Displaying publications 221 - 240 of 565 in total

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  1. Furman BL, Candasamy M, Bhattamisra SK, Veettil SK
    J Ethnopharmacol, 2020 Jan 30;247:112264.
    PMID: 31600561 DOI: 10.1016/j.jep.2019.112264
    ETHNOPHARMACOLOGICAL RELEVANCE: The global problem of diabetes, together with the limited access of large numbers of patients to conventional antidiabetic medicines, continues to drive the search for new agents. Ancient Asian systems such as traditional Chinese medicine, Japanese Kampo medicine, and Indian Ayurvedic medicine, as well as African traditional medicine and many others have identified numerous plants reported anecdotally to treat diabetes; there are probably more than 800 such plants for which there is scientific evidence for their activity, mostly from studies using various models of diabetes in experimental animals.

    AIM OF THE REVIEW: Rather than a comprehensive coverage of the literature, this article aims to identify discrepancies between findings in animal and human studies, and to highlight some of the problems in developing plant extract-based medicines that lower blood glucose in patients with diabetes, as well as to suggest potential ways forward.

    METHODS: In addition to searching the 2018 PubMed literature using the terms 'extract AND blood glucose, a search of the whole literature was conducted using the terms 'plant extracts' AND 'blood glucose' AND 'diabetes' AND 'double blind' with 'clinical trials' as a filter. A third search using PubMed and Medline was undertaken for systematic reviews and meta-analyses investigating the effects of plant extracts on blood glucose/glycosylated haemoglobin in patients with relevant metabolic pathologies.

    FINDINGS: Despite numerous animal studies demonstrating the effects of plant extracts on blood glucose, few randomised, double-blind, placebo-controlled trials have been conducted to confirm efficacy in treating humans with diabetes; there have been only a small number of systematic reviews with meta-analyses of clinical studies. Qualitative and quantitative discrepancies between animal and human clinical studies in some cases were marked; the factors contributing to this included variations in the products among different studies, the doses used, differences between animal models and the human disease, and the impact of concomitant therapy in patients, as well as differences in the duration of treatment, and the fact that treatment in animals may begin before or very soon after the induction of diabetes.

    CONCLUSION: The potential afforded by natural products has not yet been realised in the context of treating diabetes mellitus. A systematic, coordinated, international effort is required to achieve the goal of providing anti-diabetic treatments derived from medicinal plants.

