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Natural Products in Diabetes Mellitus

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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (3 August 2023) | Viewed by 43827

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Dr. Ana Angelica Feregrino-Perez

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División de Estudios de Posgrado, C.A. Bioingeniería Básicay Aplicada, Facultad de Ingeniería, Universidad Autónoma de Querétaro, C. U. Cerro de las Campanas, S/N, Querétaro 76010, Mexico
Interests: nutraceuticals; secondary metabolite; prebiotics; value added
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Dear Colleagues,

Diabetes mellitus (DM) is a chronic disease characterized by a state of hyperglycemia. This sustained increase in glucose levels induces oxidative damage, which can contribute in different ways to the development of chronic complications. Such complications have been directly or indirectly related to the high morbidity and mortality of DM. The increase in the prevalence of this disease is more marked in developing countries, although it does not exclude developed countries. Additionally, this disease represents a high cost to the health sector and to the patient. The prevention and control of DM consists of physical activity and diet modification. However, various natural products are used worldwide to aid in the control and prevention of DM.

Natural products come from various sources, such as plants, foods and microorganisms. They possess or generate bioactive compounds that may have antidiabetic activity, for which the mechanisms of action are diverse and range from the inhibition of enzymes such as alpha-amylase and alpha-glucosidase to the modification of hormonal activities involved in glucose homeostasis. Additionally, natural products can present diverse biological activities that can contribute to or generate synergy in the control and prevention of the predominant complications in DM, by reducing oxidative stress resulting from the increase in free radicals due to the high content of glucose in the blood. Therefore, natural products can contribute to antioxidant enzymatic activity.

However, the use of these natural products is generally part of traditional medicine, so there is not always information to support their use, dosage, toxicity, etc.

The study of the mechanisms of action of various natural products, either in isolation as an active substance or in a more complex form as an extract or in its natural state, is of interest since it provides knowledge for the development of therapeutic agents and adjuvant therapies for DM, in addition to generating information on dosage, toxicity, mechanisms of action, synergistic and/or antagonistic activity, etc.

For this Special Issue, we invite the submission of original contributions, reviews or short communications that contribute to the knowledge of natural products and their antidiabetic action, including either in vivo or in vitro models, therapeutic models, the characterization of compounds and extracts, and mechanisms of action.

Dr. Ana Angelica Feregrino-Perez
Guest Editor

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Keywords

natural products
hypoglycemia
phenolic compounds
diabetes mellitus
therapeutic
ROS

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Related Special Issue

Natural Products in Diabetes Mellitus: 2nd Edition in Pharmaceuticals (4 articles)

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Research

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17 pages, 1644 KiB

Open AccessArticle

LC/MS-MS Analysis of Phenolic Compounds in Hyoscyamus albus L. Extract: In Vitro Antidiabetic Activity, In Silico Molecular Docking, and In Vivo Investigation against STZ-Induced Diabetic Mice

by Sabrina Lekmine, Ouided Benslama, Kenza Kadi, Antonio Ignacio Martín-García, Mustafa Abdullah Yilmaz, Salah Akkal, Ali Boumegoura, Abdullah S. Alhomida, Mohammad Shamsul Ola and Ahmad Ali

Pharmaceuticals 2023, 16(7), 1015; https://doi.org/10.3390/ph16071015 - 18 Jul 2023

Cited by 9 | Viewed by 2918

Abstract

This study aimed to investigate the chemical composition and antidiabetic properties of cultivated Hyoscyamus albus L. The ethanol extract was analyzed using LC-MS/MS, and 18 distinct phenolic compounds were identified. Among these, p-coumaric acid (6656.8 ± 3.4 µg/g), gallic acid (6516 ± 1.7 µg/g), luteolin (6251.9 ± 1.3 µg/g), apigenin (6209.9 ± 1.1 µg/g), and rutin (5213.9 ± 1.3 µg/g) were identified as the most abundant polyphenolic molecules. In the in vitro antidiabetic experiment, the ability of the plant extract to inhibit α-glucosidase and α-amylase activities was examined. The results indicated that the extract from H. albus L. exhibited a higher inhibitory effect on α-amylase compared to α-glucosidase, with an IC50 of 146.63 ± 1.1 µg/mL and 270.43 ± 1.1 µg/mL, respectively. Docking simulations revealed that luteolin, fisetin, and rutin exhibited the most promising inhibitory activity against both enzymes, as indicated by their high contrasting inhibition scores. To further investigate the in vivo antidiabetic effects of H. albus L., an experiment was conducted using STZ-induced diabetic mice. The results demonstrated that the plant extract effectively reduced the levels of cholesterol and triglycerides. These findings suggest that H. albus L. may have therapeutic potential for managing hyperlipidemia, a common complication associated with diabetes. This highlights its potential as a natural remedy for diabetes and related conditions. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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21 pages, 7864 KiB

