Investigation of the effect of addition of Momordica charantia to glibenclamide on amelioration of endothelial dysfunction in diabetic rats by activating Takeda G protein-coupled receptor 5.

Endothelial dysfunction (ED) is a significant risk factor of blood vessel related diseases of diabetes and this study evaluate the effect of adding Momordica charantia (Mc) to glibenclamide (GLB) on ED markers in diabetic rats. Streptozotocin (STZ-40mg/kg b. w.) induced diabetic rats were randomly put into 3 groups with 10 rats/group; diabetic control [DC] group, glibenclamide treated group (GLB -2.5mg/kg) and GLB-Mc treated group (2.5mg/kg + 400mg/kg). Serum glucose was measured weekly for eight weeks whereas insulin, sVCAM-1, vWF-Ag and interleukin-6 [IL-6] were measured at week 0 and week 8. Luciferase assay was performed to determine luminescence. At week 8, GLB and GLB-Mc groups revealed improvements in blood glucose and insulin concentrations (P≤0.05) when compared to corresponding baseline values with GLB-Mc group showing slightly greater improvements. GLB-M c group also revealed improvement (P≤0.05) in vWF-Ag, sVCAM-1 and IL-6 concentrations but was non-significant in GLB group when compared to corresponding baseline values. Comparison between GLB and GLB-Mc group showed significantly high concentration of sVCAM-1 in GLB group (P≤0.05) due to its minimal effect on TGR5 activation. We conclude that adding M. charantia to GLB may be a useful choice for modulating diabetes induced ED due to its stimulatory effect on TGR5 receptors.

Evaluation of acute oral toxicity, anti-diabetic and antioxidant effects of Aloe vera flowers extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera (L.) Burm.f. is widely used in various traditional systems of medicine worldwide. Since over 5000 years ago, several cultures have used A. vera extract medicinally for conditions ranging from diabetes to eczema. It has been shown to reduce the symptoms of diabetes by enhancing insulin secretion and protecting pancreatic islets. AIM OF THE WORK: This research study aimed to investigate the in-vitro antioxidant effect, the acute oral toxicity, and the possible pharmacological in-vivo anti-diabetic activity with histological examination of the pancreas of the standardized deep red A. vera flowers methanolic extracts (AVFME). MATERIALS AND METHODS: The liquid-liquid extraction procedure and TLC technique were used to investigate chemical composition. Total phenolics and flavonoids in AVFME were quantified by Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. The present study involved evaluating the in-vitro antioxidant effect of AVFME using ascorbic acid as the reference standard, an acute oral toxicity study by using thirty-six albino rats and different concentrations of AVFME (200 mg/kg, 2, 4, 8 and 10 g/kg b.w.). Furthermore, the in-vivo anti-diabetic study was performed on alloxan-induced diabetes in rats (120 mg/kg, I.P.) and two doses of AVFME (200 and 500 mg/kg b.w., orally) were used as compared to glibenclamide (5 mg/kg, orally) as a standard hypoglycemic sulfonylurea medication. A histological examination of the pancreas was performed. RESULTS: AVFME resulted in the highest phenolic content of 150.44 ± 4.62 mg gallic acid equivalent per gram (GAE/g) along with flavonoid content of 70.38 ± 0.97 mg of quercetin equivalent per gram (QE/g). An in-vitro study revealed that the antioxidant effect of AVFME was strong as ascorbic acid. The results of the in-vivo studies showed that the AVFME didn't cause any apparent toxicity signs or death in all groups at different doses which proves the safety of this extract with a wide therapeutic index. The antidiabetic activity of AVFME demonstrated a considerable drop in blood glucose levels as glibenclamide, without severe hypoglycemia or significant weight gain which is considered an advantage of AVFME over glibenclamide use. The histopathological study of pancreatic tissues confirmed the protective effect of AVFME on the pancreatic beta-cells. The extract is proposed to have antidiabetic activity through inhibition of α-amylase, α-glucosidase, and dipeptidyl peptidase IV (DPP-IV). Molecular docking studies were conducted to understand possible molecular interactions with these enzymes. CONCLUSION: AVFME represents a promising alternative source of active constituents against diabetes mellitus (DM) based on its oral safety, antioxidant, anti-hyperglycemic activities, and pancreatic protective effects. These data revealed the antihyperglycemic activity of AVFME is mediated by pancreatic protective effects while significantly enhancing insulin secretion through increasing functioning beta cells. This suggests that AVFME has the potential as a novel antidiabetic therapy or a dietary supplement for the treatment of type 2 diabetes (T2DM).

