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Bryonia laciniosa Linn. (Cucurbitaceae) seed is used in traditional medicine for a number of ailments including metabolic disorders. This investigation was carried out to investigate the anti-hyperglycemic and anti-hyperlipidemic potential of the ethanolic extract of seeds of B. laciniosa Linn. and its saponin fraction in streptozotocin-induced diabetic rats. The ethanolic extract (250 and 500 mg/kg; p.o.) and saponin fraction (100 and 200 mg/kg; p.o.) were administered to diabetic rats and standard drug insulin (5 IU/kg; i.p.) to the group serving as a positive control. Effects of the ethanolic extract and saponin fraction on various biochemical parameters were studied in diabetic rats. Data were statistically analysed by one-way ANOVA followed by Dunnett's t-test. Oral administration of the ethanolic extract and saponin fraction for 28 days to streptozotocin-induced diabetes rats significantly (P < 0.05) decreased the levels of blood glucose and improved the levels of plasma insulin. The levels of triglycerides, cholesterol, high density lipoprotein, low density lipoprotein, very low density lipoprotein, aspartate amino transferase and alanine amino transferase, urea, and creatinine were markedly altered in streptozotocin-induced diabetic rats. Oral administration of the ethanolic extract and saponin fraction restored all these biochemical parameters to near control levels. This study reveals the efficacy of B. laciniosa seed extract and its saponin fraction in the amelioration of diabetes and its associated complications.

The current study was designed to investigate the effect of Citrus limon. (L.) Burm. (Rutaceae) fruits, commonly known as lemon, in experimental liver damage. The ethanol extract of Citrus limon. fruits was evaluated for its effects on experimental liver damage induced by carbon tetrachloride, and the ethyl acetate soluble fraction of the extract was evaluated on HepG2 cell line. The ethanol extract normalized the levels of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), and total and direct bilirubin, which were altered due to carbon tetrachloride intoxication in rats. In the liver tissue, treatment significantly reduced the levels of malondialdehyde (MDA), hence the lipid peroxidation, and raised the levels of antioxidant enzymes superoxide dismutase (SOD) and catalase. It improved the reduced glutathione (GSH) levels in treated rats in comparison with CCl4-intoxicated rats. In the histopathologic studies, treated animals exhibited restoration of t...

The current study was undertaken to investigate the effect of the root bark of Oroxylum indicum. Vent. (Bignoniaceae) against experimental gastric ulcers. The 50% alcohol extract of root bark of Oroxylum indicum. and its different fractions, viz., petroleum ether, chloroform, ethyl acetate and n.-butanol, were studied (p.o.) against ethanol-induced gastric mucosal damage. The alcohol extract (300 mg/kg) and its different fractions (100 and 300 mg/kg) showed significant reduction in gastric ulceration. Out of all these fractions, the petroleum ether (96%) and n.-butanol (99%) fractions showed maximum inhibition of gastric lesions against ethanol-induced gastric mucosal damage. The results were comparable with omeprazole (reference standard). In the ethanol-induced gastric ulcer model, treatment with both the active fractions and omeprazole showed significant antioxidant activity as evident from the reduction in the extent of lipid peroxidation that was measured in terms of malondialdehyde (MDA), al...

The current study was designed to investigate the effect of a 50% alcohol extract of Chlorophytum arundinaceum. Baker (CAE) against ethanol-induced pylorus ligation and cold stress–induced experimental gastric ulcer. The CAE was given at the dose of 100 mg/kg, p.o., in all the models, and results of those were compared with that of animals treated with omeprazole 20 mg/kg, p.o. (reference standard). Ulcer index was a common evaluating parameter in all the models. In the pylorus ligation model, acid secretory parameters (total acid, pepsin activity, and total acid output) and mucoprotective parameters (total carbohydrate, total protein, and mucin activity) were studied. In addition, lipid peroxidation and antioxidant activity were specifically studied in cold stress–induced gastric ulcer model. Effects on vascular permeability as well as gastric emptying were also studied. CAE has shown significant protection in gastric ulceration as evident from reduction (p

