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Identification of curcumin as a potential α-glucosidase and dipeptidyl-peptidase 4 inhibitor: Molecular docking study, in vitro and in vivo biological evaluation

Cao W, Chen X, Chin Y, Zheng J, Lim PE, Xue C, et al.

J Food Biochem, 2021 Apr 04.
PMID: 33817806 DOI: 10.1111/jfbc.13686

Natural compounds have tremendous potential to regulate glucose metabolism, but conventional methods for studying their bioactivities are usually labor intensive. Here, hypoglycemic properties in 22 selected food-derived compounds were examined using molecular docking. The results indicated that curcumin is an inhibitor of both α-glucosidase and dipeptidyl-peptidase 4 (DPP-4), which are important for glycemic control. These effects of curcumin were also confirmed by enzymatic determination in vitro. Furthermore, curcumin significantly improved diet-induced hyperglycemia (e.g., fasting plasma glucose levels and glycogen storage in muscle or liver) in mice. This might be attributed to its inhibitory effects on the activities of α-glucosidase and DPP-4 in vivo. Curcumin also upregulated the expression of genes (e.g., glucagon-like peptide 1) related to DPP-4 activity in the small intestine. In conclusion, curcumin is a potential ingredient of functional foods used for diet-induced hyperglycemia management. PRACTICAL APPLICATIONS: Curcumin has been widely used as a colorant in the food industry. Moreover, a growing number of studies have described its diverse biological functions, such as anti-inflammatory, anti-oxidant, and anti-angiogenic activities. Thus, curcumin is regarded as a potential ingredient in functional foods. Our results highlighted the hyperglycemic effect of curcumin, suggesting that curcumin may be included in food products for hyperglycemic patients.

Matched MeSH terms: Hypoglycemic Agents
Complementary NMR- and MS-based metabolomics approaches reveal the correlations of phytochemicals and biological activities in Phyllanthus acidus leaf extracts

Abd Ghafar SZ, Mediani A, Maulidiani M, Rudiyanto R, Mohd Ghazali H, Ramli NS, et al.

Food Res Int, 2020 10;136:109312.
PMID: 32846521 DOI: 10.1016/j.foodres.2020.109312

Proton nuclear magnetic resonance (1H NMR)- and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS)-based analytical tools are frequently used in metabolomics studies. These complementary metabolomics platforms were applied to identify and quantify the metabolites in Phyllanthus acidus extracted with different ethanol concentrations. In total, 38 metabolites were tentatively identified by 1H NMR and 39 via UHPLC-MS, including 30 compounds are reported for the first time from this plant. The partial least square analysis (PLS) revealed the metabolites that contributed to α-glucosidase and nitric oxide (NO) inhibitory activities, including kaempferol, quercetin, myricetin, phyllanthusol A, phyllanthusol B, chlorogenic, catechin, cinnamic coumaric, caffeic, quinic, citric, ellagic and malic acids. This study shows the significance of combining 1H NMR- and UHPLC-MS-based metabolomics as the best strategies in identifying metabolites in P. acidus extracts and establishing an extract with potent antioxidant, anti-diabetic, and anti-inflammatory properties.

Matched MeSH terms: Hypoglycemic Agents
Fulltext A Review on Oxidative Stress, Diabetic Complications, and the Roles of Honey Polyphenols

Pasupuleti VR, Arigela CS, Gan SH, Salam SKN, Krishnan KT, Rahman NA, et al.

Oxid Med Cell Longev, 2020;2020:8878172.
PMID: 33299532 DOI: 10.1155/2020/8878172

Despite the availability of various antidiabetic drugs, diabetes mellitus (DM) remains one of the world's most prevalent chronic diseases and is a global burden. Hyperglycaemia, a characteristic of type 2 diabetes mellitus (T2DM), substantially leads to the generation of reactive oxygen species (ROS), triggering oxidative stress as well as numerous cellular and molecular modifications such as mitochondrial dysfunction affecting normal physiological functions in the body. In mitochondrial-mediated processes, oxidative pathways play an important role, although the responsible molecular mechanisms remain unclear. The impaired mitochondrial function is evidenced by insulin insensitivity in various cell types. In addition, the roles of master antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response elements (ARE) are being deciphered to explain various molecular pathways involved in diabetes. Dietary factors are known to influence diabetes, and many natural dietary factors have been studied to improve diabetes. Honey is primarily rich in carbohydrates and is also abundant in flavonoids and phenolic acids; thus, it is a promising therapeutic antioxidant for various disorders. Various research has indicated that honey has strong wound-healing properties and has antibacterial, anti-inflammatory, antifungal, and antiviral effects; thus, it is a promising antidiabetic agent. The potential antidiabetic mechanisms of honey were proposed based on its major constituents. This review focuses on the various prospects of using honey as an antidiabetic agent and the potential insights.

