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Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes 4.0

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

Deadline for manuscript submissions: closed (28 April 2023) | Viewed by 10601

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Dr. Béla Juhász

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Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary
Interests: dyslipidemia; atherosclerosis; echocardiography; oxidative stress; cardioprotection; type 2 diabetes; bioactive compounds; chronic diseases; nutraceuticals
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Dear Colleagues,

Metabolic syndrome and type 2 diabetes are still the major causes of morbidity and mortality among elderly people, with an increasing prevalence worldwide. These disorders cause micro- and macrovascular damage, leading to consequences such as CAD, ischemia, heart failure, stroke, neuronal disturbances, reproductive and joint diseases, and other syndromes characterized by dysregulated inflammatory processes, and degradation of tissue function, despite numerous recommendations emphasizing lifestyle changes, pharmacotherapy, and surgical procedures as essential in the prevention and treatment of these syndromes, especially in more severe or chronic cases.

Bioactive compounds (phytonutrients or functional foods) and their derivates, biological antibodies, have been defined as the extra nutritional constituents that are derived from natural products in small quantities. These molecules are mainly phytochemicals that can modulate metabolic processes, resulting in the promotion of better health. The bioaccessibility and bioavailability of each bioactive compound differs greatly, since several bioactive plant compounds are produced as secondary metabolites that are not essential for the daily functioning of the plant (such as growth), but which play a significant role in competition, defense, attraction and signaling. Bioactive compounds in plants, animals, mushrooms, etc. can be specified as secondary metabolites eliciting pharmacological or toxicological effects in humans and animals. They include various molecules such as flavonoids, carotenoids, carnitine, choline, coenzyme Q, creatine, dithiolthiones, phytosterols, polysaccharides, phytoestrogens, glucosinolates, polyphenols, anthocyanins, prebiotics, taurine, other derivates or even animal toxins and/or antibodies.

This Special Issue aims to bring together food chemistry and food technology (with analysis or characterization of natural compounds) in medical interest and nutraceutical studies (for diet therapy) to identify and discuss cutting-edge research on novel ways in the treatment of metabolic syndrome and type 2 diabetes.

Dr. Béla Juhász
Guest Editor

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Keywords

metabolic syndrome
diabetes
dyslipidemia
cardiovascular diseases
obesity
insulin resistance
bioactive compounds
biological therapy
nutraceuticals
natural products and derivates
food chemistry

Published Papers (6 papers)

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Research

22 pages, 6144 KiB

Open AccessArticle

The Mechanism of Kelulut Honey in Reversing Metabolic Changes in Rats Fed with High-Carbohydrate High-Fat Diet

by Khairun-Nisa Hashim, Kok-Yong Chin and Fairus Ahmad

Molecules 2023, 28(6), 2790; https://doi.org/10.3390/molecules28062790 - 20 Mar 2023

Cited by 2 | Viewed by 1996

Abstract

Metabolic syndrome (MetS) is composed of central obesity, hyperglycemia, dyslipidemia and hypertension that increase an individual’s tendency to develop type 2 diabetes mellitus and cardiovascular diseases. Kelulut honey (KH) produced by stingless bee species has a rich phenolic profile. Recent studies have demonstrated that KH could suppress components of MetS, but its mechanisms of action are unknown. A total of 18 male Wistar rats were randomly divided into control rats (C group) (n = 6), MetS rats fed with a high carbohydrate high fat (HCHF) diet (HCHF group) (n = 6), and MetS rats fed with HCHF diet and treated with KH (HCHF + KH group) (n = 6). The HCHF + KH group received 1.0 g/kg/day KH via oral gavage from week 9 to 16 after HCHF diet initiation. Compared to the C group, the MetS group experienced a significant increase in body weight, body mass index, systolic (SBP) and diastolic blood pressure (DBP), serum triglyceride (TG) and leptin, as well as the area and perimeter of adipocyte cells at the end of the study. The MetS group also experienced a significant decrease in serum HDL levels versus the C group. KH supplementation reversed the changes in serum TG, HDL, leptin, adiponectin and corticosterone levels, SBP, DBP, as well as adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) level, area and perimeter at the end of the study. In addition, histological observations also showed that KH administration reduced fat deposition within hepatocytes, and prevented deterioration of pancreatic islet and renal glomerulus. In conclusion, KH is effective in preventing MetS by suppressing leptin, corticosterone and 11βHSD1 levels while elevating adiponectin levels. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes 4.0)