The present study was designed to investigate the effect of Mimusops elengi (Sapotaceae) against experimental gastric ulcers. The 50% alcoholic extract of Mimusops elengi (Ext E) and its different fractions namely ethyl acetate (Ext E1), n-butanol (Ext E2), methanol (Ext E3) and aqueous (Ext E4) were studied (p.o.) against ethanol-induced gastric damage. Ext E1 was also studied in ethanol-induced, pylorus-ligated and water-immersion plus stress-induced gastric ulcer models. Ranitidine HCl (80 mg kg(-1)) was used as a reference standard. In ethanol-induced gastric ulcer model, pantoprazole (20 mg kg(-1)) was also used as a reference standard. Ext E1 tested in mice up to the dose of 5000 mg kg(-1) (p.o.) did not produce any sign of toxicity. Ext E at the doses of 50, 100, 300 and 500 mg kg(-1) and its different fractions (100 mg kg(-1)) showed reduction in gastric ulceration (P0.05). Ext E1 at the doses of 10, 50 and 100 mg kg(-1) showed dose-dependent inhibition of gastric lesions against ethanol-induced gastric damage. In 19 h pylorus-ligated animals, Ext E1 at 50 and 100 mg kg(-1) doses showed significant reduction in ulcer index (P0.05). Significant reduction was also observed in total acidity, volume of gastric acid secretion, total acid output and pepsin activity (P0.05) when compared with the control group. Besides, Ext E1 showed increase in the mucosal glycoproteins that was evident from significant rise in total carbohydrates to protein ratio (TC:PR ratio) (P0.05), which is an indication of mucin activity. Ext E1 also showed protection against water-immersion plus stress-induced gastric lesions that was evident from dose-dependent decrease in ulcer index (P0.05), score for intensity (P0.05) and total lesion area (P0.05) when compared with the control group. It can be concluded from our study that Ext E1 possesses anti-ulcer activity against experimental gastric ulcers. The mechanism of anti-ulcer activity can be attributed to decrease in gastric acid secretory activity along with strengthening of mucosal defensive mechanisms.

The effects of beta(3) adrenergic receptor agonists, (S)-4-[2-hydroxy-3-phenoxy-propylamino-ethoxy]-N-(2-methoxyethyl)-phenoxyacetamide (ZD 7114) and (+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one (CGP 12177A), were studied on aspirin plus pylorus ligation-induced gastric ulcers, gastric mucosal blood flow and gastric motility in rats. Pretreatment with ZD 7114 (3 mg kg(-1), p.o.) and CGP 12177A (3.5 mg kg(-1), p.o.) resulted in significant reduction in the incidences of gastric ulceration in aspirin plus pylorus ligated rats and results were comparable with the cimetidine treated group. Ulcer index was significantly reduced by ZD 7114 (0.71+/-0.05, P0.05) and CGP 12177A (1.15+/-0.27, P0.05) when compared with the control group (4.47+/-0.38). Further, significant increase in total carbohydrates to protein content ratio (mucin activity) was also observed. However, they did not alter the acid secretory parameters such as total acidity, total acid output and pepsin activity. Effects of ZD 7114 and CGP 12177A on gastric mucosal blood flow were studied using neutral red clearance method. Both the treatments showed significant increase in gastric mucosal blood flow (GV/Bt) as compared to control group. Effect on gastric motility was evaluated by estimation of phenol red concentration in rat stomach. Significantly higher concentrations of phenol red in the stomach were observed in ZD 7114 and CGP 12177A treated rats. Both ZD 7114 and CGP 12177A showed significant gastroprotective effect in the present study. The mechanism of this effect may be attributed to enhancement of gastric mucosal blood flow, reduction in gastric motility and strengthening of gastric mucosal barrier.