    Matched MeSH terms: Hypoglycemic Agents/pharmacology*; Hypoglycemic Agents/therapeutic use
  2. Nokhala A, Siddiqui MJ, Ahmed QU, Ahamad Bustamam MS, Zakaria AZA
    Biomolecules, 2020 02 12;10(2).
    PMID: 32059529 DOI: 10.3390/biom10020287
    Stone leaf (Tetracera scandens) is a Southeast Asian medicinal plant that has been traditionally used for the management of diabetes mellitus. The underlying mechanisms of the antidiabetic activity have not been fully explored yet. Hence, this study aimed to evaluate the α-glucosidase inhibitory potential of the hydromethanolic extracts of T. scandens leaves and to characterize the metabolites responsible for such activity through gas chromatography-mass spectrometry (GC-MS) metabolomics. Crude hydromethanolic extracts of different strengths were prepared and in vitro assayed for α-glucosidase inhibition. GC-MS analysis was further carried out and the mass spectral data were correlated to the corresponding α-glucosidase inhibitory IC50 values via an orthogonal partial least squares (OPLS) model. The 100%, 80%, 60% and 40% methanol extracts displayed potent α-glucosidase inhibitory potentials. Moreover, the established model identified 16 metabolites to be responsible for the α-glucosidase inhibitory activity of T. scandens. The putative α-glucosidase inhibitory metabolites showed moderate to high affinities (binding energies of -5.9 to -9.8 kcal/mol) upon docking into the active site of Saccharomyces cerevisiae isomaltase. To sum up, an OPLS model was developed as a rapid method to characterize the α-glucosidase inhibitory metabolites existing in the hydromethanolic extracts of T. scandens leaves based on GC-MS metabolite profiling.
    Matched MeSH terms: Hypoglycemic Agents/pharmacology; Hypoglycemic Agents/chemistry
  3. Robinson S, Kwan Z, Tang MM
    Dermatol Ther, 2019 07;32(4):e12953.
    PMID: 31044492 DOI: 10.1111/dth.12953
    Insulin, insulin-like growth factor-1 (IGF-1) and essential amino acids activate the mechanistic target of rapamycin complex 1 (mTORC1), the main nutrient-sensitive kinase. Metformin, through inhibition of mTORC1 may improve acne. A 12-week, randomized, open-labeled study evaluated the efficacy and safety of metformin as an adjunct for moderate to severe facial acne. In total, 84 patients received either oral tetracycline 250 mg bd and topical benzoyl peroxide 2.5% with or without metformin 850 mg daily. Evaluations constituted lesion counts, the Cardiff Acne Disability Index (CADI), metabolic parameters and treatment success rate (Investigators Global Assessment score of 0 or 1 or improvement of two grades). Treatment success rates were higher in the metformin group (66.7% vs. 43.2%; p = .04). The mean percentage reduction from baseline in total lesion counts at Week 12 was greater in the metformin group (71.4% vs. 65.3%; p = .278). The CADI scores showed a greater mean reduction in the metformin group (4.82 vs. 4.22; p = .451). Metformin was equally efficacious in improving acne in lean and overweight subjects. Gastrointestinal symptoms were noted in 31.7% of subjects on metformin. This study presents favorable data for metformin as an adjunct for acne treatment. Further randomized placebo-controlled studies are required.
    Matched MeSH terms: Hypoglycemic Agents/administration & dosage; Hypoglycemic Agents/adverse effects
  4. Balakumar P, Dhanaraj SA
    Cell Signal, 2013 Sep;25(9):1799-803.
    PMID: 23707531 DOI: 10.1016/j.cellsig.2013.05.009
    Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system.
    Matched MeSH terms: Hypoglycemic Agents/pharmacology; Hypoglycemic Agents/therapeutic use*
  5. Ashraf A, Mudgil P, Palakkott A, Iratni R, Gan CY, Maqsood S, et al.
    J Dairy Sci, 2021 Jan;104(1):61-77.
    PMID: 33162074 DOI: 10.3168/jds.2020-18627
    The molecular basis of the anti-diabetic properties of camel milk reported in many studies and the exact active agent are still elusive. Recent studies have reported effects of camel whey proteins (CWP) and their hydrolysates (CWPH) on the activities of dipeptidyl peptidase IV (DPP-IV) and the human insulin receptor (hIR). In this study, CWPH were generated, screened for DPP-IV binding in silico and inhibitory activity in vitro, and processed for peptide identification. Furthermore, pharmacological action of intact CWP and their selected hydrolysates on hIR activity and signaling and on glucose uptake were investigated in cell lines. Results showed inhibition of DPP-IV by CWP and CWPH and their positive action on hIR activation and glucose uptake. Interestingly, the combination of CWP or CWPH with insulin revealed a positive allosteric modulation of hIR that was drastically reduced by the competitive hIR antagonist. Our data reveal for the first time the profiling and pharmacological actions of CWP and their derived peptides fractions on hIR and their pathways involved in glucose homeostasis. This sheds more light on the anti-diabetic properties of camel milk by providing the molecular basis for the potential use of camel milk in the management of diabetes.
    Matched MeSH terms: Hypoglycemic Agents/metabolism; Hypoglycemic Agents/pharmacology*
  6. Sengupta P, Chatterjee B, Pal TK
    Regul Toxicol Pharmacol, 2017 Dec;91:151-158.
    PMID: 29107617 DOI: 10.1016/j.yrtph.2017.10.029
    The prevalence of hypertension is very common amongst the diabetic patients and is reported as the major cause of mortality in diabetes. Pioglitazone reported to have an ability to alter the blood cholesterol level and cardioprotective efficiency along with its antidiabetic activity. Telmisartan, through activation of PPAR-γ receptor exerts insulin sensitizing property in addition to its primary cardioprotective efficiency. Theoretically, a combination of pioglitazone and telmisartan may be beneficial to effectively control the high blood glucose level and management of coexisting cardiovascular complication in diabetes. The aim of this research was to experimentally evaluate the pharmacokinetic interaction of pioglitazone and telmisartan when are coadministered in rat. Pioglitazone and telmisartan were administered orally as a single dose individually and in combination to the rats. The plasma samples of the pharmacokinetic study were analyzed using a validated LCMS method. The acute toxicity of the combination with a high dose in rats was also evaluated as a part of the determination of its safety profile. There was no significant change in pharmacokinetic parameters were resulted due to the coadministration of pioglitazone and telmisartan in rat. Absence of major toxicological effect supports the in vivosafety of the combination.
    Matched MeSH terms: Hypoglycemic Agents/adverse effects; Hypoglycemic Agents/pharmacology
  7. Long Q, He M, Tang X, Allotey P, Tang S
    Diabet Med, 2017 01;34(1):120-126.
    PMID: 27472098 DOI: 10.1111/dme.13193
    AIM: This study aims to investigate the medical expenditure of people with type 2 diabetes mellitus in Chongqing, China; to explore factors that contribute to the expenditure; and to examine the financial burden placed on households, particularly poor households.
    METHODS: A cross sectional survey was conducted with a sample of people diagnosed with Type 2 diabetes mellitus in 2014. Of the 664 people eligible, 76% were interviewed. Descriptive statistics and log-linear regression were used to examine respondents' age, sex and level education, location of residence, income and type of health insurance associated with out-of-pocket expenditure on accessing diabetes mellitus care.
    RESULTS: In a year, average out-of-pocket expenditure on the purchase of drugs from pharmacies and having outpatient care were US $333 and US $310, respectively. The average out-of-pocket expenditure on accessing inpatient care was 3.7 times (US $1159) that of accessing outpatient care. After adjusting for age and sex, out-of-pocket expenditure on diabetes care was significantly higher for people covered by the Urban Employee Basic Medical Insurance programme and those enrolled in the identified priority diseases reimbursement programme, which provided higher reimbursement rates for outpatient and (or) inpatient care. Out-of-pocket expenditures on the purchase of drugs from pharmacies, having outpatient and inpatient care, respectively, were 9.8%, 16.2% and 62.6% of annual household income in low-income group.
    CONCLUSION: Even with health insurance coverage, poor people with Type 2 diabetes mellitus suffered from significant financial hardship. This has significant implications for models of care and healthcare financing in China with the growing burden of diabetes.
    Study site: Township or community health centres, Chongqing, China
    Matched MeSH terms: Hypoglycemic Agents/economics; Hypoglycemic Agents/therapeutic use
  8. Azar ST, Echtay A, Wan Bebakar WM, Al Araj S, Berrah A, Omar M, et al.
    Diabetes Obes Metab, 2016 10;18(10):1025-33.
    PMID: 27376711 DOI: 10.1111/dom.12733
    AIMS: Compare effects of liraglutide 1.8 mg and sulphonylurea, both combined with metformin, on glycaemic control in patients with type 2 diabetes (T2D) fasting during Ramadan.