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17 pages, 5454 KiB

Open AccessArticle

Thioether and Ether Furofuran Lignans: Semisynthesis, Reaction Mechanism, and Inhibitory Effect against α-Glucosidase and Free Radicals

by Wisuttaya Worawalai, Nantaporn Surachaitanawat, Phonpimon Khongchai, Viwat Vchirawongkwin, Thammarat Aree and Preecha Phuwapraisirisan

Molecules 2022, 27(24), 9001; https://doi.org/10.3390/molecules27249001 - 17 Dec 2022

Cited by 1 | Viewed by 1276

Abstract

The transformation of sesame lignans is interesting because the derived products possess enhanced bioactivity and a wide range of potential applications. In this study, the semisynthesis of 28 furofuran lignans using samin (5) as the starting material is described. Our methodology involved the protonation of samin (5) to generate an oxocarbenium ion followed by the attack from two different nucleophiles, namely, thiols (RSH) and alcohols (ROH). The highly diastereoselective thioether and ether furofuran lignans were obtained, and their configurations were confirmed by 2D NMR and X-ray crystallography. The mechanism underlying the reaction was studied by monitoring ¹H NMR and computational calculations, that is, the diastereomeric α- and β-products were equally formed through the S_N1-like mechanism, while the β-product was gradually transformed via an S_N2-like mechanism to the α-congener in the late step. Upon evaluation of the inhibitory effect of the synthesized lignans against α-glucosidases and free radicals, the lignans 7f and 7o of the phenolic hydroxyl group were the most potent inhibitors. Additionally, the mechanisms underlying the α-glucosidase inhibition of 7f and 7o were verified to be of a mixed manner and noncompetitive inhibition, respectively. The results indicated that both 7f and 7o possessed promising antidiabetic activity, while simultaneously inhibiting α-glucosidases and free radicals. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes 4.0)

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19 pages, 3495 KiB

Open AccessArticle

Chalcone-1-Deoxynojirimycin Heterozygote Reduced the Blood Glucose Concentration and Alleviated the Adverse Symptoms and Intestinal Flora Disorder of Diabetes Mellitus Rats

by Pin-Jian Xiao, Jia-Cheng Zeng, Ping Lin, Dao-Bang Tang, En Yuan, Yong-Gang Tu, Qing-Feng Zhang, Ji-Guang Chen, Da-Yong Peng and Zhong-Ping Yin

Molecules 2022, 27(21), 7583; https://doi.org/10.3390/molecules27217583 - 4 Nov 2022

Cited by 3 | Viewed by 1756

Abstract

Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes 4.0)

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15 pages, 4251 KiB

Open AccessArticle

Mechanistic Insights into the Ameliorative Effect of Cichoriin on Diabetic Rats—Assisted with an In Silico Approach

by Hany Ezzat Khalil, Miada F. Abdelwahab, Hairul-Islam Mohamed Ibrahim, Khalid A. AlYahya, Ahmed Adel Mohamed, Amira Samir Radwan and Shaimaa Waz

Molecules 2022, 27(21), 7192; https://doi.org/10.3390/molecules27217192 - 24 Oct 2022

Cited by 1 | Viewed by 1468

Abstract

Type 2 diabetes mellitus is considered to be a substantial socioeconomic burden worldwide on both patients and governments. Coumarins are biomolecules with a diversity of biological activities. The current investigation aimed to explore the ameliorative effects of cichoriin, which is a type of coumarin, on high-fat diet/streptozotocin (HFD/STZ)-induced diabetic rats. Methods: Rats were allocated into five groups. Group I was considered as the control group, while the other groups were HFD/STZ-induced diabetic rats. Group II was assigned as the diabetic control. Groups III and IV were treated with cichoriin (50 or 100 mg/kg, respectively). Group V received glibenclamide (5 mg/kg) (as a positive control). The blood glucose (BG), serum insulin, triglycerides (TG), total cholesterol (TC), total antioxidant capacity (TAC), catalase, hepatic superoxide dismutase (SOD) and content of malondialdehyde (MDA) were assessed. Histopathological and immunohistochemistry analysis of pancreatic tissue were performed. mRNA and protein expressions of GLUT4, AMPK, and PI3K were estimated. Results: Cichoriin treatment ameliorated HFD/STZ-induced diabetic conditions and mitigated the histopathological characteristics of the pancreas, as well as increasing pancreatic insulin expression. This decreased the levels of BG, TG, TC, and MDA and improved the TAC, catalase and SOD contents. Cichoriin demonstrated upregulation of mRNA and protein expressions of GLUT4, AMPK, and PI3K. The in silico binding of cichoriin with GLUT4, AMPK, and PI3K supported the possible current activities. Conclusion: Collectively, this work highlighted the potential role of cichoriin in mitigating HFD/STZ-induced diabetic conditions and showed it to be a valuable product. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes 4.0)