Carbohydrate digestive enzyme inhibition, hepatoprotective, antioxidant and antidiabetic benefits of Persea americana.

The medicinal use of Persea americana in the treatment of some diseases like hypertension, diabetes, is often with dearth of supporting scientific proof. Thus, we evaluated its ethnomedicinal benefits for possible scientific justification. Thirty healthy Wistar rats were randomly grouped in fives. Alloxan was used to induce diabetes in the rats in groups II to VI. The diabetic rats in group II were treated with glibenclamide, while those in group III were not treated. Also, the diabetic rats in groups IV to VI were treated with the ethanol extracts of the stem bark, leaf, and root of P. americana respectively. The parts of P. americana comparatively possess highest amounts of phenols (250.50 ± 0.68-bark), saponin (436.80 ± 3.76-leaf), flavonoid (382.80 ± 0.67-leaf) and tannins (58.34 ± 0.09-root). The extracts exhibited high reducing property (FRAP and total reducing), as well as high ABTS and DPPH free radical scavenging ability. The enzyme (alpha-glycosidase and alpha-amylase) inhibitory activity of P. americana increases with increasing concentration of the extracts. Administration of methanol extracts of P. americana bark, leaf and root to alloxan-induced diabetic rats resulted in significant (P < 0.05) decreases in AST, ALP, ALT, Total bilirubin, LPO, plasma glucose and significant (P < 0.05) increases in GSH, CAT and SOD. These effects were like that of glibenclamide. The enzyme inhibitory, hepatoprotective, antioxidant and antidiabetic properties of P. americana are some of the benefits derived from its consumption and ethnomedicinal use.

The protective effect of green tea on diabetes-induced hepato-renal pathological changes: a histological and biochemical study.

We investigated the protective effect of green tea on diabetic hepato-renal complications. Thirty male Wistar rats were randomly divided into five equal groups: normal control, diabetic control, glibenclamide-treated, green tea-treated, and combined therapy-treated groups; ethical approval number "BERC-014-01-20." After eight weeks, animals were sacrificed by CO2 euthanasia method, liver and kidney tissues were processed and stained for pathological changes, and blood samples were collected for biochemical analysis. Diabetic rats showed multiple hepato-renal morphological and apoptotic changes associated with significantly increased some biochemical parameters, while serum albumin and HDL decreased significantly compared to normal control (p < .05). Monotherapy can induce significant improvements in pathological and biochemical changes but has not been able to achieve normal patterns. In conclusion, green tea alone has a poor hypoglycaemic effect but can reduce diabetic complications, whereas glibenclamide cannot prevent diabetic complications. The addition of green tea to oral hypoglycaemic therapy has shown a potent synergistic effect.

Stink bean (Parkia speciosa) empty pod: a potent natural antidiabetic agent for the prevention of pancreatic and hepatorenal dysfunction in high fat diet/streptozotocin-induced type 2 diabetes in rats.

The present study investigated the effect of polyphenol-rich extract of Parkia speciosa (PPS) against pancreatic and hepatorenal dysfunction in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetes. Diabetic rats were treated with PPS (100 and 400 mg/kg) and glibenclamide. The results revealed that diabetic rats displayed marked hyperglycaemia, hyperlipidaemia, hypoinsulinemia as well as alterations in serum renal and kidney function markers. Furthermore, diabetic rats showed significant increase in hepatorenal level of malonaldehyde as well as suppression of antioxidant enzyme activities. Whereas, diabetic rats that received PPS displayed marked attenuation in most of the aforementioned parameters compared to the untreated diabetic rats. Additionally, histological examination revealed restoration of histopathological alterations of the pancreas, liver, and kidney of PPS treated diabetic rats. In conclusion, the results demonstrated that PPS could decrease serum lipids and blood glucose level, enhance insulin level and hepatorenal antioxidant capacity, as well as ameliorate hepatorenal dysfunction in rats.

The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes.