Open AccessArticle

D-Pinitol Content and Antioxidant and Antidiabetic Activities of Five Bougainvillea spectabilis Willd. Cultivars

by Fatma Abo-Elghiet, Amal H. Ahmed, Hanan F. Aly, Eman A. Younis, Mohamed A. Rabeh, Saad Ali Alshehri, Khalid S. A. Alshahrani and Shaza A. Mohamed

Pharmaceuticals 2023, 16(7), 1008; https://doi.org/10.3390/ph16071008 - 15 Jul 2023

Cited by 6 | Viewed by 2476

Abstract

Diabetes mellitus is a major challenge for global health, and Bougainvillea spectabilis Willd. (B. spectabilis) is a widely used herbal remedy with diverse cultivars traditionally used for diabetes treatment. However, the comparative efficacy of these cultivars remains ambiguous. This study aimed to evaluate the D-pinitol content and DPPH radical-scavenging activity of methanolic leaves extracts of five B. spectabilis cultivars. Furthermore, the effects of these cultivars on various parameters, including blood glucose levels, oxidative stress markers, inflammatory cytokines, lipid profiles, liver enzymes, renal function markers, and histopathological changes, were assessed in STZ-induced diabetic rats after one month of oral daily treatment. All tested cultivars demonstrated significant improvements in the measured parameters, albeit to varying extents. Notably, the LOE cultivar, distinguished by its orange bracts, exhibited the highest efficacy, surpassing the effectiveness of glibenclamide, an antidiabetic medication, and displayed the highest concentration of D-pinitol. These findings underscore the importance of carefully selecting the appropriate B. spectabilis cultivar to maximize the antidiabetic efficacy, with a particular emphasis on the correlation between antidiabetic activity and D-pinitol concentrations. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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17 pages, 4744 KiB

Open AccessArticle

Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance

by Ming Han, Yuting Lu, Yunhua Tao, Xinwen Zhang, Chengqiu Dai, Bingqian Zhang, Honghong Xu and Jingya Li

Pharmaceuticals 2023, 16(7), 975; https://doi.org/10.3390/ph16070975 - 7 Jul 2023

Cited by 8 | Viewed by 1915

Abstract

Diabetes, which is mainly characterized by increased apoptosis and dysfunction of beta (β) cells, is a metabolic disease caused by impairment of pancreatic islet function. Previous studies have demonstrated that death-associated protein kinase-related apoptosis-inducing kinase-2 (Drak2) is involved in regulating β cell survival. Since natural products have multiple targets and often are multifunctional, making them promising compounds for the treatment of diabetes, we identified Drak2 inhibitors from a natural product library. Among the identified products, luteolin, a flavonoid, was found to be the most effective compound. In vitro, luteolin effectively alleviated palmitate (PA)-induced apoptosis of β cells and PA-induced impairment of primary islet function. In vivo, luteolin showed a tendency to lower blood glucose levels. It also alleviated STZ-induced apoptosis of β cells and metabolic disruption in mice. This function of luteolin partially relied on Drak2 inhibition. Furthermore, luteolin was also found to effectively relieve oxidative stress and promote autophagy in β cells, possibly improving β cell function and slowing the progression of diabetes. In conclusion, our findings show the promising effect of Drak2 inhibitors in relieving diabetes and offer a potential therapeutic target for the protection of β cells. We also reveal some of the underlying mechanisms of luteolin’s cytoprotective function. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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14 pages, 634 KiB