    MATERIALS AND METHODS: In this up to 33-week, open-label, active-controlled, parallel-group trial, adults [glycated haemoglobin (HbA1c) 7%-10% (53-86 mmol/mol); body mass index ≥20 kg/m(2) ; intent to fast] were randomized (1:1) ≥10 weeks before Ramadan to either switch to once-daily liraglutide (final dose 1.8 mg) or continue pre-trial sulphonylurea at maximum tolerated dose, both with metformin.

    PRIMARY ENDPOINT: change in fructosamine, a validated marker of short-term glycaemic control, during Ramadan.

    RESULTS: Similar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide (-12.8 µmol/L); sulphonylurea (-16.4 µmol/L); estimated treatment difference (ETD) 3.51 µmol/L (95% CI: -5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide-treated (2%, three subjects) versus sulphonylurea-treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: -0.54 kg; 95% CI: -0.94;-0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: -0.59% (-6.40 mmol/mol), 95% CI: -0.79; -0.38%; -8.63; -4.17 mmol/mol; p 

    Matched MeSH terms: Hypoglycemic Agents/administration & dosage*; Hypoglycemic Agents/adverse effects
  9. Shafie AA, Ng CH, Tan YP, Chaiyakunapruk N
    Pharmacoeconomics, 2017 02;35(2):141-162.
    PMID: 27752998 DOI: 10.1007/s40273-016-0456-2
    BACKGROUND: Insulin analogues have a pharmacokinetic advantage over human insulin and are increasingly used to treat diabetes mellitus. A summary of their cost effectiveness versus other available treatments was required.