The effect of cromakalim, a potassium-channel opener, was studied on pylorus ligation-induced, aspirin-induced and water-immersion plus restraint stress-induced gastric ulcers in rats and on histamine-induced duodenal ulcer in guinea-pigs. Pretreatment with cromakalim (50–500 μg kg−1, p.o.) resulted in a significant reduction in the incidence of gastric and duodenal ulceration in each model. The anti-ulcer activity of cromakalim was comparable with that of cimetidine. Cromakalim at 100, 250 and 500 μg kg−1 caused a reduction in the volume of the gastric content in pylorus-ligated rats, and a dose of 250 μg kg−1 resulted in a significant reduction in total acidity (28.81 ± 11.73 mEq L−1, P < 0.02) in the pylorus ligation model. A significant reduction in total acid output was observed at doses of 250 μg kg−1 (84.27 ± 22.33 mEqH+, P < 0.02) and 500 μg kg−1 (120.17 ± 24.49 mEq H+, P < 001) in pylorus-ligated rats. A significant reduction in the ulcer index in pylorus-ligated rats was observed at all cromakalim doses: 50 μg kg−1 (0.23 ± 009, P < 0.05), 100 μg kg−1 (0.15 ± 0009, P < 0.02), 250 μg kg−1 (0.12 ± 0.05, P < 0.01) and 500 μg kg−1 (0.14 ± 0.03, P < 0.02). A significant reduction in the ulcer index of aspirin-treated rats was also observed at all cromakalim dose levels: 50 μg kg−1 (0.39 ± 0.03. P < 0.01), 100 μg kg−1 (0.28 ± 0.06, P < 0.01), 250 μg kg−1 (0.22 ± 0.04, P < 0.001) and 500 μg kg−1 (0.28 ± 0.03, P < 0.01). In the water-immersion plus restraint stress-induced gastric ulcer model, cromakalim significantly reduced gastric ulceration at all the dose levels: 50 μg kg−1 (28.2 ± 2.12, P < 0.001), 100 μg kg−1 (20.24 ± 1.71, P < 0.01), 250 μg kg−1 (19.95 ± 1.46, P < 0.001) and 500 μg kg−1 (21.61 ± 3.00, P < 0.001) but there was no consistent reduction of gastric bleeding. In addition to gastric ulcers, duodenal lesions were also reduced by pretreatment with cromakalim at all dose levels: 50 μg kg−1 (97.87 ± 20.03 mm2, P < 0.02). 100 μg kg−1 (70.72 ± 12.82 mm2, P < 0.02), 250 μg kg−1 (48.32 ± 8.42 mm2, P < 0.01) and 500 μg kg−1 (55.50 ± 12.50 mm2, P < 0.01). Cromakalim at a dose of 100 μg kg−1 also reduced total acidity (99.36 ± 9.12 mEq L−1, P < 0.02) and total acid output (172.22 ± 45.33 mEq of H+, P < 0.05) in this model. These findings demonstrate the anti-ulcer activity of cromakalim in different experimental models and suggest its potential use in ulcer therapy.

An ethanol extract (ASE) of the defatted seeds of Annona squamosa was screened for various pharmacological activities using experimental models. At an oral dose of 250 mg/kg in rats, it produced a depressant effect on the central nervous system, potentiated the hypnotic effect of pentobarbitone, showed anticonvulsant activity against electrically-induced convulsions and raised the pain threshold when tested by analgesiometer. ASE failed to inhibit paw edema induced by carra-geenan. It produced negative inotropic and negative chronotropic effects on perfused frog's heart which were unaltered by atropine pretreatment. Incubation with 0.3 mg/ml ASE stimulated rabbit and rat ileum and the effect was not altered by atropine pretreatment. On frog rectus abdominis muscle, a potentiation of acetylcholine action was observed. Phytochemical analyses revealed the presence of alkaloids.