This study was conducted to evaluate the anti-diabetic and antioxidant effects of hydroalcoholic pomegranate peel extract (APE) in alloxan-induced diabetes rat models. We divided 60 rats into the following six equal groups (n = 10): Healthy control; diabetic control (100 mg/kg alloxan); sham + glibenclamide (10 mg/kg); diabetic + glibenclamide (10 mg/kg); sham + APE (200 mg/kg) and diabetic + APE (200 mg/kg). After 8 weeks, kidneys were taken out for biochemical and molecular studies. Following APE treatment, biochemical parameters including malondialdehyde (MDA), and glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) significantly induced in the treated group as compared with the control group (p < 0.05). Also, gene expression of GPx (3-fold), CAT (2.6-fold), and SOD (1.5-fold) were increased as compared to controls (p < 0.05). Overall, our results indicated that pomegranate can be used as an antioxidant agent to reduce complications from diseases associated with oxidative stress.

Vulgarin, a Sesquiterpene Lactone from Artemisia judaica, Improves the Antidiabetic Effectiveness of Glibenclamide in Streptozotocin-Induced Diabetic Rats via Modulation of PEPCK and G6Pase Genes Expression.

The current investigation assessed the effect of the eudesmanolid, Vulgarin (VGN), obtained from Artemisia judaica (A. judaica), on the antidiabetic potential of glibenclamide (GLB) using streptozotocin (STZ) to induce diabetes. Seven groups of rats were used in the study; the first group received the vehicle and served as normal control. The diabetic rats of the second to the fifth groups were treated with the vehicle (negative control), GLB at 5 mg/kg (positive control), VGN at 10 mg/kg (VGN-10) and VGN at 20 mg/kg (VGN-20), respectively. The diabetic rats of the sixth and seventh groups were administered combinations of GLB plus VGN-10 and GLB plus VGN-20, respectively. The diabetic rats treated with GLB plus VGN-20 combination showed marked improvement in the fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c), as well as the lipid profile, compared with those treated with GLB alone. Further, the pancreatic tissues of the diabetic rats that received the GLB+VGN-20 combination showed superior improvements in lipid peroxidation and antioxidant parameters than those of GLB monotherapy. The insulin content of the ß-cells was restored in all treatments, while the levels of glucagon and somatostatin of the α- and δ-endocrine cells were reduced in the pancreatic islets. In addition, the concurrent administration of GLB+VGN-20 was the most effective in restoring PEPCK and G6Pase mRNA expression in the liver. In conclusion, the results demonstrated that the GLB+VGN-20 combination led to greater glycemic improvement in diabetic rats compared with GLB monotherapy through its antioxidant effect and capability to modulate PEPCK and G6Pase gene expression in their livers.

Investigation of the Chemical Composition, Antihyperglycemic and Antilipidemic Effects of Bassia eriophora and Its Derived Constituent, Umbelliferone on High-Fat Diet and Streptozotocin-Induced Diabetic Rats.

This study was designed to investigate the chemical profile, antihyperglycemic and antilipidemic effect of total methanolic extract (TME) of Bassia eriophora and isolated pure compound umbelliferone (UFN) in high-fat diet (HFD)- and streptozotocin (STZ)- induced diabetic rats. TME was subjected to various techniques of chromatography to yield UFN. Diabetes was induced after eight weeks of HFD by administration of STZ (40 mg/kg) intraperitoneally, and experimental subjects were divided into five groups. The diabetic control showed an increase in levels of blood glucose throughout the experiment. Treatments were initiated in the other four groups with glibenclamide (GLB) (6 mg/kg), TME (200 mg/kg and 400 mg/kg) and isolated UFN (50 mg/kg) orally. The effect on blood glucose, lipid profile and histology of the pancreatic and adipose tissues was assessed. Both 200 and 400 mg/kg of TME produced a comparably significant decrease in blood glucose levels and an increase in insulin levels with GLB. UFN began to show a better blood sugar-lowering effect after 14 days of treatment, comparatively. However, both 400 mg/kg TME and UFN significantly returned blood glucose levels in diabetic rats compared to normal rats. Analysis of the lipid profile showed that while HFD + STZ increased all lipid profile parameters, TME administration produced a significant decrease in their levels. Histopathological examinations showed that treatment with TME and UFN revealed an improved cellular architecture, with the healthy islets of Langerhans and compact glandular cells for pancreatic cells distinct from damaged cells in non-treated groups. Conversely, the adipose tissue displayed apparently normal polygonal fat cells. Therefore, these results suggest that TME has the potential to ameliorate hyperglycemia conditions and control lipid profiles in HFD + STZ-induced diabetic rats.

