scholarly journals Investigation on the Enzymatic Profile of Mulberry Alkaloids by Enzymatic Study and Molecular Docking

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1776 ◽  
Author(s):  
Zhihua Liu ◽  
Ying Yang ◽  
Wujun Dong ◽  
Quan Liu ◽  
Renyun Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Molecular Docking ◽  
Side Effects ◽  
Inhibitory Effect ◽  
Active Ingredients ◽  
Wide Range ◽  
Consensus Score

α-glucosidase inhibitors (AGIs) have been an important category of oral antidiabetic drugs being widely exploited for the effective management of type 2 diabetes mellitus. However, the marketed AGIs not only inhibited the disaccharidases, but also exhibited an excessive inhibitory effect on α-amylase, resulting in undesirable gastrointestinal side effects. Compared to these agents, Ramulus Mori alkaloids (SZ-A), was a group of effective alkaloids from natural Morus alba L., and showed excellent hypoglycemic effect and fewer side effects in the Phase II/III clinical trials. Thus, this paper aims to investigate the selective inhibitory effect and mechanism of SZ-A and its major active ingredients (1-DNJ, FA and DAB) on different α-glucosidases (α-amylase and disaccharidases) by using a combination of kinetic analysis and molecular docking approaches. From the results, SZ-A displayed a strong inhibitory effect on maltase and sucrase with an IC50 of 0.06 μg/mL and 0.03 μg/mL, respectively, which was similar to the positive control of acarbose with an IC50 of 0.07 μg/mL and 0.68 μg/mL. With regard to α-amylase, SZ-A exhibited no inhibitory activity at 100 μg/mL, while acarbose showed an obvious inhibitory effect with an IC50 of 1.74 μg/mL. The above analysis demonstrated that SZ-A could selectively inhibit disaccharidase to reduce hyperglycemia with a reversible competitive inhibition, which was primarily attributed to the three major active ingredients of SZ-A, especially 1-DNJ molecule. In the light of these findings, molecular docking study was utilized to analyze their inhibition mechanisms at molecular level. It pointed out that acarbose with a four-ring structure could perform desirable interactions with various α-glucosidases, while the three active ingredients of SZ-A, belonging to monocyclic compounds, had a high affinity to the active site of disaccharidases through forming a wide range of hydrogen bonds, whose affinity and consensus score with α-amylase was significantly lower than that of acarbose. Our study illustrates the selective inhibition mechanism of SZ-A on α-glucosidase for the first time, which is of great importance for the treatment of type 2 diabetes mellitus.

scholarly journals Prospects for application of phytopreparations in the complex treatment of type 2 diabetes mellitus

2021 ◽  
pp. 18-22
Author(s):  
Viktoria Rybak ◽  
Lyudmila Maloshtan ◽  
Victoria Korol
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Side Effects ◽  
Herbal Medicine ◽  
Medicinal Plants ◽  
Complex Treatment ◽  
Practical Medicine ◽  
Wide Range

Diabetes mellitus (DM) occupies an important place in the structure of mortality, as well as among the causes of disability and deterioration in the quality of life of the population. In this regard, the study of phytopreparations is promising for practical medicine in order to identify new medicinal plants that actively affect metabolic processes to prevent complications of DM, and create new phytopreparations. That drugs could enhance the effect of sulfonamides and potentiate the effect of insulin, thereby reducing the dose of the latter, and it is important for long-term chronic diseases, such as DM. The aim. To study the prospects for the use of phytopreparations in the complex treatment of type 2 diabetes mellitus. Materials and methods. The analytical, logical, generalization methods were used in the work. The analytical method of the study involved deepening the search for phytopreparations and the prospects for their use in the complex treatment of type 2 diabetes mellitus and generalization of the data obtained. The logical method of exploratory research of promising phytopreparations was applied in a certain logical sequence, as a result of which the specificity, stage-by-stage and generalization of the relevance of the use of phytopreparations in the complex treatment of type 2 diabetes mellitus was provided for scientific research. The generalizing research method was to determine and prove the characteristics of phytopreparations (analysis and synthesis) and their advantages over synthetic drugs. Results and discussion. The main directions of herbal medicine for DM are associated with reproduction of the effects of insulin, normalization of glucose uptake, stimulation of regeneration of β-cells of the Langerhans islets, elimination of excess glucose from the body – phytopreparations with diuretic properties; elimination of hypoxia – phytopreparations-antihypoxants. In DM, herbal medicine will reduce the frequency of side effects in classical antidiabetic therapy. For any type of diabetes, herbal medicine is prescribed to patients as an improvement in the microcirculation of tissues, normalization of the functions of the cardiovascular and nervous systems, kidneys and eyes. Conclusions. Despite a wide range of drugs used to correct the hemodynamic and metabolic manifestations of the insulin resistance syndrome, they do not fully meet the needs of practical medicine due to the presence of pronounced side effects. In addition, the pharmaceutical market of herbal medicines is very limited and represented mainly by species of medicinal plants, which have certain inconveniences in their use. All this indicates the relevance of the search, creation and introduction of effective and, at the same time, low-toxic drugs based on the medicinal plant raw material into medical practice for the pharmacotherapy of type 2 diabetes and its complications