Matched MeSH terms: Hypoglycemic Agents
Evaluation of wound healing activity of plumbagin in diabetic rats

Shao Y, Dang M, Lin Y, Xue F

Life Sci, 2019 Aug 15;231:116422.
PMID: 31059689 DOI: 10.1016/j.lfs.2019.04.048

This study was performed to evaluate the antidiabetic and wound healing activity of plumbagin in diabetic rats by macroscopical, biochemical, histological, immunohistochemical and molecular methods. Percentage of wound closure and contraction was delayed in diabetic rats when compared to non-diabetic group. There was significant reduction in period of epithelialization, collagen and protein content. Serum insulin level was significantly lowered together with increase in glucose level in diabetic rats. Lipid levels were increased significantly with concomitant decrease in HDL level. The mRNA levels of Nrf2, collagen-1, TGF-β and α-SMA were significantly lowered whereas Keap-1 levels were increased in diabetic rats. The level of lipid peroxides was increased while the levels of antioxidants were lowered significantly. ELISA results reveal upregulated levels of inflammatory markers. Western blot result shows upregulated levels of CD68 and CD163 proteins in wound area of diabetic rats. Histopathological observation revealed increased inflammatory cells infiltration in diabetic control. Immunofluorescent staining and immunohistochemical analysis also displayed delayed wound healing in diabetic groups. Diabetic rats treated with 10% and 20% plumbagin showed increased epithelialization, collagen deposition, increased serum insulin level and increased antioxidant status. Lipid peroxides and lipid levels were lowered significantly with increase in HDL level. Inflammatory markers were lowered, and growth factors expressions were increased markedly. Thus, the results of the study indicated that plumbagin administration could improve wound healing activity and could serve as a potent antidiabetic and anti-inflammatory agent.

Matched MeSH terms: Hypoglycemic Agents
Giganteone A and malabaricone C as potential pharmacotherapy for diabetes mellitus

Sivasothy Y, Leong KH, Loo KY, Adbul Wahab SM, Othman MA, Awang K

Nat Prod Res, 2021 Feb 16.
PMID: 33593208 DOI: 10.1080/14786419.2021.1885405

The use of antidiabetic agents which control glycemic levels in the blood and simultaneously inhibit oxidative stress is an important strategy in the prevention of Diabetes Mellitus and its complications. In our previous study, malabaricone C (3) and its dimer, giganteone A (5) exhibited significant DPPH free radical scavenging activities which were lower than the activity of the positive control, ascorbic acid. These compounds were evaluated for their α-glucosidase inhibitory activities at different concentrations (0.02-2.5 mM) in the present study. Compounds 3 (IC50 59.61 µM) and 5 (IC50 39.52 µM) were identified as active alpha-glucosidase inhibitors, each respectively being 24 and 37 folds more potent than the standard inhibitor, acarbose. Based on the molecular docking studies, compounds 3 and 5 docked into the active site of the α-glucosidase enzyme, forming mainly hydrogen bonds in the active site.

Matched MeSH terms: Hypoglycemic Agents
Extraction methods of butterfly pea (Clitoria ternatea) flower and biological activities of its phytochemicals

Jeyaraj EJ, Lim YY, Choo WS

J Food Sci Technol, 2021 Jun;58(6):2054-2067.
PMID: 33967304 DOI: 10.1007/s13197-020-04745-3

