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Fulltext Glibenclamide induced chronic cholestasis simulating primary biliary cirrhosis: a case report

Ramanathan M, Wahinuddin S, Kew ST

Med J Malaysia, 1996 Mar;51(1):140-3.
PMID: 10967995

A 43-year-old lady with long standing non-insulin dependent diabetes mellitus on glibenclamide presented with cholestatic liver disease. Initially she was thought to have developed primary biliary cirrhosis (PBC). When she made a spontaneous recovery following the withdrawal of glibenclamide, it became obvious that the patient had been suffering from drug-induced chronic cholestasis (DICC). The subtle differences between PBC and DICC are highlighted.

Matched MeSH terms: Glyburide/adverse effects*
Fulltext A comparison between the pregnancy outcome of women with gestation diabetes treated with glibenclamide and those treated with insulin

Lim JMH, Tayob Y, O'Brien PM, Shaw RW

Med J Malaysia, 1997 Dec;52(4):377-81.
PMID: 10968114

The pregnancy outcome of 33 women with gestational diabetes who were treated with glibenclamide and changed to insulin if glibenclamide failed, were compared with the pregnancy outcome of 21 women with gestational diabetes treated conventionally with insulin. The pregnancy outcome, with regard to the overall glycaemic control, rates of preterm labour, neonatal hypoglycaemia, fetal macrosomia, perinatal morbidity and mortality, were not statistically different between the two treatment groups. The limited number of women studied, and the non-random allocation of these women to each treatment group however, could have influenced these results. There were a few observed differences in the pregnancy outcome between the two treatment groups, which although were not statistically significant, caused some concern. In particular we noted an increased rate of fetal macrosomia in the glibenclamide treated group, which in theory could have been drug mediated.

Matched MeSH terms: Glyburide/therapeutic use*
Efficacy and safety of single versus multiple daily doses of glibenclamide in type 2 diabetes mellitus

Wan Mohamad WB, Tun Fizi A, Ismail RB, Mafauzy M

Diabetes Res Clin Pract, 2000 Aug;49(2-3):93-9.
PMID: 10963819 DOI: 10.1016/s0168-8227(00)00138-8

Although long acting, glibenclamide is frequently given in split doses for type 2 diabetes mellitus. This may discourage compliance. It is thus appropriate to consider dosing it less frequently. We therefore studied glibenclamide effects when used once daily and when used in split doses. Our objective was to assess the feasibility of using once daily dosing as a regimen of choice. We measured plasma glucose, insulin, glibenclamide, lipids, HbAl and body mass index associated with the regimens. We also compared the number of hypoglycemic episodes occurring with them. Thirty type 2 diabetics on multiple daily glibenclamide were enrolled. Their regimens were changed over to once daily. Blood for glucose, insulin, lipids, HbAl and glibenclamide and body weight measurements were determined before and after the crossover period. We found no major difference in the sugar and insulin profiles with the two regimens. Fasting total cholesterol and triglyceride were also similar and so were plasma glibenclamide. The HbAl levels and body mass index and number of minor and major hypoglycemic episodes and hospital admissions for hypoglycemia also did not differ. We conclude that single daily dosing of glibenclamide was equivalent to multiple daily dose regimens. It can be used to an advantage to improve patient's compliance.

Matched MeSH terms: Glyburide/adverse effects; Glyburide/blood; Glyburide/therapeutic use*
Repaglinide versus glibenclamide treatment of Type 2 diabetes during Ramadan fasting

Mafauzy M

Diabetes Res Clin Pract, 2002 Oct;58(1):45-53.
PMID: 12161056 DOI: 10.1016/s0168-8227(02)00104-3

This study compared treatment with a prandial glucose regulator (repaglinide) and a sulphonylurea (glibenclamide) in Muslim Type 2 diabetic patients who practice Ramadan fasting. Two hundred and thirty-five patients, previously treated with a sulphonylurea, were randomised to receive either repaglinide (n=116, preprandially three-times daily) or glibenclamide (n=119, preprandially once- or twice-daily) 6 weeks before Ramadan. During Ramadan, patients changed their eating pattern to two meals daily, and the daily dose of repaglinide was redistributed to two preprandial doses. After Ramadan, patients resumed their regular meal pattern and treatment dosage for 4 weeks. During Ramadan, a statistically significant reduction in mean serum fructosamine concentration from baseline was observed in the repaglinide group (-16.9+/-4.9 micromol/l, -3.8%, P<0.05) but not the glibenclamide group (-6.9+/-4.8 micromol/l, -0.8%). Difference in change in HbA(1c) from baseline was not statistically significant between groups. The number of hypoglycaemic events with midday blood glucose <4.5 mmol/l was significantly lower in the repaglinide group (2.8%) than the glibenclamide group (7.9%) (P=0.001). Apart from hypoglycaemia, both treatments were equally well tolerated. Type 2 diabetic Muslims using prandial repaglinide showed a trend towards better glycaemic control and had a lower frequency of hypoglycaemia than patients using glibenclamide during Ramadan.

