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Medicinal Plants and Diabetes

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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 (30 July 2018) | Viewed by 53346

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Prof. Dr. Oluwafemi Oguntibeju

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Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, P.O. Box 1906, Bellville 7535, South Africa
Interests: antioxidants; oxidative stress; phytochemical; free radical biology
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Dear Colleagues,

Diabetes mellitus (DM) is a major public health burden, increasing dramatically with 25% of global population believed to be diabetic. It has been predicted that over 552 million people will be diabetic with the projection that 1 in 10 non-diabetic adults will become diabetic by 2030. Plants with medicinal values are known to play significant role globally particularly in African and Asian regions in the management and treatment of various chronic diseases including diabetes. In African and Asian regions, due to low socio-economic patterns, about 80% of these populations predominantly depend on plant products as their primary healthcare sources. The interest in medicinal plants has grown possibly due to their availability, accessibility and the general belief that they demonstrate minimum side effects. The relative cost of pharmacological drugs globally has raised concerns of diversion from orthodox medicines to herbal remedies. The treatment and management cost of DM in developing countries is expensive and majority of the population cannot afford, hence the heavy reliance on medicinal plants for the management several chronic diseases including diabetes mellitus. Over a thousand plant species have been used in the treatment and management of diabetes. Therapeutic effects of plant extracts have been linked to the presence of phytochemicals, such as glycosides, alkaloids, terpenoids, flavonoids, cartenoids, beta glycans and caretoniods and that the bioactive constituents provide therapeutic effects either by combating reactive oxygen species or acting as hypoglycaemic, anti-hyperglycaemic, anti-inflammatory and apoptotic agents. This Special Issue of the journal will focus on diabetes in general and diabetes and the role of medicinal plants in the treatment and management of diabetes.

Prof. Oluwafemi Oguntibeju
Guest Editor

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Keywords

Diabetes mellitus and medicinal plants
Diabetes and oxidative stress
Medicinal plants and obesity
Oxidative stress and medicinal plants
Diabetic complications and medicinal plants
Bone health-related diabetes complications and medicinal plants
Toxicity and medicinal plants
Diabetes-related inflammation and medicinal plants
Diabetic-related apoptosis and medicinal plants

Published Papers (11 papers)

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Research

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16 pages, 1019 KiB

Open AccessArticle

Timbe (Acaciella angustissima) Pods Extracts Reduce the Levels of Glucose, Insulin and Improved Physiological Parameters, Hypolipidemic Effect, Oxidative Stress and Renal Damage in Streptozotocin-Induced Diabetic Rats

by Adriana Jheny Rodríguez-Méndez, Wendy Carmen-Sandoval, Consuelo Lomas-Soria, Ramón G. Guevara-González, Rosalía Reynoso-Camacho, María Elena Villagran-Herrera, Luis Salazar-Olivo, Irineo Torres-Pacheco and Ana A. Feregrino-Pérez

Molecules 2018, 23(11), 2812; https://doi.org/10.3390/molecules23112812 - 30 Oct 2018

Cited by 10 | Viewed by 3004

Abstract

In Mexico one in 14 deaths are caused by diabetes mellitus (DM) or by the macro and microvascular disorders derived from it. A continuous hyperglycemic state is characteristic of DM, resulting from a sustained state of insulin resistance and/or a dysfunction of β-pancreatic cells. Acaciella angustissima is a little studied species showing a significant antioxidant activity that can be used as treatment of this disease or preventive against the complications. The objective of this study was to explore the effect of oral administration of A. angustissima methanol extract on physiological parameters of streptozotocin-induced diabetic rats. The results indicated a significant reduction in blood glucose levels, an increase in serum insulin concentration, a decrease in lipid levels and an improvement in the parameters of kidney damage by applying a concentration of 100 mg/Kg B.W. However, glucose uptake activity was not observed in the adipocyte assay. Moreover, the extract of A. angustissima displayed potential for the complementary treatment of diabetes and its complications likely due to the presence of bioactive compounds such as protocatechuic acid. This study demonstrated that methanol extract of Acacciella angustissima has an antidiabetic effect by reducing the levels of glucose, insulin and improved physiological parameters, hypolipidemic effect, oxidative stress and renal damage in diabetic rats. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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18 pages, 2612 KiB

Open AccessArticle

A Study on Neonatal Intake of Oleanolic Acid and Metformin in Rats (Rattus norvegicus) with Metabolic Dysfunction: Implications on Lipid Metabolism and Glucose Transport

by Mmahiine Molepo, Ademola Ayeleso, Trevor Nyakudya, Kennedy Erlwanger and Emmanuel Mukwevho

