Antidiabetic Medicines Research Articles

SGLT-2 inhibitors as potential anticonvulsants: empagliflozin, but not dapagliflozin, renders a pronounced effect and potentiates the sodium valproate activity in pentylenetetrazole-induced seizures

On the way to the search for effective adjuvant medicines for epilepsy treatment, antidiabetic medicines such as sodium-glucose cotransporter-2 inhibitors, which are expressed not only in the kidneys but also in the brain, attract attention. From previous studies, it is known that dapagliflozin improves electroencephalographic parameters in rats on the model of pentylenetetrazole-induced seizures. However, the anticonvulsant potential of other medicines from this group needs to be clarified.
 The aim of the study is to estimate the effect of empagliflozin, dapagliflozin per se and their combinations with sodium valproate on pentylenetetrazole-induced seizures, as well as on muscle tone and motor coordination in mice.
 Material and methods. 42 random-bred male albino mice weighing 24-28 g were used in the experiments. Empagliflozin (20 mg/kg) and dapagliflozin (50 mg/kg) were administered intragastrically for 3 days. The classic anticonvulsant sodium valproate (150 mg/kg) per se, in combination with the medicines mentioned above, was administered in a similar regimen. On the second day, 30 minutes after administering all medicines, their effect on muscle tone and coordination of movements was determined in the rotarod test. On the third day, 30 minutes after the last administration of the medicines, their effect on pentylenetetrazole-induced (80 mg/kg subcutaneously) seizures was studied.
 Results. For the first time, a pronounced anticonvulsant effect of empagliflozin was established both when used alone (a significant increase in latency of the convulsions and a decrease in lethality by 43 %) and especially in combination with sodium valproate (a significant increase in latency of the convulsions, a decrease in the number and severity of seizures and a decrease in lethality by 83 %), as well as the absence of a muscle relaxant effect in both cases. Dapagliflozin has neither its anticonvulsant properties nor its effect on the action of sodium valproate. However, this medicine caused muscle relaxation, especially when combined with sodium valproate.
 Conclusions. The results suggest that empagliflozin, unlike dapagliflozin, has a high potential as an adjuvant medicine in treating epilepsy, as it enhances the efficacy of the classic anticonvulsant sodium valproate without muscle relaxant side effects

The socio-economic burden of expenditure for diabetes mellitus treatment: A cross sectional study

Background: Diabetes mellitus is a chronic disorder, non-curable, only controlled by medicines and /or insulin therapy. The aim of this study was to evaluate the expenditure on diagnoses and treatment of diabetes mellitus patients with economic burden to households. Methodology: We collected data by directly interacting with the pre-informed diabatic patients regarding the duration of diabetes, types of insulin therapy and oral hypoglycemic agent, cost of medicine/month and cost of blood sugar test by glucometer/month. Results: A total of 254 patients were enrolled in the study of which 30.71% (n=78) belongs to upper cost family (UCF), 44.88% (n=114) belongs to middle cost family (MCF), and 24.41% (n=62) belongs to lower cost family (LCF), categorized according to their total score. While studying, it was found that the mean family income (rupees)/month of UCF, MCF and LCF are Rs. 33860.26, Rs. 9326.75 and Rs. 7551.79 respectively. The mean blood sugar test cost (rupees)/month for UCF, MCF and LCF are Rs. 377.44, Rs. 382.89 and Rs. 360.00 respectively. Whereas the mean medicine purchase cost (rupees)/month for UCF, MCF and LCF are Rs. 1004.81, Rs. 784.40 and Rs. 721.79 Respectively. The total cost (rupees)/month for sugar test and purchasing medicine that is taken from their family income are Rs. 1382.24, Rs. 1167.30 and Rs. 1081.79 for UCF, MCF and LCF respectively. We also derived that, the UCF, MCF, LCF spent 1.19%, 2.28%, 4.84% of their monthly income on blood sugar test respectively and spent 3.20%, 4.76%, 9.95% of their monthly income on medicine purchase respectively. The percentage of cost, the UCF, MCF, and LCF has spent on both the blood sugar test and medicine purchase is 4.39%, 7.04%, 14.80% respectively. Conclusion: The urgent need should be arisen for better health care policies for making low or no cost blood glucose monitoring device (alternative to glucometer) with low-cost anti-diabetic medicines by Government, for diabetes management.

