A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes

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Abstract

Diabetes mellitus is a multifactorial global health disorder that is rising at an alarming rate. Cardiovascular diseases, kidney damage and neuropathy are the main cause of high mortality rates among individuals with diabetes. One effective therapeutic approach for controlling hyperglycemia associated with type-2 diabetes is to target alpha-amylase and alpha-glucosidase, enzymes that catalyzes starch hydrolysis in the intestine. At present, approved inhibitors for these enzymes are restricted to acarbose, miglitol and voglibose. Although these inhibitors retard glucose absorption, undesirable gastrointestinal side effects impede their application. Therefore, research efforts continue to seek novel inhibitors with improved efficacy and minimal side effects. Natural products of plant origin have been a valuable source of therapeutic agents with lesser toxicity and side effects. The anti-diabetic potential through alpha-glucosidase inhibition of plant-derived molecules are summarized in this review. Eight molecules (Taxumariene F, Akebonoic acid, Morusin, Rhaponticin, Procyanidin A2, Alaternin, Mulberrofuran K and Psoralidin) were selected as promising drug candidates and their pharmacokinetic properties and toxicity were discussed where available.

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The online version contains supplementary material available at 10.1007/s11101-021-09773-1.

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The carbohydrate-active enzymes database (CAZy) in 2013

Vincent Lombard, Hemalatha Golaconda Ramulu, Elodie Drula … (2013)

The Carbohydrate-Active Enzymes database (CAZy; http://www.cazy.org) provides online and continuously updated access to a sequence-based family classification linking the sequence to the specificity and 3D structure of the enzymes that assemble, modify and breakdown oligo- and polysaccharides. Functional and 3D structural information is added and curated on a regular basis based on the available literature. In addition to the use of the database by enzymologists seeking curated information on CAZymes, the dissemination of a stable nomenclature for these enzymes is probably a major contribution of CAZy. The past few years have seen the expansion of the CAZy classification scheme to new families, the development of subfamilies in several families and the power of CAZy for the analysis of genomes and metagenomes. This article outlines the changes that have occurred in CAZy during the past 5 years and presents our novel effort to display the resolution and the carbohydrate ligands in crystallographic complexes of CAZymes.

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Association between insulin resistance and the development of cardiovascular disease

Valeska Ormazabal, Soumyalekshmi Nair, Omar Elfeky … (2018)

For many years, cardiovascular disease (CVD) has been the leading cause of death around the world. Often associated with CVD are comorbidities such as obesity, abnormal lipid profiles and insulin resistance. Insulin is a key hormone that functions as a regulator of cellular metabolism in many tissues in the human body. Insulin resistance is defined as a decrease in tissue response to insulin stimulation thus insulin resistance is characterized by defects in uptake and oxidation of glucose, a decrease in glycogen synthesis, and, to a lesser extent, the ability to suppress lipid oxidation. Literature widely suggests that free fatty acids are the predominant substrate used in the adult myocardium for ATP production, however, the cardiac metabolic network is highly flexible and can use other substrates, such as glucose, lactate or amino acids. During insulin resistance, several metabolic alterations induce the development of cardiovascular disease. For instance, insulin resistance can induce an imbalance in glucose metabolism that generates chronic hyperglycemia, which in turn triggers oxidative stress and causes an inflammatory response that leads to cell damage. Insulin resistance can also alter systemic lipid metabolism which then leads to the development of dyslipidemia and the well-known lipid triad: (1) high levels of plasma triglycerides, (2) low levels of high-density lipoprotein, and (3) the appearance of small dense low-density lipoproteins. This triad, along with endothelial dysfunction, which can also be induced by aberrant insulin signaling, contribute to atherosclerotic plaque formation. Regarding the systemic consequences associated with insulin resistance and the metabolic cardiac alterations, it can be concluded that insulin resistance in the myocardium generates damage by at least three different mechanisms: (1) signal transduction alteration, (2) impaired regulation of substrate metabolism, and (3) altered delivery of substrates to the myocardium. The aim of this review is to discuss the mechanisms associated with insulin resistance and the development of CVD. New therapies focused on decreasing insulin resistance may contribute to a decrease in both CVD and atherosclerotic plaque generation.

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Type 1 diabetes.

Mark A Atkinson, George S Eisenbarth, Aaron W Michels (2014)

Over the past decade, knowledge of the pathogenesis and natural history of type 1 diabetes has grown substantially, particularly with regard to disease prediction and heterogeneity, pancreatic pathology, and epidemiology. Technological improvements in insulin pumps and continuous glucose monitors help patients with type 1 diabetes manage the challenge of lifelong insulin administration. Agents that show promise for averting debilitating disease-associated complications have also been identified. However, despite broad organisational, intellectual, and fiscal investments, no means for preventing or curing type 1 diabetes exists, and, globally, the quality of diabetes management remains uneven. This Seminar discusses current progress in epidemiology, pathology, diagnosis, and treatment of type 1 diabetes, and prospects for an improved future for individuals with this disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

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Author and article information

Contributors

Lina F. Yousef:

ORCID: http://orcid.org/0000-0002-0766-5318

lina.yousef@ku.ac.ae

Journal

Journal ID (nlm-ta): Phytochem Rev

Journal ID (iso-abbrev): Phytochem Rev

Title: Phytochemistry Reviews

Publisher: Springer Netherlands (Dordrecht )

ISSN (Print): 1568-7767

ISSN (Electronic): 1572-980X

Publication date (Electronic): 16 August 2021

Pages: 1-31

Affiliations

[1 ]GRID grid.440568.b, ISNI 0000 0004 1762 9729, Department of Chemistry, , Khalifa University, ; Abu Dhabi, UAE

[2 ]GRID grid.440568.b, ISNI 0000 0004 1762 9729, Center for Membranes and Advances Water Technology, , Khalifa University, ; Abu Dhabi, UAE

Author information

Lina F. Yousef http://orcid.org/0000-0002-0766-5318

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Publisher ID: 9773

DOI: 10.1007/s11101-021-09773-1

PMC ID: 8364835

PubMed ID: 34421444

SO-VID: 843f7e68-1c75-4957-b2be-16f5a05aa129

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

History

Date received : 15 October 2020

Date accepted : 27 July 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004070, Khalifa University of Science, Technology and Research;

A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes

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GLUT4 biology

Most cited references 190

The carbohydrate-active enzymes database (CAZy) in 2013

Association between insulin resistance and the development of cardiovascular disease

Type 1 diabetes.

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