Molecules 2018, 23(10), 2528; https://doi.org/10.3390/molecules23102528 - 03 Oct 2018

Cited by 11 | Viewed by 3780

Abstract

Metabolic syndrome, a cluster of different disorders which include diabetes, obesity and cardiovascular diseases, is a global epidemic that is growing at an alarming rate. The origins of disease can be traced back to early developmental stages of life. This has increased mortalities and continues to reduce life expectancies of individuals across the globe. The aim of this study was to investigate the sub-acute and long term effects of neonatal oral administration of oleanolic acid and metformin on lipids (free fatty acids, FFAs) and genes associated with lipid metabolism and glucose transport using a neonatal rat experimental model. In the first study, seven days old pups were randomly grouped into control—distilled water (DW); oleanolic acid (60 mg/kg), metformin (500 mg/kg), high fructose diet (20% w/v, HF), oleanolic acid (OA) + high fructose diet (OA + HF), and Metformin + high fructose diet (MET + HF) groups. The pups were treated for 7 days, and then terminated on postnatal day (PD) 14. In the second study, rat pups were initially treated similarly to study 1 and weaned onto normal rat chow and plain drinking water on PD 21 till they reached adulthood (PD112). Tissue and blood samples were collected for further analyses. Measurement of the levels of free fatty acids (FFAs) was done using gas chromatography-mass spectrometry. Quantitative polymerase chain reaction (qPCR) was used to analyze the gene expression of glut-4, glut-5, fas, acc-1, nrf-1 and cpt-1 in the skeletal muscle. The results showed that HF accelerated accumulation of saturated FFAs within skeletal muscles. The HF fed neonatal rats had increased stearic acid, which was associated with decreased glucose, suppressed expression of glut-4, glut-5, nrf-1 and cpt-1 genes, and increased expression of acc-1 (p < 0.01) and fas. OA + HF and MET + HF treated groups had increased mono- and polyunsaturated FFAs; oleic, and octadecadienoic acids than the HF group. These unsaturated FFAs were associated with increased glut-4, glut-5 and nrf-1 (p < 0.01) and decreased acc-1 and fas (p < 0.05) in both OA + HF and MET + HF treated groups. Conclusions: The present study shows that neonatal oral administration of oleanolic acid and metformin potentially protects against the development of fructose-induced metabolic dysfunction in the rats in both short and long time periods. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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14 pages, 3629 KiB

Open AccessArticle

Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio

by Hongxing Zheng, Shanshan Qi and Chen Chen

Molecules 2018, 23(9), 2398; https://doi.org/10.3390/molecules23092398 - 19 Sep 2018

Cited by 38 | Viewed by 4457

Abstract

Postmenopausal diabetic women have a high risk of fractures. Salidroside has preventive effects on estrogen deficiency-induced osteoporosis and has hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits bone loss in postmenopausal diabetic patients is still unknown. Here, we established a rat model of osteoporosis to investigate the protective effects of salidroside on bone loss induced by ovariectomy combined with diabetes, also investigating the underlying mechanisms. Two-month-old female Sprague-Dawley rats were divided into three equal groups (10 rats in each group): control group (with sham operation, treated with drug vehicle); OVX/T1DM group (ovariectomized diabetic rats); OVX/T1DM-SAL group, comprising ovariectomized diabetic rats treated with salidroside (20 mg/kg body weight) by gavage. The results showed that after 60 consecutive days of treatment, the bone mineral density (BMD) of OVX/T1DM-SAL increased significantly compared with the OVX/T1DM group (p < 0.01). The level of serum bone turnover markers, including alkaline phosphatase (ALP), cross linked c-telopeptide of type I collagen (CTX-1), osteocalcin, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase 5b (TRACP 5b) were all increased in the OVX/T1DM group compared with the control (p < 0.01), and those were decreased by salidroside treatment. Meanwhile, the bone histopathological changes were also attenuated, and the bone marrow adipogenesis was inhibited in salidroside treated rats. Moreover, protein and mRNA ratio of bone osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) was upregulated in ovariectomized diabetic rats by salidroside treatment. The results above indicated that the protective effect of salidroside on bone loss induced by ovariectomy and diabetes was mainly due to its ability to suppress bone turnover, inhibit bone marrow adipogenesis, and up-regulate the OPG/RANKL ratio. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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12 pages, 1632 KiB

Open AccessArticle

The Chemical Composition and Functional Properties of Essential Oils from Four Species of Schisandra Growing Wild in the Qinling Mountains, China

by Xiaorui Wang, Yan Liu, Yuanyuan Niu, Nongxue Wang and Wei Gu

Molecules 2018, 23(7), 1645; https://doi.org/10.3390/molecules23071645 - 05 Jul 2018