Phytochemical Screening, GC-MS and FTIR analysis of Bioactive Compounds in Methanolic Leaf Extracts of Costus igneus (CIMLE) as a Natural Source of Drug Lead Molecules for Next-generation Drug-design, Development and Therapeutics

Diabetes mellitus (DM) is a metabolic disorder that affects people of all ages. Increased prevalence of diabetes worldwide has led to the development of synthetic drugs to provide an interim solution to the ill effects of the issue. However, such drugs, although effective as antihyperglycemic agents, are accompanied by significant side effects, costly, and inaccessible to majority of people in remote in underdeveloped countries. Local medicinal plants have been used by such indigenous people through ages to treat such complicate ailments due to their ease of availability and GRAS nature. As diabetes continues to become prevalent, health care practitioners are considering PBNPs as a potential source of antidiabetic drugs due to their high potency and fewer side effects. To better understand the mechanism of action of medicinal plants, their active phytoconstituents are being isolated and investigated thoroughly. Phytochemical screening followed by GCMS analysis of methanolic leaf extracts of Costus igneus depicted the presence of 19 bioactive compounds viz., Bicyclo [3.1.1]heptane, 2,6,6- trimethyl-; 2-Pentadecanone, 6,10,14-trimethyl-; phthalic acid; 3,7,11,15-Tetramethyl-2-hexadecen- 1-ol; 5,9,13-Pentadecatrien-2-one, 6,10,14- trimethyl; 2(3H)-Furanone,dihydro-5-methyl-5- pentyl; Hexamethyl-2,6,10,14,18,22- tetracosahexaen-1-yl]-6-methox.; Oxalic acid, cyclohexyl isohexyl ester; 6-Octadecenoic acid; Phytol; 4,8,12,16-Tetramethylheptadecan-4- olide; 5-methyl-2,3-dihydro-1H-indole; Bis(2-ethylhexyl) phthalate; Adamantane-1-carboxylic acid methyl ester; Benzopyran-6-ol,3,4-dihydro-; Benzoquinoline; gamma-Tocopherol; dimethyl-5,5'-diphenyl-1H,; 1H-benzo[b]furo[2,3-f]indole that may be ADMET predicted for potential biomedical application in the treatment of diabetics and long term complications associated with the disease. 
 Keywords: Costus igneus; CIMLE; GCMS; Phytochemical Screening; Antidiabetic Leads; NDDT; Antidiabetic Medicinal Plant

Potential of UK and US newspapers for shaping patients' knowledge and perceptions about antidiabetic medicines: a content analysis

BackgroundInformation about how newspapers portray antidiabetic medicines to readers is lacking. This study investigated the reporting on antidiabetic medicines in the most widely circulated newspapers published in the United Kingdom (UK) and the United States (US) over a 10-year period.MethodsThe Nexis UK database was used to identify and select relevant articles. Systematic content analysis of the articles which met the inclusion criteria (articles of any format that contained reference to antidiabetic medicines) within the highest circulated newspapers in the UK and US between 2009 and 2018 was conducted. Inter-rater reliability of coding was established using a 10% sample of the identified articles.ResultsA total of 560 (369 UK and 191 US) relevant newspaper articles were retrieved. In the UK, the number of relevant articles showed a slightly increasing trend over the study period, while in the US, article numbers declined over the study period. Safety/risk of antidiabetic medicines was the most frequent theme covered by the articles (34.6%). Over one-third of the newspaper articles were written from a clinical perspective (37.7%). Insulin was the most commonly discussed class of antidiabetic medicine (23.1%). Control of blood sugar levels (53.1%) and side effects/toxicity (92.7%) were the most frequently reported benefit and risk of antidiabetic medicines, respectively. The most frequently reported organ systems harmed by antidiabetic medicines were the cardiovascular, endocrine and gastrointestinal systems. The UK newspapers were more likely to report the benefits of antidiabetic medicines (p = 0.005), while the US articles were more likely to report on harms/risks (p = 0.001). The majority of relevant articles (91.8%) were judged as having a balanced judgement, while 8.2% of the articles were rated as exaggerated.ConclusionsThis study has revealed that antidiabetic medicines are indeed reported on by UK and US newspapers. As media portrayal has the potential to negatively or positively influence patients’ views of their medication for diabetes, healthcare professionals should check on patients’ beliefs and knowledge about their medication and proactively provide objective and balanced information (including promotion of medication adherence).