The whole-plant, Pergularia daemia (Family: Asclepediaceae), extract (50% alcohol) was investigated for its antiurolithiatic and diuretic activity. Ethylene glycol (0.75% in water) feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and phosphate. Alcoholic extract (400 mg/kg) of P. daemia was given orally in curative and preventive regimens over a period of 28 days. Supplementation with extract significantly (P < 0.001) lowered the urinary excretion and kidney retention levels of oxalate, calcium and phosphate. Furthermore, high serum levels of urea nitrogen, creatinine and uric acid were significantly (P < 0.001) reduced by the extract. The results were comparable with the standard drug, cystone (750 mg/kg). The reduction of stone-forming constituents in urine and their decreased kidney retention reduces the solubility product of crystallizing salts such as calcium oxalate and calcium phosphate, which could contribute to the antiurolithiatic property of the extract. The extract exhibited significant diuretic activity at dose of 400 mg/kg body weight as evidenced by increased total urine volume and the urine concentration of Na(+), and K(+). These findings affirm assertions made regarding the effectiveness of the extract of this plant against urinary pathologies in the Indian folk medicine.

Roots of Premna integrifolia Linn. Mant. (Verbanacea) are important rasayana (Adaptogenic) drugs and are considered to be useful in the treatment of variety of ailments. The present study was aimed at evaluating the for its anti-inflammatory and antioxidant activities. Pretreatment with a single dose of methanolic extract of P. integrifolia (PIM) (300 mg/kg b.w.) produced significant inhibition on carrageenan-induced rat hind paw edema, histamine induced wheal formation, and acetic acid-induced mouse vascular permeation. In a 7-day study, daily administration of PIM suppressed formalin induced paw edema and cotton pellet-induced rat granuloma formation. The extract also showed significant inhibition of cyclo-oxygenase (COX-I) activity on rat uterus and plasma membrane stabilization. Apart from this, the antioxidant activity (in vitro) of the extracts was evaluated using the anti radical, superoxide scavenging, erythrocyte membrane stability, anti lipid peroxidation, hydroxyl radical scavenging, nitric oxide scavenging and reducing power (ferric thiocynate method and β-carotene bleaching test) assays. PIM showed significant anti-oxidant activity. In addition, PIM (300mg/kg b.w.) produced no observable sub acute toxicity in mice with in 15 days. The results scientifically demonstrated the antiinflammatory activity of P. integrifolia roots in various experimental models probably through their antihistaminic, antikinin, COX-inhibitory and antioxidant action. This therefore justifies the folkloric use of the plant.

BACKGROUND The present study was designed as an open label, multiple-dose, randomized, parallel trial to evaluate the pharmacodynamic drug-drug interaction of lisinopril and concomitantly administered diclofenac sodium in non-diabetic and diabetic, mild to moderate hypertensive, osteoarthritic patients. METHODS Post-screening and on inclusion, patients were put on a 2-week washout period and then randomly assigned to either only lisinopril 10 mg or combination of lisinopril 10 mg and diclofenac sodium 100 mg treatments for 8-12 weeks in diseased states of hypertension and osteoarthritis with or without type 2 diabetes mellitus. RESULTS The blood pressure (BP) control with lisinopril was reduced by concomitantly administered diclofenac sodium in non-diabetic (SBP: p=0.00002; DBP: p=0.000008) and diabetic (SBP: p=0.002; DBP: p=0.001) patients when compared with the patients receiving lisinopril alone. Insulin sensitivity was improved (p=0.00002) and urinary albumin excretion rate was better controlled (p=0.0096) in lisinopril-treated patients when compared with the combination treatment in diabetic pool. Serum creatinine levels increased significantly in non-diabetic patients (p=0.00004) receiving combination treatment. In addition, creatinine clearance (CLCR) and blood urea nitrogen (BUN) were significantly higher in diabetic (CLCR: p