Open AccessArticle

Antidiabetic and Anticancer Potentials of Mangifera indica L. from Different Geographical Origins

by Rizwan Ahmad, Aljawharah Alqathama, Mohammed Aldholmi, Muhammad Riaz, Ashraf N. Abdalla, Fatema Aljishi, Ebtihal Althomali, Mohd Amir, Omeima Abdullah, Muntathir Ali Alamer, Deema Alaswad, Wala Alsulais and Ahad Alsulays

Pharmaceuticals 2023, 16(3), 350; https://doi.org/10.3390/ph16030350 - 24 Feb 2023

Cited by 4 | Viewed by 2806

Abstract

Mango fruit is well known for its nutritional and health benefits due to the presence of a plethora of phytochemical classes. The quality of mango fruit and its biological activities may change depending upon the variation in geographical factors. For the first time, this study comprehensively screened the biological activities of all four parts of the mango fruit from twelve different origins. Various cell lines (MCF7, HCT116, HepG2, MRC5) were used to screen the extracts for their cytotoxicity, glucose uptake, glutathione peroxidase activity, and α-amylase inhibition. MTT assays were carried out to calculate the IC₅₀ values for the most effective extracts. The seed part from Kenya and Sri Lanka origins exhibited an IC₅₀ value of 14.44 ± 3.61 (HCT116) and 17.19 ± 1.60 (MCF7). The seed part for Yemen Badami (119 ± 0.08) and epicarp part of Thailand (119 ± 0.11) mango fruit showed a significant increase in glucose utilization (50 μg/mL) as compared to the standard drug metformin (123 ± 0.07). The seed extracts of Yemen Taimoor seed (0.46 ± 0.05) and Yemen Badami (0.62 ± 0.13) produced a significant reduction in GPx activity (50 μg/mL) compared to the control cells (100 μg/mL). For α-amylase inhibition, the lowest IC₅₀ value was observed for the endocarp part of Yemen Kalabathoor (108.8 ± 0.70 μg/mL). PCA, ANOVA, and Pearson’s statistical models revealed a significant correlation for the fruit part vs. biological activities, and seed part vs. cytotoxicity and α-amylase activity (p = 0.05). The seed of mango fruit exhibited significant biological activities; hence, further in-depth metabolomic and in vivo studies are essential to effectively utilize the seed part for the treatment of various diseases. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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21 pages, 3258 KiB

Open AccessArticle

Combined Gamma Conglutin and Lupanine Treatment Exhibits In Vivo an Enhanced Antidiabetic Effect by Modulating the Liver Gene Expression Profile

by Paloma Lucía Guerra-Ávila, Tereso J. Guzmán, José Alfredo Domínguez-Rosales, Pedro Macedonio García-López, Alejandra Beatriz Cervantes-Garduño, Michael Wink and Carmen Magdalena Gurrola-Díaz

Pharmaceuticals 2023, 16(1), 117; https://doi.org/10.3390/ph16010117 - 13 Jan 2023

Cited by 5 | Viewed by 2950

Abstract

Previous studies have individually shown the antidiabetic potential of gamma conglutin (Cγ) and lupanine from lupins. Until now, the influence of combining both compounds and the effective dose of the combination have not been assessed. Moreover, the resulting gene expression profile from this novel combination remains to be explored. Therefore, we aimed to evaluate different dose combinations of Cγ and lupanine by the oral glucose tolerance test (OGTT) to identify the higher antidiabetic effect on a T2D rat model. Later, we administered the selected dose combination during a week. Lastly, we evaluated biochemical parameters and liver gene expression profile using DNA microarrays and bioinformatic analysis. We found that the combination of 28 mg/kg BW Cγ + 20 mg/kg BW lupanine significantly reduced glycemia and lipid levels. Moreover, this treatment positively influenced the expression of Pdk4, G6pc, Foxo1, Foxo3, Ppargc1a, Serpine1, Myc, Slc37a4, Irs2, and Igfbp1 genes. The biological processes associated with these genes are oxidative stress, apoptosis regulation, and glucose and fatty-acid homeostasis. For the first time, we report the beneficial in vivo effect of the combination of two functional lupin compounds. Nevertheless, further studies are needed to investigate the pharmacokinetics and pharmacodynamics of the Cγ + lupanine combined treatment. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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22 pages, 4850 KiB