Matched MeSH terms: Glyburide/adverse effects; Glyburide/therapeutic use*
Effect of acidosis on the mechanism(s) of insulin-induced vasorelaxation in normal Wistar-Kyoto (WKY) rat aorta

Subramaniam G, Achike FI, Mustafa MR

Regul. Pept., 2009 Jun 5;155(1-3):70-5.
PMID: 19362578 DOI: 10.1016/j.regpep.2009.04.008

The effect of acidosis on insulin-induced relaxation was studied in thoracic aortic rings (from Wistar-Kyoto (WKY) rats) with (+ED) or without (-ED) endothelium. The rings were mounted in normal (pH 7.4) or acidotic (pH 7.2) Krebs solution for isometric tension recording. Phenylephrine (PE, 3.0 microM)-contracted tissues were exposed to insulin in the presence or absence of various inhibitors. Insulin exerted similar concentration-dependent relaxation of +ED tissues in normal and acidotic pH. Endothelium denudation, significantly (p<0.05) reduced insulin effect in normal, but not acidotic pH. Under normal pH, treatment with L-NAME or methylene blue significantly (p<0.05) reduced insulin responses in the +ED (but not the -ED) tissues. The insulin effect was also significantly (p<0.05) inhibited by tetraethylammonium (TEA; BK(Ca) blocker), 4-Aminopyridine (4-AP; K(V) channel blocker), combined treatments (L-NAME+4-AP+TEA, in +ED tissues) or (4-AP+TEA, in -ED tissues). In either +ED or -ED tissues, indomethacin (cyclo-oxygenase inhibitor), glibenclamide (K(ATP) channel blocker), barium chloride (K(ir) channel blocker) or Ouabain (a Na(+)/K(+)-ATPase inhibitor) had no effect. Except for methylene blue (effect on +ED tissues), none of the drug treatments inhibited insulin vasodilator effect in acidosis (+ED or -ED tissues). These data indicate that insulin exerts an endothelium-dependent and -independent vasodilatation in rat aorta which in normal pH is mediated via BK(Ca) and K(v) channels, including the EDNO-cGMP cascade. Acidosis abolishes the endothelium-dependent relaxation mechanism unraveling a novel mechanism that is as efficacious and is cGMP-, but not EDNO-, BK(Ca)- or K(v)-mediated.

Matched MeSH terms: Glyburide/pharmacology
Fulltext Antioxidant protective effect of glibenclamide and metformin in combination with honey in pancreas of streptozotocin-induced diabetic rats

Erejuwa OO, Sulaiman SA, Wahab MS, Salam SK, Salleh MS, Gurtu S

Int J Mol Sci, 2010 May 05;11(5):2056-66.
PMID: 20559501 DOI: 10.3390/ijms11052056

Hyperglycemia exerts toxic effects on the pancreatic beta-cells. This study investigated the hypothesis that the common antidiabetic drugs glibenclamide and metformin, in combination with tualang honey, offer additional protection for the pancreas of streptozotocin (STZ)-induced diabetic rats against oxidative stress and damage. Diabetes was induced in male Sprague Dawley rats by a single dose of STZ (60 mg/kg; ip). Diabetic rats had significantly elevated levels of lipid peroxidation (TBARS), up-regulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) while catalase (CAT) activity was significantly reduced. Glibenclamide and metformin produced no significant effects on TBARS and antioxidant enzymes except GPx in diabetic rats. In contrast, the combination of glibenclamide, metformin and honey significantly up-regulated CAT activity and down-regulated GPx activity while TBARS levels were significantly reduced. These findings suggest that tualang honey potentiates the effect of glibenclamide and metformin to protect diabetic rat pancreas against oxidative stress and damage.