Effectiveness And Safety Of Low Dose Vitamin D As An Adjunct Therapy In Patients With Type 2 Diabetes Mellitus: A Double-Blind, Randomised, Controlled Study

Background: The metabolic condition Type 2 Diabetes Mellitus causes insulin resistance and beta-cell malfunction. The presence of low-grade inflammation caused by an elevation in the cytokine’s tumour necrosis factor-alpha and interleukin-6 in the blood is the most crucial indicator of T2DM. Given its potent immunosuppressive properties, specific pro-inflammatory cytokine genes, including interleukin-2, interleukin-12, and tumour necrosis factor-alpha, can be inhibited by vitamin D.Methodology: Participants who satisfied the inclusion criteria and were already getting treatment for type 2 diabetes mellitus were screened from the general medicine outpatient department of a Tertiary Care Hospital in South India for this double-blind, randomised, controlled trial. Participants were split into two groups at random, with group 1 getting capsule vitamin D 6,000IU once a week for 16 weeks while group 2 got a placebo.Results: Low Dose vitamin D proved to be more effective and safer in controlling HbA1c after 16 weeks compared to placebo.Conclusion: Vitamin D is proven safe and cost-effective addition to anti-diabetic medicines

Should antidiabetic medicines be considered to reduce cardiometabolic risk in patients with serious mental illness?

Substantially reduced life expectancy for people with serious mental illness compared with the general population is primarily driven by physical health issues, of which cardiovascular disease is the leading cause. In this narrative review, we examine the evidence base for use of metformin and other antidiabetic agents as a means for reducing this excess cardiometabolic disease burden. Evidence from randomised controlled trials (RCTs) suggests substantial potential for metformin to prevent or manage weight gain and glycaemic impairment induced by atypical antipsychotic medications, whereas the impact of metformin on other cardiometabolic risk factors is less consistent. Evidence from RCTs also suggests potential benefits from glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly for addressing cardiometabolic risk factors in people using atypical antipsychotic medications, but this is based on a small number of trials and remains an emerging area of research. Trials of both metformin and GLP-1RAs suggest that these medications are associated with a high prevalence of mild-moderate gastrointestinal side effects. The heterogeneous nature of participant eligibility criteria and of antipsychotic and antidiabetic drug regimens, alongside short trial durations, small numbers of participants and paucity of clinical endpoints as trial outcomes, warrants investment in definitive trials to determine clinical benefits for both metformin and GLP-1RAs. Such trials would also help to confirm the safety profile of antidiabetic agents with respect to less common but serious adverse effects. The weight of RCT evidence suggests that an indication for metformin to address antipsychotic-induced weight gain is worth considering in Australia. This would bring us into line with other countries.

Long-term exposure to PM2.5 constituents in relation to glucose levels and diabetes in middle-aged and older Chinese