    OBJECTIVE: Our objective was to systematically review the published cost-effectiveness studies of insulin analogues for the treatment of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).

    METHODS: We searched major databases and health technology assessment agency reports for economic evaluation studies published up until 30 September 2015. Two reviewers performed data extraction and assessed the quality of the data using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines.

    RESULTS: Seven of the included studies assessed short-acting insulin analogues, 12 assessed biphasic insulin analogues, 30 assessed long-acting insulin analogues and one assessed a combination of short- and long-acting insulin analogues. Only 17 studies involved patients with T1DM, all were modelling studies and 12 were conducted in Canada. The incremental cost-effectiveness ratios (ICERs) for short-acting insulin analogues ranged from dominant to $US435,913 per quality-adjusted life-year (QALY) gained, the ICERs for biphasic insulin analogues ranged from dominant to $US57,636 per QALY gained and the ICERs for long-acting insulin analogues ranged from dominant to $US599,863 per QALY gained. A total of 15 studies met all the CHEERS guidelines reporting quality criteria. Only 26 % of the studies assessed heterogeneity in their analyses.

    CONCLUSION: Current evidence indicates that insulin analogues are cost effective for T1DM; however, evidence for their use in T2DM is not convincing. Additional evidence regarding compliance and efficacy is required to support the broader use of long-acting and biphasic insulin analogues in T2DM. The value of insulin analogues depends strongly on reductions in hypoglycaemia event rates and its efficacy in lowering glycated haemoglobin (HbA1c).

    Matched MeSH terms: Hypoglycemic Agents/administration & dosage; Hypoglycemic Agents/economics
  10. Lee YK, Lee PY, Ng CJ, Teo CH, Abu Bakar AI, Abdullah KL, et al.
    Inform Health Soc Care, 2018 Jan;43(1):73-83.
    PMID: 28139158 DOI: 10.1080/17538157.2016.1269108
    This study aimed to evaluate the usability (ease of use) and utility (impact on user's decision-making process) of a web-based patient decision aid (PDA) among older-age users. A pragmatic, qualitative research design was used. We recruited patients with type 2 diabetes who were at the point of making a decision about starting insulin from a tertiary teaching hospital in Malaysia in 2014. Computer screen recording software was used to record the website browsing session and in-depth interviews were conducted while playing back the website recording. The interviews were analyzed using the framework approach to identify usability and utility issues. Three cycles of iteration were conducted until no more major issues emerged. Thirteen patients participated: median age 65 years old, 10 men, and nine had secondary education/diploma, four were graduates/had postgraduate degree. Four usability issues were identified (navigation between pages and sections, a layout with open display, simple language, and equipment preferences). For utility, participants commented that the website influenced their decision about insulin in three ways: it had provided information about insulin, it helped them deliberate choices using the option-attribute matrix, and it allowed them to involve others in their decision making by sharing the PDA summary printout.
    Study site: urban tertiary teaching hospital outpatient clinic in Malaysia (primary care clinic, University Malaya Medical Centre, UMMC, Kuala Lumpur, Malaysia)
    Matched MeSH terms: Hypoglycemic Agents/administration & dosage*; Hypoglycemic Agents/therapeutic use
  11. Lim SY, Tham PY, Lim HYL, Heng WS, Chang YP
    J Food Sci, 2018 Jun;83(6):1522-1532.
    PMID: 29745989 DOI: 10.1111/1750-3841.14155
    The valorization of guava waste requires compositional and functional studies. We tested three byproducts of guava purée processing, namely refiner, siever, and decanter. We analyzed the chemical composition and quantified the prebiotic activity score and selected carbohydrates; we also determined the water holding (WHC), oil holding (OHC), cation exchange capacities, bile acid binding, and glucose dialysis retardation (GDR) of the solid fraction and the antioxidative and α-amylase inhibitory capacities (AIC) of the ethanolic extract. Refiner contained 7.7% lipid, 7.08% protein and a relatively high phytate content; it had a high prebiotic activity score and possessed the highest binding capacity with deoxycholic acid. Siever contained high levels of low molecular weight carbohydrates and total tannin but relatively low crude fiber and cellulose contents. It had the highest binding with chenodeoxycholic acid (74.8%), and exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity. Decanter was rich in cellulose and had a high prebiotic activity score. The WHC and OHC values of decanter were within a narrow range and also exhibited the highest binding with cholic acid (86.6%), and the highest values of GDR and AIC. The refiner waste could be included in animal feed but requires further processing to reduce the high phytate levels. All three guava byproducts had the potential to be a source of antioxidant dietary fiber (DF), a finding that warrants further in vivo study.

