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Research Progress of Plant Compounds for Diabetes and Its Complications

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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 (29 February 2024) | Viewed by 29564

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Dr. Cosmin Mihai Vesa

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Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
Interests: physiology; diabetes mellitus; metabolic diseases; obesity; nutrition
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Prof. Dr. Dana Zaha

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Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
Interests: laboratory analysis in metabolic disease; diabetes mellitus
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Dear Colleagues,

Numerous chronic complications appear in the evolution of diabetes mellitus type 2 and type 1, and they significantly influence the duration of life of the patient. Diabetes mellitus is a metabolic disease where pro-oxidant, pro-inflammatory mechanisms are very expressed. Given the numerous beneficial effects that compounds extracted from different plants have, such as reduction in insulin resistance, improvement of endothelial function, improvement of beta-cell function, improvement of lipid metabolism, antioxidant effect, anti-inflammatory effect, the idea behind this Special Issue is to present significant results from original research or from international data in review articles. It is not only the potential chemical substances extracted form plants that are important, but also the delivery of these substances to target tissues; therefore, the issue will also focus on modalities to improve the biological effects of these substances, such as nanotechnology. Standardization of these substances and their potential evolution toward drug development is the key concept of this Special Issue, with the ultimate goal to develop new drugs starting from beneficial plant compounds to target the complications of diabetes mellitus at the molecular level.

Dr. Cosmin Mihai Vesa
Prof. Dr. Dana Carmen Zaha
Guest Editors

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Keywords

plant compounds
antioxidant
anti-inflammatory
biomarkers
diabetes mellitus
microvascular diabetes complications
insulin resistance
metabolic diseases
nanotechnology

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Research Progress of Plant Compounds for Diabetes and Its Complications, 2nd Edition in Metabolites

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24 pages, 16314 KiB

Open AccessArticle

Effects of Gold Nanoparticles Phytoreduced with Rutin in an Early Rat Model of Diabetic Retinopathy and Cataracts

by Mădălina Moldovan, Ana-Maria Păpurică, Mara Muntean, Raluca Maria Bungărdean, Dan Gheban, Bianca Moldovan, Gabriel Katona, Luminița David and Gabriela Adriana Filip

Metabolites 2023, 13(8), 955; https://doi.org/10.3390/metabo13080955 - 18 Aug 2023

Cited by 1 | Viewed by 1819

Abstract

Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycaemia. Plant-based therapies are characterised by low tissue bioavailability. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Eye fundus of retinal arterioles, transmission electron microscopy (TEM) of lenses, and histopathology of retinas were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fibre disorganisation. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately oedematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA and increased antioxidant capacity. Retinal edema and disorganisation in lens fibres were still present. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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17 pages, 5286 KiB

Open AccessArticle

Comparative Antihyperglycemic and Antihyperlipidemic Effects of Lawsone Methyl Ether and Lawsone in Nicotinamide-Streptozotocin-Induced Diabetic Rats

by Muhammad Khan, Muhammad Ajmal Shah, Mustafa Kamal, Mohammad Shamsul Ola, Mehboob Ali and Pharkphoom Panichayupakaranant

Metabolites 2023, 13(7), 863; https://doi.org/10.3390/metabo13070863 - 20 Jul 2023

Cited by 6 | Viewed by 1910

Abstract

Our previous study uncovered potent inhibitory effects of two naphthoquinones from Impatiens balsamina, namely lawsone methyl ether (2-methoxy-1,4-naphthoquinone, LME) and lawsone (2-hydroxy-1,4-naphthoquinone), against α-glucosidase. This gave us the insight to compare the hypoglycemic and hypolipidemic effects of LME and lawsone in high-fat/high-fructose-diet- and nicotinamide-streptozotocin-induced diabetic rats for 28 days. LME and lawsone at the doses of 15, 30, and 45 mg/kg, respectively, produced a substantial and dose-dependent reduction in the levels of fasting blood glucose (FBG), HbA1c, and food/water intake while boosting the insulin levels and body weights of diabetic rats. Additionally, the levels of total cholesterol (TC), triglycerides (TGs), high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), aspartate transaminase (AST), alanine transaminase (ALT), creatinine, and blood urea nitrogen (BUN) in diabetic rats were significantly normalized by LME and lawsone, without affecting the normal rats. LME at a dose of 45 mg/kg exhibited the most potent antihyperglycemic and antihyperlipidemic effects, which were significantly comparable to glibenclamide but higher than those of lawsone. Furthermore, the toxicity evaluation indicated that both naphthoquinones were entirely safe for use in rodent models at doses ≤ 50 mg/kg. Therefore, the remarkable antihyperglycemic and antihyperlipidemic potentials of LME make it a promising option for future drug development. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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16 pages, 2596 KiB

