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Frontiers of Natural Antidiabetic Drug Discovery

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A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 9276

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Special Issue Editors

Dr. Prawej Ansari

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Guest Editor

1. Department of Pharmacy, School of pharmacy and public health, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
2. Diabetes Research Group, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK
Interests: diabetes mellitus; traditional antidiabetic medicinal plants; impact of dietary fibre in carbohydrate digestion and absorption in gut, phytoconstituents; insulin; insulin secretion; insulin resistance, obesity; nutrition and metabolic disorders

Dr. Yasser Abdel-Wahab

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Guest Editor

Diabetes Research Group, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK
Interests: diabetes mellitus; endocrinology and metabolism; adipocytes; peptides; natural products; phytoconstituents; glucose uptake and insulin action; insulin secretion; insulin resistance; obesity

Special Issue Information

Dear Colleagues,

Diabetes mellitus, one of the most common metabolic disorders, is characterized by pancreatic β-cell dysfunction and insulin resistance or both and it currently affects approximately 500 million people around the world. Diabetes associated hyperglycaemia causes long-term complications, including cardiovascular disease, peripheral and cerebrovascular disease, neuropathy, retinopathy, and nephropathy. Recent evidence has suggested a direct link between diabetes and Alzheimer’s disease which might be due to defective in insulin signaling in the brain, that leads to synaptic disruption and cognitive deficiencies. Currently, various pharmacological agents including sulfonylureas, SGLT-2 inhibitors, DPP-IV inhibitors, GLP-1 and GIP analogues, and synthetic insulin are used for the treatment of diabetes. However, these drugs come with numerous adverse effects as well as being expensive and are not readily available, especially in developing nations. Therefore, research is being focused on alternative medicine specifically traditional medicinal plants (TMP) for diabetes therapy. TMPs have been used in folkloric medicine as remedy for many diseases such as diabetes, gastritis, inflammation, and skin disorders. These plants contain many antidiabetic phytoconstituents such as flavonoids which possess insulinotropic properties. Furthermore, TMPs contain high dietary fibre, which slows down the rate of food absorption in the gut, and thus regulates blood glucose levels and improves diabetic complications. TMPs and their phytomolecules are often easily available, inexpensive and have negligible side effects which make them good candidates for drug discovery. In this special issue we welcome submissions on research across various antidiabetic medicinal plants, phytoconstituents as well as peptides and their role in the treatment of various diseases including but not limited to diabetes, fatty liver, cardiovascular and neurodegenerative diseases. The primary target of this issue is to characterize traditional medicinal plants, peptides together with identifying the possible phytocompounds that may be useful for diabetes therapy and other metabolic disorders.

Dr. Prawej Ansari
Dr. Yasser Abdel-Wahab
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

diabetes mellitus
traditional antidiabetic medicinal plants
phytoconstituents
insulin secretion
insulin action
insulin resistance
obesity
DPP-IV enzymes
GLP-1 and GIP
antioxidant
Alzheimer’s disease

Published Papers (4 papers)

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Research

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20 pages, 2671 KiB

Open AccessArticle

Comparative Insights into Four Major Legume Sprouts Efficacies for Diabetes Management and Its Complications: Untargeted versus Targeted NMR Biochemometrics Approach

by Mohamed A. Farag, Asmaa F. Aboul Naser, Ahmed Zayed and Mohamed G. Sharaf El-Dine

Metabolites 2023, 13(1), 63; https://doi.org/10.3390/metabo13010063 - 31 Dec 2022

