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Natural Products as Potential Sources of Antidiabetic Compounds

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Bioorganic Chemistry and Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 31548

Special Issue Editor

Special Issue Information

Dear Colleagues,

Natural products (NPs) have played a crucial role in the drug discovery process in order to treat numerous diseases. Plants, fungi, bacteria, and other natural sources produce NPs with intriguing chemical diversity illustrating interesting biological effects for numerous disease treatments. Notably, NP-based drugs are usually considered to be safer, cheaper, and easily available. Diabetes is one of the chronic disorders associated with high mortality risk. Unfortunately, the currently used drugs have been identified with one or more adverse effects. This indicates that there is still an urgent need for the development of novel antidiabetic drugs with a unique mechanism of action.

The focus of this Special Issue is on natural products (NPs)-based antidiabetic molecules and NPs-based synthetic antidiabetic compounds. Furthermore, this Issue will also place emphasis on the relationship between the chemical structure and the biological activity of the molecules at the molecular level together with applying bioinformatics in diabetes. Moreover, this Special Issue also welcomes articles on the antidiabetic effects of α-glucosidase, amylase, protein tyrosine phosphatase 1B (PTP1B), and dipeptidyl peptidase (DPP)-4 inhibition at the molecular level (kinetic studies). This Special Issue will also focus on the development of new therapeutic agents for diabetes treatment, employing the newest techniques of pharmacology, biotechnology, and genetic engineering. This Issue welcomes original articles, communications, and reviews dealing with diabetes treatment.

Prof. Dr. Hidayat Hussain
Guest Editor

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Keywords

  • Natural products
  • Natural product derivatives
  • Antidiabetic agents
  • α-Glucosidase inhibitors
  • Amylase inhibitors
  • PTP1B inhibitors
  • DPP-4 inhibitors
  • Molecular level
  • Kinetic studies
  • In vitro studies
  • In vivo studies
  • Computational methods
  • Mode of action

Published Papers (11 papers)

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Editorial

Jump to: Research, Review, Other

4 pages, 217 KiB  
Editorial
Editorial for Special Issue “Natural Products as Potential Source of Antidiabetic Compounds”
by Hidayat Hussain
Curr. Issues Mol. Biol. 2023, 45(4), 2699-2702; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45040176 - 24 Mar 2023
Viewed by 1014
Abstract
Natural products (NPs) are characterized by possessing intriguing scaffold diversity along with structural complexity and have been a comprehensive source of lead compounds for drug discovery [...] Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)

