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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 21514

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Dr. Eman M. Othman

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Guest Editor

Bioinformatic Department, Biocenter, University of Wuerzburg, Wuerzburg, Germany
Interests: diabetes mellitus; obesity; carcinogenesis; oxidative stress; natural products

Special Issue Information

Dear Colleagues,

Diabetes mellitus (DM), specially type 2 diabetes mellitus (T2DM), is recognized as a serious public health concern with a considerable impact on human life and is referred to a metabolic disorder of multiple etiologies along with serious complications. Despite of the presence of many antidiabetic drugs in the marke, there are invaluable pool of studies to discover biologically active lead compounds or even new therapeutic agents, the main reason for the continuous search for new antidiabetic drugs; is the common side effects.

The biggest challenge today in pre-clinical drug discovery is the identification of a drug candidate that is, effective with low cost production as well as non-toxic such as drugs derived from natural soures.

Papers focusing on these aspects of the treatment of diabetes mellitus with natural compounds are welcome.

Dr. Eman M. Othman
Guest Editor

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Keywords

natural products
extracts and isolated compounds
diabetes mellitus
complications prevention
prophylaxis

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Published Papers (5 papers)

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Research

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18 pages, 1689 KiB

Open AccessArticle

Integration of Deep Learning and Sequential Metabolism to Rapidly Screen Dipeptidyl Peptidase (DPP)-IV Inhibitors from Gardenia jasminoides Ellis

by Huining Liu, Shuang Yu, Xueyan Li, Xinyu Wang, Dongying Qi, Fulu Pan, Xiaoyu Chai, Qianqian Wang, Yanli Pan, Lei Zhang and Yang Liu

Molecules 2023, 28(21), 7381; https://doi.org/10.3390/molecules28217381 - 1 Nov 2023

Cited by 2 | Viewed by 1583

Abstract

Traditional Chinese medicine (TCM) possesses unique advantages in the management of blood glucose and lipids. However, there is still a significant gap in the exploration of its pharmacologically active components. Integrated strategies encompassing deep-learning prediction models and active validation based on absorbable ingredients can greatly improve the identification rate and screening efficiency in TCM. In this study, the affinity prediction of 11,549 compounds from the traditional Chinese medicine system’s pharmacology database (TCMSP) with dipeptidyl peptidase-IV (DPP-IV) based on a deep-learning model was firstly conducted. With the results, Gardenia jasminoides Ellis (GJE), a food medicine with homologous properties, was selected as a model drug. The absorbed components of GJE were subsequently identified through in vivo intestinal perfusion and oral administration. As a result, a total of 38 prototypical absorbed components of GJE were identified. These components were analyzed to determine their absorption patterns after intestinal, hepatic, and systemic metabolism. Virtual docking and DPP-IV enzyme activity experiments were further conducted to validate the inhibitory effects and potential binding sites of the common constituents of deep learning and sequential metabolism. The results showed a significant DPP-IV inhibitory activity (IC₅₀ 53 ± 0.63 μg/mL) of the iridoid glycosides’ potent fractions, which is a novel finding. Genipin 1-gentiobioside was screened as a promising new DPP-IV inhibitor in GJE. These findings highlight the potential of this innovative approach for the rapid screening of active ingredients in TCM and provide insights into the molecular mechanisms underlying the anti-diabetic activity of GJE. Full article

(This article belongs to the Special Issue Novel Natural Compounds in Treatment of Diabetes)

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10 pages, 825 KiB

Open AccessArticle

Hydroethanolic Extract of Urtica dioica L. (Stinging Nettle) Leaves as Disaccharidase Inhibitor and Glucose Transport in Caco-2 Hinderer

by Mohammad A. Altamimi, Ibrahim M. Abu-Reidah, Almothana Altamimi and Nidal Jaradat

Molecules 2022, 27(24), 8872; https://doi.org/10.3390/molecules27248872 - 14 Dec 2022

Cited by 12 | Viewed by 2608

Abstract

Herbal treatment for diabetes mellitus is widely used. The pharmacological activity is thought to be due to the phenolic compounds found in the plant leaves. The present study aims to investigate the phytochemical composition of Urtica dioica (UD) hydroethanolic extract and to screen its antidiabetic activity by disaccharidase hindering and glucose transport in Caco-2 cells. The results have shown that a total of 13 phenolic compounds in this work, viz. caffeic and coumaric acid esters (1, 2, 4–7, 10), ferulic derivative (3), and flavonoid glycosides (8, 9, 11–13), were identified using HPLC-DAD-ESI/MS². The most abundant phenolic compounds were 8 (rutin) followed by 6 (caffeoylquinic acid III). Less predominant compounds were 4 (caffeoylquinic acid II) and 11 (kaempferol-O-rutinoside). The UD hydroethanolic extract showed 56%, 45%, and 28% (1.0 mg/mL) inhibition level for maltase, sucrase, and lactase, respectively. On the other hand, glucose transport was 1.48 times less at 1.0 mg/mL UD extract compared with the control containing no UD extract. The results confirmed that U. dioica is a potential antidiabetic herb having both anti-disaccharidase and glucose transport inhibitory properties, which explained the use of UD in traditional medicine. Full article

(This article belongs to the Special Issue Novel Natural Compounds in Treatment of Diabetes)