Open AccessArticle

Combinatory Effect and Modes of Action of Chrysin and Bone Marrow-Derived Mesenchymal Stem Cells on Streptozotocin/Nicotinamide-Induced Diabetic Rats

by Hesham M. Sayed, Ashraf S. Awaad, Fatma El-Zahraa S. Abdel Rahman, M. Al-Dossari, N. S. Abd El-Gawaad and Osama M. Ahmed

Pharmaceuticals 2023, 16(1), 34; https://doi.org/10.3390/ph16010034 - 27 Dec 2022

Cited by 10 | Viewed by 2763

Abstract

The purpose of this study was to see how chrysin and/or bone marrow-derived mesenchymal stem cells (BM-MSCs) affected streptozotocin (STZ)/nicotinamide (NA)-induced diabetic rats as an animal model of type 2 diabetes mellitus (T2DM). Male Wistar rats were given a single intraperitoneal (i.p.) injection of 60 mg STZ/kg bodyweight (bw) 15 min after an i.p. injection of NA (120 mg/kg bw) to induce T2DM. The diabetic rats were given chrysin orally at a dose of 100 mg/kg bw every other day, BM-MSCs intravenously at a dose of 1 × 10⁶ cells/rat/week, and their combination for 30 days after diabetes induction. The rats in the diabetic group displayed impaired oral glucose tolerance and a decrease in liver glycogen content and in serum insulin, C-peptide, and IL-13 levels. They also had significantly upregulated activities in terms of liver glucose-6-phosphatase and glycogen phosphorylase and elevated levels of serum free fatty acids, IL-1β, and TNF-α. In addition, the diabetic rats exhibited a significant elevation in the adipose tissue resistin protein expression level and a significant decrease in the expression of adiponectin, insulin receptor-beta subunit, insulin receptor substrate-1, and insulin receptor substrate-2, which were associated with a decrease in the size of the pancreatic islets and in the number of β-cells and insulin granules in the islets. The treatment of diabetic rats with chrysin and/or BM-MSCs significantly improved the previously deteriorated alterations, with chrysin combined with BM-MSCs being the most effective. Based on these findings, it can be concluded that combining chrysin with BM-MSCs produced greater additive therapeutic value than using them separately in NA/STZ-induced T2DM rats. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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13 pages, 1446 KiB

Open AccessArticle

Biological Screening of Glycyrrhiza glabra L. from Different Origins for Antidiabetic and Anticancer Activity

by Rizwan Ahmad, Aljawharah Alqathama, Mohammed Aldholmi, Muhammad Riaz, Mohammed H. Mukhtar, Fatema Aljishi, Ebtihal Althomali, Muntathir Ali Alamer, Mohammed Alsulaiman, Abdulmalik Ayashy and Mohsen Alshowaiki

Pharmaceuticals 2023, 16(1), 7; https://doi.org/10.3390/ph16010007 - 21 Dec 2022

Cited by 7 | Viewed by 3348

Abstract

Background: Geographical variation may affect the phytochemistry as well as the biological activities of Glycyrrhiza glabra (licorice) root. Herein, a series of biological activities were performed to evaluate the impact of geographical origin on the biological potential of eight different licorice samples. Methodology: Cell culture studies were performed for cytotoxicity (MCF7, HCT116, HepG2, and MRC5), glucose uptake assay (HepG2), and glutathione peroxidase activity (HepG2), whereas α-amylase inhibition activity was tested for antidiabetic potential. Results: The Indian sample was observed to be more cytotoxic against MCF7 (22%) and HCT116 (43%) with an IC₅₀ value of 56.10 (±2.38) μg/mL against the MCF7 cell line. The glucose uptake was seen with a mean value of 96 (±2.82) and a range of 92–101%. For glutathione peroxidase activity (GPx), the Syrian (0.31 ± 0.11) and Pakistani samples (0.21 ± 0.08) revealed a significant activity, whereas the Palestinian (70 ± 0.09) and Indian samples (68±0.06) effectively inhibited the α-amylase activity, with the lowest IC₅₀ value (67.11 ± 0.97) μg/mL for the Palestinian sample. The statistical models of PCA (principal component analysis) and K-mean cluster analysis were performed to correlate the geographical origin, extract yield, and biological activities for the eight licorice samples of different origins. Conclusion: The licorice samples exhibited significant cytotoxic, GPx, and α-amylase inhibitory activity. The samples with higher extract yield showed more potential in these biological activities. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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26 pages, 6476 KiB