    PRACTICAL APPLICATION: To differing extents, the guava byproducts exhibited useful physicochemical binding properties and so possessed the potential for health-promoting activity. These byproducts could also be upgraded to other marketable products so the manufacturers of processed guava might be able to develop their businesses sustainably by making better use of them.

    Matched MeSH terms: Hypoglycemic Agents/analysis; Hypoglycemic Agents/pharmacology*
  12. Zulkawi N, Ng KH, Zamberi NR, Yeap SK, Satharasinghe DA, Tan SW, et al.
    Drug Des Devel Ther, 2018;12:1373-1383.
    PMID: 29872261 DOI: 10.2147/DDDT.S157803
    Background: Fermented food has been widely consumed as health food to ameliorate or prevent several chronic diseases including diabetes. Xeniji™, a fermented food paste (FFP), has been previously reported with various bioactivities, which may be caused by the presence of several metabolites including polyphenolic acids, flavonoids, and vitamins. In this study, the anti-hyperglycemic and anti-inflammatory effects of FFP were assessed.

    Methods: In this study, type 2 diabetes model mice were induced by streptozotocin and high-fat diet (HFD) and used to evaluate the antihyperglycemic and anti-inflammatory effects of FFP. Mice were fed with HFD and challenged with 30 mg/kg body weight (BW) of streptozotocin for 1 month followed by 6 weeks of supplementation with 0.1 and 1.0 g/kg BW of FFP. Metformin was used as positive control treatment.

    Results: Xeniji™-supplemented hyperglycemic mice were recorded with lower glucose level after 6 weeks of duration. This effect was contributed by the improvement of insulin sensitivity in the hyperglycemic mice indicated by the oral glucose tolerance test, insulin tolerance test, and end point insulin level. In addition, gene expression study has shown that the antihyperglycemic effect of FFP is related to the improvement of lipid and glucose metabolism in the mice. Furthermore, both 0.1 and 1 g/kg BW of FFP was able to reduce hyperglycemia-related inflammation indicated by the reduction of proinflammatory cytokines, NF-kB and iNOS gene expression and nitric oxide level.

    Conclusion: FFP potentially demonstrated in vivo antihyperglycemic and anti-inflammatory effects on HFD and streptozotocin-induced diabetic mice.

    Matched MeSH terms: Hypoglycemic Agents/pharmacology*; Hypoglycemic Agents/chemistry
  13. Perumalsamy S, Aqilah Mohd Zin NA, Widodo RT, Wan Ahmad WA, Vethakkan SRDB, Huri HZ
    Curr Pharm Des, 2017;23(25):3689-3698.
    PMID: 28625137 DOI: 10.2174/1381612823666170616081256
    BACKGROUND: Chemerin is an adipokine that induces insulin resistance by the mechanism of inflammation in adipose tissue but these are still unclear. A high level of chemerin in humans is considered as a marker of inflammation in insulin resistance and obesity as well as in type 2 diabetes mellitus. Despite the role of chemerin in insulin resistance progression, chemerin as one of the novel adipokines is proposed to be involved in high cancer risk and mortality.

    AIM: The aim of this paper was to review the role of CMKLR-1 receptor and the potential therapeutic target in the management of chemerin induced type 2 diabetes mellitus and cancer.

    PATHOPHYSIOLOGY: Increased chemerin secretion activates an inflammatory response. The inflammatory response will increase the oxidative stress in adipose tissue and consequently results in an insulin-resistant state. The occurrence of inflammation, oxidative stress and insulin resistance leads to the progression of cancers.

    CONCLUSION: Chemerin is one of the markers that may involve in development of both cancer and insulin resistance. Chemokine like receptor- 1 (CMKLR-1) receptor that regulates chemerin levels exhibits a potential therapeutic target for insulin resistance, type 2 diabetes and cancer treatment.