Matched MeSH terms: Glyburide/pharmacology*
Exploring the mechanism of endothelial involvement in acidosis-induced vasodilatation of aortic tissues from normal and diabetic rats

Yeo JL, Tan BT, Achike FI

Eur J Pharmacol, 2010 Sep 10;642(1-3):99-106.
PMID: 20553918 DOI: 10.1016/j.ejphar.2010.05.040

Acidosis modulates physiologic and pathophysiologic processes but the mechanism of acidotic vasodilatation remains unclear. We therefore explored this in aortic rings from normal and streptozotocin-induced diabetic Sprague-Dawley rats. Phenylephrine (PE)-induced contraction in endothelium-intact and -denuded rings were recorded under normal and acidotic pH with or without drug probes. Acidosis exerted a relaxant effect in endothelium-intact and -denuded euglycaemic and diabetic tissues. l-NAME or methylene blue partially inhibited acidotic relaxation in these endothelium-intact but not the -denuded tissues, with greater inhibition in the diabetic tissues, indicating that acidosis induces relaxation by endothelium-dependent and -independent mechanisms, the former being EDNO-cGMP mediated. Indomethacin had no effect on the tissues, indicating that cyclooxygenase products are neither involved in acidosis-induced vasodilatation nor in the modulation of phenylephrine-contraction. In euglycaemic tissues under normal pH, no K(+) channel blocker altered phenylephrine-contraction, but all (except glibenclamide) enhanced diabetic tissue contraction, indicating that normally, these channels (K(ir), K(V), BK(Ca), K(ATP)) do not modulate phenylephrine-contraction, but they (except K(ATP)) are expressed in diabetes where they attenuate phenylephine-induced contraction and modulate acidosis. Only the K(ir) channel modulates acidotic relaxation in euglycaemic tissues. Only tetraethylammonium and iberiotoxin enhanced phenylephrine-induced contraction in endothelium-denuded diabetic tissues indicating that BK(Ca) attenuates phenylephrine-contraction and that acidotic relaxation in this condition is modulated by a tetraethylammonium-sensitive mechanism. In conclusion, acidosis causes vasodilatation in normal and diabetic tissues via endothelium-dependent and -independent mechanisms differentially modulated by a combination of a NO-cGMP process and K(+) channels, some of which are dormant in the normal state but activated in diabetes mellitus.

Matched MeSH terms: Glyburide/pharmacology
Momordica charantia for type 2 diabetes mellitus

Ooi CP, Yassin Z, Hamid TA

Cochrane Database Syst Rev, 2010.
PMID: 20166099 DOI: 10.1002/14651858.CD007845.pub2

Background: Momordica charantia is not only a nutritious vegetable, but is also used in traditional medical practices to treat type 2 diabetes mellitus. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control.

Objectives: To assess the effects of mormodica charantia for type 2 diabetes mellitus.

Search strategy: Several electronic databases were searched, among these The Cochrane Library (issue 4, 2009), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to November 2009), combined with handsearches. No language restriction was used.

Selection criteria: Randomized controlled trials that compared momordica charantia with a placebo or a control intervention with or without pharmacological or non-pharmacological interventions were included.

Data collection and analysis: Two authors independently extracted the data. Risk of bias of trials was evaluated using the parameters of randomization, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in interventions (no similar preparation was tested twice).

Main results: Three randomised controlled trials with up to three months duration and investigating 350 participants met the inclusion criteria. Risk of bias of these trials (only one study was published as a full peer-reviewed publication) was generally high. Two RCTs compared the effect of preparations from different parts of the momordica charantia plants and placebo on the glycemic control in type 2 diabetes mellitus. There was no statistically significant difference compared to placebo. The effects of preparation from the leaves of the plant and glibenclamide were comparable in the third trial. No serious adverse effects were reported in all the trials. There were no documentations of death from any cause, morbidity, (health-related) quality of life and costs.

Authors' conclusions: There is insufficient evidence to recommend momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.

Matched MeSH terms: Glyburide/therapeutic use
In vitro vascular effects produced by crude aqueous extract of green marine algae, Cladophora patentiramea (Mont.) Kützing, in aorta from normotensive rats

Lim YL, Mok SL

Med Princ Pract, 2010;19(4):260-8.
PMID: 20516701 DOI: 10.1159/000312711

To investigate the antihypertensive activity of aqueous extracts obtained from Malaysian coastal seaweeds and to determine the pharmacological mechanisms of the extracts on rat aorta in vitro.