Abstract 234: Treatment Satisfaction Levels among Adults with Concomitant Conditions of Type 2 Diabetes Mellitus and Hypertension

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Kathleen M Fox ◽  
Susan Grandy ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Heart Disease ◽  
Side Effects ◽  
Diabetes Medication ◽  
Medication Therapy ◽  
The Us ◽  
Medication Side

Objective: This investigation evaluated the satisfaction with therapy for adults with the concomitant conditions of type 2 diabetes mellitus (T2DM) and hypertension (HTN). Methods: Respondents to the US S tudy to H elp I mprove E arly evaluation and management of risk factors L eading to D iabetes (SHIELD) 2009 survey reported their disease conditions, current medications, and satisfaction with therapy. Respondents reporting T2DM with concomitant HTN were identified. Current medications were catalogued, as respondents referred to their prescription bottles to record the name of each medication. Therapy satisfaction was captured with 3 separate questions as satisfaction/dissatisfaction with: 1) ability of the medication to prevent or treat your condition, 2) side effects of the medication, and 3) the medication overall; and scored using a 0 (completely dissatisfied) to 5 (completely satisfied) scale for heart disease treatment and diabetes treatment, separately. Scores of 0-2 were categorized as dissatisfied, score of 3 was neutral and scores 4-5 were satisfied. Results: A total of 911 adults with T2DM and HTN reported their satisfaction with therapy. For those who were dissatisfied with their diabetes medication (n = 63), 52.6% were also dissatisfied with their heart disease medication's ability to treat their HTN, 64.5% were dissatisfied with the side effects of their heart medications, and 61.9% were dissatisfied with their heart medication overall. For those who were dissatisfied with their heart disease medication (n = 59), 74.5% were also dissatisfied with their diabetes medication's ability to treat their diabetes, 56.6% were dissatisfied with the side effects of their diabetes medication, and 66.1% were dissatisfied with their diabetes medication overall. Conclusions: Although most respondents with T2DM and HTN were satisfied with their treatment, dissatisfaction with treatment for one condition was associated with therapy dissatisfaction in the other condition. Approximately 53%-65% of respondents who were dissatisfied with their diabetes medication were also dissatisfied with their HTN medication overall and in the ability to treat the condition and medication side effects.

scholarly journals Oxidative stress in patients with type 2 diabetes mellitus treated with metformin

2017 ◽  
Vol 27 (2) ◽  
pp. 25857
Author(s):  
Samuel Selbach Dries ◽  
Bárbara Da Silveira Soares ◽  
Ana Luiza Ziulkoski ◽  
Simone Gasparin Verza ◽  
Rafael Linden ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Superoxide Dismutase ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Side Effects ◽  
Diabetic Complications