BackgroundPrevious studies have indicated the associations between fine particulate matter (PM2.5) exposure and diabetes or glucose levels. However, evidence linking PM2.5 constituents and diabetes or glucose levels was extensively scarce, particularly in developing countries. This study aimed to investigate the associations of exposure to PM2.5 and its five constituents (black carbon [BC], organic matter [OM], nitrate [NO3-], sulfate [SO42-], and ammonium [NH4+]) with diabetes and glucose levels among the middle-aged and elderly Chinese populations. MethodsA national cross-sectional sample of participants aged 45+ years was enrolled from 28 provinces across China’s mainland. Health examination and questionnaire survey for each respondent were performed during 2011−2012. Diabetes was determined by alternative definitions, and the main definition (MD) was self-report diabetes or antidiabetic medicine use or HbA1c ≥6.5 or fasting glucose ≥7 mmol/L or random glucose ≥11.1 mmol/L. Monthly exposure to PM2.5 mass and its five constituents (BC, OM, NO3-, SO42-, and NH4+) for each participant at residence were estimated using satellite-based spatiotemporal prediction models. Generalized linear models and linear mixed-effects models were used to assess the effects of exposure to PM2.5 and its constituents on diabetes or glucose levels, respectively. Stratification analyses were done by sex and age. ResultsWe included a total of 17,326 adults over 45 years in this study. The 3-year mean (interquartile range [IQR]) concentrations of PM2.5, BC, OM, NO3-, SO42-, and NH4+ were 47.9 (27.4) µg/m3, 2.9 (2.2) µg/m3, 9.2 (6.6) µg/m3, 10.2 (9.4) µg/m3, 11.0 (5.2) µg/m3, and 7.1 (4.4) µg/m3, respectively. Per IQR rise in exposure to PM2.5 was significantly associated with an increase of 0.133 mmol/L (95% confidence interval, 0.048−0.219) in glucose concentrations. Similar positive associations were observed for BC (0.097 mmol/L [0.012−0.181]), OM (0.160 mmol/L [0.065−0.256]), NO3- (0.145 mmol/L [0.039−0.251]), SO42- (0.111 mmol/L [0.026−0.196]), and NH4+ (0.135 mmol/L [0.041−0.230]). Under different diabetes definitions, PM2.5 mass and selected constituents with the exception of SO42- were all associated with a higher risk of prevalent diabetes. In MD-based analysis, similar positive associations were observed for four constituents, with corresponding odds ratios of 1.180 (1.097−1.270) for PM2.5, 1.154 (1.079−1.235) for BC, 1.170 (1.079−1.270) for OM, 1.200 (1.098−1.312) for NO3-, and 1.123 (1.037−1.215) for NH4+. Stratified analyses showed a significantly higher risk of diabetes in males (1.225 [1.064−1.411]) than females (1.024 [0.923−1.136]) when exposed to PM2.5. Participants under 65 years were generally more vulnerable to diabetes hazards related to PM2.5 constituents exposure. ConclusionsExposures to PM2.5 and its constituents (i.e., BC, OM, NO3-, and NH4+) were positively associated with increased risks of prevalent diabetes and elevated glucose levels in middle-aged and older adults.

Impact of Adherence on Treatment Outcomes in Diabetic Patients

Diabetes mellitus is still a burden in Indonesia. Failure of treatment may cause the worsening of this disease. This study aimed to define the association between patient adherence and treatment outcomes. We used a cross-sectional design with data from a public hospital in Java. We collected the patients’ characteristics, medical treatments and treatment outcomes from their medical records. The inclusion criteria were adult diabetes mellitus patients without any comorbidities or complications and using antidiabetic medicine (oral and/or injection). The patients’ adherence was assessed using the MARS questionnaire. We recruited 167 subjects from the hospital. Most of the subjects were male (60.0%), the average age was 60.47 (SD: 10.80), 43.7% had single treatment and 50.3% did not adhere. 58.7% subjects had uncontrolled fasting blood glucose (FBG) and 86.6% subjects had uncontrolled HbA1C. After adjusting for subjects’ characteristics, there was a significant association between FBG and adherence. Adherence may increase FBG by as much as 1.95 times (95% CI: 1.04- 3.65). We also found a significant association between adherence and the treatment outcome. Thus, we recommend that health care for diabetes mellitus patients must be complemented with education to increase adherence and improve outcomes.
 Keywords: diabetes, adherence, treatment outcomes

Antidiabetic Medicinal Plants Used in the Eastern Cape Province of South Africa: An Updated Review

Oral antidiabetic drugs are usually costly and are associated with several adverse side effects. This has led to the use of medicinal plants that are considered to have multiple therapeutic targets and are readily accessible. In the Eastern Cape province of South Africa, the number of people using medicinal plants for the management of diabetes has been climbing steadily over the past two decades due to their cultural acceptability, accessibility, affordability, efficacy, and safety claims. In this study, a review of antidiabetic medicinal plants used in the Eastern Cape province of South Africa was conducted. A comprehensive literature survey was thoroughly reviewed using several scientific databases, ethnobotanical books, theses and dissertations. About forty-eight (48) plant species were identified as being used to treat diabetes by the people of Eastern Cape province. Among the plant species, only eight (8) species have not been scientifically evaluated for their antidiabetic activities and twenty antidiabetic compounds were isolated from these medicinal plants. This review has confirmed the use and potential of the antidiabetic medicinal plants in the Eastern Cape province and identified several promising species for further scientific investigation.

Readiness of the primary health care units and associated factors for the management of hypertension and type II diabetes mellitus in Sidama, Ethiopia.

