The Role of Plant-Derived Compounds in Managing Diabetes Mellitus: A Review of Literature from 2014 To 2019

2020 ◽  
Vol 28 ◽  
Author(s):  
Heba A.S. El-Nashar ◽  
Nada M. Mostafa ◽  
Mohamed El-Shazly ◽  
Omayma A. Eldahshan
Keyword(s):  
Diabetes Mellitus ◽  
Glycogen Synthase ◽  
Direct Action ◽  
Tyrosine Phosphatase ◽  
Natural Compounds ◽  
Antidiabetic Activity ◽  
Peroxisome Proliferator ◽  
Dipeptidyl Peptidase 4 ◽  
Glut4 Expression ◽  
Sensitizing Effect

Background:: Diabetes mellitus (DM) represents a global health problem characterized by hyperglycemia due to insufficient insulin secretion or failure of insulin activity. There is an imperative need for the discovery of alternative therapeutic agents that overcome the drawbacks of the current synthetic antidiabetic drugs. Objectives:: This review critically summarizes the reports on the known and novel natural compounds including alkaloids, flavonoids, and saponins with a potent antidiabetic activity that were recently published from 2014 to 2019. We discussed the underlying mechanisms of action that put these compounds in the category of effective antidiabetic candidates. Methods: Information was obtained from Google Scholar, Scirus, PubMed, and Science Direct. Discussion and Conclusion:: The reported natural compounds showed promising antidiabetic activity through different mechanisms such as the inhibition of α-amylase, α-glucosidase, insulin-sensitizing effect, direct action on protein tyrosine phosphatase 1B (PTP1B), peroxisome proliferator-activated receptors (PPARs), GLUT4 expression, insulin receptor substrate- 1 (IRS-1) and glycogen synthase kinase-3β (GSK-3β) as well as dipeptidyl peptidase-4 (DPP-4) enzyme. Some compounds inhibited the formation of advanced glycation end products (AGEs). Other compounds prevented the risk of diabetic complications such as cardiovascular diseases, retinopathy, and nephropathy. This review provides a critical overview of the most recent discoveries of antidiabetic agents from natural sources. This overview could help researchers to focus on the most prominent candidates aiming to develop new drug leads.

A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Jessica Lynn ◽  
Mingi Park ◽  
Christiana Ogunwale ◽  
George K. Acquaah-Mensah
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Insulin Receptors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Main Component ◽  
The Impact

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.

scholarly journals Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4

2019 ◽  
Vol 20 (3) ◽  
pp. 530 ◽  
Author(s):  
Po-Kai Huang ◽  
Shian-Ren Lin ◽  
Jirawat Riyaphan ◽  
Yaw-Syan Fu ◽  
Ching-Feng Weng
Keyword(s):  
Single Dose ◽  
Natural Compounds ◽  
Dipeptidyl Peptidase ◽  
Antidiabetic Activity ◽  
Drug Candidate ◽  
Diabetic Patients ◽  
Dose Administration ◽  
Dipeptidyl Peptidase 4

Serine protease dipeptidyl peptidase 4 (DPP-4) is involved in self/non-self-recognition and insulin sensitivity. DPP-4 inhibitors are conventional choices for diabetic treatment; however, side effects such as headache, bronchus infection, and nasopharyngitis might affect the daily lives of diabetic patients. Notably, natural compounds are believed to have a similar efficacy with lower adverse effects. This study aimed to validate the DPP-4 inhibitory activity of clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) from Polyalthia longifolia, rutin, quercetin, and berberine, previously selected through molecular docking. The inhibitory potency of natural DPP-4 candidates was further determined by enzymatic, in vitro Caco-2, and ERK/PKA activation in myocyte and pancreatic cells. The hypoglycemic efficacy of the natural compounds was consecutively analyzed by single-dose and multiple-dose administration in diet-induced obese diabetic mice. All the natural-compounds could directly inhibit DPP-4 activity in enzymatic assay and Caco-2 inhibition assay, and HCD showed the highest inhibition of the compounds. HCD down-regulated LPS-induced ERK phosphorylation in myocyte but blocked GLP-1 induced PKA expression. For in vivo tests, HCD showed hypoglycemic efficacy only in single-dose administration. After 28-days administration, HCD exhibited hypolipidemic and hepatoprotective efficacy. These results revealed that HCD performed potential antidiabetic activity via inhibition of single-dose and long-term administrations, and could be a new prospective anti-diabetic drug candidate.

scholarly journals Phytopharmacological Strategies in the Management of Type 2 Diabetes Mellitus