Vitamin D Supplementation Could Enhance the Effectiveness of Glibenclamide in Treating Diabetes and Preventing Diabetic Nephropathy: A Biochemical, Histological and Immunohistochemical Study.

Diabetes mellitus is an oxidative stress-related disease characterized by hyperglycemia and a variety of complications, including nephropathy. Vitamin D has variable functions extending beyond the calcium metabolism to prevent oxidative tissue damage. We aimed to investigate whether vitamin D supplements could enhance Glibenclamide's effectiveness in treating diabetes and minimize the risk of associated pathology. Wistar rats were divided into normal control (n = 10) and diabetic (n = 30), where animals received two low doses of Streptozotocin 30 mg/kg/BW intraperitoneally to develop diabetes. The diabetic rats were then randomly divided into three equal groups: untreated, treated with Glibenclamide (0.6 mg/kg), and treated with Glibenclamide and Vitamin D3 (500 IU/kg). After eight weeks, the animals were sacrificed, and blood samples and kidney tissues were collected to evaluate biochemical, anti-oxidant, and pro-inflammatory cytokine levels and histological and immunohistochemical changes. Diabetic animals had significantly increased fasting blood glucose, lipid profile, blood urea, serum creatinine, and Malondialdehyde levels, whereas serum insulin, albumin, and the anti-oxidant enzymes superoxide dismutase and catalase were significantly decreased compared to normal control (p < 0.01). Furthermore, some renal histological changes were observed together with significantly increased immunoreactivity of anti-p53, anti-TNF-α, and anti-IL-6 antibodies when compared to the normal control. All abnormal parameters improved significantly with Glibenclamide therapy (p < 0.01), but combination therapy with vitamin D produced a much better result. In conclusion, vitamin D supplementation along with anti-diabetic medication can help prevent or reduce the severity of diabetic nephropathy due to its potent antioxidant, anti-inflammatory, and anti-apoptotic properties.

Ameliorative role of Cyanus depressus (M.Bieb.) Soják plant extract against diabetes-associated oxidative-stress-induced liver, kidney, and pancreas damage in rats.

In this original article, we aimed to assess the ameliorative role of Cyanus depressus (CD) plant ethanolic extract treatment of streptozotocin (STZ)-induced liver, kidney, and pancreas damage in rats. The rats were divided into five groups (n = 7): control, CD, Diabetes mellitus (DM), DM + CD, and DM + glibenclamide (Gly). The DM groups were injected with a single dose of 50 mg/kg STZ intraperitoneally (i.p.). While the CD and DM + CD groups received 400 mg/kg/day intragastrically for 21 days, the DM + Gly group received 3 mg/kg/day of Gly intragastrically throughout the experiment. Statistically significance was accepted as p < .05. According to our liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) data, quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid were the major compounds, in descending order. Weekly blood glucose, serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and urea, malondialdehyde (MDA) (liver and pancreas), and blood glycosylated hemoglobin % (HbA1c %) were significantly decreased, whereas finally live body weights (LBWs), reduced glutathione (GSH), glutathione S-transferase (GST) and catalase (CAT) (pancreas), and pancreatic islet diameter and area were increased significantly in the CD-treated diabetic group. Moreover, CD administration was found to be effective in the protection of the histology of the liver, kidneys, and pancreatic islets in the STZ-induced rats. Consequently, we concluded that CD administration reduces hyperglycemia, oxidative stress, and histopathology in STZ-induced experimental rats by improving antioxidant defenses. PRACTICAL APPLICATIONS: Today, the prevalence of diabetes is increasing rapidly throughout the world and it causes complications such as kidney damage, blindness, amputations, and cardiovascular diseases. Despite medical technological advances, people's interest in medicinal herbal products is gradually increasing. Biochemical and histopathological findings showed that the use of the plant CD at the determined dose (400 mg/kg/day) in rats with DM by STZ had strong antioxidant and antidiabetic effects. CD may have a drug potential in preventing DM and its complications because of its phytochemical content including some phenolic acids such as quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid. Isolation of bioactive compounds from CD and investigation of their therapeutic effects could be planned as further studies.