Clitoria ternatea or commonly known as 'Butterfly pea' has been used traditionally in Ayurvedic medicine in which various parts of the plants are used to treat health issues such as indigestion, constipation, arthritis, skin diseases, liver and intestinal problems. The flowers of C. ternatea are used worldwide as ornamental flowers and traditionally used as a food colorant. This paper reviews the recent advances in the extraction and biological activities of phytochemicals from C. ternatea flowers. The application of maceration or ultrasound assisted extraction greatly increased the yield (16-247% of increase) of phytochemicals from C. ternatea flowers. Various phytochemicals such as kaempferol, quercetin and myricetin glycosides as well as anthocyanins have been isolated from C. ternatea flowers. Clitoria ternatea flower extracts were found to possess antimicrobial, antioxidant, anti-inflammatory, cytotoxic and antidiabetic activities which are beneficial to human health. Clitoria ternatea flower is a promising candidate for functional food applications owing to its wide range of pharmacotherapeutic properties as well as its safety and effectiveness.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Purification and characterization of charantin from Momordica charantia Linn.

Oh, J. H., Lim, P. K., Hamzah, S., Tan, C. P., Chan, Sook Wah

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):43-43.
MyJurnal

Introduction: Diabetes mellitus (DM) is one of the top diseases that lead public health concern in Malaysia. It was believed to rise in number up to 4.5 million on cases by year 2020 based on the current figure. Momordica charantia Linn (MC), a climber belonging to family Cucurbitaceae, is well known in treating diabetic-related conditions. In earlier studies related to the hypoglycemic properties of MC mainly utilized the crude extract, which contain a mixture of bioactives (charantins, insulin-like peptides and alkaloids). Till now, there is no conclusive result on the major bioactives that play role in the hypoglycemic effect of MC and research regarding the charantin purification was not well established. Hence, the objectives of this study were to purify the charantin from MC and to characterize the purified charantin before further subjected to in vivo hypoglycemic study. Methods: The crude was first extracted from MC using ethanol as solvent via Soxhlet extraction following by a series of purification steps via washing, centrifugation, and C-18 cartridges. Results: The HPLC analysis showed that the charantin of purified extract after passing out from the cartridge exuded at 12.50 min with a concentration of 500 ppm, which is relatively 20 times higher than the crude extract (25 ppm). The structural properties of purified charantin were studied using FTIR and it showed strong peaks of carboxylic acids (2884 nm), alcohols (1023 nm) and diethyl ether (1114 nm) as compared
with the standard. The compound was reconfirmed in LC-MS analysis. The result displayed mass spectrum in positive mode indicates the presence of similar compound in the purified extract and standard charantin, as presented by ion m/z = 300. Conclusion: The charantin was successfully purified from MC and can act as a potent plant-based hypoglycemic agent for diabetes.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Isolation of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro and In Silico Validation

Maher S, Choudhary MI, Saleem F, Rasheed S, Waheed I, Halim SA, et al.

Biology (Basel), 2020 Jul 30;9(8).
PMID: 32751610 DOI: 10.3390/biology9080197

Withania coagulans (W. coagulans) is well-known in herbal medicinal systems for its high biological potential. Different parts of the plant are used against insomnia, liver complications, asthma, and biliousness, as well as it is reported to be sedative, emetic, diuretic, antidiabetic antimicrobial, anti-inflammatory, antitumor, hepatoprotective, antihyperglycemic, cardiovascular, immuno-suppressive and central nervous system depressant. Withanolides present in W. coagulans have attracted an immense interest in the scientific field due to their diverse therapeutic applications. The current study deals with chemical and biological evaluation of chloroform, and n-butanol fractions of W. coagulans. The activity-guided fractionation of both extracts via multiple chromatographic steps and structure elucidation of pure isolates using spectroscopies (NMR, mass spectrometry, FTIR and UV-Vis) led to the identification of a new withanolide glycoside, withacogulanoside-B (1) from n-butanol extract and five known withanolides from chloroform extract [withanolid J (2), coagulin E (3), withaperuvin C (4), 27-hydroxywithanolide I (5), and ajugin E (6)]. Among the tested compounds, compound 5 was the most potent α-glucosidase inhibitor with IC50 = 66.7 ± 3.6 µM, followed by compound 4 (IC50: 407 ± 4.5 µM) and compound 2 (IC50: 683 ± 0.94 µM), while no antiglycation activity was observed with the six isolated compounds. Molecular docking was used to predict the binding potential and binding site interactions of these compounds as α-glucosidase inhibitors. Consequently, this study provides basis to discover specific antidiabetic compounds from W. coagulans.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Descriptive Regional Subanalysis of a Real-World Study in Patients with Type 2 Diabetes Treated with Gliclazide MR During Fasting: DIA-RAMADAN

Hassanein M, Al Sifri S, Shaikh S, Raza SA, Akram J, Rudijanto A, et al.