Matched MeSH terms: Glyburide/pharmacology
Effects of Momordica charantia on pancreatic histopathological changes associated with streptozotocin-induced diabetes in neonatal rats

Abdollahi M, Zuki AB, Goh YM, Rezaeizadeh A, Noordin MM

Histol Histopathol, 2011 01;26(1):13-21.
PMID: 21117023 DOI: 10.14670/HH-26.13

The aim of this research was to determine the effects of Momordica charantia (MC) fruit aqueous extract on pancreatic histopathological changes in neonatal STZ-induced type-II diabetic rats. Diabetes mellitus was induced in one day Sprague-Dawley neonatal rats using a single intrapretoneal injection of streptozotocin (STZ) (85 mg/kg body weight) and monitored for 12 weeks thereafter. The diabetic rats were separated into three groups, as follows: the diabetic control group (i.e. nSTZ), the diabetic group (i.e. nSTZ/M) - which was orally given 20 mg/kg of MC fruit extract, and the diabetic group (i.e. nSTZ/G) - that was treated with glibenclamide, 0.1 mg/kg for a period of four weeks. At the end of treatment, the animals were sacrificed and blood samples were collected from the saphenous vein to measure the blood glucose and serum insulin level. The pancreatic specimens were removed and processed for light microscopy, electron microscopy examination and immunohistochemical study. The results of this study showed that MC fruit aqueous extract reduced the blood glucose level as well as glibenclamide and increased the serum insulin level in the treated diabetic rats (P<0.05). The fruit extract of MC alleviated pancreatic damage and increased the number of β-cells in the diabetic treated rats (P<0.05). Our results suggest that oral feeding of MC fruit extract may have a significant role in the renewal of pancreatic β-cells in the nSTZ rats.

Matched MeSH terms: Glyburide/therapeutic use
Fulltext Glibenclamide or metformin combined with honey improves glycemic control in streptozotocin-induced diabetic rats

Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KN, Salleh MS, Gurtu S

Int J Biol Sci, 2011 Mar 14;7(2):244-52.
PMID: 21448302 DOI: 10.7150/ijbs.7.244

Diabetes mellitus is associated with deterioration of glycemic control and progressive metabolic derangements. This study investigated the effect of honey as an adjunct to glibenclamide or metformin on glycemic control in streptozotocin-induced diabetic rats. Diabetes was induced in rats by streptozotocin. The diabetic rats were randomized into six groups and administered distilled water, honey, glibenclamide, glibenclamide and honey, metformin or metformin and honey. The animals were treated orally once daily for four weeks. The diabetic control rats showed hypoinsulinemia (0.27 ± 0.01 ng/ml), hyperglycemia (22.4 ± 1.0 mmol/L) and increased fructosamine (360.0 ± 15.6 µmol/L). Honey significantly increased insulin (0.41 ± 0.06 ng/ml), decreased hyperglycemia (12.3 ± 3.1 mmol/L) and fructosamine (304.5 ± 10.1 µmol/L). Although glibenclamide or metformin alone significantly (p < 0.05) reduced hyperglycemia, glibenclamide or metformin combined with honey produced significantly much lower blood glucose (8.8 ± 2.9 or 9.9 ± 3.3 mmol/L, respectively) compared to glibenclamide or metformin alone (13.9 ± 3.4 or 13.2 ± 2.9 mmol/L, respectively). Similarly, glibenclamide or metformin combined with honey produced significantly (p < 0.05) lower fructosamine levels (301.3 ± 19.5 or 285.8 ± 22.6 µmol/L, respectively) whereas glibenclamide or metformin alone did not decrease fructosamine (330.0 ± 29.9 or 314.6 ± 17.9 µmol/L, respectively). Besides, these drugs or their combination with honey increased insulin levels. Glibenclamide or metformin combined with honey also significantly reduced the elevated levels of creatinine, bilirubin, triglycerides, and VLDL cholesterol. These results indicate that combination of glibenclamide or metformin with honey improves glycemic control, and provides additional metabolic benefits, not achieved with either glibenclamide or metformin alone.