Cited by 9 | Viewed by 3863

Abstract

The aim of this study was to investigate the chemical composition and functional properties of the essential oils from the plants Schisandra grandiflora (Wall.) Hook. f. et Thoms, Schisandra rubriflora (Franch). Rehd. et Wils., Schisandra sphenanthera Rehd. et Wils., and Schisandra propinqua (Wall.) Baill var. sinensis Oliv. collected in the Qinling Mountains. Under the optimum conditions of the ultrasonic-assisted extraction method, the extraction yields were 7.51% (S. grandiflora), 6.91% (S. rubriflora), 6.11% (S. sphenanthera), and 5.88% (S. propinqua). A total of 86 components were identified from four species of Schisandra and 16 components were shared among the essential oils of all samples with different contents. However, some components were identified only in a certain plant, for example, β-caryophyllen (S. grandiflora), α-bulnesene (S. rubriflora), and α-Chamigrene (S. propinqua). Terpenoids (sesquiterpenes and oxygenated sesquiterpenes), accounting for 73.87–82.08% of the total compounds, were the main components. Meanwhile, the antioxidant activities of the essential oils were evaluated through three free radical scavenging assays and a reducing power assay, which were related to the contents of the individual bioactive composition. These results provide a phytochemical foundation for the use of four species, and for the further study of the identification of Schisandra species. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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17 pages, 749 KiB

Open AccessArticle

Antidiabetic Effect of Cyclocarya paliurus Leaves Depends on the Contents of Antihyperglycemic Flavonoids and Antihyperlipidemic Triterpenoids

by Yang Liu, Yanni Cao, Shengzuo Fang, Tongli Wang, Zhiqi Yin, Xulan Shang, Wanxia Yang and Xiangxiang Fu

Molecules 2018, 23(5), 1042; https://doi.org/10.3390/molecules23051042 - 29 Apr 2018

Cited by 62 | Viewed by 5772

Abstract

Cyclocarya paliurus has been used commonly to treat diabetes in China. However, the effective components and the effect of plant origin remain unclear. In this study, C. paliurus leaves with different chemical compositions were selected from five geographical locations, and their effects on streptozotocin (STZ)-induced diabetic mice were evaluated with both ethanol and aqueous extracts. Glucose levels, lipid levels, and biomarkers of liver and kidney function were measured. The principal components of both C. paliurus ethanol and aqueous extracts from different geographical locations differed quantitatively and qualitatively. Results showed that C. paliurus extracts with better antihyperglycemic effects were characterized by higher contents of total flavonoids, especially quercetin-3-O-glucuronide and kaempferol-3-O-glucuronide. Furthermore, significantly negative correlations were found between triterpenoids contents and lipid levels. These results revealed the potential antihyperglycemic capacity of C. paliurus flavonoids and the antihyperlipidemic effect of C. paliurus triterpenoids. Thus, we suggest that the composition of C. paliurus compounds might help to design therapeutic alternatives for the treatment of diabetes mellitus. However, geographic origins and the extraction solvents can also affect the effectiveness of the treatment as these factors influence the chemical compositions and thereby the biological activities. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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14 pages, 2102 KiB

Open AccessArticle

Anti-Diabetic Effects of Acankoreagenin from the Leaves of Acanthopanax Gracilistylus Herb in RIN-m5F Cells via Suppression of NF-κB Activation

by Man-Xia Lu, Yang Yang, Qin-Peng Zou, Jiao Luo, Bin-Bei Zhang, Xiang-Qian Liu and Eun-Hee Hwang

Molecules 2018, 23(4), 958; https://doi.org/10.3390/molecules23040958 - 19 Apr 2018

Cited by 17 | Viewed by 5011

Abstract

Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. In this manuscript, acankoreagenin isolated from the leaves of Acanthopanax gracilistylus (LAG) is thought to possess excellent anti-diabetic properties. In vitro, anti-diabetic activities were assessed based on the inhibitory activities with α-glucosidase (IC₅₀ 13.01 μM), α-amylase (IC₅₀ 30.81 μM), and PTP1B (IC₅₀ 16.39 μM). Acankoreagenin showed better anti-diabetic effects. Then, an investigation was performed to analyze the insulin secretion effects of the insulin-secreting cell line in RIN-m5F cells. It was found that acankoreagenin could increase the insulin release in RIN-m5F cells. It was also found that acankoreagenin reduced NO production, activity of caspase-3, and the reactive oxygen species levels in the cells injured by processing of cytokines. In western blotting, inactivation of NF-κB signaling was confirmed. Acankoreagenin (20 μM) showed a higher I-κBα expression and lower NF-κB expression than the control group and showed a better expression than the positive control L-NAME (1 mM) (p < 0.05). This study demonstrates the anti-diabetic effects of acankoreagenin in vitro and suggests acankoreagenin might offer therapeutic potential for treating diabetes mellitus. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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10 pages, 522 KiB