Open AccessArticle

The Beneficial Effect of Swimming Training Associated with Quercetin Administration on the Endothelial Nitric Oxide-Dependent Relaxation in the Aorta of Rats with Experimentally Induced Type 1 Diabetes Mellitus

by Irina-Camelia Chis, Carmen-Maria Micu, Alina Toader, Remus Moldovan, Laura Lele, Simona Clichici and Daniela-Rodica Mitrea

Metabolites 2023, 13(5), 586; https://doi.org/10.3390/metabo13050586 - 24 Apr 2023

Cited by 2 | Viewed by 2145

Abstract

Type 1 diabetes mellitus is related to the vascular oxidative and nitrosative stress, the trigger for atherosclerosis and cardiovascular complications. The effects of moderate swimming training associated with quercetin oral administration were evaluated in aorta of rats with experimentally induced type 1 diabetes mellitus (T1DM), by analysing the nitric oxide-endothelial dependent relaxation (NO-EDR). T1DM rats received daily quercetin 30 mg/kg and followed the protocol of 5-weeks swimming exercise (30 min/day; 5 days/week). Aorta relaxation to acetylcholine (Ach) and sodium nitroprusside (SNP) were measured at the end of the experiment. Ach-induced endothelial dependent relaxation was significantly decreased in phenylephrine (PE) pre-contracted aorta of diabetic rats. Swimming exercise with quercetin administration preserved Ach-induced EDR but did not have any impact on SNP-induced endothelium-independent relaxation in the diabetic aorta. These findings suggest that quercetin administration associated with moderate swimming exercise could improve the endothelial NO-dependent relaxation in the aorta of rats with experimentally induced type 1 diabetes mellitus, showing that this therapeutical combination may improve and even prevent the vascular complications that occur in diabetic patients. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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11 pages, 794 KiB

Open AccessArticle

Influence of Flavonoid-Rich Fraction of Monodora tenuifolia Seed Extract on Blood Biochemical Parameters in Streptozotocin-Induced Diabetes Mellitus in Male Wistar Rats

by Samuel Nzekwe, Adetoun Morakinyo, Monde Ntwasa, Oluwafemi Oguntibeju, Oluboade Oyedapo and Ademola Ayeleso

Metabolites 2023, 13(2), 292; https://doi.org/10.3390/metabo13020292 - 16 Feb 2023

Cited by 4 | Viewed by 1972

Abstract

Diabetes mellitus is a metabolic disorder caused by either the total destruction of the pancreatic beta cells that secrete insulin for the uptake of glucose from the circulation or as a result of the inability of body cells to respond to the presence of insulin in the blood. The present study investigated the effect of a flavonoid-rich fraction of Monodora tenuifolia seed extract (FFMTSE) on blood parameters in streptozotocin (STZ)-induced diabetic male Wistar rats. The rats were divided into seven groups (n = 6). Group 1: normal control rats, Group 2: rats + FFMTSE (25 mg/kgbwt), Group 3: rats + FFMTSE (50 mg/kgbwt), Group 4: diabetic control rats, Group 5: diabetic rats + FFMTSE (25 mg/kgbwt), Group 6: diabetic rats + FFMTSE (50 mg/kgbwt), and Group 7: diabetic rats + Metformin. The assessment of the lipid profile, kidney functions (urea and creatinine), and cardiac biomarkers (LDH and CK-MB) were carried out in the plasma using established protocols. The results showed a significant increase in the concentrations of triacylglycerol, cholesterol, LDL-cholesterol, VLDL-cholesterol, urea, and creatinine, as well as in cardiac enzyme activities in diabetic rats. However, the administration of the FFMTSE significantly improved the observed biochemical parameters. In addition, an increased concentration of HDL-cholesterol concentration was observed in the diabetic rats upon treatment with FFMTSE. These findings indicate that FFMTSE could be a potent anti-nephropathy and anti-cardiomyopathy agent in diabetic conditions. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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16 pages, 4112 KiB