Diabetes Ther, 2021 Jun;12(6):1703-1719.
PMID: 33974216 DOI: 10.1007/s13300-021-01067-1

INTRODUCTION: To analyse the safety and effectiveness of gliclazide modified release (MR) in adults with type 2 diabetes mellitus participating in Ramadan from three geographically and culturally different regions of the world included in the DIA-RAMADAN study.
METHODS: DIA-RAMADAN was a real-world, observational, international, non-comparative study. The global study population was divided into three regional subgroups, with data gathered at inclusion 6-8 weeks prior to Ramadan (V0), during Ramadan (4.5 weeks) and 4-6 weeks after Ramadan (V1). Primary endpoint was the proportion of patients reporting ≥ 1 symptomatic hypoglycaemic events (HE), which were collected using a patient diary along with other adverse events.
RESULTS: Patient numbers from the three regions were n = 564 (46.5%; Indian sub-continent), n = 354 (29.1%; Middle East) and n = 296 (24.4%; South-East Asia). Patient baseline characteristics, demographics, fasting habits and antidiabetic treatments varied between regions. There were similar proportions of symptomatic HE between regions, with no severe HE. Significant weight reductions were observed in all regions following Ramadan, along with reductions in HbA1c and fasting plasma glucose.
CONCLUSION: These real-world study data indicate that gliclazide MR is safe and effective for management of type 2 diabetes during Ramadan in all three regions studied as part of DIA-RAMADAN.
TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04132934. INFOGRAPHIC.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Antihyperglycaemic and Toxicological Evaluations of Extract and Fractions of Gynura procumbens Leaves

Algariri K, Atangwho IJ, Meng KY, Asmawi MZ, Sadikun A, Murugaiyah V

Trop Life Sci Res, 2014 Aug;25(1):75-93.
PMID: 25210589 MyJurnal

The acute and sub-chronic antihyperglycaemic activity, safety margin evaluations and chemical composition of ethanol extract (EE) and fractions of Gynura procumbens (GP) were studied. Streptozotocin (STZ)-induced diabetic rats (SDRs) and the Organisation for Economic Cooperation and Development (OECD) guidelines 425 and 407 were used in the antidiabetic and toxicity studies, respectively. Biochemical and haematological data obtained from both acute and sub-chronic procedures suggest that the extract is safe at the limit test dose (2000 mg/kg); thus, the oral lethal dose (LD50) exceeds 2000 mg/kg. The acceptable daily intake (ADI) was determined to be 700 mg/kg/day. In the acute antihyperglycaemic study, the n-butanol fraction (n-BF) was found to consistently lower glucose levels the most effectively, which was also demonstrated in the 14-day study. Not only did the n-BF show the highest dose-dependent glucose-lowering action (51.2% and 62.0% at 500 mg/kg and 1000 mg/kg, respectively), its effect was the closest to that of metformin (63.6%, p<0.05). The estimated amount of flavonoids in n-BF were 62.90% and 79.68% higher than the ethyl acetate fraction (EAF) and aqueous fraction (AF), respectively (p<0.05), with a corresponding value of 61.22% and 49.33% for phenolics (p<0.05). GP leaves have a no-observed-adverse-effect-level (NOAEL) and antihyperglycaemic activity corresponding to the high content of phenols and flavonoids. Therefore, GP leaves are a promising source of new antidiabetic natural products.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Antidiabetic and In Vitro Enzyme Inhibition Studies of Methanol Extract of Ocimum tenuiflorum Linn Leaves and Its Fractions

Mousavi L, Salleh RM, Murugaiyah V

Trop Life Sci Res, 2020 Apr;31(1):141-158.
PMID: 32963716 DOI: 10.21315/tlsr2020.31.1.9