Open AccessArticle

Natural Compounds of Lasia spinosa (L.) Stem Potentiate Antidiabetic Actions by Regulating Diabetes and Diabetes-Related Biochemical and Cellular Indexes

by Md. Mamunur Rashid, Md. Atiar Rahman, Md. Shahidul Islam, Md. Amjad Hossen, A. M. Abu Ahmed, Mirola Afroze, Alaa H. Habib, Manal M. S. Mansoury, Hend F. Alharbi, Reham M. Algheshairy, Walla Alelwani, Afnan M. Alnajeebi, Jitbanjong Tangpong, Srabonti Saha, Alaa Qadhi and Wedad Azhar

Pharmaceuticals 2022, 15(12), 1466; https://doi.org/10.3390/ph15121466 - 25 Nov 2022

Cited by 6 | Viewed by 3982 | Correction

Abstract

Natural biometabolites of plants have been reported to be useful in chronic diseases including diabetes and associated complications. This research is aimed to investigate how the biometabolites of Lasia spinosa methanol stem (ME_XLS) extract ameliorative diabetes and diabetes-related complications. ME_XLS was examined for in vitro antioxidant and in vivo antidiabetic effects in a streptozotocin-induced diabetes model, and its chemical profiling was done by gas chromatography-mass spectrometry analysis. The results were verified by histopathological examination and in silico ligand-receptor interaction of characterized natural biometabolites with antidiabetic receptor proteins AMPK (PDB ID: 4CFH); PPARγ (PDB ID: 3G9E); and mammalian α-amylase center (PDB ID: 1PPI). The ME_XLS was found to show a remarkable α-amylase inhibition (47.45%), strong antioxidant action, and significant (p < 0.05) decrease in blood glucose level, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein (LDL), urea, uric acid, creatinine, total cholesterol, triglyceride (TG), liver glycogen, creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase in serum insulin, glucose tolerance, and high-density lipoprotein (HDL). Rat’s pancreas and kidney tissues were found to be partially recovered in histopathological analyses. Methyl α-d-galactopyranoside displayed the highest binding affinity with AMPK (docking score, −5.764), PPARγ (docking score, −5.218), and 1PPI (docking score, −5.615) receptors. Data suggest that the ME_XLS may be an exciting source to potentiate antidiabetic activities affirming a cell-line study. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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15 pages, 3705 KiB

Open AccessArticle

Heliciopsides A−E, Unusual Macrocyclic and Phenolic Glycosides from the Leaves of Heliciopsis terminalis and Their Stimulation of Glucose Uptake

by Byeol Ryu, Eun-Jin Park, Thi-Phuong Doan, Hyo-Moon Cho, Jin-Pyo An, Thi-Linh-Giang Pham, Ha-Thanh-Tung Pham and Won-Keun Oh

Pharmaceuticals 2022, 15(11), 1315; https://doi.org/10.3390/ph15111315 - 25 Oct 2022

Cited by 3 | Viewed by 2100

Abstract

Ten phenolic constituents, including three new macrocyclic glycosides (1–3), a new phenolic glycoside (5), a new biphenyl glycoside (6), and five known compounds (4, 7–10), were isolated from a 70% MeOH extract of the leaves of Heliciopsis terminalis by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-guided molecular networking. The chemical structures of new compounds 1–3, 5 and 6 were established based on comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS techniques. All isolated compounds (1–10) were evaluated for their stimulation of glucose uptake in differentiated 3T3-L1 adipocytes using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a fluorescent glucose analog. Compounds 3, 6 and 8 showed stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells. Among them, compounds 3 and 6 activated the AMPK signaling pathway in differentiated C2C12 myoblasts. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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18 pages, 2515 KiB