Research

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15 pages, 18625 KiB  
Article
Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment
by Mohamed Rafiullah, Hicham Benabdelkamel, Afshan Masood, Aishah A. Ekhzaimy, Mohthash Musambil, Salini Scaria Joy and Assim A. Alfadda
Curr. Issues Mol. Biol. 2023, 45(2), 1407-1421; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45020092 - 06 Feb 2023
Cited by 5 | Viewed by 1668
Abstract
Diabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes [...] Read more.
Diabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear. Twelve male patients with T2DM (pre and post liraglutide treatment) and HbA1c between 8% and 11% were recruited. In the present study, a two-dimensional difference gel electrophoresis (2D-DIGE) matrix-assisted laser desorption/ionization-time of flight (MALDI TOF) mass spectrometric approach combined with bioinformatics and network pathway analysis was used to explore the urine proteomic profile. The mean age of the patients was 52.4 ± 7.5 years. After treatment with liraglutide, a statistically significant change (p < 0.006) was observed in HbA1c with no significant changes in body weight or markers of dyslipidemia. Two-dimensional difference gel electrophoresis identified significant changes (≥1.5-fold change, ANOVA, p ≤ 0.05) in 32 proteins (4 down- and 28 upregulated) in liraglutide post treatment compared to the pre-treatment state. Albumin, serotransferrin, metallothionein-2 (MT-2), and keratins K1 and K10 were found to be upregulated after liraglutide treatment. The patients showed significant improvement in glycemic control after the 12-week treatment with liraglutide. The renoprotective effect of liraglutide may be linked to the increased urinary abundance of MT-2 and the decreased abundance of zinc alpha 2-glycoprotein (ZAG) and Alpha-1 antitrypsin (α1-AT). More studies are needed to elucidate the molecular mechanisms behind the renoprotective effects of liraglutide. Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)
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15 pages, 1753 KiB  
Article
Evaluation of Antidiabetic, Antioxidant and Anti-Hyperlipidemic Effects of Solanum indicum Fruit Extract in Streptozotocin-Induced Diabetic Rats
by Manoj M. Gadewar, Prashanth G K, Prabhu Chandra Mishra, Ghulam Md Ashraf, Majed N. Almashjary, Steve Harakeh, Vijay Upadhye, Abhijit Dey, Pallavi Singh, Niraj Kumar Jha and Saurabh Kumar Jha
Curr. Issues Mol. Biol. 2023, 45(2), 903-917; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45020058 - 19 Jan 2023
Cited by 3 | Viewed by 2919
Abstract
Background: Globally, diabetes mellitus is the most common cause of premature mortality after cardiovascular diseases and tobacco chewing. It is a heterogeneous metabolic disorder characterised by the faulty metabolism of carbohydrates, fats and proteins as a result of defects in insulin secretion or [...] Read more.
Background: Globally, diabetes mellitus is the most common cause of premature mortality after cardiovascular diseases and tobacco chewing. It is a heterogeneous metabolic disorder characterised by the faulty metabolism of carbohydrates, fats and proteins as a result of defects in insulin secretion or resistance. It was estimated that approximately 463 million of the adult population are suffering from diabetes mellitus, which may grow up to 700 million by 2045. Solanum indicum is distributed all over India and all of the tropical and subtropical regions of the world. The different parts of the plant such as the roots, leaves and fruits were used traditionally in the treatment of cough, asthma and rhinitis. However, the hypoglycaemic activity of the plant is not scientifically validated. Purpose: The present study aimed to evaluate the antioxidant, antidiabetic and anti-hyperlipidaemic activity of methanolic fruit extract of Solanum indicum (SIE) in streptozotocin (STZ) induced diabetic rats. Method: Experimentally, type II diabetes was induced in rats by an i.p. injection of STZ at a dose of 60 mg/kg. The effect of the fruit extract was evaluated at doses of 100 and 200 mg/kg body weight in STZ-induced diabetic rats for 30 days. Result: The oral administration of fruit extract caused a significant (p < 0.05) reduction in the blood glucose level with a more prominent effect at 200 mg/kg. The fruit extract showed dose-dependent α-amylase and α-glycosidase inhibitory activity. It reduced the serum cholesterol and triglyceride levels remarkably in diabetic rats compared to normal. The extract showed the reduced activity of endogenous antioxidants, superoxide dismutase, glutathione peroxidase and catalase in the liver of STZ diabetic rats. Conclusion: The result confirmed that the fruit extract of Solanum indicum showed a dose-dependent blood glucose lowering effect and significantly reduced elevated blood cholesterol and triglycerides. It prevented oxidative stress associated with type II diabetes in STZ rats. Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)
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15 pages, 1975 KiB  
Article
Essential Oil of Carvone Chemotype Lippia alba (Verbenaceae) Regulates Lipid Mobilization and Adipogenesis in Adipocytes
by Katherin Bonilla-Carvajal, Elena E. Stashenko and Natalia Moreno-Castellanos
Curr. Issues Mol. Biol. 2022, 44(11), 5741-5755; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb44110389 - 18 Nov 2022
Cited by 5 | Viewed by 1658
Abstract
Obesity is characterized by an expansion of adipose tissue due to excessive accumulation of triglycerides in adipocytes, causing hypertrophy and hyperplasia, followed by hypoxia, alterations in adipocyte functionality, and chronic inflammation. However, current treatments require changes in lifestyle that are difficult to achieve [...] Read more.