The current study aimed to determine the best dose of methanol extract of Ocimum tenuiflorum L. leaves extract, and it is a fraction to blood-glucose-lowering in diabetic rats, and evaluated the α-amylase, α-glucosidase inhibitors and insulin level of diabetic rats used to achieve greater control over hyperglycemia. The result of the antihyperglycaemic of oral administration of a different dose of methanol extract in streptozotocin-induced rats showed that the highest dose of methanol extract significantly reduced the blood glucose level compared to another dose. Also, the result of repeated administration of methanol fractions indicates that ethyl acetate-butanol fraction exhibited a stronger antihyperglycemic effect than chloroform and ethanol-water fractions. Moreover, the result showed that effect of methanol extract and its fraction on α-glucosidase and α-amylase enzymes activities and its insulin level by in vitro study, ethyl acetate-butanol fraction could control with low concentration compared to other fractions and acarbose that used as a positive control. From the result of insulin level, methanol extract and fraction did not show any significant. These findings indicated that the active crude extract (methanol) and its active fractions (ethyl acetate/butanol) could exert significant glucose-lowering effect due to the presence of polyphenolics active constituents. In conclusion, isolation of the active components of Ocimum tenuiflorum L. may pave the way to the development of new agents for the treatment of diabetes and its complications.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Pharmacoinformatics and UPLC-QTOF/ESI-MS-Based Phytochemical Screening of Combretum indicum against Oxidative Stress and Alloxan-Induced Diabetes in Long-Evans Rats

Forid MS, Rahman MA, Aluwi MFFM, Uddin MN, Roy TG, Mohanta MC, et al.

Molecules, 2021 Jul 30;26(15).
PMID: 34361788 DOI: 10.3390/molecules26154634

This research investigated a UPLC-QTOF/ESI-MS-based phytochemical profiling of Combretum indicum leaf extract (CILEx), and explored its in vitro antioxidant and in vivo antidiabetic effects in a Long-Evans rat model. After a one-week intervention, the animals' blood glucose, lipid profile, and pancreatic architectures were evaluated. UPLC-QTOF/ESI-MS fragmentation of CILEx and its eight docking-guided compounds were further dissected to evaluate their roles using bioinformatics-based network pharmacological tools. Results showed a very promising antioxidative effect of CILEx. Both doses of CILEx were found to significantly (p < 0.05) reduce blood glucose, low-density lipoprotein (LDL), and total cholesterol (TC), and increase high-density lipoprotein (HDL). Pancreatic tissue architectures were much improved compared to the diabetic control group. A computational approach revealed that schizonepetoside E, melianol, leucodelphinidin, and arbutin were highly suitable for further therapeutic assessment. Arbutin, in a Gene Ontology and PPI network study, evolved as the most prospective constituent for 203 target proteins of 48 KEGG pathways regulating immune modulation and insulin secretion to control diabetes. The fragmentation mechanisms of the compounds are consistent with the obtained effects for CILEx. Results show that the natural compounds from CILEx could exert potential antidiabetic effects through in vivo and computational study.

Matched MeSH terms: Hypoglycemic Agents/isolation & purification; Hypoglycemic Agents/pharmacology*; Hypoglycemic Agents/chemistry
Fulltext Decision making in hyperglycaemia seen in pregnancy

Kavitha Nagandla, Sivalingam Nalliah

International e-Journal of Science, Medicine & Education, 2014;8(1):8-18.
MyJurnal

Delay in childbearing, family history of type 2 diabetes mellitus and obesity in childbearing years increases a possibility of glucose intolerance or overt diabetes in pregnancy which may remain unrecognised unless an oral glucose tolerance test is done.The International Association of Diabetes and Pregnancy Study Group (IADPSG, 2010) recommended the detection and diagnosis of hyperglycaemic disorders in pregnancy at two stages of pregnancy, the first stage looking for ‘overt diabetes’ in early pregnancy based on risk factors like age, past history of gestational diabetes and obesity and the second stage where ‘gestational diabetes’ at 24-28 weeks with 75 g oral glucose tolerance test. Although the one step approach with 75 g of glucose offers operational convenience in diagnosing gestational diabetes, there are concerns raised by the National Institute of Health in the recent consensus statement, supporting the two step approach (50-g, 1-hour loading test screening 100-g, 3-hour oral glucose tolerance test) as the recommended approach for detecting gestational diabetes. Medical nutrition therapy (MNT) with well-designed meal plan and appropriate exercise achieves normoglycemia without inducing ketonemia and weight loss in most pregnant women with glucose intolerance. Rapidly acting insulin analogues, such as insulin lispro and aspart are safe in pregnancy and improve postprandial glycemic control in women with pre-gestational diabetes. The long acting analogues (Insulin detemir and glargine) though proven to be safe in pregnancy, do not confer added advantage if normoglycemia is achieved with intermediate insulin (NPH). Current evidence indicates the safe use of glyburide and metformin in the management of Type 2 diabetes and gestational diabetes as other options. However, it is prudent to communicate to the women that there is no data available on the long-term health of the offspring and the safety of these oral hypoglycemic drugs are limited to the prenatal period.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Phytochemistry, pharmacology and toxicology properties of Strobilanthes crispus