Open AccessArticle

Quercetin, a Plant Flavonol Attenuates Diabetic Complications, Renal Tissue Damage, Renal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats

by Arshad Husain Rahmani, Mohammed A. Alsahli, Amjad Ali Khan and Saleh A. Almatroodi

Metabolites 2023, 13(1), 130; https://doi.org/10.3390/metabo13010130 - 15 Jan 2023

Cited by 20 | Viewed by 3413

Abstract

Diabetes mellitus is a metabolic syndrome characterized by increased glucose levels, oxidative stress, hyperlipidemia, and frequently decreased insulin levels. The current research was carried out for eight consecutive weeks to evaluate the possible reno-protective effects of quercetin (50 mg/kg b.w.) on streptozotocin (STZ) (55 mg/kg b.w.) induced diabetes rat models. Various physiological, biochemical, and histopathological parameters were determined in control, diabetic control, and quercetin-treated diabetic rats. The current findings demonstrated that diabetes control rats showed significantly decreased body weights (198 ± 10 vs. 214 ± 13 g) and insulin levels (0.28 ± 0.04 vs. 1.15 ± 0.05 ng/mL) in comparison to normal control. Besides this, the other parameters showed increased values, such as fasting blood glucose, triglyceride (TG), and total cholesterol levels (99 ± 5 vs. 230 ± 7 mg/dL, 122.9 ± 8.7 vs. 230.7 ± 7.2 mg/dL, 97.34 ± 5.7 vs. 146.3 ± 8 mg/dL) (p < 0.05). In addition, the urea and creatinine levels (39.9 ± 1.8 mg/dL and 102.7 ± 7.8 μmol/L) were also high in diabetes control rats. After 8 weeks of quercetin treatment in STZ-treated animals, body weight, insulin, and fasting blood sugar levels were significantly restored (p < 0.05). The inflammatory markers (TNF-α, IL-6, and IL-1β) were significantly increased (52.64 ± 2, 95.64 ± 3, 23.3 ± 1.2 pg/mL) and antioxidant enzymes levels (SOD, GST, CAT, and GSH) were significantly decreased (40.3 ± 3 U/mg, 81.9 ± 10 mU/mg, 14.2 ± 2 U/mg, 19.9 ± 2 μmol/g) in diabetic rats. All the parameters in diabetic animals treated with quercetin were restored towards their normal values. Histopathological findings revealed that the quercetin-treated group showed kidney architecture maintenance, reduction of fibrosis, and decreased expression of COX-2 protein. These results determined that quercetin has reno-protective effects, and conclude that quercetin possesses a strong antidiabetic potential and might act as a therapeutic agent in the prevention or delay of diabetes-associated kidney dysfunction. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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15 pages, 1469 KiB

Open AccessArticle

The Combined Intervention of Aqua Exercise and Burdock Extract Synergistically Improved Arterial Stiffness: A Randomized, Double-Blind, Controlled Trial

by Min-Seong Ha, Jae-Hoon Lee, Woo-Min Jeong, Hyun Ryun Kim and Woo Hyeon Son

Metabolites 2022, 12(10), 970; https://doi.org/10.3390/metabo12100970 - 13 Oct 2022

Cited by 3 | Viewed by 2108

Abstract

Metabolic syndrome (MS), characterized by the presence of risk factors for various metabolic disorders, including impaired glucose tolerance, dyslipidemia, hypertension, and insulin resistance, has a high incidence in the Asian population. Among the various approaches used for improving MS, the combination of exercise and nutrition is of increasing importance. In this randomized controlled trial, we evaluated the effects of combined aqua exercise and burdock extract intake on blood pressure, insulin resistance, arterial stiffness, and vascular regulation factors in older women with MS. A total of 42 participants were randomly assigned into one of four groups (control, exercise, burdock, and exercise + burdock) and underwent a 16-week double-blinded intervention. Blood pressure, insulin resistance, arterial stiffness, and vascular regulation factors were evaluated before and after the intervention. The 16-week intervention of aqua exercise decreased the levels of insulin, glucose, homeostasis model assessment of insulin resistance, and thromboxane A2, but increased the levels of the quantitative insulin sensitivity check index and prostaglandin I2. The combined burdock extract intake and aqua exercise intervention had an additional effect, improving the augmentation index, augmentation index at 75 beats per min, and pulse wave velocity. In conclusion, aqua exercise could improve insulin resistance and vascular regulation factors in older women with MS. Furthermore, combined treatment with burdock extract intake could improve arterial stiffness via a synergistic effect. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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17 pages, 3429 KiB