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30 pages, 55704 KiB

Open AccessArticle

Syringic Acid Ameliorates Cardiac, Hepatic, Renal and Neuronal Damage Induced by Chronic Hyperglycaemia in Wistar Rats: A Behavioural, Biochemical and Histological Analysis

by Anwarbaig C. Mirza, Shital S. Panchal, Ahmed A. Allam, Sarah I. Othman, Milan Satia and Sanjay N. Mandhane

Molecules 2022, 27(19), 6722; https://doi.org/10.3390/molecules27196722 - 9 Oct 2022

Cited by 9 | Viewed by 1899

Abstract

This study investigated the effects of syringic acid (SA) on renal, cardiac, hepatic, and neuronal diabetic complications in streptozotocin-induced neonatal (nSTZ) diabetic rats. STZ (110 mg/kg i.p) was injected into Wistar rat neonates as a split dose (second and third postnatal day). Diabetes mellitus was diagnosed in adults by measuring fasting blood glucose levels, urine volume, and food and water intake. The treatment of SA (25 mg/kg, 50 mg/kg p.o) was given from the 8th to 18th postnatal week. To assess the development of diabetic complications and the effect of therapy, biochemical indicators in serum and behavioural parameters were recorded at specific intervals during the study period. SA (25 mg/kg, 50 mg/kg p.o) treatment reduced hyperglycaemia, polydipsia, polyphagia, polyuria, relative organ weight, cardiac hypertrophic indices, inflammatory markers, cell injury markers, glycated haemoglobin, histopathological score, and oxidative stress, and increased Na/K ATPase activity. These findings suggest that SA might significantly alleviate diabetic complications and/or renal, neuronal, cardiac, and hepatic damage in nSTZ diabetic rats. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes 4.0)

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17 pages, 2283 KiB

Open AccessFeature PaperArticle

Regulatory Effects of Metformin, an Antidiabetic Biguanide Drug, on the Metabolism of Primary Rat Adipocytes

by Tomasz Szkudelski, Klaudia Konieczna and Katarzyna Szkudelska

Molecules 2022, 27(16), 5250; https://doi.org/10.3390/molecules27165250 - 17 Aug 2022

Cited by 5 | Viewed by 1622

Abstract

Metformin is a biguanide compound commonly applied in humans with type 2 diabetes. The drug affects different tissues, including fat tissue. The direct influence of metformin on cells of fat tissue, i.e., adipocytes, is poorly elucidated. In the present study, the short-term (4-h) effects of metformin on lipogenesis, glucose transport, lipolysis, and lactate release in primary rat adipocytes were explored. It was demonstrated that metformin reduced insulin-induced lipogenesis and increased glucose transport into adipocytes. The tested compound also decreased lactate release from fat cells. It was shown that metformin substantially limited lipolysis stimulated by epinephrine (adrenergic receptor agonist) and dibutyryl-cAMP (direct activator of protein kinase A). Moreover, metformin decreased the lipolytic process triggered by DPCPX (adenosine A₁ receptor antagonist). In the case of each lipolytic stimulator, the drug evoked a similar inhibitory effect in the presence of 3 and 12 mM glucose. The lipolytic response of adipocytes to epinephrine was also found to be reduced by metformin when glucose was replaced by alanine. It was demonstrated that the tested compound limits the release of both glycerol and fatty acids from fat cells. The results of the present study provided evidence that metformin significantly affects the metabolism of primary rat adipocytes. Its action covers processes related to lipid accumulation and release and occurs after relatively short-term exposure. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes 4.0)

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