Blood pressure and blood sugar-lowering effects of purified gambir on diabetic hypertensive Wistar Kyoto rats.

OBJECTIVES: Antioxidants protect people from diabetes and its cardiovascular complication. Purified gambir (Uncaria gambir Roxb.) is a potential medicinal plant for treating this condition based on the antioxidant activity of its catechin compound. This study tries to reveal the potential activity of purified gambir as a blood pressure-lowering drug while lowering blood glucose in diabetic hypertensive rats induced by oral NaCl-Prednisone and Alloxan. METHODS: Rats were induced by oral NaCl 0.8% and Prednisone 5 mg/kg BW for 14 days to obtain hypertensive condition. Alloxan 125 mg/kg BW was given intra peritoneal injection on the 8th day to obtain diabetic hypertensive condition. The animal was divided into five groups, normal control group treated with vehicle, treatment groups were treated with purified gambir at dose of 2.5; 5 and 10 mg/kg BW respectively, while the positive control group were treated with a combination of captopril-glibenclamide at dose of 2.25 and 0.45 mg/kg BW. All animals were treated orally for 14 days. Fasting blood glucose and cardiovascular parameters (SBP, DBP, MAP, HR, BF and BV) were measured on days 1, 3, 7, and 14. NO level were measured on day 0 and day 14. Data were analyzed using two-way ANOVA followed by Duncan Multiple Range Test. RESULTS: The purified gambir has blood pressure and blood sugar-lowering activity (p<0.05). The NO levels of the treatment group also increased significantly (p<0.05). CONCLUSIONS: This study indicated that purified gambir could be an alternative medicine to manage blood glucose and blood pressure in the diabetic hypertensive model.

Hypoglycemic, hypolipidemic and hepatoprotective effects of Alpinia officinarum on nicotinamide/streptozotocin induced type II diabetic rats.

OBJECTIVES: Alpinia officinarum Hance, commonly known as lesser galangal, is a member of the ginger family (Zingiberaceae) traditionally used for many decades to treat inflammation, pain, stomach ache and cold. In the present study, the antidiabetic and hypolipidemic potentials of the hydroalcoholic extract of A. officinarum (AO) were investigated in the nicotinamide/streptozotocin induced type II diabetic rats. METHODS: Male Wistar rats were divided into following six groups: Group I was normal control rats. Group II: normal diabetic control, Group III: Diabetic rats treated with glibenclamide (0.25 mg/kg), IV, V and VI: Diabetic rats treated with 100, 200 and 500 mg/kg AO hydroalcoholic extract by daily gavage for 28 days, respectively. At the end of treatment, biochemical analysis, histological study, phytochemical analysis and acute toxicity tests were carried out. RESULTS: The results show significant reduction in blood glucose, serum lipid profiles, and liver enzyme levels in diabetic rats compared with diabetic control in AO treated group. CONCLUSIONS: In conclusion, the present study demonstrated that AO extract had significant (p<0.05) antidiabetic and anti-hyperlipidemia effects in addition to hepatoprotective effect in type II diabetic rats.

The effect of co-administration of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rat liver.

It is possible to use plant-derived antioxidant molecules in the form of dietary supplements. However, dietary supplement-drug interaction pattern has not been well defined for most of these products. The aim of this study was to determine the effects of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rats. Streptozotocin was administered to create experimental diabetes. Resveratrol (5 mg/kg) (R), glibenclamide (5 mg/kg) (G), and berberine (10 mg/kg) (B) were administered individually or in combinations in DMSO by intraperitoneal administration route to the diabetic rats. DMSO was also given to non-diabetic control (C) and diabetic control (D) groups. Livers of rats were taken under anesthesia at the end of the treatment period (12 days). Ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD), aniline 4-hydroxylase (A4H), erythromycin N-demethylase (ERND), glutathione S-transferase (GST), catalase (CAT), and glutathione reductase (GR) activities were measured in microsomes and cytosols. In addition, histomorphological studies were also performed in the liver tissues. EROD activity of D+R was significantly higher than C and D+R+B. PROD activity of D+R was significantly higher than C, D, D+R+G, D+R+B, and D+R+B+ G. PROD activity of D+B was significantly higher than C and D+R+B. ERND activity of D+R was significantly higher than D+R+G and D+R+B. GST activity of D+R was significantly higher than D+R+G. CAT activity of D+B was significantly lower than C. It is clear that co-administration of resveratrol, berberine, and glibenclamide modifies some of the important xenobiotic metabolizing enzyme activities. Resveratrol and berberine have the potential to cause dietary supplement-drug interaction.