BackgroundIn low-income nations such as Ethiopia, noncommunicable diseases (NCDs) are becoming more common. The Ethiopian Ministry of Health has prioritized NCD prevention, early diagnosis, and management. However, research on the readiness of public health facilities to address NCDs, particularly hypertension and type II diabetes mellitus, is limited.MethodsThe study used a multistage cluster sampling method and a health facility-based cross-sectional study design. A total of 83 health facilities were evaluated based on WHO’s Service Availability and Readiness Assessment (SARA) tool to investigate the availability of services and the readiness of the primary health care unit (PHCU) to manage type II diabetes and Hypertension. Trained data collectors interviewed with PHCU head or NCD focal persons. The study tried to investigate (1) the availability of basic amenities and the four domains: staff and guidelines, basic equipment, diagnostic materials, and essential medicines used to manage DM and HPN, (2) the readiness of the PHCU to manage DM and HPN. The data were processed by using SPSS version 24. Descriptive statistics, including frequency and percentage, inferential statistics like the chi-square test, and logistic regression models were used to analyze the data.ResultsOf the 82 health facilities, only 29% and 28% of the PHCU identified as ready to manage HPN and DM. Facility type, facility location, presence of guidelines, trained staff, groups of antihypertensive and antidiabetic medicines had a significant impact (P < 0.05) on the readiness of the PHCU to manage HPN and DM at a 0.05 level of significance. Facilities located in urban were 8.2 times more likely to be ready to manage HPN cases than facilities located in rural (AOR = 8.2, 95% CI [2.4–28.5]) and P < 0.05.Conclusion and recommendationThe results identified comparatively poor and deprived readiness to offer HPN and DM services at lower-level health facilities(health centers). Equipping the lower-level health facilities with screening and diagnostic materials, essential medicines, and provision of basic training for the health care providers and NCD guidelines should be available, especially in the lower health care facilities.

Effects of two triterpenoids from Nigella sativa seeds on insulin resistance of 3T3-L1 adipocytes.

Insulin resistance (IR) is a physiological abnormality that occurs when insulin fails to activate the signal transduction pathway in target organs. It was found that supplementation of Nigella sativa seeds with oral antidiabetic medicines helps improve blood glucose control by enhanced β cells activity and alleviation of IR. However, the activities and related mechanisms of phytochemicals from N. sativa seeds have not been thoroughly explored. In this study, the effects of two triterpenoids, 3-O-[β-D-xylopyranose-(1→3)-α-L-rhamnose-(1→2)-α-L-arabinose]-28-O-[α-L-rhamnose-(1→4)-β-D-glucopyranose-L-(1→6)-β-D-glucopyranose]-hederagenin (Hxrarg) and 3-O-[β-D-xylopyranose-(1→3)-α-L-rhamnose-(1→2)-α-L-arabinose]-hederagenin (Hxra), on IR were studied by 3T3-L1 adipocytes model. The results demonstrated that Hxrarg and Hxra inhibited maturation of 3T3-L1 preadipocytes, dramatically stimulated glucose uptake of IR-3T3-L1 adipocytes, promoted transcription of IRS, AKT, PI-3K, and GLUT4 mRNA. Western Blot results suggested that Hxrarg and Hxra were able to markedly up-regulate expression of p-IRS, p-AKT, PI-3K, and GLUT4 proteins. These findings could provide a basic foundation for the continued development and application of N. sativa in medicine and functional foods.

Metformin Exhibits an Attractive Antineoplastic Effect on Human Endometrial Cancer by Regulating the Hippo Signaling Pathway.

Metformin, the first-line oral antidiabetic medicine, has shown great antineoplastic potential in various cancer types, despite an unclear mechanism. This study aimed to elucidate the possible mechanism of metformin as a chemotherapy agent with less reproductive and genetic toxicity in human endometrial cancer. The type I endometrial carcinoma cell lines Ishikawa and RL95-2 were treated with metformin. Cell functions, such as proliferation, migration, and invasion, were analyzed. Flow cytometry was performed for cell cycle and apoptosis analyses. Simultaneously, RT-qPCR and western blotting were performed to explore the possible mechanism. Moreover, YAP1 knockout Ishikawa cells were established via lentivirus to demonstrate the underlying mechanism. The results showed that metformin mediated Ishikawa and RL95-2 cell growth inhibition in a dose- and time-dependent manner. The IC50 values of metformin in Ishikawa and RL95-2 cells were 10 mM and 8 mM, respectively. The migration and invasion abilities were also inhibited in the metformin-treated group using wound healing assays and transwell migration and invasion assays, and Ishikawa and RL95-2 cells were arrested in the G1 or G2 phase, respectively. Moreover, the cell proportions of cells in both early and late apoptosis stages were dramatically elevated when treated with metformin, as was the ratio of Bax/Bcl-2 expression. Additionally, the expression levels of YAP1 mRNA and protein in the treatment group were much lower than those in the control group. The cellular behaviors of YAP1 knockout Ishikawa cells were similar to those in the metformin-treated group. Our results demonstrated that it is an attractive alternative to cytotoxic chemotherapy in human endometrial cancer, and YAP of the Hippo pathway may be a potential molecular target. This study provides novel ideas for the adjuvant therapy of endometrial cancer patients, especially for women with strong fertility desires and demands.