Foods ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 271 ◽  
Author(s):  
Ana M. Duarte ◽  
Maria P. Guarino ◽  
Sónia Barroso ◽  
Maria M. Gil
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Side Effects ◽  
Tyrosine Phosphatase ◽  
Therapeutic Strategies ◽  
Lifestyle Changes ◽  
Dipeptidyl Peptidase 4 ◽  
And Control

Type 2 Diabetes Mellitus (T2DM) is a chronic disease which corresponds to 90% of the worldwide cases of diabetes, mainly due to epigenetic factors such as unhealthy lifestyles. First line therapeutic approaches are based on lifestyle changes, most of the time complemented with medication mostly associated with several side effects and high costs. As a result, the scientific community is constantly working for the discovery and development of natural therapeutic strategies that provide lower financial impact and minimize side effects. This review focus on these nature-based therapeutic strategies for prevention and control of T2DM, with a special emphasis on natural compounds that present pharmacological activity as dipeptidyl peptidase-4 (DPP4), alpha-amylase, alpha-glucosidase, lipase, and protein tyrosine phosphatase 1B (PTP1B) inhibitors.

scholarly journals In-Vivo Antidiabetic Activity and In-Silico Mode of Action of LC/MS-MS Identified Flavonoids in Oleaster Leaves

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5073 ◽  
Author(s):  
Hamza Mechchate ◽  
Imane Es-Safi ◽  
Mohammed Bourhia ◽  
Andrii Kyrylchuk ◽  
Abdelfattah El Moussaoui ◽  
...  
Keyword(s):  
Mode Of Action ◽  
In Silico ◽  
Diabetes Management ◽  
Tyrosine Phosphatase ◽  
Olive Tree ◽  
Bioactive Molecules ◽  
Antidiabetic Activity ◽  
Dipeptidyl Peptidase 4 ◽  
Olea Europea

Background: Olea europea L. subsp. europaea var. sylvestris (Mill) Lehr (Oleaster) is a wild endemic olive tree indigenous to the Mediterranean region. Olea europea leaves represent a natural reservoir of bioactive molecules that can be used for therapeutic purposes. Aim of the study: This work was conducted to study antidiabetic and antihyperglycemic activities of flavonoids from oleaster leaves using alloxan-induced diabetic mice. The mode of action of flavonoids against eight receptors that have a high impact on diabetes management and complication was also investigated using molecular docking. Results: During 28 days of mice treatment with doses 25 and 50 mg/kg b.w, the studied flavonoids managed a severe diabetic state (<450 mg/dL), exhibiting a spectacular antidiabetic and antihyperglycemic activity, and improved mice health status compared to diabetic control. The in-silico mode of action of oleaster flavonoids revealed the inhibition of protein tyrosine phosphatase 1B (PTP1B), Dipeptidyl-peptidase 4 (DPP4), α-Amylase (AAM), α-Glucosidase inhibition, Aldose reductase (AldR), Glycogen phosphorylase (GP), and the activation of free fatty acid receptor 1 (FFAR1). Conclusion: The findings obtained in the present work indicate that the flavonoids from the oleaster may constitute a safe multi-target remedy to treat diabetes.

Natural Antidiabetic Agents: Molecular Docking Study using Extra Precision Method

2020 ◽  
Vol 17 ◽  
Author(s):  
Sandip Firke ◽  
Ashish Dhote ◽  
Ravindra Patil ◽  
Atul Shirlhedkar ◽  
Sanjay Surana
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Active Sites ◽  
Chemical Constituents ◽  
Molecular Targets ◽  
Docking Study ◽  
Peroxisome Proliferator ◽  
Elevated Concentration ◽  
Molecular Docking Study ◽  
Dipeptidyl Peptidase 4

Background: Diabetes mellitus (DM) is the most severe, chronic metabolic disorder with abnormally elevated concentration of plasma glucose levels, leading to significant complications, such as diabetic neuropathy, retinopathy, and cardiovascular illnesses. Objective: Synthetic drugs have some disadvantages and limitations. Therefore, there is a continuous global and insisting need for new and better treatment options for the Diabetes Mellitus. Method: In this study, 42 natural antidiabetic constituents like alkaloids, glycosides and flavonoids were selected on the basis of mechanism of action on various molecular targets such as, Glucokinase activator, Dipeptidyl peptidase 4 (DPP-4), peroxisome proliferator-activated receptors (PPARγ), and α-glucosidase inhibitor. To investigate the potential molecular targets for natural antidiabetcs agents molecular docking study was carried out using Glide module of Schrodinger Suit. Results and Discussion: Interactions of specific amino acid of the targets with the atoms of the chemical constituents and their Gscore indicate the proper binding of the chemical constituents with target. The results revealed that Myricetin, Quercetin are interactiing with active sites of the target chosen and can be used for the designing of novel compounds as antidibetics. Conclusion: Calculated GScore could be used as a preliminary tool for screening of antidiabetic drugs before performing experimental activity.