Matched MeSH terms: Glyburide/therapeutic use*
Fulltext Possible participation of nitric oxide/cyclic guanosine monophosphate/protein kinase C/ATP-sensitive K(+) channels pathway in the systemic antinociception of flavokawin B

Mohamad AS, Akhtar MN, Khalivulla SI, Perimal EK, Khalid MH, Ong HM, et al.

Basic Clin Pharmacol Toxicol, 2011 Jun;108(6):400-5.
PMID: 21214864 DOI: 10.1111/j.1742-7843.2010.00670.x

The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg/kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with L-arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K(+) channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO/cyclic guanosine monophosphate/PKC/ATP-sensitive K(+) channel pathway possibly participated in the antinociceptive action induced by FKB.

Matched MeSH terms: Glyburide/pharmacology
Fulltext Comparison of antioxidant effects of honey, glibenclamide, metformin, and their combinations in the kidneys of streptozotocin-induced diabetic rats

Erejuwa OO, Sulaiman SA, Wahab MS, Salam SK, Salleh MS, Gurtu S

Int J Mol Sci, 2011;12(1):829-43.
PMID: 21340016 DOI: 10.3390/ijms12010829

Hyperglycemia-induced increase in oxidative stress is implicated in diabetic complications. This study investigated the effect of metformin and/or glibenclamide in combination with honey on antioxidant enzymes and oxidative stress markers in the kidneys of streptozotocin (60 mg/kg; intraperitoneal)-induced diabetic rats. Diabetic rats were randomized into eight groups of five to seven rats and received distilled water (0.5 mL); honey (1.0 g/kg); metformin (100 mg/kg); metformin (100 mg/kg) and honey (1.0 g/kg); glibenclamide (0.6 mg/kg); glibenclamide (0.6 mg/kg) and honey (1.0 g/kg); metformin (100 mg/kg) and glibenclamide (0.6 mg/kg); or metformin (100 mg/kg), glibenclamide (0.6 mg/kg) and honey (1.0 g/kg) orally once daily for four weeks. Malondialdehyde (MDA) levels, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significantly elevated while catalase (CAT) activity, total antioxidant status (TAS), reduced glutathione (GSH), and GSH:oxidized glutathione (GSSG) ratio was significantly reduced in the diabetic kidneys. CAT, glutathione reductase (GR), TAS, and GSH remained significantly reduced in the diabetic rats treated with metformin and/or glibenclamide. In contrast, metformin or glibenclamide combined with honey significantly increased CAT, GR, TAS, and GSH. These results suggest that combination of honey with metformin or glibenclamide might offer additional antioxidant effect to these drugs. This might reduce oxidative stress-mediated damage in diabetic kidneys.

Matched MeSH terms: Glyburide/therapeutic use*
Fulltext Glycaemic control and cost analysis when changing from gliclazide co-administered with metformin to pre-combined glibenclamide-metformin tablets in type 2 diabetes mellitus

Lim PC, Lim SL, Oiyammaal C

Med J Malaysia, 2012 Feb;67(1):21-4.
PMID: 22582544

Type-2 diabetes mellitus (T2DM) patients who were on gliclazide co-administered with metformin were changed to pre-combined glibenclamide-metformin tablets in the Endocrine Clinic, Penang Hospital. We conducted a retrospective study to evaluate the differences in glycaemic control and treatment cost following the change. Eighty patients (60% females) with a mean age of 55 years old were studied. Mean glycosylated haemoglobin (HbAlc) reduction was -0.92% (p<0.01) and -0.83% (p<0.01) after three and six months respectively. Patients with baseline HbA1c > or =8% had greater reduction in mean HbA1c (-1.36%) after six months. The treatment cost per month was reduced by 45% at 3 months (p<0.01)) and 44% at 6 months (p<0.01). The change to pre-combined glibenclamide-metformin tablets resulted in significant improvement in glycaemia and reduction in treatment cost.

Matched MeSH terms: Glyburide/administration & dosage*
Fulltext Bioassay-guided antidiabetic study of Phaleria macrocarpa fruit extract

Ali RB, Atangwho IJ, Kaur N, Abraika OS, Ahmad M, Mahmud R, et al.