    Matched MeSH terms: Hypoglycemic Agents/administration & dosage*; Hypoglycemic Agents/metabolism
  14. Azam AA, Pariyani R, Ismail IS, Ismail A, Khatib A, Abas F, et al.
    BMC Complement Altern Med, 2017 May 25;17(1):278.
    PMID: 28545435 DOI: 10.1186/s12906-017-1777-1
    BACKGROUND: Orthosiphon stamineus (OS) is a herb known in ethnomedicine for treating diabetes mellitus (DM). In this study, a (1)H NMR based urine metabolomics tool has been used for the first time to identify the metabolic protective mechanism of OS in DM using Streptozotocin (STZ) induced experimental model in rats.

    METHODS: Four different solvent extracts of OS, namely aqueous, ethanolic, 50% aqueous ethanolic and methanolic, at a dose of 500 mg/kg body weight (bw) were orally administered for 14 days to diabetic rats induced via intraperitoneal injection of 60 mg/kg bw STZ. NMR metabolomics approach using pattern recognition combined with multivariate statistical analysis was applied in the rat urine to study the resulted metabolic perturbations.

    RESULTS: OS aqueous extract (OSAE) caused a reversal of DM comparable to that of 10 mg/kg bw glibenclamide. A total of 15 urinary metabolites, which levels changed significantly upon treatment were identified as the biomarkers of OSAE in diabetes. A systematic metabolic pathways analysis identified that OSAE contributed to the antidiabetic activity mainly through regulating the tricarboxylic acid cycle, glycolysis/gluconeogenesis, lipid and amino acid metabolism.

    CONCLUSIONS: The results of this study validated the ethnopharmacological use of OS in diabetes and unveiled the biochemical and metabolic mechanisms involved.

    Matched MeSH terms: Hypoglycemic Agents/administration & dosage*; Hypoglycemic Agents/chemistry
  15. Hidayat AFA, Chan CK, Mohamad J, Kadir HA
    J Ethnopharmacol, 2018 Nov 15;226:120-131.
    PMID: 30118836 DOI: 10.1016/j.jep.2018.08.020
    ETHNOPHARMACOLOGICAL IMPORTANCE: Leptospermum flavescens has been used traditionally in Malaysia to treat various ailments such as constipation, hypertension, diabetes and cancer.

    AIM OF STUDY: To investigate the potential protective effects of L. flavescens in pancreatic β cells through inhibition of apoptosis and autophagy cell death mechanisms in in vitro and in vivo models.

    MATERIALS AND METHODS: L. flavescens leaves were extracted using solvent in increasing polarities: hexane, ethyl acetate, methanol and water. All extracts were tested for INS-1 β cells viability stimulated by streptozotocin (STZ). The extract which promotes the highest cell protective activity was further evaluated for insulin secretion, apoptosis and autophagy signaling pathways. Then, the acute toxicity of extract was carried out in SD rats according to OECD 423 guideline. The active extract was tested in diabetic rats where the pancreatic β islets were evaluated for insulin, apoptosis and autophagy protein.

    RESULTS: The methanolic extract of L. flavescens (MELF) was found to increase INS-1 β cells viability and insulin secretion against STZ. In addition, MELF has been shown to inhibit INS-1 β cells apoptosis and autophagy activity. Notably, there was no toxicity observed in SD rats when administered with MELF. Furthermore, MELF exhibited anti-hyperglycemic activity in diabetic rats where apoptosis and autophagy protein expression was found to be suppressed in pancreatic β islets.

    CONCLUSION: MELF was found to protect pancreatic β cells function from STZ-induced apoptosis and autophagy in in vitro and in vivo.