Nurraihana, H., Norfarizan-Hanoon, N.A.

International Food Research Journal, 2013;20(5):2045-2056.
MyJurnal

Strobilanthes crispus (S. crispus) is an herbal medicine plant which is native to countries from Madagascar to Indonesia. The plants contained high amount of mineral content and vitamin C, B1 and B2. This plant are used in medicinal and to treat a variety of ailments in the various traditional systems of medicine. Phytochemical investigations have revealed that the plant contain polyphenols, flavonoids, catechins, alkaloids, caffeine, tannins, compounds known to possess multiple health beneficial effects. Preclinical studies have shown that the plant possess antioxidant, free radical scavenging, anticancer, antidiabetic, antimicrobial, wound healing and antiulcerogenic activities. This review presents the comprehensive overview of phytochemical constituents, pharmacological and toxicological properties of S. crispus and to provide preliminary information for future research and for commercial exploitation.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Psychological insulin resistance (PIR) among type 2 diabetes patients at public health clinics in Federal Territory of Malaysia

Nur Azmiah Z, Zulkarnain AK, Tahir A

International Medical Journal Malaysia, 2011;10(2):7-12.
MyJurnal

Introduction: Insulin has been viewed as a treatment option of last resort in type 2 diabetes management. The decision to start insulin therapy is often difﬁ cult. Patients are usually reluctant to begin insulin and many cases delay the initiation of insulin therapy. The aim of this study is to determine the magnitude of insulin refusal or recognize as psychological insulin resistance (PIR) and to identify its predictors. Materials and Methods: This is a cross-sectional study and data was collected from two primary public health clinics in Kuala Lumpur and Putrajaya. The study sample consisted of 404 insulin naive patients with type 2 diabetes. A self-administered questionnaire was used to obtain demographic and clinical information. Results: Fifty-one percent of patients with type 2 diabetes were found to be unwilling to take insulin. Regression analysis revealed that females were 2.7 times more likely to resist insulin treatment compared to males and those with uncontrolled diabetes were 1.8 times more likely to resist insulin treatment compared to controlled diabetics. Patients will refuse insulin if they perceived their diabetes worsen with insulin use. After controlling for other attitudinal belief factors in the model, an increase in one unit of perceived disease severity will increase the likelihood of PIR around 2 times. Conclusion: Several misconceptions regarding insulin therapy were identiﬁed and speciﬁ c education intervention is recommended for successful transition to insulin therapy.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Hesperidin, a plant flavonoid accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats: Role of TGF-ß/Smads and Ang-1/Tie-2 signaling pathways

Li W, Kandhare AD, Mukherjee AA, Bodhankar SL

EXCLI J, 2018;17:399-419.
PMID: 29805347 DOI: 10.17179/excli2018-1036

Background: Delayed wound healing is a diverse, multifactorial, complex and inter-related complication of diabetes resulting in significant clinical morbidity. Hesperidin possesses potent antidiabetic and wound healing activity. Aim: To evaluate the potential of hesperidin against experimentally induced diabetes foot ulcers. Methods: Diabetes was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.) in Sprague Dawley rats (180-220 g) and wounds were created on the dorsal surface of the hind paw of rats. Hesperidin (25, 50 and 100 mg/kg, p.o.) was administered for 21 days after wound stabilization. Various biochemical, molecular and histopathological parameters were evaluated in wound tissue. Results: STZ-induced decrease in body weight and increase in blood glucose, food, and water intake was significantly (p < 0.05) inhibited by hesperidin (50 and 100 mg/kg) treatment. It showed a significant increase (p < 0.05) in percent wound closure and serum insulin level. The STZ-induced decrease in SOD and GSH level, as well as elevated MDA and NO levels, were significantly (p < 0.05) attenuated by hesperidin (50 and 100 mg/kg) treatment. Intraperitoneal administration of STZ caused significant down-regulation in VEGF-c, Ang-1, Tie-2, TGF-β and Smad 2/3 mRNA expression in wound tissues whereas hesperidin (50 and 100 mg/kg) treatment showed significant up-regulation in these mRNA expressions. STZ-induced alteration in would architecture was also attenuated by hesperidin (50 and 100 mg/kg) treatment. Conclusion: Together, treatment with hesperidin accelerate angiogenesis and vasculogenesis via up-regulation of VEGF-c, Ang-1/Tie-2, TGF-β and Smad-2/3 mRNA expression to enhance wound healing in chronic diabetic foot ulcers.