Serine proteases such as thrombin, mast cell tryptase, trypsin, or cathepsin G, for example, are highly active mediators with diverse biological activities. So far, proteases have been considered to act primarily as degradative enzymes in the extracellular space. However, their biological actions in tissues and cells suggest important roles as a part of the body's hormonal communication system during inflammation and immune response. These effects can be attributed to the activation of a new subfamily of G protein-coupled receptors, termed protease-activated receptors (PARs). Four members of the PAR family have been cloned so far. Thus, certain proteases act as signaling molecules that specifically regulate cells by activating PARs. After stimulation, PARs couple to various G proteins and activate signal transduction pathways resulting in the rapid transcription of genes that are involved in inflammation. For example, PARs are widely expressed by cells involved in immune responses and inflammation, regulate endothelial-leukocyte interactions, and modulate the secretion of inflammatory mediators or neuropeptides. Together, the PAR family necessitates a paradigm shift in thinking about hormone action, to include proteases as key modulators of biological function. Novel compounds that can modulate PAR function may be potent candidates for the treatment of inflammatory or immune diseases.

Serine proteases such as thrombin, mast cell tryptase, trypsin, or cathepsin G, for example, are highly active mediators with diverse biological activities. So far, proteases have been considered to act primarily as degradative enzymes in the extracellular space. However, their biological actions in tissues and cells suggest important roles as a part of the body's hormonal communication system during inflammation and immune response. These effects can be attributed to the activation of a new subfamily of G protein-coupled receptors, termed protease-activated receptors (PARs). Four members of the PAR family have been cloned so far. Thus, certain proteases act as signaling molecules that specifically regulate cells by activating PARs. After stimulation, PARs couple to various G proteins and activate signal transduction pathways resulting in the rapid transcription of genes that are involved in inflammation. For example, PARs are widely expressed by cells involved in immune responses and inflammation, regulate endothelial-leukocyte interactions, and modulate the secretion of inflammatory mediators or neuropeptides. Together, the PAR family necessitates a paradigm shift in thinking about hormone action, to include proteases as key modulators of biological function. Novel compounds that can modulate PAR function may be potent candidates for the treatment of inflammatory or immune diseases.

Context: Bryonia laciniosa Linn. (Cucurbitaceae) seed is used in traditional medicine for a number of ailments including metabolic disorders. Aim: This study evaluated the anti-diabetic action of the ethanol extract of B. laciniosa seeds and saponin fraction of it through its effect on hyperglycemia, dyslipidaemia and oxidative stress in neonatally streptozotocin (n-STZ)-induced diabetic rats (n-STZ diabetic rats). Materials and Methods: Ethanol extract (250 and 500 mg/kg; p.o.), saponin fraction (100 and 200 mg/kg; p.o.) and standard drug glibenclamide (3 mg/kg; p.o.) were administered to diabetic rats when the rats were 6 weeks old and continued for 10 consecutive weeks. Effects of ethanol extract and saponin fraction on various biochemical parameters were studied in diabetic rats. Results: The treatment with ethanol extract and saponin fraction for 10 weeks decrease in the levels of glucose, triglycerides, cholesterol, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, serum urea, serum creatinine and diminished activities of aspartate transaminase, and alanine transaminase. The anti-hyperglycemic nature of B. laciniosa is probably brought about by the extra- the pancreatic mechanism as evidenced from unchanged levels of plasma insulin. B. laciniosa modulated effect of diabetes on the liver malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity. Administration of ethanol extract and saponin fraction to diabetic rats showed a significant reversal of disturbed antioxidant status. Significant increase in SOD, CAT, and levels of GSH was observed in treated n-STZ diabetic rats. Conclusion: The present study reveals the efficacy of B. laciniosa seed extract and its saponin fraction in the amelioration of n-STZ diabetic rats.

Although coenzyme Q10 (CoQ10) is a component of the oxidative phosphorylation process in mitochondria that converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis, its effect in type I diabetes is not clear. We have studied the effect of 4 wk of treatment with CoQ10 (10 mg/kg, ip, daily) in streptozotocin (STZ)-induced (40 mg/kg, iv in adult rats) type I diabetes rat models. Treatment with CoQ10 produced a significant decrease in elevated levels of glucose, cholesterol, triglycerides, very-low-density lipoprotein, low-density lipoprotein, and atherogenic index and increased high-density lipoprotein cholesterol levels in diabetic rats. CoQ10 treatment significantly decreased the area under the curve over 120 min for glucose in diabetic rats, without affecting serum insulin levels and the area under the curve over 120 min for insulin in diabetic rats. CoQ10 treatment also reduced lipid peroxidation and increased antioxidant parameters like superoxide dismutase, catalase, and glutathione in the liver homogenates of diabetic rats. CoQ10 also lowered the elevated blood pressure in diabetic rats. In conclusion, CoQ10 treatment significantly improved deranged carbohydrate and lipid metabolism of experimental chemically induced diabetes in rats. The mechanism of its beneficial effect appears to be its antioxidant property.