Open AccessArticle

Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy

by Fatai Oladunni Balogun, Kaylene Naidoo, Jamiu Olaseni Aribisala, Charlene Pillay and Saheed Sabiu

Metabolites 2022, 12(10), 937; https://doi.org/10.3390/metabo12100937 - 2 Oct 2022

Cited by 10 | Viewed by 2374

Abstract

Recently, dipeptidyl peptidase-IV (DPP-IV) has become an effective target in the management of type-2 diabetes mellitus (T2D). The study aimed to determine the efficacy of shikimate pathway-derived phenolic acids as potential DPP-IV modulators in the management of T2D. The study explored in silico (molecular docking and dynamics simulations) and in vitro (DPP-IV inhibitory and kinetics assays) approaches. Molecular docking findings revealed chlorogenic acid (CA) among the examined 22 phenolic acids with the highest negative binding energy (−9.0 kcal/mol) showing a greater affinity for DPP-IV relative to the standard, Diprotin A (−6.6 kcal/mol). The result was corroborated by MD simulation where it had a higher affinity (−27.58 kcal/mol) forming a more stable complex with DPP-IV than Diprotin A (−12.68 kcal/mol). These findings were consistent with in vitro investigation where it uncompetitively inhibited DPP-IV having a lower IC₅₀ (0.3 mg/mL) compared to Diprotin A (0.5 mg/mL). While CA showed promising results as a DPP-IV inhibitor, the findings from the study highlighted the significance of medicinal plants particularly shikimate-derived phenolic compounds as potential alternatives to synthetic drugs in the effective management of T2DM. Further studies, such as derivatisation for enhanced activity and in vivo evaluation are suggested to realize its full potential in T2D therapy. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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11 pages, 1255 KiB

Open AccessArticle

First Report on Comparative Essential Oil Profile of Stem and Leaves of Blepharispermum hirtum Oliver and Their Antidiabetic and Anticancer Effects

by Muddaser Shah, Saif Khalfan Al-Housni, Faizullah Khan, Saeed Ullah, Jamal Nasser Al-Sabahi, Ajmal Khan, Balqees Essa Mohammed Al-Yahyaei, Houda Al-Ruqaishi, Najeeb Ur Rehman and Ahmed Al-Harrasi

Metabolites 2022, 12(10), 907; https://doi.org/10.3390/metabo12100907 - 26 Sep 2022

Cited by 5 | Viewed by 2100

Abstract

The current research was designed to explore the Blepharispermum hirtum Oliver (Asteraceae) stem and leaves essential oil (EO) composition extracted through hydro-distillation using gas chromatography-mass spectrometry (GC-MS) analysis for the first time. The EOs of the stem and leaves of B. hirtum were comparatively studied for the in vitro antidiabetic and anticancer potential using in vitro α-glucosidase and an MTT inhibition assay, respectively. In both of the tested samples, the same number of fifty-eight compounds were identified and contributed 93.88% and 89.07% of the total oil composition in the EOs of the stem and leaves of B. hirtum correspondingly. However, camphene was observed as a major compound (23.63%) in the stem EO, followed by β-selinene (5.33%) and β-elemene (4.66%) and laevo-β-pinene (4.38%). While in the EO of the leaves, the dominant compound was found to be 24-norursa-3,12-diene (9.08%), followed by β-eudesmol (7.81%), β-selinene (7.26%), thunbergol (5.84%), and caryophyllene oxide (5.62%). Significant antidiabetic potential was observed with an IC₅₀ of 2.10 ± 0.57 µg/mL by the stem compared to the EO of the leaves of B. hirtum, having an IC₅₀ of 4.30 ± 1.56 µg/mL when equated with acarbose (IC₅₀ = 377.71 ± 1.34 µg/mL). Furthermore, the EOs offered considerable cytotoxic capabilities for MDA-MB-231. However, the EO of the leaves presented an IC₅₀ = 88.4 ± 0.5 μg/mL compared to the EO of the stem of B. hirtum against the triple-negative breast cancer (MDA-MB-231) cell lines with an IC₅₀ = 123.6 ± 0.8 μg/mL. However, the EOs were also treated with the human breast epithelial (MCF-10A) cell line, and from the results, it has been concluded that these oils did not produce much harm to the normal cell lines. Hence, the present research proved that the EOs of B. hirtum might be used to cure diabetes mellitus and human breast cancer. Moreover, further studies are considered to be necessary to isolate the responsible bioactive constituents to devise drugs for the observed activities. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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Review