Obesity is characterized by an expansion of adipose tissue due to excessive accumulation of triglycerides in adipocytes, causing hypertrophy and hyperplasia, followed by hypoxia, alterations in adipocyte functionality, and chronic inflammation. However, current treatments require changes in lifestyle that are difficult to achieve and some treatments do not generate sustained weight loss over time. Therefore, we evaluated the effect of the essential oil (EO) of Lippia alba (Verbenaceae) carvone chemotype on viability, lipid mobilization, and adipogenesis of adipocytes in two normal and pathological cellular models in vitro. In 3T3-L1 adipocytes, a normal and a pathological model of obesity were induced, and then the cells were treated with L. alba carvone chemotype EO to evaluate cell viability, lipid mobilization, and adipogenesis. L. alba carvone chemotype EO does not decrease adipocyte viability at concentrations of 0.1, 1, and 5 µg/mL; furthermore, there was evidence of changes in lipid mobilization and adipogenesis, leading to a reversal of adipocyte hypertrophy. These results could be due to effects produced by EO on lipogenic and lipolytic pathways, as well as modifications in the expression of adipogenesis genes. L. alba carvone chemotype EO could be considered as a possible treatment for obesity, using the adipocyte as a therapeutic target. Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)
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12 pages, 1049 KiB  
Article
Higher NADH Dehydrogenase [Ubiquinone] Iron–Sulfur Protein 8 (NDUFS8) Serum Levels Correlate with Better Insulin Sensitivity in Type 1 Diabetes
by Justyna Flotyńska, Daria Klause, Michał Kulecki, Aleksandra Cieluch, Regina Chomicka-Pawlak, Dorota Zozulińska-Ziółkiewicz and Aleksandra Uruska
Curr. Issues Mol. Biol. 2022, 44(9), 3872-3883; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb44090266 - 26 Aug 2022
Cited by 4 | Viewed by 2025
Abstract
Objective: The aim of the study was to evaluate NADH dehydrogenase [ubiquinone] iron–sulfur protein 8 (NDUFS8) serum concentration as a marker of Complex I, and the relationship with insulin resistance in type 1 diabetes mellitus (T1DM). Design and methods: Participants were adults with [...] Read more.
Objective: The aim of the study was to evaluate NADH dehydrogenase [ubiquinone] iron–sulfur protein 8 (NDUFS8) serum concentration as a marker of Complex I, and the relationship with insulin resistance in type 1 diabetes mellitus (T1DM). Design and methods: Participants were adults with T1DM, recruited over the course of 1 year (2018–2019). NDUFS8 protein serum concentration was measured using the ELISA test. Insulin resistance was evaluated with indirect marker estimated glucose disposal rate (eGDR). The group was divided on the base of median value of eGDR (higher eGDR—better insulin sensitivity). Results: The study group consists of 12 women and 24 men. Medians of eGDR and NDUFS8 protein concentration are 7.6 (5.58–8.99) mg/kg/min and 2.25 (0.72–3.81) ng/mL, respectively. The group with higher insulin sensitivity has higher NDUFS8 protein serum concentration, lower waist to hip ratio (WHR), body mass index (BMI), and they are younger. A negative correlation is observed between NDUFS8 protein serum concentration and WHR (rs = −0.35, p = 0.03), whereas a positive correlation is observed between NDUFS8 protein serum concentration and eGDR (rs = 0.43, p = 0.008). Univariate logistic regression shows a significant association between insulin sensitivity and lower age, as well as a higher NDUFS8 serum level. A multivariate logistic regression model confirms the significance (AOR 2.38 (1.04–5.48). p = 0.042). Multivariate linear regression confirms a significant association between insulin sensitivity and better mitochondrial function (beta = 0.54, p = 0.003), independent of age, duration of diabetes, and smoking. Conclusions: Higher NDUFS8 protein serum concentration is associated with higher insulin sensitivity among adults with T1DM. Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)
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13 pages, 3384 KiB  
Article
Ascorbic Acid Ameliorates Cardiac and Hepatic Toxicity Induced by Azithromycin-Etoricoxib Drug Interaction
by Reham Z. Hamza, Fatima S. Alaryani, Fatma Omara, Mahmoud A. A. Said, Sayed A. Abd El-Aziz and Sawsan M. El-Sheikh
Curr. Issues Mol. Biol. 2022, 44(6), 2529-2541; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb44060172 - 31 May 2022
Cited by 4 | Viewed by 2681
Abstract
The complexity of prescribing safe and effective drug therapy is still challenging. Due to the increased number of medications taken by patients, the potential for drug-drug interactions has clinically important consequences. This study focuses on the potential drug-drug interaction between azithromycin and etoricoxib [...] Read more.