Matched MeSH terms: Hypoglycemic Agents
Fulltext A fatal case of metformin and gliclazide poisoning and its management

Low, Qin Jian, Chew, Soo Foong

Borneo Journal of Medical Sciences, 2017;11(3):35-40.
MyJurnal

Both metformin and gliclazide have been used extensively in the management of type II diabetes mellitus. Metformin and gliclazide overdose can lead to severe hypoglycaemia refractory to intravenous (IV) dextrose rescue therapy. A 21-year-old man complained of vomiting and felt dizzy after four hours of taking 70 tablets of Metformin 500 mg and 40 tablets of Gliclazide 80 mg. He had major depressive disorder and wanted to commit suicide. He was given IV Dextrose 50% 50 cc immediately. Octreotide had been used successfully to reverse the refractory hypoglycaemia caused by gliclazide overdose. Unfortunately, he developed severe lactic acidosis with acute kidney injury. Dialysis had been done by continuous venovenous haemodiafiltrationa and intravenous sodium bicarbonate 8.4% infusion was given. However, the patient succumbed due to the severe lactic acidosis and kidney failure despite of urgent dialysis. Octreotide infusion helps in preventing refractory hypoglycaemia secondary to sulfonylurea overdose by inhibit calcium-mediated insulin release. Metformin overdose causes severe lactic acidosis due to conversion of glucose to lactate. Sodium bicarbonate therapy in metformin induced lactic acidosis is also controversial. Though sulfonylurea and metformin are the most commonly-prescribed anti-hypoglycaemic agents, thus during prescribing everyone has to be careful about the overdoses and side effects of these drugs.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Co-morbid hypertension, diabetes mellitus or dyslipidemia among patients prescribed with second generation antipsychotic: a comparison study between aripiprazole, quetiapine and clozapine based on pharmacy prescription database

Ng CG, Chan PL, Said MA

Malaysian Journal of Psychiatry, 2015;24(2):0-0.
MyJurnal

Introduction: Second generation antipsychotic (SGA) was linked to increased risk of metabolic syndrome. The risk varies between different SGA. We aim to study this risk by examining the co-prescription of antihypertensive, antidiabetic and lipid lowering drugs in patients prescribed with either aripiprazole, quetiapine or clozapine.
Methods: This is a retrospective cohort study based on the prescription records of a teaching hospital. Prescription records between January 1, 2013 and December 31, 2014 for
psychiatric unit were extracted. Patients with at least one prescription of any antipsychotic were included. The odds of antihypertensive, antidiabetic and lipid lowering drugs co-prescription in patients with either aripiprazole, quetiapine or clozapine were calculated.
Results: Of the 1742 study subjects, 88 patients were prescribed with aripiprazole, 175 patients with clozapine and 124 patients with quetiapine. Patients prescribed with quetiapine had
higher odds of co-prescribed with antihypertensive (OR = 1.71, 95% CI = 1.11, 2.63), antidiabetic drugs (OR = 1.81, 95% CI = 1.11, 2.95) and lipid lowering drugs (OR = 1.94, 95% CI = 1.19, 3.16). There were higher odds of co-prescription of antihypertensive (OR = 1.54, 95% CI = 1.05, 2.25), antidiabetic drugs (OR = 1.69, 95% CI = 1.10, 2.59) and lipid lowering drugs
(OR = 1.90, 95% CI = 1.24, 2.91) in patients with clozapine. However, there were no increase odds of co-prescription of the three agents in patients with aripiprazole.
Conclusion: We need to monitor the risk of metabolic syndrome in patients treated with SGA. Aripiprazole has lower risk of metabolic syndrome.

