subjects .…”

Section: Therapeutic Mechanisms Of Hesperetin On Diabetes and Related...mentioning

confidence: 99%

Hesperetin, a Promising Treatment Option for Diabetes and Related Complications: A Literature Review

Yang

Wang

et al. 2022

J. Agric. Food Chem.

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The morbidity and mortality of diabetes have increased dramatically in recent decades. Novel strategies for treating diabetes and its complications with minimal side effects are in urgent need. New monomeric molecules extracted from herbal medicine, which is a form of alternative medicine, are being sought as drug candidates for the treatment of diabetes and its complications. Hesperetin (Hst), a citrus flavonoid, is of increasing interest in scientific studies recently due to its properties in combating diabetes and its complications, whereas existing studies are scattered and unsystematic. Here, we summarized the literature studies over the last 10 years to review the potential therapeutic role of Hst in the prevention and mitigation of diabetes and its complications, intending to provide promising strategies for the clinical management of diabetes and its complications.

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Antidiabetic efficacy of Trifolium alexandrinum extracts hesperetin and quercetin in ameliorating carbohydrate metabolism and activating IR and AMPK signaling in the pancreatic tissues of diabetic rats

Cited by 22 publications

References 68 publications

Investigation of the Renal Protective Effect of Combined Dietary Polyphenols in Streptozotocin-Induced Diabetic Aged Rats

Investigation of the Renal Protective Effect of Combined Dietary Polyphenols in Streptozotocin-Induced Diabetic Aged Rats

Quercetin targets VCAM1 to prevent diabetic cerebrovascular endothelial cell injury

Hesperetin, a Promising Treatment Option for Diabetes and Related Complications: A Literature Review

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