The complexity of prescribing safe and effective drug therapy is still challenging. Due to the increased number of medications taken by patients, the potential for drug-drug interactions has clinically important consequences. This study focuses on the potential drug-drug interaction between azithromycin and etoricoxib and the possibility of counteracting this adverse reaction by giving ascorbic acid intraperitoneally to male albino rats. Sixty adult male albino rats weighing 150–180 g were used. The rats were allocated into six equal groups. One group was a control, and the others were given azithromycin, etoricoxib, either alone or combination, with one group treated with ascorbic acid and the last group treated with the drug combination and ascorbic acid. Blood samples were collected for measuring AST, ALT, LDH, CK-MB, and troponin alongside antioxidant enzymes and histopathological examination for both liver and heart tissue. The results showed both hepatic and cardiac damage in azithromycin and etoricoxib groups represented by increasing levels of heaptoc enzymes (ALT, AST, LDH, CK-MB, and troponin) with declining antioxidant enzymes and elevation of malondialdehyde and the appearance of hepatic and cardiac toxicities. Upon administration, ascorbic acid ameliorated all the mentioned biochemical parameters. In conclusion, ascorbic acid has great antioxidant capacities and hepatic and cardiac ameliorative effects and can alleviate drug interaction toxicity. Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)
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18 pages, 5104 KiB  
Article
Antidiabetic Drug Sitagliptin with Divalent Transition Metals Manganese and Cobalt: Synthesis, Structure, Characterization Antibacterial and Antioxidative Effects in Liver Tissues
by Samy M. El-Megharbel, Najah M. Al-Baqami, Eman H. Al-Thubaiti, Safa H. Qahl, Bander Albogami and Reham Z. Hamza
Curr. Issues Mol. Biol. 2022, 44(5), 1810-1827; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb44050124 - 20 Apr 2022
Cited by 7 | Viewed by 2349
Abstract
Metals and their complexes have an increasing number of medical applications. Sitagliptin (STG) acts as an antidiabetic drug. Mn(II) and Co(II) complexes were studied and characterized based on physical characterization, FT-IR, DG/TG, XRD, ESM, and TEM. Data revealed that STG acts as a [...] Read more.
Metals and their complexes have an increasing number of medical applications. Sitagliptin (STG) acts as an antidiabetic drug. Mn(II) and Co(II) complexes were studied and characterized based on physical characterization, FT-IR, DG/TG, XRD, ESM, and TEM. Data revealed that STG acts as a bidentate ligand through the oxygen atom of a carbonyl group and the nitrogen atom of an amino group. Magnetic measurement data revealed that the Mn/STG metal complex has a square planner geometry. The experiment was performed on 40 male albino rats who were divided into four groups: the control group, STG group, group treated with STG/Mn, and group treated with Co/STG. Biomarkers for hepatic enzymes and antioxidants were found in the blood, and hepatic tissue histology was evaluated. STG in combination with Mn and Co administration showed potent protective effects against hepatic biochemical alterations induced by STG alone, as well as suppressing oxidative stress and structural alterations. These complexes prevented any stress and improved hepatic enzymatic levels more than STG alone. The STG/Mn complex was highly effective against Bacillus subtilis and Streptococcus pneumonia, while STG/Co was highly effective against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureas. Therefore, STG combined with Mn and Co produced a synergistic effect against oxidative stress and improved the histological structure of the liver tissues. STG metal complexes with Mn and Co showed the most potential ameliorative antioxidant and hepatoprotective effects. Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)
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25 pages, 7834 KiB  
Article
Molecular Structure-Based Screening of the Constituents of Calotropis procera Identifies Potential Inhibitors of Diabetes Mellitus Target Alpha Glucosidase
by Cynthia A. Adinortey, Gabriel B. Kwarko, Russell Koranteng, Daniel Boison, Issaka Obuaba, Michael D. Wilson and Samuel K. Kwofie
Curr. Issues Mol. Biol. 2022, 44(2), 963-987; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb44020064 - 21 Feb 2022
Cited by 13 | Viewed by 3532
Abstract
Diabetes mellitus is a disorder characterized by higher levels of blood glucose due to impaired insulin mechanisms. Alpha glucosidase is a critical drug target implicated in the mechanisms of diabetes mellitus and its inhibition controls hyperglycemia. Since the existing standard synthetic drugs have [...] Read more.
Diabetes mellitus is a disorder characterized by higher levels of blood glucose due to impaired insulin mechanisms. Alpha glucosidase is a critical drug target implicated in the mechanisms of diabetes mellitus and its inhibition controls hyperglycemia. Since the existing standard synthetic drugs have therapeutic limitations, it is imperative to identify new potent inhibitors of natural product origin which may slow carbohydrate digestion and absorption via alpha glucosidase. Since plant extracts from Calotropis procera have been extensively used in the treatment of diabetes mellitus, the present study used molecular docking and dynamics simulation techniques to screen its constituents against the receptor alpha glucosidase. Taraxasterol, syriogenin, isorhamnetin-3-O-robinobioside and calotoxin were identified as potential novel lead compounds with plausible binding energies of −40.2, −35.1, −34.3 and −34.3 kJ/mol against alpha glucosidase, respectively. The residues Trp481, Asp518, Leu677, Leu678 and Leu680 were identified as critical for binding and the compounds were predicted as alpha glucosidase inhibitors. Structurally similar compounds with Tanimoto coefficients greater than 0.7 were reported experimentally to be inhibitors of alpha glucosidase or antidiabetic. The structures of the molecules may serve as templates for the design of novel inhibitors and warrant in vitro assaying to corroborate their antidiabetic potential. Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)
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Review