Cited by 7 | Viewed by 1604

Abstract

Interest in the consumption of seed sprouts is gradually increasing as functional foods in the modern Western diet owing to their several nutritional and health benefits. The present study aims to investigate four major legume sprouts derived from faba bean (Vicia faba L.), lentil (Lens esculenta L.), chickpea (Cicer arietinum L.), and fenugreek (Trigonella foenum-greacum L.) for their antidiabetic activity and mitigation of associated complications, i.e., oxidative stress, liver dysfunction, and lipid metabolism, compared with glibenclamide. Biochemical results presented herein further showed that the four sprouts exhibited significant hypoglycemic effects (p < 0.05), with improvement in decreasing of blood glucose levels at different degrees and with faba bean sprout most active at 348% improvement, compared to 364.3% for glibenclamide. Further biochemometric analysis based on a comparison between targeted versus untargeted partial least square (PLS) and regression analyses revealed that faba bean sprouts’ richness in flavonoids was a determinant key factor for such efficacy. In addition, correlation with previously investigated NMR fingerprinting aided in pinpointing other active agents, such as betaine and L-DOPA. Furthermore, the effect on serum liver enzymes, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase; oxidative stress markers; and lipid profiles showed significant improvement, especially in the case of faba bean sprout. The study revealed the potential health benefits of legume sprouts in the treatment of diabetes and its associated complications, as well as the potential role of biochemometrics in active agents’ identification in such a complex matrix to be considered for other functional foods investigation. Full article

(This article belongs to the Special Issue Frontiers of Natural Antidiabetic Drug Discovery)

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31 pages, 5845 KiB

Open AccessArticle

In Vitro, In Silico and Network Pharmacology Mechanistic Approach to Investigate the α-Glucosidase Inhibitors Identified by Q-ToF-LCMS from Phaleria macrocarpa Fruit Subcritical CO₂ Extract

by Md. Abdur Rashid Mia, Qamar Uddin Ahmed, Sahena Ferdosh, Abul Bashar Mohammed Helaluddin, Md. Shihabul Awal, Murni Nazira Sarian, Md. Zaidul Islam Sarker and Zainul Amiruddin Zakaria

Metabolites 2022, 12(12), 1267; https://doi.org/10.3390/metabo12121267 - 15 Dec 2022

Cited by 1 | Viewed by 1847

Abstract

The fruit of Phaleria macrocarpa have been traditionally used as an antidiabetic remedy in Malaysia and neighbouring countries. Despite its potential for diabetes treatment, no scientific study has ever been conducted to predict the inhibitor interaction of the protein α-glucosidase identified in an extract prepared with a non-conventional extraction technique. Hence, the major aim of this research was to evaluate the in vitro antioxidant, the α-glucosidase inhibitors, and the molecular dynamic simulations of the α-glucosidase inhibitors identified by Quadrupole Time-of-Flight Liquid Chromatography Mass Spectrometry (Q-ToF-LCMS) analysis. Initially, dry fruit were processed using non-conventional and conventional extraction methods to obtain subcritical carbon dioxide extracts (SCE-1 and SCE-2) and heating under reflux extract (HRE), respectively. Subsequently, all extracts were evaluated for their in vitro antioxidative and α-glucosidase inhibitory potentials. Subsequently, the most bioactive extract (SCE-2) was subjected to Q-ToF-LCMS analysis to confirm the presence of α-glucosidase inhibitors, which were then analysed through molecular dynamic simulations and network pharmacology approaches to confirm their possible mechanism of action. The highest inhibitory effects of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and α-glucosidase on SCE-2 was found as 75.36 ± 0.82% and 81.79 ± 0.82%, respectively, compared to the SCE-1 and HRE samples. The Q-ToF-LCMS analysis tentatively identified 14 potent α-glucosidase inhibitors. Finally, five identified compounds, viz., lupenone, swertianolin, m-coumaric acid, pantothenic acid, and 8-C-glucopyranosyleriodictylol displayed significant stability, compactness, stronger protein-ligand interaction up to 100 ns further confirming their potential as α-glucosidase inhibitors. Consequently, it was concluded that the SCE-2 possesses a strong α-glucosidase inhibitory effect due to the presence of these compounds. The findings of this study might prove useful to develop these compounds as alternative safe α-glucosidase inhibitors to manage diabetes more effectively. Full article

(This article belongs to the Special Issue Frontiers of Natural Antidiabetic Drug Discovery)

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21 pages, 3035 KiB

Open AccessArticle

Polyphenol-Rich Leaf of Annona squamosa Stimulates Insulin Release from BRIN-BD11 Cells and Isolated Mouse Islets, Reduces (CH₂O)_n Digestion and Absorption, and Improves Glucose Tolerance and GLP-1 (7-36) Levels in High-Fat-Fed Rats

by Prawej Ansari, J.M.A. Hannan, Veronique Seidel and Yasser H.A. Abdel-Wahab

Metabolites 2022, 12(10), 995; https://doi.org/10.3390/metabo12100995 - 20 Oct 2022