Gastroprotective action of the ethanol extract of Leonurus sibiricus L. (Lamiaceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus sibiricus L. (Lamiaceae) is a medicinal plant known in Brazil as "rubim" or "erva de macaé". It is used for various purposes, including stomach disorders. AIM OF THE STUDY: To evaluate the effect of the ethanol extract of the aerial parts of L. sibiricus (EELs) in models of gastric damage in mice. MATERIAL AND METHODS: The effect of EELs (50, 100 and 300 mg/kg, p.o., 1 h before induction) was tested on acidified ethanol (ACEt)-induced gastric ulcers. Additionally, we tested the effect of EELs (by intraduodenal administration) in the pylorus ligation (PL) model. RESULTS: Pretreatment with EELs, at 300 mg/kg, but not 50 and 100 mg/kg, reduced the relative area of gastric ulcers induced by ACEt (p < 0.01) and lipoperoxidation (p < 0.001), and increased the sulfhydryl content (p < 0.01) in the stomach in comparison with the vehicle group. Pretreatment with N-ethylmaleimide (a blocker of non-protein sulfhydryl groups, 10 mg/kg, i.p.) or glibenclamide (a KATP channel blocker, 10 mg/kg, i.p.) inhibited the gastroprotective response caused by EELs (300 mg/kg; p < 0.001), but there were no alterations due to pretreatments with inhibitors of the synthesis of prostaglandins (indomethacin, 10 mg/kg), nitric oxide (L-NAME, 70 mg/kg) or hydrogen sulfide (DL-propargylglycine, 10 mg/kg). Treatment with EELs (300 mg/kg) reduced mucus production (p < 0.001) and the volume of gastric secretion (p < 0.001) after PL without affecting gastric acidity or pH. CONCLUSIONS: These results provide evidence that EELs exerts gastroprotective action in mice, with the participation of oxidative stress and mediation of NP-SH, KATP channels and mucus production.

Marjoram extract prevents ischemia reperfusion-induced myocardial damage and exerts anti-contractile effects in aorta segments of male wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Marjoram (Origanum majorana L.) is an herb traditionally used as a medicine in different countries, as Morocco and Iran, because of its beneficial cardiovascular effects. Some studies suggest that these effects are due, at least in part, to the presence of phenolic compounds such as rosmarinic acid (RA) and luteolin. AIM OF THE STUDY: To analyze the possible cardiprotective effects of a marjoram extract (ME) reducing myocardial damage after coronary ischemia-reperfusion (IR) and its possible antihypertensive effects reducing the response of aorta segments to the vasoconstrictors noradrenaline (NA) and endothelin-1 (ET-1). MATERIALS AND METHODS: Male Wistar rats (300g) were used. After sacrifice, the heart was immediately removed and mounted in a perfusion system (Langendorff). The aorta was carefully dissected and cut in 2 mm segments to perform vascular reactivity experiments. RESULTS: In the heart, ME perfusion after IR reduced heart rate and prevented IR-induced decrease of cardiac contractility, possibly through vasodilation of coronary arteries and through the upregulation of antioxidant markers in the myocardium that led to reduced apoptosis of cardiomyocytes. In the aorta, ME decreased the vasoconstrictor response to NA and ET-1 and exerted a potent anti-inflammatory and antioxidant effect. Neither RA nor 6-hydroxi-luteolin-O-glucoside, major compounds of this ME, were effective in improving cardiac contractility after IR or attenuating vasoconstriction to NA and ET-1 in aorta segments. CONCLUSION: In conclusion, ME reduces the myocardial damage induced by IR and the contractile response to vasoconstrictors in the aorta. Thus, it may be useful for the treatment of cardiovascular diseases such as myocardial infarction and hypertension.