Open AccessArticle

Valorisation of the Inhibitory Potential of Fresh and Dried Fruit Extracts of Prunus spinosa L. towards Carbohydrate Hydrolysing Enzymes, Protein Glycation, Multiple Oxidants and Oxidative Stress-Induced Changes in Human Plasma Constituents

by Anna Magiera, Joanna Kołodziejczyk-Czepas, Karolina Skrobacz, Monika Ewa Czerwińska, Magdalena Rutkowska, Aleksandra Prokop, Piotr Michel and Monika Anna Olszewska

Pharmaceuticals 2022, 15(10), 1300; https://doi.org/10.3390/ph15101300 - 21 Oct 2022

Cited by 5 | Viewed by 2452

Abstract

Prunus spinosa fruits (sloes), both fresh and dried, are underexplored dietary components and ethno-phytotherapeutic remedies applied to treat chronic oxidative-stress-related diseases, including diabetes. The present study aimed to evaluate drying-related changes in the antidiabetic potential of sloe extracts and some bioactivity mechanisms, which might be connected with their traditional application. The polyphenol-enriched extracts, prepared by fractionated extraction and phytochemically standardised, i.a., by LC-MS/MS, were tested in vitro using a set of biological and chemical models. The experiments revealed the significant extracts’ ability to counteract the generation of advanced glycation end products (AGEs) and inhibit the activity of key glycolytic enzymes, i.e., α-glucosidase and α-amylase. Moreover, they were proved to effectively scavenge multiple oxidants of physiological importance (O₂^•−, HO^•, H₂O₂, NO^•, HOCl), increase the non-enzymatic antioxidant capacity of human plasma (NEAC) under oxidative stress conditions induced by peroxynitrite, and protect plasma proteins and lipids against peroxidation and nitration at in vivo-relevant levels (1–50 µg/mL, equivalent to 0.03–6.32 µg polyphenols/mL). In most cases, the activity of fresh fruit extracts surpassed that of dried-based products. The correlation studies and tests on model compounds proved polyphenols as dominant contributors to the observed effects. Furthermore, the co-occurring representatives of various polyphenolic classes were found to contribute to the biological activity of sloes through additive and synergistic effects. Considering the extraction yield and activity parameters, especially the superior outcomes compared to anti-diabetic drugs aminoguanidine and acarbose in the anti-glycation and α-glucosidase inhibition tests, the methanol–water (75:25, v/v) extract of fresh fruits and its phenolic-enriched fractions revealed the most advantageous potential for functional application. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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12 pages, 1929 KiB

Open AccessArticle

Anti-Alzheimer and Antioxidant Effects of Nelumbo nucifera L. Alkaloids, Nuciferine and Norcoclaurine in Alloxan-Induced Diabetic Albino Rats

by Shahnaz Khan, Hidayat Ullah Khan, Farman Ali Khan, Afzal Shah, Abdul Wadood, Shujaat Ahmad, Mazen Almehmadi, Ahad Amer Alsaiari, Farid Ullah Shah and Naveed Kamran

Pharmaceuticals 2022, 15(10), 1205; https://doi.org/10.3390/ph15101205 - 28 Sep 2022