Open AccessArticle

Proteomic Analysis of Differentially-Expressed Proteins in the Liver of Streptozotocin-Induced Diabetic Rats Treated with Parkia biglobosa Protein Isolate

by Bolajoko Idiat Ogunyinka, Babatunji Emmanuel Oyinloye, Foluso Oluwagbemiga Osunsanmi, Andrew Rowland Opoku and Abidemi Paul Kappo

Molecules 2018, 23(2), 156; https://doi.org/10.3390/molecules23020156 - 24 Jan 2018

Cited by 4 | Viewed by 3790

Abstract

Protein isolate from Parkia biglobosa seeds is believed to possess excellent anti-diabetic properties. The purpose of this study was to identify differentially expressed proteins in liver of streptozotocin-induced diabetic rats treated with Parkia biglobosa seeds protein isolate (PBPi). In this study, total proteins extracted from rat liver were separated on one-dimensional SDS polyacrylamide gel (1D SDS-PAGE) and stained with Coomassie brilliant blue (CBB) to visualize protein bands. We observed that protein bands in the region of 10–15 kDa were altered by the different treatments; these bands were selected and excised for in-gel digestion and peptide extraction followed by nLC-MS, MALDI-TOF MS, and LIFT MS/MS. A database search with the Mascot algorithm positively identified four differentially expressed proteins. These proteins are known to be responsible for diverse biological functions within various organs and tissues. The present result gives insight and understanding into possible molecular mechanisms by which streptozotocin causes various alterations in proteins found in the liver of diabetic rats and the possible modulatory role of PBPi in the management of streptozotocin-induced diabetes. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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2526 KiB

Open AccessArticle

The Benefits of the Citrus Flavonoid Diosmin on Human Retinal Pigment Epithelial Cells under High-Glucose Conditions

by Wayne Young Liu, Shorong-Shii Liou, Tang-Yao Hong and I-Min Liu

Molecules 2017, 22(12), 2251; https://doi.org/10.3390/molecules22122251 - 18 Dec 2017

Cited by 22 | Viewed by 4836

Abstract

We investigate diosmin for its effect on the ARPE-19 human retinal pigment epithelial cells exposed to high glucose, a model of diabetic retinopathy (DR). After incubation for 4 days with a normal (5 mmol/L) concentration of D-glucose, ARPE-19 cells were exposed separately to normal or high concentrations of D-glucose (30 mmol/L) with or without diosmin at different concentrations (0.1, 1, 10 μg/mL) for another 48 h. Next, we assessed cell viability, reactive oxygen species (ROS) generation and antioxidant enzyme activities. In order to examine the underlying molecular mechanisms, we meanwhile analyzed the expressions of Bax, Bcl-2, total and phosphorylated JNK and p38 mitogen-activated protein kinase (MAPK). Diosmin dose dependently enhanced cell viability following high glucose treatment in ARPE-19 cells. The activities of superoxide dismutase and glutathione peroxidase, as well as the levels of reduced glutathione were decreased, while it was observed that levels of ROS in high glucose cultured ARPE-19 cells increased. High glucose also disturbed Bax and Bcl-2 expression, interrupted Bcl-2/Bax balance, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by diosmin. Furthermore, diosmin could abrogate high glucose-induced apoptosis as well as JNK and P38 MAPK phosphorylation in ARPE-19 cells. Our results suggest that treatment ARPE-19 cells with diosmin halts hyperglycemia-mediated oxidative damage and thus this compound may be a candidate for preventing the visual impairment caused by DR. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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Review

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19 pages, 676 KiB

Open AccessReview

Medicinal Plants Used for the Traditional Management of Diabetes in the Eastern Cape, South Africa: Pharmacology and Toxicology

by Samuel Odeyemi and Graeme Bradley

Molecules 2018, 23(11), 2759; https://doi.org/10.3390/molecules23112759 - 25 Oct 2018