Cited by 3 | Viewed by 1828

Abstract

Annona squamosa, commonly known as custard apple, is traditionally used for the treatment of various diseases including diabetes, cardiovascular disease (CVD), and gastritis. This study was undertaken to investigate the effects of an ethanolic (80% v/v) extract of A. squamosa (EEAS) leaves in vitro on insulin secretion from clonal pancreatic BRIN BD11 β-cells and mouse islets, including mechanistic studies on the effect of EEAS on membrane potential and intracellular calcium ion concentration. Additional in vitro glucose-lowering actions were assessed. For in vivo studies, high-fat-fed (HFF) obese/normal rats were selected. EEAS increased insulin secretion in vitro in a dose-dependent manner. This effect was linked to β-cell membrane depolarisation and cytoplasmic Ca²⁺ influx. In the presence of isobutyl methylxanthine (IBMX), tolbutamide, or KCl, the insulin-releasing effect of EEAS was increased, suggesting its effect was also mediated via a K_ATP-independent pathways. EEAS inhibited insulin glycation, glucose absorption, and DPP-IV enzyme activity in vitro and enhanced glucose uptake and insulin action in 3T3L1 cells. In vivo, gut motility, food intake, glucose tolerance, plasma insulin, and active GLP-1 (7-36) levels were improved, whereas plasma DPP-IV levels were reduced in HFF rats. EEAS attenuated the absorption of sucrose and glucose as well as decreased serum glucose levels after sucrose loading and in situ intestinal perfusion in non-diabetic rats. Rutin, proanthocyanidin, and squafosacin G were putatively identified as the anti-hyperglycaemic phytomolecules in EEAS using HPLC followed by LC-MS analysis. This study illustrates the potential of A. squamosa and its phytoconstituents as a source of potential antidiabetic agents. Full article

(This article belongs to the Special Issue Frontiers of Natural Antidiabetic Drug Discovery)

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Review

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27 pages, 2326 KiB

Open AccessReview

Antidiabetic Properties of Plant Secondary Metabolites

by Stanislav Sukhikh, Olga Babich, Alexander Prosekov, Olga Kalashnikova, Svetlana Noskova, Alina Bakhtiyarova, Olesia Krol, Elena Tsvetkova and Svetlana Ivanova

Metabolites 2023, 13(4), 513; https://doi.org/10.3390/metabo13040513 - 3 Apr 2023

Cited by 7 | Viewed by 3057

Abstract

The prevalence of diabetes mellitus is one of the major medical problems that the modern world is currently facing. Type 1 and Type 2 diabetes mellitus both result in early disability and death, as well as serious social and financial problems. In some cases, synthetic drugs can be quite effective in the treatment of diabetes, though they have side effects. Plant-derived pharmacological substances are of particular interest. This review aims to study the antidiabetic properties of secondary plant metabolites. Existing review and research articles on the investigation of the antidiabetic properties of secondary plant metabolites, the methods of their isolation, and their use in diabetes mellitus, as well as separate articles that confirm the relevance of the topic and expand the understanding of the properties and mechanisms of action of plant metabolites, were analyzed for this review. The structure and properties of plants used for the treatment of diabetes mellitus, including plant antioxidants, polysaccharides, alkaloids, and insulin-like plant substances, as well as their antidiabetic properties and mechanisms for lowering blood sugar, are presented. The main advantages and disadvantages of using phytocomponents to treat diabetes are outlined. The types of complications of diabetes mellitus and the effects of medicinal plants and their phytocomponents on them are described. The effects of phytopreparations used to treat diabetes mellitus on the human gut microbiota are discussed. Plants with a general tonic effect, plants containing insulin-like substances, plants-purifiers, and plants rich in vitamins, organic acids, etc. have been shown to play an important role in the treatment of type 2 diabetes mellitus and the prevention of its complications. Full article

(This article belongs to the Special Issue Frontiers of Natural Antidiabetic Drug Discovery)

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