Cited by 20 | Viewed by 2947

Abstract

The present study is aimed to determine the efficacy and dose response of the nuciferine (1), norcoclaurine (2) and crude extract of Nelumbo nucifera in managements of diabetes, Alzheimer disease and related allergies. Experimentally, alloxan (100 mg/kg body weight (b.w.))-induced diabetic rats (200–250 g) were divided into seven groups (n = 6). Group I: normal control, Group II: diabetic control, Group III: standard treated with glibenclamide and Group lV-VII: treated with methanolic crude extracts (100, 200 mg/kg), nuciferine and norcoclaurine (10 mg/kg b.w.) for 15 days. Different tests were performed, including blood glucose, body weights and antioxidant enzyme assays, i.e., superoxide dismutase (SOD), catalase test (CAT), lipid peroxidation assay (TBARS), glutathione assay (GSH) and acetylcholinesterase (AChE) assay. Nuciferine and norcoclaurine significantly reduced blood glucose (p < 0.05) and restored body weight in diabetic rats. Moreover, nuciferine and norcoclaurine (10 mg/kg) significantly recovered the antioxidant enzymes (SOD, CAT, GPx and GSH) which decreased during induced diabetes. Significant increase in TBARS was also observed in the diabetic group and nuciferine as well as norcoclaurine (10 mg/kg) inhibited the increase in TBARS in diabetic animals (p < 0.05), as compared to glibenclamide. AChE activity was significantly recovered by nuciferine and norcoclaurine (10 mg/kg) both in the blood and brain of the diabetic group (p < 0.05). Nuciferine and norcoclaurine showed potent inhibitory effects against α-glucosidase and α-amylase with IC₅₀, 19.06 ± 0.03, 15.03 ± 0.09 μM and 24.07 ± 0.05, 18.04 ± 0.021 μM, as confirmed by molecular docking studies. This study concludes that nuciferine and norcoclaurine significantly improve memory and could be considered as an effective phytomedicine for diabetes, Alzheimer’s disease (AD) and oxidative stress. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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Review

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18 pages, 1395 KiB

Open AccessReview

Modulatory Effect of Medicinal Plants and Their Active Constituents on ATP-Sensitive Potassium Channels (K_ATP) in Diabetes

by Lina T. Al Kury

Pharmaceuticals 2023, 16(4), 523; https://doi.org/10.3390/ph16040523 - 31 Mar 2023

Cited by 2 | Viewed by 2349

Abstract

Hyperglycemia, which is a chronic metabolic condition caused by either a defect in insulin secretion or insulin resistance, is a hallmark of diabetes mellitus (DM). Sustained hyperglycemia leads to the onset and development of many health complications. Despite the number of available antidiabetic medications on the market, there is still a need for novel treatment agents with increased efficacy and fewer adverse effects. Many medicinal plants offer a rich supply of bioactive compounds that have remarkable pharmacological effects with less toxicity and side effects. According to published evidence, natural antidiabetic substances influence pancreatic β-cell development and proliferation, inhibit pancreatic β-cell death, and directly increase insulin output. Pancreatic ATP-sensitive potassium channels play an essential role in coupling glucose metabolism to the secretion of insulin. Although much of the literature is available on the antidiabetic effects of medicinal plants, very limited studies discuss their direct action on pancreatic K_ATP. The aim of this review is to focus on the modulatory effects of antidiabetic medicinal plants and their active constituents on pancreatic K_ATP. The K_ATP channel should be regarded as a key therapeutic milestone in the treatment of diabetes. Therefore, continuous research into the interaction of medicinal plants with the K_ATP channel is crucial. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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23 pages, 802 KiB

Open AccessReview

Role of Fenugreek, Cinnamon, Curcuma longa, Berberine and Momordica charantia in Type 2 Diabetes Mellitus Treatment: A Review

by Marisol Cortez-Navarrete, Karina G. Pérez-Rubio and Miriam de J. Escobedo-Gutiérrez

Pharmaceuticals 2023, 16(4), 515; https://doi.org/10.3390/ph16040515 - 30 Mar 2023

Cited by 7 | Viewed by 7353

Abstract

Type 2 diabetes mellitus (T2DM) is a complex disease that has become a major global health concern. Given the efficacy of antidiabetic drugs, pharmacological therapy is considered the first-line treatment of T2DM; however, due to their potential side effects and high costs, new and cost-effective treatments with minimal side effects are needed. Medicinal plants have been used for centuries as part of traditional medicine to treat T2DM. Among these, fenugreek, cinnamon, Curcuma longa, berberine, and Momordica charantia have demonstrated different degrees of hypoglycemic activity in clinical studies and animal models. Therefore, the aim of this review is to synthesize the mechanisms of action of five medicinal plants, as well as the experimental and clinical evidence of their hypoglycemic activity from the published literature. Full article

(This article belongs to the Special Issue Natural Products in Diabetes Mellitus)

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