Molecules, 2012 Apr 30;17(5):4986-5002.
PMID: 22547320 DOI: 10.3390/molecules17054986

An earlier anti-hyperglycemic study with serial crude extracts of Phaleria macrocarpa (PM) fruit indicated methanol extract (ME) as the most effective. In the present investigation, the methanol extract was further fractionated to obtain chloroform (CF), ethyl acetate (EAF), n-butanol (NBF) and aqueous (AF) fractions, which were tested for antidiabetic activity. The NBF reduced blood glucose (p < 0.05) 15 min after administration, in an intraperitoneal glucose tolerance test (IPGTT) similar to metformin. Moreover, it lowered blood glucose in diabetic rats by 66.67% (p < 0.05), similar to metformin (51.11%), glibenclamide (66.67%) and insulin (71.43%) after a 12-day treatment, hence considered to be the most active fraction. Further fractionation of NBF yielded sub-fractions I (SFI) and II (SFII), and only SFI lowered blood glucose (p < 0.05), in IPGTT similar to glibenclamide. The ME, NBF, and SFI correspondingly lowered plasma insulin (p < 0.05) and dose-dependently inhibited glucose transport across isolated rat jejunum implying an extra-pancreatic mechanism. Phytochemical screening showed the presence of flavonoids, terpenes and tannins, in ME, NBF and SFI, and LC-MS analyses revealed 9.52%, 33.30% and 22.50% mangiferin respectively. PM fruit possesses anti-hyperglycemic effect, exerted probably through extra-pancreatic action. Magniferin, contained therein may be responsible for this reported activity.

Matched MeSH terms: Glyburide/administration & dosage; Glyburide/therapeutic use; Glyburide/chemistry
Momordica charantia for type 2 diabetes mellitus

Ooi CP, Yassin Z, Hamid TA

Cochrane Database Syst Rev, 2012 Aug 15.
PMID: 22895968 DOI: 10.1002/14651858.CD007845.pub3

BACKGROUND: Momordica charantia (bitter gourd) is not only a nutritious vegetable but it is also used in traditional medical practices to treat type 2 diabetes mellitus. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control.
OBJECTIVES: To assess the effects of mormodica charantia for type 2 diabetes mellitus.
SEARCH METHODS: Several electronic databases were searched, among these were The Cochrane Library (Issue 1, 2012), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to February 2012), combined with handsearches. No language restriction was used.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared momordica charantia with placebo or a control intervention, with or without pharmacological or non-pharmacological interventions.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. Risk of bias of the trials was evaluated using the parameters of randomisation, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in the interventions (no similar preparation was tested twice).
MAIN RESULTS: Four randomised controlled trials with up to three months duration and investigating 479 participants met the inclusion criteria. Risk of bias of these trials (only two studies were published as a full peer-reviewed publication) was generally high. Two RCTs compared the effects of preparations from different parts of the momordica charantia plant with placebo on glycaemic control in type 2 diabetes mellitus. There was no statistically significant difference in the glycaemic control with momordica charantia preparations compared to placebo. When momordica charantia was compared to metformin or glibenclamide, there was also no significant change in reliable parameters of glycaemic control. No serious adverse effects were reported in any trial. No trial investigated death from any cause, morbidity, health-related quality of life or costs.
AUTHORS' CONCLUSIONS: There is insufficient evidence on the effects of momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.

Matched MeSH terms: Glyburide/therapeutic use
Fulltext Erectogenic Effects of Clerodendron capitatum: Involvement of Phosphodiesterase Type-5 Inhibition

Abdelwahab SI, Mohamed AH, Mohamed OY, Oall M, Taha MM, Mohan S, et al.

Evid Based Complement Alternat Med, 2012;2012:137386.
PMID: 21747892 DOI: 10.1155/2012/137386

Clerodendron capitatum (Willd) (family: verbenaceae) is locally named as Gung and used traditionally to treat erectile dysfunction. Therefore, the current study was designed to investigate the erectogenic properties of C. capitatum. The relaxation effect of this plant was tested on phenylephrine precontracted rabbit corpus cavernosum smooth muscle (CCSM). The effects of C. capitatum were also examined on isolated Guinea pig atria alone, in the presence of calcium chloride (Ca(2+) channel blocker), atropine (cholinergic blocker), and glibenclamide (ATP-sensitive K(+) channel blocker). These effects were confirmed on isolated rabbit aortic strips. The extract, when tested colorimetrically for its inhibitory activities on phosphordiesterase-5 (PDE-5) in vitro towards p-nitrophenyl phenyl phosphate (PNPPP), was observed to induce significant dose-dependent inhibition of PDE-5, with an ID(50) of 0.161 mg/ml (P < .05). In conclusion, our results suggest that C. capitatum possesses a relaxant effect on CCSM, which is attributable to the inhibition of PDE-5, but not mediated by the release calcium, activation of adrenergic or cholinergic receptors, or the activation of potassium channels.