*** Oxidative stress in patients with type 2 diabetes mellitus treated with metformin ***AIMS: To evaluate oxidative stress parameters in patients with type 2 diabetes mellitus treated with metformin, relating these values to its side effects, plasma levels, glycemic control, diabetic complications, lipid profile, and the influence of pharmacotherapeutic follow-up.METHODS: Patients with type 2 diabetes mellitus, on metformin and in pharmacotherapeutic follow-up for four months, were evaluated. The pharmacotherapeutic follow-up consisted in providing information and answering patients’ questions about medication and disease. In addition, administration times, dosages, and presence or absence of side effects related to the use of metformin were verified. Glycemic and lipid profile, oxidative stress (superoxide dismutase and malondialdehyde) and plasma metformin were evaluated. Pearson’s correlation and Spearman’s correlation were performed to evaluate the relationship between the variables at the beginning of the study. The independent t-test and Mann-Whitney U test were used to assess the difference between the groups with and without diabetic complications. The range of values between the beginning and  end of the study was evaluated using Student’s t-test or Wilcoxon U test. The significance level was set at 5%.RESULTS: The initial sample consisted of 49 patients aged 59±9 years with a body mass index of 29.8±5.1 kg/m2, who have had diabetes for a median time of 36 months (interquartile range of 1-240) and have been on metformin for a median time of 36 months (interquartile range of 1-180). Twenty-five patients left the study between the second and fourth meetings. Malondialdehyde levels differed between before and after pharmacotherapeutic follow-up, being positively correlated with blood glucose, glycohemoglobin, and triglyceride level, and negatively correlated with metformin and superoxide dismutase. Blood glucose, glycohemoglobin, and malondialdehyde levels increased, whereas metformin levels decreased in the group with diabetic complications, and there was a correlation between malondialdehyde and the number of diabetic complications per patient.CONCLUSIONS: In this sample of patients with type 2 diabetes mellitus treated with metformin, oxidative stress was more pronounced in those with poor glycemic control and diabetic complications.

scholarly journals Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guozhen Yuan ◽  
Shuai Shi ◽  
Qiulei Jia ◽  
Jingjing Shi ◽  
Shuqing Shi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Fluid Shear Stress ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Active Ingredients

Rapid increases in metabolic disorders, such as type 2 diabetes mellitus (T2DM) and hyperlipidemia, are becoming a substantial challenge to worldwide public health. Traditional Chinese medicine has a long history and abundant experience in the treatment of diabetes and hyperlipidemia, and Puerariae lobatae Radix (known as Gegen in Chinese) is one of the most prevalent Chinese herbs applied to treat these diseases. The underlying mechanism by which Gegen simultaneously treats diabetes and hyperlipidemia, however, has not been clearly elucidated to date. Therefore, we systematically explored the potential mechanism of Gegen in the treatment of T2DM complicated with hyperlipidemia based on network pharmacology. We screened the potential targets of Gegen, T2DM, and hyperlipidemia in several online databases. Then, the hub targets were analyzed by performing protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays, and finally, the complicated connections among compounds, targets, and pathways were visualized in Cytoscape. We found that isoflavones, including daidzein, genistein, and puerarin, as well as β-sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways, such as the PI3K-Akt signaling pathway; the AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis; the PPAR signaling pathway; insulin resistance; the HIF-1 signaling pathway; the TNF signaling pathway; and others. These active ingredients also target multiple biological processes, including the regulation of glucose and lipid metabolism, the maintenance of metabolic homeostasis, and anti-inflammatory and antioxidant pathways. In conclusion, Gegen is a promising therapeutic phytomedicine for T2DM with hyperlipidemia that targets multiple proteins, biological processes, and pathways.

scholarly journals Chemical Composition andα-Glucosidase Inhibitory Activity of VietnameseCitrusPeels Essential Oils

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Nguyen Hai Dang ◽  
Pham Huong Nhung ◽  
Bui Thi Mai Anh ◽  
Dinh Thi Thu Thuy ◽  
Chau Van Minh ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chemical Composition ◽  
Essential Oil ◽  
Essential Oils ◽  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Potential Use

Background. Inhibition ofα-glucosidase is an important factor to control postprandial hyperglycemia in type 2 diabetes mellitus.Citrusessential oils (CEO) are among the most widely used essential oils, and some of them exhibited promising antidiabetic effect. However, theα-glucosidase inhibition of CEO has not been investigated so far. The present work aims to evaluate theα-glucosidase inhibition of essential oils from six VietnameseCitruspeels.Methods. The chemical composition of essential oils obtained by hydrodistillation from sixCitruspeels was analyzed by GC-MS. All essential oils were tested for their inhibitory activity onα-glucosidase usingp-nitrophenyl-α-D-glucopyranoside as substrate.Results. In Buddha’s hand and lime peels, the major components were limonene (59.0–61.31%) andγ-terpinene (13.98–23.84%) while limonene (90.95–95.74%) was most abundant in pomelo, orange, tangerine, and calamondin peels. Among the essential oils, the Buddha’s hand oil showed the most significantα-glucosidase inhibitory effect with the IC50value of 412.2 μg/mL. The combination of the Buddha’s hand essential oil and the antidiabetic drug acarbose increased the inhibitory effect.Conclusions. The results suggested the potential use of Buddha’s hand essential oil as an alternative in treatment of type 2 diabetes mellitus.

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