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18 pages, 2081 KiB

Open AccessReview

Recent Updates on Source, Biosynthesis, and Therapeutic Potential of Natural Flavonoid Luteolin: A Review

by Nandakumar Muruganathan, Anand Raj Dhanapal, Venkidasamy Baskar, Pandiyan Muthuramalingam, Dhivya Selvaraj, Husne Aara, Mohamed Zubair Shiek Abdullah and Iyyakkannu Sivanesan

Metabolites 2022, 12(11), 1145; https://doi.org/10.3390/metabo12111145 - 20 Nov 2022

Cited by 46 | Viewed by 4027

Abstract

Nature gives immense resources that are beneficial to humankind. The natural compounds present in plants provide primary nutritional values to our diet. Apart from food, plants also provide chemical compounds with therapeutic values. The importance of these plant secondary metabolites is increasing due to more studies revealing their beneficial properties in treating and managing various diseases and their symptoms. Among them, flavonoids are crucial secondary metabolite compounds present in most plants. Of the reported 8000 flavonoid compounds, luteolin is an essential dietary compound. This review discusses the source of the essential flavonoid luteolin in various plants and its biosynthesis. Furthermore, the potential health benefits of luteolins such as anti-cancer, anti-microbial, anti-inflammatory, antioxidant, and anti-diabetic effects and their mechanisms are discussed in detail. The activity of luteolin and its derivatives are diverse, as they help to prevent and control many diseases and their life-threatening effects. This review will enhance the knowledge and recent findings regarding luteolin and its therapeutic effects, which are certainly useful in potentially utilizing this natural metabolite. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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Other

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23 pages, 1425 KiB

Open AccessSystematic Review

The Potential of the Flavonoid Content of Ipomoea batatas L. as an Alternative Analog GLP-1 for Diabetes Type 2 Treatment—Systematic Review

by Ni Kadek Santi Maha Dewi, Yan Ramona, Made Ratna Saraswati, Desak Made Wihandani and I Made Agus Gelgel Wirasuta

Metabolites 2024, 14(1), 29; https://doi.org/10.3390/metabo14010029 - 31 Dec 2023

Cited by 4 | Viewed by 3953

Abstract

Ipomoea batatas L. (IBL) has gained significant popularity as a complementary therapy or herbal medicine in the treatment of anti-diabetes. This review seeks to explore the mechanism by which flavonoid compounds derived from IBL exert their anti-diabetic effects through the activation of GLP-1. The review article refers to the PRISMA guidelines. In order to carry out the literature search, electronic databases such as Science Direct, Crossref, Scopus, and Pubmed were utilized. The search query was based on specific keywords, including Ipomoea batatas OR sweet potato AND anti-diabetic OR hypoglycemic. After searching the databases, we found 1055 articles, but only 32 met the criteria for further review. IBL contains various compounds, including phenolic acid, flavonols, flavanols, flavones, and anthocyanins, which exhibit activity against anti-diabetes. Flavonols, flavanols, and flavones belong to a group of flavonoids that possess the ability to form complexes with AlCl₃ and Ca²⁺. The intracellular L cells effectively retain Ca²⁺, leading to the subsequent release of GLP-1. Flavonols, flavones, and flavone groups have been found to strongly interact with DPP-IV, which inhibits the degradation of GLP-1. The anti-diabetic activity of IBL is attributed to the mechanism that effectively increases the duration of GLP-1 in the systemic system, thereby prolonging its half-life. Full article

(This article belongs to the Special Issue Research Progress of Plant Compounds for Diabetes and Its Complications)

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