Matched MeSH terms: Glyburide
Fulltext In-vivo functional study on the involvement of CFTR, SLC26A6, NHE-1 and CA isoenzymes II and XII in uterine fluid pH, volume and electrolyte regulation in rats under different sex-steroid influence

Gholami K, Muniandy S, Salleh N

Int J Med Sci, 2013;10(9):1121-34.
PMID: 23869188 DOI: 10.7150/ijms.5918

Precise control of uterine fluid pH, volume and electrolytes is important for the reproductive processes. In this study, we examined the functional involvement of multiple proteins including Cystic Fibrosis Transmembrane Regulator (CFTR), Cl(-)/HCO3 (-) exchanger (SLC26A6), sodium-hydrogen exchanger-1 (NHE-1) and carbonic anhydrase (CA) in the regulation of these uterine fluid parameters.

Matched MeSH terms: Glyburide/pharmacology
Fulltext Rhinacanthus nasutus Improves the Levels of Liver Carbohydrate, Protein, Glycogen, and Liver Markers in Streptozotocin-Induced Diabetic Rats

Visweswara Rao P, Madhavi K, Dhananjaya Naidu M, Gan SH

Evid Based Complement Alternat Med, 2013;2013:102901.
PMID: 24204387 DOI: 10.1155/2013/102901

The present study was designed to investigate the total carbohydrate, total protein, and glycogen levels in the liver and to measure functional liver markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in streptozotocin-(STZ-) induced diabetic rats after treatment with methanolic extract of Rhinacanthus nasutus (R. nasutus). The methanolic extract of R. nasutus was orally administered at 200 mg/kg/day while glibenclamide was administered at 50 mg/kg/day. All animals were treated for 30 days before being sacrificed. The amounts of carbohydrate, glycogen, proteins, and liver markers (AST and ALT) were measured in the liver tissue of the experimental animals. The levels of carbohydrate, glycogen, and proteins were significantly reduced in the diabetic rats but were augmented considerably after 30 days of R. nasutus treatment. The elevated AST and ALT levels in diabetic rats showed a significant decline after treatment with R. nasutus for 30 days. These results show that the administration of R. nasutus ameliorates the altered levels of carbohydrate, glycogen, proteins, and AST and ALT observed in diabetic rats and indicate that R. nasutus restores overall metabolism and liver function in experimental diabetic rats. In conclusion, the outcomes of the present study support the traditional belief that R. nasutus could ameliorate the diabetic state.

Matched MeSH terms: Glyburide
Fulltext Rhinacanthus nasutus Ameliorates Cytosolic and Mitochondrial Enzyme Levels in Streptozotocin-Induced Diabetic Rats

Visweswara Rao P, Madhavi K, Dhananjaya Naidu M, Gan SH

Evid Based Complement Alternat Med, 2013;2013:486047.
PMID: 23662138 DOI: 10.1155/2013/486047

The present study was conducted to evaluate the therapeutic efficacy of Rhinacanthus nasutus (R. nasutus) on mitochondrial and cytosolic enzymes in streptozotocin-induced diabetic rats. The rats were divided into five groups with 6 rats in each group. The methanolic extract of R. nasutus was orally administered at a dose of 200 mg/kg/day, and glibenclamide was administered at a dose of 50 mg/kg/day. All animals were treated for 30 days and were sacrificed. The activities of both intra- and extramitochondrial enzymes including glucose-6-phosphate dehydrogenase (G6PDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH) were measured in the livers of the animals. The levels of G6PDH, SDH, and GDH were significantly reduced in the diabetic rats but were significantly increased after 30 days of R. nasutus treatment. The increased LDH level in diabetic rats exhibited a significant reduction after treatment with R. nasutus. These results indicate that the administration of R. nasutus altered the activities of oxidative enzymes in a positive manner, indicating that R. nasutus improves mitochondrial energy production. Our data suggest that R. nasutus should be further explored for its role in the treatment of diabetes mellitus.

Matched MeSH terms: Glyburide

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