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25 pages, 501 KiB  
Review
Nutraceutical Prevention of Diabetic Complications—Focus on Dicarbonyl and Oxidative Stress
by Mark F. McCarty, James J. DiNicolantonio and James H. O’Keefe
Curr. Issues Mol. Biol. 2022, 44(9), 4314-4338; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb44090297 - 18 Sep 2022
Cited by 3 | Viewed by 2923
Abstract
Oxidative and dicarbonyl stress, driven by excess accumulation of glycolytic intermediates in cells that are highly permeable to glucose in the absence of effective insulin activity, appear to be the chief mediators of the complications of diabetes. The most pathogenically significant dicarbonyl stress [...] Read more.
Oxidative and dicarbonyl stress, driven by excess accumulation of glycolytic intermediates in cells that are highly permeable to glucose in the absence of effective insulin activity, appear to be the chief mediators of the complications of diabetes. The most pathogenically significant dicarbonyl stress reflects spontaneous dephosphorylation of glycolytic triose phosphates, giving rise to highly reactive methylglyoxal. This compound can be converted to harmless lactate by the sequential activity of glyoxalase I and II, employing glutathione as a catalyst. The transcription of glyoxalase I, rate-limiting for this process, is promoted by Nrf2, which can be activated by nutraceutical phase 2 inducers such as lipoic acid and sulforaphane. In cells exposed to hyperglycemia, glycine somehow up-regulates Nrf2 activity. Zinc can likewise promote glyoxalase I transcription, via activation of the metal-responsive transcription factor (MTF) that binds to the glyoxalase promoter. Induction of glyoxalase I and metallothionein may explain the protective impact of zinc in rodent models of diabetic complications. With respect to the contribution of oxidative stress to diabetic complications, promoters of mitophagy and mitochondrial biogenesis, UCP2 inducers, inhibitors of NAPDH oxidase, recouplers of eNOS, glutathione precursors, membrane oxidant scavengers, Nrf2 activators, and correction of diabetic thiamine deficiency should help to quell this. Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)
22 pages, 3235 KiB  
Review
Proteomic Changes to the Updated Discovery of Engineered Insulin and Its Analogs: Pros and Cons
by Naeema Hanif, Hezhou Wu, Peizhou Xu, Yun Li, Amir Bibi, Asma Zulfiqar, Muhammad Zafar Iqbal, Muhammad Tahir, Xiangyang Zhang and Asif Ali
Curr. Issues Mol. Biol. 2022, 44(2), 867-888; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb44020059 - 11 Feb 2022
Cited by 3 | Viewed by 3891
Abstract
The destruction of β-cells of the pancreas leads to either insulin shortage or the complete absence of insulin, which in turn causes diabetes Mellitus. For treating diabetes, many trials have been conducted since the 19th century until now. In ancient times, insulin from [...] Read more.
The destruction of β-cells of the pancreas leads to either insulin shortage or the complete absence of insulin, which in turn causes diabetes Mellitus. For treating diabetes, many trials have been conducted since the 19th century until now. In ancient times, insulin from an animal’s extract was taken to treat human beings. However, this resulted in some serious allergic reactions. Therefore, scientists and researchers have tried their best to find alternative ways for managing diabetes with progressive advancements in biotechnology. However, a lot of research trials have been conducted, and they discovered more progressed strategies and approaches to treat type I and II diabetes with satisfaction. Still, investigators are finding more appropriate ways to treat diabetes accurately. They formulated insulin analogs that mimic the naturally produced human insulin through recombinant DNA technology and devised many methods for appropriate delivery of insulin. This review will address the following questions: What is insulin preparation? How were these devised and what are the impacts (both positive and negative) of such insulin analogs against TIDM (type-I diabetes mellitus) and TIIDM (type-II diabetes mellitus)? This review article will also demonstrate approaches for the delivery of insulin analogs into the human body and some future directions for further improvement of insulin treatment. Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)
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Other