Cited by 38 | Viewed by 7318

Abstract

The use of medicinal plants for the management of diabetes mellitus is on the rise in the developing countries, including South Africa. There is increasing scientific evidence that supports the claims by the traditional healers. In this review, we compare the families of previously reported anti-diabetic plants in the Eastern Cape by rating the anti-diabetic activity, mode of action and also highlight their therapeutic potentials based on the available evidence on their pharmacology and toxicity. Forty-five plants mentioned in ethnobotanical surveys were subjected to a comprehensive literature search in the available electronic databases such as PubMed, ScienceDirect, Google Scholar and Elsevier, by using “plant name” and “family” as the keywords for the primary searches to determine the plants that have been scientifically investigated for anti-diabetic activity. The search returned 25 families with Asteraceae highly reported, followed by Asphodelaceae and Alliaceae. Most of the plants have been studied for their anti-diabetic potentials in vivo and/or in vitro, with most of the plants having a higher percentage of insulin release and inhibition against carbohydrate digesting enzymes as compared with insulin mimetic and peripheral glucose uptake. Almost all the investigated plants also inhibit oxidative stress as part of their hypoglycemic activity with less toxicity. However, the isolation of their bioactive molecules is still lacking. This review provides a resource to enable thorough assessments of the therapeutic profiles of available medicinal plants used for the management of diabetes in the Eastern Cape, South Africa. Further studies such as the identification of the active ingredients of potent plants still need to be carried out; this may lead to new molecules in drug discovery and development. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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17 pages, 309 KiB

Open AccessReview

Therapeutic Potential of Brazilian Cerrado Campomanesia Species on Metabolic Dysfunctions

by Carla Maiara Lopes Cardozo, Aline Carla Inada, Gabriela Marcelino, Priscila Silva Figueiredo, Daniela Granja Arakaki, Priscila Aiko Hiane, Claudia Andrea Lima Cardoso, Rita De Cássia Avellaneda Guimarães and Karine De Cássia Freitas

Molecules 2018, 23(9), 2336; https://doi.org/10.3390/molecules23092336 - 13 Sep 2018

Cited by 12 | Viewed by 3862

Abstract

Obesity, in conjunction with other metabolic disorders such as insulin resistance and dyslipidemia, is a feature of metabolic syndrome which is characterized by a pro-inflammatory state and increased oxidative stress. Therefore, antioxidant foods are proposed to prevent and treat these disorders. Medicinal plants are one of the main strategies in this regard. Guavira, a Brazilian Cerrado plant, contains different bioactive compounds with a high antioxidant capacity and without clinical or reproductive toxicity effects. Though there are different varieties of guavira, the principal Brazilian Cerrado guaviras demonstrated hypoglycemic, anti-inflammatory, and hypocholesterolemic actions. There is also a potential antiplatelet agent in C. xanthocarpa, while C. adamantium displayed hypocholesterolemic actions in animal models and human clinical trials. On the other hand, even with a lack of studies related to C. pubescens, it demonstrated anti-inflammatory effects and an antioxidant capacity in in vitro studies. Despite the fact that most of the studies were not performed to evaluate pathological conditions specific to obese animal models or obese subjects, guavira demonstrated effects in metabolic disorders that are commonly related to the obesity context, such as cardiovascular disturbances and hyperglycemia status. This suggests that guavira is a potential therapeutic approach to obesity-induced metabolic syndrome. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

30 pages, 1903 KiB

Open AccessReview

Phytochemicals: Target-Based Therapeutic Strategies for Diabetic Retinopathy

by Amna Parveen, Jin Hyun Kim, Byeong Gyu Oh, Lalita Subedi, Zahra Khan and Sun Yeou Kim

Molecules 2018, 23(7), 1519; https://doi.org/10.3390/molecules23071519 - 23 Jun 2018

Cited by 37 | Viewed by 6545

Abstract

Background: A variety of causative factors are involved in the initiation of diabetic retinopathy (DR). Current antidiabetic therapies are expensive and not easily accessible by the public. Furthermore, the use of multiple synthetic drugs leads to severe side effects, which worsen the diabetic patient’s condition. Medicinal plants and their derived phytochemicals are considered safe and effective treatment and their consumption can reduce the DR risk. In this article, we discuss a variety of medicinal plants, and their noteworthy bio-active constituents, that will be utilized as target based therapeutic strategies for DR. Methods: A broad-spectrum study was conducted using published English works in various electronic databases including Science Direct, PubMed, Scopus, and Google Scholar. Results: Targeting the multiple pathological factors including ROS, AGEs formation, hexosamine flux, PARP, PKC, and MAPK activation through variety of bioactive constituents in medicinal plants, diabetes progression can be delayed with improved loss of vision. Conclusions: Data reveals that traditional herbs and their prominent bioactive components control and normalize pathological cellular factors involved in DR progression. Therefore, studies should be carried out to explore the protective retinopathy effects of medicinal plants using experimental animal and humans models. Full article

(This article belongs to the Special Issue Medicinal Plants and Diabetes)

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