    Matched MeSH terms: Hypoglycemic Agents/pharmacology*; Hypoglycemic Agents/therapeutic use
  16. Che Hassan NKN, Taher M, Susanti D
    Biomed Pharmacother, 2018 Oct;106:1378-1389.
    PMID: 30119210 DOI: 10.1016/j.biopha.2018.07.087
    The purpose of this study was to determine the phytochemical constituents and pharmacological properties of Garcinia xanthochymus which is commonly known as gamboge, yellow mangosteen and false mangosteen. The phytochemicals constituents, pharmacological benefits and their mechanisms were previously presented in a number of studies including in vitro and in vivo studies from published books, journals and articles. The literature used in this review were published between 1970 and 2017 and were available from databases such as Google Scholar, ScienceDirect, Scopus, PubMed, ProQuest and others. The chemical structures in this paper are drawn using ChemBio Ultra 14.0. G. xanthocymus contains many phytochemicals that can be extracted from its constituent parts; the bark, fruits, leaves, roots, twigs and seeds. The predominant extracted phytochemicals are xanthones, benzophenones, flavonoids, depsidones and isocoumarins. These phytochemicals contribute to the pharmacological activities of this plant as an antioxidant, antidiabetic, and for having Nerve Growth Factor-potentiating, antimicrobial and cytotoxic activities. This species contains a broad range of phytochemicals with curative properties that can be greatly beneficial to man. Notably, this review focused on those studies of the pharmacological effects of this plant that were concentrated on by previous researchers. Thus, further study needs to be done on G. xanthocymus in order to unlock additional potential activities and to pinpoint the exact mechanisms of how these activities can be induced, leading to new drug discoveries which have fewer side effects.
    Matched MeSH terms: Hypoglycemic Agents/isolation & purification; Hypoglycemic Agents/pharmacology
  17. Hellal K, Maulidiani M, Ismail IS, Tan CP, Abas F
    Molecules, 2020 Mar 10;25(5).
    PMID: 32164186 DOI: 10.3390/molecules25051247
    Claims of effective therapy against diabetes using plants including Peganum harmala L., Zygophyllum album, Anacyclus valentinus L., Ammodaucus leucotrichus, Lupinus albus, and Marrubium vulgare in Algerian empirical medicine prompted our interest in evaluating their antidiabetic activity by screening their free radical scavenging (DPPH), α-glucosidase, and nitric oxide (NO) inhibitory activities as well as the total phenolic content (TPC). Extracts of the selected plants were prepared using different ratios of ethanol (0, 50, 80, and 100%). In this study, 100%, and 80% ethanol extracts of L. albus were found to be the most potent, in inhibiting α-glucosidase activity with IC50 values of 6.45 and 8.66 μg/mL, respectively. The 100% ethanol extract of A. leucotrichus exhibited the highest free radical scavenging activity with an IC50 value of 26.26 μg/mL. Moreover, the highest TPC of 612.84 μg GAE/mg extract was observed in M. vulgare, extracted with 80% ethanol. Metabolite profiling of the active extract was conducted using 1H-NMR metabolomics. Partial least square analysis (PLS) was used to assess the relationship between the α-glucosidase inhibitory activity of L. albus and the metabolites identified in the extract. Based on the PLS model, isoflavonoids (lupinoisoflavone G, lupisoflavone, lupinoisolone C), amino acids (asparagine and thiamine), and several fatty acids (stearic acid and oleic acid) were identified as metabolites that contributed to the inhibition of α-glucosidase activity. The results of this study have clearly strengthened the traditional claim of the antihyperglycemic effects of L. albus.
    Matched MeSH terms: Hypoglycemic Agents/pharmacology; Hypoglycemic Agents/chemistry
  18. Akinyede KA, Oyewusi HA, Hughes GD, Ekpo OE, Oguntibeju OO
    Molecules, 2021 Dec 28;27(1).
    PMID: 35011387 DOI: 10.3390/molecules27010155
    Diabetes mellitus (DM) is a chronic metabolic condition that can lead to significant complications and a high fatality rate worldwide. Efforts are ramping up to find and develop novel α-glucosidase and α-amylase inhibitors that are both effective and potentially safe. Traditional methodologies are being replaced with new techniques that are less complicated and less time demanding; yet, both the experimental and computational strategies are viable and complementary in drug discovery and development. As a result, this study was conducted to investigate the in vitro anti-diabetic potential of aqueous acetone Helichrysum petiolare and B.L Burtt extract (AAHPE) using a 2-NBDG, 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxy-d-glucose uptake assay. In addition, we performed molecular docking of