Synergistic antidiabetic activity of Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. polyherbal combination.

Type 2 Diabetes Mellitus accounts for 90% of most diabetes cases. Many commercial drugs used to treat this disease come with adverse side effects and eventually fail to restore glucose homeostasis. Therefore, an effective, economical and safe antidiabetic remedy from dietary source is considered. Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. were chosen since both are used for centuries as traditional medicine to treat various ailments and diseases. In this study, the antidiabetic properties of a polyherbal combination of T. officinale and M. charantia ethanol extracts are evaluated. The bioactive solvent extracts of the samples selected from in vitro antidiabetic assays; α-amylase, α-glucosidase, and dipeptidyl peptidase-4 (DPP-4) inhibition, and glucose-uptake in L6 muscle cells were combined (1:1) to form the polyherbal combination. The antidiabetic efficacy of polyherbal combination was evaluated employing the above stated in vitro antidiabetic assays and in vivo oral glucose tolerance test and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat model. A quadrupole time-of-flight liquid chromatography-mass spectrometry (Q-TOF LCMS) analysis was done to identify active compounds. The polyherbal combination exerted improved antidiabetic properties; increased DPP-4, α-amylase, and α-glucosidase inhibition. The polyherbal combination tested in vivo on diabetic rats showed optimum blood glucose-lowering activity comparable to that of Glibenclamide and Metformin. This study confirms the polyherbal combination of T. officinale and M. charantia to be rich in various bioactive compounds, which exhibited antidiabetic properties. Therefore, this polyherbal combination has the potential to be further developed as complex phytotherapeutic remedy for the treatment of Type 2 Diabetes Mellitus.

Streblus asper attenuates alloxan-induced diabetes in rats and demonstrates antioxidant and cytotoxic effects.

CONTEXT: Streblus asper Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation. OBJECTIVE: The study evaluates antidiabetic effects, antioxidant potential, and cytotoxicity of leaf and bark extracts of S. asper. MATERIALS AND METHODS: Antidiabetic effects were assessed by inducing diabetes in Wistar albino rats (n = 5, six groups included 30 rats) by injecting alloxan [0.25 mg/kg body weight (bw)] intraperitoneally, and efficacy of methanol extracts of leaf and bark, and aqueous extract of leaves were evaluated by oral administration of 300 mg/kg bw of extracts for 3 weeks. Glibenclamide (Dibenol™) was used as a control (10 mg/kg bw). Antioxidant properties were examined by DPPH free radical scavenging activity, and cytotoxicity was investigated using a brine shrimp lethality assay. RESULTS: Methanol extracts of leaves and bark, and the aqueous extract of leaves of S. asper, caused significant reductions in blood glucose levels in diabetic rats of 36.83, 70.33, and 52.71%, respectively, after 21 days of treatment. IC50 values in DPPH radical scavenging assessment for those extracts were 58.92, 88.54, and 111.36 µg/mL, respectively. LC50 values for brine shrimp lethality for the extracts were 173.80, 32.36, and 3235.9 µg/mL, respectively. DISCUSSION AND CONCLUSIONS: The methanol bark extract of S. asper showed significant antidiabetic activity. This study will significantly contribute to establishing the plant as an alternative medicinal resource for rural populations of Bangladesh and provides an opportunity for further research to identify the primary active compound(s) and establish new drug candidates.

Syzygium jambos extract mitigates pancreatic oxidative stress, inflammation and apoptosis and modulates hepatic IRS-2/AKT/GLUT4 signaling pathway in streptozotocin-induced diabetic rats.