Impact of Pomegranate Juice, Antidiabetic Therapy on Glycemic Control and Lipid Subfraction Status

Over the last decade, studies have linked the beneficial effect of pomegranate juice on glycemic control. They have a significant secretory influence on beta-cell, carbohydrate, and lipid metabolism turnover in preventing and treating type ii diabetes. However, hypoglycaemic drugs have side effects such as lactic acidosis and abdominal discomfort. Hence, we aimed for a new treatment regime that included oral antidiabetic drugs and pomegranate juice, which works as an anti-oxidant and a potential antidiabetic agent. The study included randomly chosen145 type 2 diabetes mellitus male subjects and 36 healthy male participants. The study was carried out in two stages. Initially, all subjects were allowed to be on their respective antidiabetic drugs/insulin and to have a regular check-up of blood glucose twice a week for four weeks, after which they were redistributed into three groups, one of which was given pomegranate juice along with their respective antidiabetic drugs. After a 4-week run-in period, patients improved their ability to self-monitor blood glucose values and a wash-out period of 3 weeks, during which oral hypoglycaemic drugs and insulin were discontinued. The subjects were randomly assigned to follow the treatment protocol. Subjects received either an antidiabetic medicine or insulin, while the others received 200 ml of pomegranate fruit juice every day, along with antidiabetic therapy assigned to two-month treatment intervals. Glycemic rate and lipid profile changes were observed at the end of the period. The subjects with Pomegranate Juice with drug treatment showed a significant reduction in the levels of HbAlc (6.2 ± 0.2% vs. 8.2 ± 0.3%.)), LDL cholesterol concentration (120.61 ± 12.81, vs 136.23 ± 16.58 mg/dl P &lt; 0.05), and Phospotidyl choline (27.20 ± 1.98 vs 22.80 ± 2.20 mg/cc. P &lt; 0.05 as compared to other groups. This study has observed that pomegranate juice combined with an antidiabetic therapy regime has outstanding potential advantages in glucose control and a significant reduction in dyslipidemia and increased phospholipids levels compared to insulin or drug alone. These changes are linked to disease progression in numerous tissues. Pomegranate juice therapy may lower the need for diabetic medication or insulin, and natural diet fruits may impact pancreatic cell activation.

A novel approach to patients with schizophrenia and type 2 diabetes showing low treatment compliance

IntroductionPatients with schizophrenia usually demonstrate low compliance to medication. This could be a component of the disorder or a fact that they are not being properly cared.Objectives To prevent this in, we tried to treat these patients with long term action antidiabetic agents, in order to achieve better compliance.MethodsHbA1C measurements of patients suffering from schizophrenia and at the same time receiving oral antidiabetic treatment were conducted. 62 patients were found that fell under the criteria of non regulated type 2 diabetes and at the same time presented less than 70% complied with their antidiabetic pharmaceutical treatment. We modified the antidiabetic treatment of these patients, with the introduction of dulaglutide.ResultsWithout intervening with their nutritional habits there was a decline in HbA1C measurements from the average rate of 9,4% to the average rate of 7,6%, as well as an average 6,31% reduction of their body weight.ConclusionsDue to the improvement of the general medical condition of these patients, the answer to the question whether these patients should be treated with a long term antidiabetic medicines, is positive. The arrival of new long term action antidiabetic medicines in the near future, promises to improve the life quality of schizophrenic patients furthermor.DisclosureNo significant relationships.