the flavonoid constituents identified and quantified by liquid chromatography-mass spectrometry (LC-MS) from AAHPE with the potential to serve as effective and safe α-amylase and α-glucosidase inhibitors, which are important in drug discovery and development. The results showed that AAHPE is a potential inhibitor of both α-amylase and α-glucosidase, with IC50 values of 46.50 ± 6.17 (µg/mL) and 37.81 ± 5.15 (µg/mL), respectively. This is demonstrated by a significant increase in the glucose uptake activity percentage in a concentration-dependent manner compared to the control, with the highest AAHPE concentration of 75 µg/mL of glucose uptake activity being higher than metformin, a standard anti-diabetic drug, in the insulin-resistant HepG2 cell line. The molecular docking results displayed that the constituents strongly bind α-amylase and α-glucosidase while achieving better binding affinities that ranged from ΔG = -7.2 to -9.6 kcal/mol (compared with acarbose ΔG = -6.1 kcal/mol) for α-amylase, and ΔG = -7.3 to -9.0 kcal/mol (compared with acarbose ΔG = -6.3 kcal/mol) for α-glucosidase. This study revealed the potential use of the H. petiolare plant extract and its phytochemicals, which could be explored to develop potent and safe α-amylase and α-glucosidase inhibitors to treat postprandial glycemic levels in diabetic patients.
    Matched MeSH terms: Hypoglycemic Agents/pharmacology*; Hypoglycemic Agents/chemistry*
  19. Thent ZC, Lin TS, Das S, Zakaria Z
    PMID: 23983373
    Cardiovascular complications are one of the major causes of death in diabetes mellitus. Piper sarmentosum (P.s) is an herb that possesses antihyperglycaemic effects. The main aim of the study was to observe the histological changes in the heart and the proximal aorta of streptozotocin-induced diabetic rats following P.s administration. Twenty-four male Sprague-Dawley rats (n=24) were equally randomized into four groups: control group supplemented with normal saline (C); control group supplemented with P.s (CTx) ; diabetic group supplemented with normal saline (D) and, diabetic group supplemented with P.s (DTx). Diabetes was induced by STZ (50mg/kg body weight) intramuscularly. P.s extract (0.125g/kg) was administered orally for 28 days, following four weeks of STZ induction. The cardiac and aortic tissues were collected and processed under different stains: Haematoxylin and Eosin (H & E), Verhoeff-Van Gieson (VVG), Masson's Trichome (MT) and Periodic Acid- Schiff (PAS). There were abnormal cardiomyocytes nuclei, disarray of myofibres and increase in connective tissue deposits in cardiac tissues of the diabetic untreated group. The thickness of tunica media and ratio of tunica intima to media were found to be significantly increased in the aorta of diabetic untreated group (P < 0.05) compared to the control group. There were degenerative changes in the proximal aorta in diabetic untreated groups. All the histological damages of cardiac and aortic tissues were found to be lesser in the diabetic treated groups. Supplementation with P.s extract prevented the oxidative damage arising from diabetes mellitus, and reduced its complications.
    Matched MeSH terms: Hypoglycemic Agents/pharmacology; Hypoglycemic Agents/therapeutic use
  20. Md Isa SH, Najihah I, Nazaimoon WM, Kamarudin NA, Umar NA, Mat NH, et al.
    Diabetes Res Clin Pract, 2006 Apr;72(1):48-52.
    PMID: 16253380 DOI: 10.1016/j.diabres.2005.09.011
    We studied the efficacy of four different treatment regimens (sulphonylurea and metformin+/-acarbose versus glimepiride and rosiglitazone versus glimepiride and bedtime NPH insulin versus multiple actrapid and NPH insulin injections) in poorly controlled type 2 diabetes subjects on hs-CRP, VCAM-1 and AGE at 4, 8 and 12 weeks of treatment. Multiple insulin injections rapidly improved HbA(1c) by 0.6+/-0.9% (p<0.005), 1.2+/-1.3% (p<0.0005) and 1.3+/-1.4% (p<0.0005) at week 4, at week 8 and week 12, respectively. Subjects who continued their existing combination treatment of sulphonylurea, metformin+/-acarbose also showed a significant reduction in HbA(1c) (p<0.05). Although effective in reducing glycemic parameters, there was no reduction in CRP levels in either treatment group. The treatment regimen consisting of rosiglitazone and glimepiride significantly lowered hs-CRP by -2.6 (3.9) mg/L (p<0.05) at week 12 in spite of no improvement in blood glucose. AGE improved in all groups irrespective of type of treatment, glycaemic control and CRP levels. Our data indicate rapid glycaemic control alone does not necessarily result in improvement in markers of inflammation in type 2 diabetes patients.
    Matched MeSH terms: Hypoglycemic Agents/administration & dosage; Hypoglycemic Agents/therapeutic use
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