Effects of the flavonoid rich fraction of the stem bark of Manilkara hexandra (Roxb.) Dubard, have been studied on ethanol, ethanol-indomethacin and pylorus ligated gastric ulcers in experimental animals. Oral administration of the ethyl acetate extract (extract A3) inhibited the formation of gastric lesions induced by ethanol in a dose dependent manner. The protective effect of extract A3 against ethanol induced gastric lesions was not abolished by pretreatment with indomethacin (10 mg kg−1). Further, extract A3 inhibited increase in vascular permeability due to ethanol administration. Extent of lipid peroxidation was significantly reduced in animals treated with extract. Extract A3 also inhibited the formation of gastric ulcers induced by pylorus ligation, when administered both orally and intraperitoneally. Moreover, pretreatment with extract A3 increased mucus production and glycoprotein content, which was evident from the rise in mucin activity and TC: PR ratio. Copyright © 2004 John Wiley & Sons, Ltd.

The present study was undertaken to investigate the mechanism of cytoprotective effects of magaldrate in aspirin plus pylorus-ligation model and ethanol-induced gastric ulcer model in rats. Magaldrate (60 mg/kg, p.o.) produced a significant reduction in the ulcer index and significant increase in mucus content in ethanol-induced gastric ulceration in rats. In aspirin plus pylorus-ligation model magaldrate produced significant decrease in ulcer index, total acidity and protein content (PR). It did not produce any significant change in volume of gastric secretion. However, it produced significant increase in total carbohydrate (TC) level but not in ratio between TC and proteins. It also produced a significant decrease in lipid peroxidation (as expressed by thiobarbituric acid reactive substance). Our data suggests the cytoprotective action of magaldrate on gastric mucosal cells which may be due to protection of gastric mucosa from lipid peroxidation.

Present investigation was undertaken to study the effects of 6 week treatment with spirapril (2 mg/kg po) on insulin sensitivity, and serum lipid levels in streptozotocin (STZ)-diabetic and spontaneously hypertensive (SH) rats. Treatment of rats with spirapril in diabetic and diabetic with hypertensive animals significantly prevented STZ-induced loss of body weight, hypertension, and bradycardia. It also partially but significantly prevented STZ-induced hyperglycaemia in both diabetic Wistar and SH animals. Insulin level was not altered by spirapril treatment. There was significant reduction in cholesterol levels in the diabetic rats. In conclusion, the present investigation presents a number of beneficial effects of spirapril treatment in diabetic and/or hypertensive rats. Spirapril may be considered as one of the drugs of choice in treatment of hypertension when associated with diabetes

The present study was undertaken to investigate the possible factors which may contribute to the altered digoxin levels in diabetic patients. The digoxin levels were found to be significantly higher in diabetics (1.74 +/- 0.09 ng/ml) as compared to non-diabetics (0.76 +/- 0.07 ng /ml). There was a positive correlation between digoxin levels and glycosylated haemoglobin levels. All diabetic patients had serum creatinine, urea and potassium levels within normal limits. However, serum TSH levels were found to be significantly higher in diabetics as compared to controls. Serum tri-iodo-1-thyronine (T3) levels were found to be lower in diabetics as compared to non-diabetics. Our data suggests that diabetes-mellitus causes alteration of digoxin levels. One of the causes of this increase in digoxin levels may be a tendency towards mild hypothyroidism associated with diabetes mellitus.