Matched MeSH terms: Hypoglycemic Agents
Fulltext Comparison between aripiprazole with quetiapine in patients with bipolar disorder: a retrospective outcomes study

Ng, C.G., Seed, H.F., Thong, K.S.

Malaysian Journal of Psychiatry, 2016;25(2):0-0.
MyJurnal

Introduction: Atypical antipsychotic drugs are effective in the treatment of bipolar disorder. Studies have shown that atypical antipsychotic drugs are more superior to typical antipsychotic in term of neurocognitive function, negative symptoms and extrapyramidal side effects. Both aripiprazole and quetiapine are atypical antipsychotic drugs that are effective and commonly used in all phases of bipolar disorder treatment. Objective: The aim of this study is to examine and compare the clinical outcomes of aripiprazole and quetiapine in bipolar disorder patients. Method: This was a retrospective cohort study among patients from psychiatric unit, University Malaya Medical Center. Prescription records dated between January 1, 2013 and December 31, 2014 for psychiatric unit were extracted. The data of the subjects with prescription of the two atypical antipsychotic, namely aripiprazole and quetiapine was extracted. The outcome measures were the co-prescription of antihypertensive drugs, antidiabetic drugs and lipid lowering drugs. Results: A total of 58 subjects were recruited, 11 were on aripiprazole and 47 were on quetiapine. Statistical analysis has shown that both aripiprazole and quetiapine do not have any association with compliance to the medication and also follow up. Study also revealed that there is no association between the aripiprazole and quetiapine group with the metabolic side effects that were measured such as systolic or diastolic blood pressure, waist circumference, weight, glucose level and body mass index. Conclusion: This study has shown that both aripiprazole and quetiapine were similar in terms of metabolic side effect, compliance to medications and follow up.

Matched MeSH terms: Hypoglycemic Agents
Antidiabetic activities of chloroform fraction of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes

Anyanwu GO, Iqbal J, Khan SU, Zaib S, Rauf K, Onyeneke CE, et al.

J Ethnopharmacol, 2018 Oct 18.
PMID: 30342966 DOI: 10.1016/j.jep.2018.10.021

ETHNOPHARMACOLOGICAL RELEVANCE: Anthocleista vogelii Planch is a medicinal plant traditionally used in West Africa for the management and treatment of diabetes mellitus.
AIM OF THE STUDY: To determine the antidiabetic activities of chloroform fraction (CF) of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes.
MATERIALS AND METHODS: Inhibitory activities of CF against α-amylase and α-glucosidase activities were determined in vitro. Three weeks old rats were fed with high-fat diet for 9 weeks to induce obesity prior to further induction of diabetes using alloxan (150mg/kg body weight, i.p.). Blood glucose levels and body weight were measured every 7 days throughout the experiment. Glucose tolerance was assessed in normal and CF-treated rats on day 21. Terminal blood samples were collected from sacrificed animals for the measurement of serum insulin levels. Pancreases were excised from treated and untreated animals for histopathological examination.
RESULTS: LCMS/MS chromatographic profile of CF via positive and negative modes revealed 13 and 23 compounds respectively. Further analysis revealed quebrachitol (QCT), loganin, sweroside, oleoside 11-methyl ester and ferulic acid, which have been previously reported for their antidiabetic activities, as constituents of CF. CF inhibited activities of α-amylase (IC50 = 51.60 ± 0.92µg/ml) and α-glucosidase (IC50 = 5.86 ± 0.97µg/ml) in a dose-dependent manner. Treatment of animals with obesity-diabetes with 100 and 200mg/kg CF significantly improved glucose tolerance (P<0.001) and enhanced serum insulin levels (P<0.05) compared to diabetic control rats.
CONCLUSIONS: Antidiabetic activities of CF might be mediated via inhibition of α-amylase and α-glucosidase activities, elevation of serum insulin concentration, and enhancement of insulin and leptin sensitivity in obesity-diabetes rats. This study further substantiates the traditional use of A. vogelii in the management and treatment of diabetes in Africa and encourages further studies to investigate its mechanism of action.

Matched MeSH terms: Hypoglycemic Agents

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