19 pages, 1277 KiB  
Systematic Review
Evidence from a Systematic Review and Meta-Analysis Pointing to the Antidiabetic Effect of Polyphenol-Rich Plant Extracts from Gymnema montanum, Momordica charantia and Moringa oleifera
by Michal Krawczyk, Izabela Burzynska-Pedziwiatr, Lucyna Alicja Wozniak and Malgorzata Bukowiecka-Matusiak
Curr. Issues Mol. Biol. 2022, 44(2), 699-717; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb44020049 - 28 Jan 2022
Cited by 8 | Viewed by 5016
Abstract
In vitro and animal model studies are of great interest for selecting new phytochemicals, including polyphenols with antioxidative properties, as candidates for antidiabetic drugs. This review provides evidence from a critical literature data analysis on the effects of plant extract supplementation in diabetes [...] Read more.
In vitro and animal model studies are of great interest for selecting new phytochemicals, including polyphenols with antioxidative properties, as candidates for antidiabetic drugs. This review provides evidence from a critical literature data analysis on the effects of plant extract supplementation in diabetes mellitus management. We considered and meta-analyzed the efficacy of oral supplementation of plant extracts in animal model studies and examined physiological and oxidative stress parameters. Finally, 23 articles were included in the meta-analysis, revealing three plants with experimentally confirmed in vivo and in vitro antidiabetic properties: Gymnema montanum, Momordica charantia and Moringa oleifera. The following parameter changes resulted from an investigation of the supplementation: reduced oxidative stress, decreased insulin resistance, increased insulin release, reduced adiposity, and a modulatory effect on glycolysis and gluconeogenesis, as well as attenuation of diabetes-associated weight loss, reduced fasting blood glucose and lowered oxidative status. A comparison of Gymnema montanum versus Glybenclamide revealed the superiority of extracts over drug administration in some aspects. Although the analyzed extracts are promising candidates for antidiabetic treatment, there is much inconsistent data in the literature. Therefore, ultimate references for using these compounds in the prevention of diabetes are currently not applicable. Full article
(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)
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