Virtual Screening of Alpha Glucosidase Inhibition Using Common-Urban Herbs in Indonesia

Indonesia as a mega-biodiversity country have rich potential of herbal medicine that can growth easily at rural and urban area. Recently, Indonesian urban people are encouraged to have their own family herb plants namely tanaman obat keluarga or TOGA, which can increasing the health quality as well as economically. The urban herbs that are commonly planted may have esthetical and medical purposes. However the common urban herbs for medical purposes have not been proved yet scientifically. The objective of this study was to screening virtually the antidiabetic potential of bioactive compounds in common-urban herbs including Catharanthus roseus, Peperomia pellucida, Areta catechu, Physalis angulata, Apium graveolens, Imperata cylindrica, and Cassia siamea. Based on the references we selected the candidate of bioactives that contained in those common urban herbs such as Lochnerine, Cylindrene, Dihydroquercetin, Limonene, Vindolidine, Withangulatin-A, and Yohimbine. The selected bioactives were performed as ligands which their 3D structure were searched from the database of Pubchem prior to molecular docking analysis toward alpha glucosidase using PyRx method. Among the selected bioactives from common urban herbs, we found that withangulatin-A from Physalis angulata has the highest potential of antidiabetic medicine herbal via alpha glucosidase inhibition.

Synthesis and Inhibitory Activity of Curculigoside A Derivatives as Potential Anti-Diabetic Agents with β-Cell Apoptosis

• It is the aim to synthesize aglycone of curculigoside A derivatives using acyl chloride in a mild condition by using imidazole and operating at room temperature. • Compounds 1, 2 , and 6 inhibit α-glucosidase are more effectively than acarbose. • Compounds 3, 4 , and 6 are inhibited TNF-α receptors better than or comparable to acarbose • Compound 6 has the potential to be an anti-diabetic by improving insulin resistance as well as inducing β-cell death. Diabetes mellitus (T1D, T2D, and DD) is a chronic metabolic condition that affected 4.2 million people in 2019 and is expected to reach 700 million by 2045. Hybrid or double diabetes (DD), which presents symptoms of both T1D and T2D, is caused by β-cell failure and apoptosis. The aglycone of curculigoside A derivatives was assessed in silico to optimize the pharmacokinetics and safety profile, as well as the binding mechanism and stability of anti-diabetic medicines with α-glucosidase. The objectives of this study are to synthesize, evaluate the biological activity of α-glucosidase, and simulate the inhibitory activity of the aglycone of curculigoside A derivatives on the tumor necrosis factor alpha (TNF-α) receptor as prospective anti-diabetic agents with β-cell apoptosis. Synthesis was carried out by using the esterification technique with halogenated carboxylic acids under moderate reaction conditions. Synthesized compounds 1 - 6 were assessed for their insulin resistance using α-glucosidase and investigated in silico by using the TNF-α receptor for its action in β-cell destruction. Compounds 3 - 6 have pharmacochemical properties that can be absorbed in the gastrointestinal tract, whereas compounds 1 and 2 are more water-soluble. The proposed methodology for the synthesis of the aglycone of curculigoside A derivatives by the esterification technique using halogenated carboxylic acids under moderate reaction conditions gives good yields. The biological evaluation study indicates that compounds 1, 2 , and 6 inhibit α-glucosidase more effectively than acarbose. By in silico study, compounds 3, 4 , and 6 inhibited TNF-α receptors are better than or comparable to acarbose, indicating that they have the ability to reduce β-cell apoptosis. In conclusion, 4-hydroxybenzyl-4-fluorobenzoat (compound 6 ) has the potential to be an anti-diabetic by inducing β-cell death.

Clinical and biochemical outcomes of sodium-glucose co-transporter-2 (SGLT2) inhibitors in type 2 diabetes mellitus patients as a fourth oral anti diabetic medicine

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The Antioxidant Properties of Mushroom Polysaccharides can Potentially Mitigate Oxidative Stress, Beta-Cell Dysfunction and Insulin Resistance.