scholarly journals Citrus Flavanone Narirutin, In Vitro and In Silico Mechanistic Antidiabetic Potential

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1818
Author(s):  
Ashraf Ahmed Qurtam ◽  
Hamza Mechchate ◽  
Imane Es-safi ◽  
Mohammed Al-zharani ◽  
Fahd A. Nasr ◽  
...  
Keyword(s):  
In Silico ◽  
Tyrosine Phosphatase ◽  
In Vitro Study ◽  
Alpha Amylase ◽  
In Vitro Tests ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dipeptidyl Peptidase 4 ◽  
Alpha Glucosidase

Citrus fruits and juices have been studied extensively for their potential involvement in the prevention of various diseases. Flavanones, the characteristic polyphenols of citrus species, are the primarily compounds responsible for these studied health benefits. Using in silico and in vitro methods, we are exploring the possible antidiabetic action of narirutin, a flavanone family member. The goal of the in silico research was to anticipate how narirutin would interact with eight distinct receptors implicated in diabetes control and complications, namely, dipeptidyl-peptidase 4 (DPP4), protein tyrosine phosphatase 1B (PTP1B), free fatty acid receptor 1 (FFAR1), aldose reductase (AldR), glycogen phosphorylase (GP), alpha-amylase (AAM), peroxisome proliferator-activated receptor gamma (PPAR-γ), alpha-glucosidase (AGL), while the in vitro study looked into narirutin’s possible inhibitory impact on alpha-amylase and alpha-glucosidase. The results indicate that the studied citrus flavanone interacted remarkably with most of the receptors and had an excellent inhibitory activity during the in vitro tests suggesting its potent role among the different constituent of the citrus compounds in the management of diabetes and also its complications.

Hypoxemic stimulation of heart glycogen synthase and synthesis. Effects of insulin and diabetes mellitus

Diabetes ◽  
1991 ◽  
Vol 40 (3) ◽  
pp. 385-390 ◽  
Author(s):  
M. R. Laughlin ◽  
C. Morgan ◽  
E. J. Barrett
Keyword(s):  
Diabetes Mellitus ◽  
Glycogen Synthase ◽  
Stimulation Of

Linagliptin: A Novel Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor for Treatment of Type II Diabetes Mellitus

2011 ◽  
Vol 7 (5) ◽  
pp. 325-335 ◽  
Author(s):  
Somsuvra B. Ghatak ◽  
Devang S. Patel ◽  
Neeraj Shanker ◽  
Ambrish Srivastava ◽  
Shrikalp S. Deshpande ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Dipeptidyl Peptidase ◽  
Type Ii ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor

Radioprotective effect of pioglitazone against genotoxicity induced by ionizing radiation in human healthy lymphocytes

2020 ◽  
Vol 18 ◽  
Author(s):  
Roya Kazemi ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Ionizing Radiation ◽  
Human Lymphocytes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Mean ◽  
Anti Inflammatory ◽  
Sensitizing Effect ◽  
Binucleated Lymphocytes ◽  
Inflammatory Effect

Objective: Pioglitazone (PG) is used to control high blood sugar in patients with type 2 diabetes mellitus. PG acts as a peroxisome proliferator-activated receptor γ agonist. In addition to the insulin-sensitizing effect, PG possesses anti-inflammatory effect. In this study, the protective effect of PG was evaluated against DNA damage induced by ionizing radiation in human healthy lymphocytes. Methods: The microtubes containing human whole blood were treated with PG at various concentrations (1-50 μM) for three hours. Then, the blood samples were irradiated with X-ray. Lymphocytes were cultured for determining the frequency of micronuclei as a genotoxicity biomarker in binucleated lymphocytes. Results: The mean percentage of micronuclei was significantly increased in human lymphocytes when were exposed to IR, while it was decreased in lymphocytes pre-treated with PG. The maximum reduction in the frequency of micronuclei in irradiated lymphocytes was observed at 5 μM of PG treatment (48% decrease). Conclusion: The anti-inflammatory property is suggested the mechanism action of PG for protection human lymphocytes against genotoxicity induced by ionizing radiation.

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