The protective effect of Syzygium jambos (SJ) bark extract against streptozotocin-induced diabetes was tested in rats. Animals were treated with 100 or 200 mg/kg of the extract or glibenclamide, 0.5 mg/kg per os, once daily: started 2 days before streptozotocin (STZ) injection and lasted for 14 days after STZ injection. The effect of the extract was also evaluated on normal rats in comparison with glibenclamide. Diabetic animals showed an elevated blood glucose level, positive glycosuria, elevated fructosamine, pancreatic malondialdehyde, pancreatic TNF-a, and pancreatic caspase-3 levels and decreased serum insulin, pancreatic IL-10, pancreatic BCL-2, reduced glutathione (GSH), liver insulin substrate-2, liver phosphorylated protein kinase B (p-AKT) and liver glucose transporter 4 (GLUT4) levels. Histopathological examination of diabetic rats revealed islets destruction and vacuolation and collagen fibers deposition. All these changes were mitigated dose dependently by the extract. The high dose of the extract exerted comparable effects with glibenclamide in most studied parameters. These results indicated the protective role of SJ against the STZ diabetogenic action. In the pancreatic and hepatic tissue of diabetic rats, SJ effectively recovered pancreatic cells by reducing hyperglycemia through activating endogenous antioxidants, dynamic insulin production, and suppressing inflammation and apoptosis. The observed results might be attributed to the existence of 10 secondary metabolites as annotated by LC-MS. Taken together, S. jambos is a potential candidate for further studies to confirm its activities as a therapeutic agent for diabetic patients.

Inhibitory effect of Salvia coccinea on inflammatory responses through NF-κB signaling pathways in THP-1 cells and acute rat diabetes mellitus.

Hyperglycemia-induced oxidative stress has been implicated in diabetes and its complications. Medicinal plants possessing antioxidant activity may decrease oxidative stress by scavenging radicals and reducing power activity and would be a promising strategy for the treatment of inflammatory disorders like diabetes. This study was designed to evaluate the antioxidant effect of Aqueous Extract of S.coccinea leaf (AESL) in HG treated THP-1 cells and streptozotocin (STZ)-induced diabetic Wistar rats. AESL and the standard antidiabetic drug glibenclamide were administered orally by intragastric tube for 14 days and pre-treated HG grown THP-1 cells. AESL treatment reduced HG induced increase in ROS production, NF-κB dependent proinflammatory gene expression by influencing NF-κB nuclear translocation in THP-1 cells. Oral administration of AESL inhibited STZ-induced increase in serum lipid peroxidation, aspartate transaminase, alanine transaminase, and Lactate dehydrogenase of diabetic rats. Significant increase in activity of superoxide dismutase, catalase and glutathione peroxidase, and a reduced level of glutathione, were observed in AESL treatment. The results demonstrate that AESL is useful in controlling blood glucose and also has antioxidant potential to influence the translocation of NF-κB, protect damage caused by hyperglycemia-induced inflammation.

Effect of Co-administration of Glibenclamide and Aqueous Calyx Extract of Hibiscus Sabdariffa on Oxidative Stress Markers in Streptozotocin-Induced Diabetic Rats.

The hyperglycaemia of diabetes mellitus (DM) induces oxidative stress which damages the tissues. Glibenclamide, an oral hypoglycaemic drug used in the treatment of DM has associated side effects. Natural products are considered safe in the treatment of chronic diseases. Hibiscus sabdariffa (HS) is a plant that has demonstrated antidiabetic activity. We aimed to determine the potential benefits of co-administration of HS and glibenclamide in ameliorating oxidative stress in streptozotocin (STZ)-induced diabetic rats.  A total of 25 male albino Wistar rats were divided randomly into five groups: control (Non-DM), diabetic (DM), diabetic treated with 600µg/kg BW of glibenclamide (DM + GLIB), diabetic treated with 500mg/kg BW of HS (DM + HS), diabetic treated with both 600µg/kg BW of glibenclamide and 500mg/kg BW of HS (DM + GLIB + HS). The interventions were administered for a period of 28 days. The Non-DM rats were significantly heavier (p<0.01) compared to rats in the other treatment groups. Glibenclamide or HS alone and in combination, significantly lowered (p < 0.001) the final fasting blood glucose concentration of the rats in the respective treatment groups. HS and a combination of HS+ GLIB resulted in increased (p<0.05) serum activity of catalase, glutathione peroxidase and superoxide dismutase compared to the DM untreated rats.  The serum level of malondialdehyde was significantly lowered (p=0.000) in rats that received a combination of HS + GLIB compared to the DM untreated rats. Coadministration of HS + GLIB showed beneficial regeneration of islet-cells in the pancreas. Co-administration of HS + GLIB appears to be more beneficial in the treatment of DM and associated oxidative stress than when given as single agents. Thus, a case for their incorporation as a combined therapy for DM should be considered.