Diabetes mellitus is a prevalent metabolic and endocrine illness affecting people all over the world and is of serious health and financial concern. Antidiabetic medicine delivered through pharmacotherapy, including synthetic antidiabetic drugs, are known to have several negative effects. Fortunately, several natural polysaccharides have antidiabetic properties, and the use of these polysaccharides as adjuncts to conventional therapy is becoming more common, particularly in underdeveloped nations. Oxidative stress has a critical role in the development of diabetes mellitus (DM). The review of current literature presented here focusses, therefore, on the antioxidant properties of mushroom polysaccharides used in the management of diabetic complications, and discusses whether these antioxidant properties contribute to the deactivation of the oxidative stress-related signalling pathways, and to the amelioration of β-cell dysfunction and insulin resistance. In this study, we conducted a systematic review of the relevant information concerning the antioxidant and antidiabetic effects of mushrooms from electronic databases, such as PubMed, Scopus or Google Scholar, for the period 1994 to 2021. In total, 104 different polysaccharides from mushrooms have been found to have antidiabetic effects. Most of the literature on mushroom polysaccharides has demonstrated the beneficial effects of these polysaccharides on reactive oxygen and nitrogen species (RONS) levels. This review discuss the effects of these polysaccharides on hyperglycemia and other alternative antioxidant therapies for diabetic complications through their applications and limits, in order to gain a better understanding of how they can be used to treat DM. Preclinical and phytochemical investigations have found that most of the active polysaccharides extracted from mushrooms have antioxidant activity, reducing oxidative stress and preventing the development of DM. Further research is necessary to confirm whether mushroom polysaccharides can effectively alleviate hyperglycemia, and the mechanisms by which they do this, and to investigate whether these polysaccharides might be utilized as a complementary therapy for the prevention and management of DM in the future.

Cardiac effects of dapagliflozin in diabetic rats with subacute exposure

Background and Aims: Dapagliflozin (DAPA) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of type 2 diabetes mellitus (T2DM) as a monotherapy or combination therapy with other antidiabetic medicines. The Food and Drug Administration (FDA) recently approved DAPA to minimize the risk of hospitalization due to heart failure in patients with T2DM because of its antihypertensive and antihyperglycemic activities. However, further study of DAPA is necessary to ensure the safety of patients. Methods: T2DM was induced by streptozotocin (STZ) injection (35 mg/kg b.w. i.p.) in male rats that were fed a high-fat diet for two weeks before STZ injection. The diabetic rats were exposed to 10 mg/kg DAPA by oral gavage during sub-acute treatment. Total cholesterol levels and oxidative stress parameters were evaluated. Heart tissues were histologically examined, and cardiac troponin T (cTnT) levels were measured. Results: DAPA has the potential to inhibit diabetes-induced oxidative stress and morphologic damage to heart tissue, and increased cTnT levels of the heart, which is important for cardiac contractility. Conclusion: DAPA might have a protective effect on the heart at a 10 mg/kg oral dose; however, further experimental and clinical studies are required to clarify the cardio-protective potential of DAPA.

An in-vivo herb-drug interaction study of Tinospora cordifolia extract on the pharmacokinetics of gliclazide in normal Wistar rats

Background and Aims: Tinospora cordifolia (Willd.) Miers (TC), from the Menispermaceae family, is a well-known traditional herb used to treat diabetes mellitus and a variety of other ailments, according to traditional Indian literature. Herbal treatments are commonly used as alternatives to medicines. Anti-diabetic herbal medicines containing TC are available in the market. TC has been identified as a powerful CYP2C9 inhibitor, boosting the risk of herb-drug interactions (HDI) when used with medications metabolized via the CYP pathway. The present study evaluated the pharmacokinetic HDI of TC extract with Gliclazide (GL) after oral co-administration in Wistar rats using in vivo pharmacokinetic studies. Methods: A simple, sensitive &amp; accurate RP-HPLC/PDA method was developed and validated. Chromatographic separations were performed on a C18 analytical column with a mobile phase of acetonitrile and 40 mM ammonium acetate buffer (55:45 v/v) pH 3.0 and flow rate gradient programming. The drug concentrations in plasma were measured using the RP-HPLC method after oral co-administration of TC extract (100 mg/kg) with GL (8.3 mg/kg) in Wistar rats. Results: The pharmacokinetic (PK) interaction studies showed that the bioavailability of GL had significantly increased, with a significant influence on Cmax, AUC0-48, and suppression of volume of distribution (Vd), with no change in Tmax. Conclusion: The results obtained from this in vivo study proposed that there is a potentially significant PK HDI when GL and TC extract are administered together. This knowledge of potential HDI could be beneficial to healthcare providers and diabetic patients on GL medication. Further research is needed to anticipate this pharmacokinetics HDI of GL in humans.