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16 pages, 2491 KiB

Open AccessArticle

Combined Effects of Lycopene and Metformin on Decreasing Oxidative Stress by Triggering Endogenous Antioxidant Defenses in Diet-Induced Obese Mice

by Bruno Pereira Motta, Camila Graça Pinheiro, Ingrid Delbone Figueiredo, Felipe Nunes Cardoso, Juliana Oriel Oliveira, Rachel Temperani Amaral Machado, Patrícia Bento da Silva, Marlus Chorilli, Iguatemy Lourenço Brunetti and Amanda Martins Baviera

Molecules 2022, 27(23), 8503; https://doi.org/10.3390/molecules27238503 - 3 Dec 2022

Cited by 9 | Viewed by 1950

Abstract

Since lycopene has antioxidant activity, its combination with metformin may be useful to contrast diabetic complications related to oxidative stress. This study aimed to investigate the effects of metformin combined with lycopene on high-fat diet (HFD)-induced obese mice. Seventy-two C57BL-6J mice were divided into six groups: C (control diet-fed mice), H (HFD-fed mice for 17 weeks), H-V (HFD-fed mice treated with vehicle), H-M (HFD-fed mice treated with 50 mg/kg metformin), H-L (HFD-fed mice treated with 45 mg/kg lycopene), and H-ML (HFD-fed mice treated with 50 mg/kg metformin + 45 mg/kg lycopene). Treatments were administered for 8 weeks. Glucose tolerance, insulin sensitivity, fluorescent AGEs (advanced glycation end products), TBARS (thiobarbituric acid-reactive substances), and activities of antioxidant enzymes paraoxonase-1 (PON-1; plasma), superoxide dismutase, catalase and glutathione peroxidase (liver and kidneys) were determined. Metformin plus lycopene reduced body weight; improved insulin sensitivity and glucose tolerance; and decreased AGEs and TBARS in plasma, liver and kidneys. Combined therapy significantly increased the activities of antioxidant enzymes, mainly PON-1. Lycopene combined with metformin improved insulin resistance and glucose tolerance, and caused further increases in endogenous antioxidant defenses, arising as a promising therapeutic strategy for combating diabetic complications resulting from glycoxidative stress. Full article

(This article belongs to the Special Issue Novel Natural Compounds in Treatment of Diabetes)

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43 pages, 1899 KiB

Open AccessReview

Food Polyphenols and Type II Diabetes Mellitus: Pharmacology and Mechanisms

by Rabia Naz, Fatima Saqib, Samir Awadallah, Muqeet Wahid, Muhammad Farhaj Latif, Iram Iqbal and Mohammad S. Mubarak

Molecules 2023, 28(10), 3996; https://doi.org/10.3390/molecules28103996 - 10 May 2023

Cited by 41 | Viewed by 10752

Abstract

Type II diabetes mellitus and its related complications are growing public health problems. Many natural products present in our diet, including polyphenols, can be used in treating and managing type II diabetes mellitus and different diseases, owing to their numerous biological properties. Anthocyanins, flavonols, stilbenes, curcuminoids, hesperidin, hesperetin, naringenin, and phenolic acids are common polyphenols found in blueberries, chokeberries, sea-buckthorn, mulberries, turmeric, citrus fruits, and cereals. These compounds exhibit antidiabetic effects through different pathways. Accordingly, this review presents an overview of the most recent developments in using food polyphenols for managing and treating type II diabetes mellitus, along with various mechanisms. In addition, the present work summarizes the literature about the anti-diabetic effect of food polyphenols and evaluates their potential as complementary or alternative medicines to treat type II diabetes mellitus. Results obtained from this survey show that anthocyanins, flavonols, stilbenes, curcuminoids, and phenolic acids can manage diabetes mellitus by protecting pancreatic β-cells against glucose toxicity, promoting β-cell proliferation, reducing β-cell apoptosis, and inhibiting α-glucosidases or α-amylase. In addition, these phenolic compounds exhibit antioxidant anti-inflammatory activities, modulate carbohydrate and lipid metabolism, optimize oxidative stress, reduce insulin resistance, and stimulate the pancreas to secrete insulin. They also activate insulin signaling and inhibit digestive enzymes, regulate intestinal microbiota, improve adipose tissue metabolism, inhibit glucose absorption, and inhibit the formation of advanced glycation end products. However, insufficient data are available on the effective mechanisms necessary to manage diabetes. Full article

(This article belongs to the Special Issue Novel Natural Compounds in Treatment of Diabetes)

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11 pages, 2505 KiB

Open AccessReview

Anthocyanins: Potential Therapeutic Approaches towards Obesity and Diabetes Mellitus Type 2

by Denise Franco-San Sebastián, Samary Alaniz-Monreal, Griselda Rabadán-Chávez, Natalia Vázquez-Manjarrez, Marcela Hernández-Ortega and Gabriela Gutiérrez-Salmeán

Molecules 2023, 28(3), 1237; https://doi.org/10.3390/molecules28031237 - 27 Jan 2023

Cited by 9 | Viewed by 3542

Abstract

Overweight and obesity are present in about three-quarters of the adult population in Mexico. The inflammatory mechanisms subjacent to visceral white adipose tissue are accountable for the initiation and development of cardiometabolic alterations, including type 2 diabetes. Lifestyle changes are pillars within its therapeutics and, thus, current dietary modifications should include not only hypocaloric prescriptions with balanced macronutrient intake, preferably by increasing the amount of whole grains, fruits, vegetables, nuts and legumes, but in concomitance, bioactive substances, such as anthocyanins, have been correlated with lower incidence of this disease. Full article

(This article belongs to the Special Issue Novel Natural Compounds in Treatment of Diabetes)

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