ABSTRACT
Pongamia pinnata has been advocated in Ayurveda for the treatment of various inflammatory conditions and dyspepsia. The present work includes initial phytochemical screening and study of ulcer protective and healing effects of methanolic extract of seeds of P. pinnata (PPSM) in rats. Phytochemical tests indicated the presence of flavonoids in PPSM. PPSM when administered orally (po) showed dose-dependent (12.5-50 mg/kg for 5 days) ulcer protective effects against gastric ulcer induced by 2 h cold restraint stress. Optimal effective dose of PPSM (25 mg/kg) showed antiulcerogenic activity against acute gastric ulcers (GU) induced by pylorus ligation and aspirin and duodenal ulcer induced by cysteamine but not against ethanol-induced GU. It healed chronic gastric ulcer induced by acetic acid when given for 5 and 10 days. Further, its effects were studied on various parameters of gastric offensive acid-pepsin secretion, lipid peroxidation (LPO) and nitric oxide (NO) and defensive mucosal factors like mucin secretion and mucosal cell shedding, glycoproteins, proliferation and antioxidants; catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) levels. PPSM tended to decrease acid output and increased mucin secretion and mucosal glycoproteins, while it decreased gastric mucosal cell shedding without any effect on cell proliferation. PPSM significantly reversed the increase in gastric mucosal LPO, NO and SOD levels caused by CRS near to the normal level while it tended to increase CAT and GSH level decreased by CRS and ethanol respectively. Thus, the ulcer protective effects of PPSM may be attributed to the presence of flavonoids and the actions may be due to its effects both on mucosal offensive and defensive factors.
Subject(s)
Duodenal Ulcer/prevention & control , Gastric Mucosa/drug effects , Millettia/chemistry , Plant Extracts/pharmacology , Seeds/chemistry , Stomach Ulcer/prevention & control , Acetic Acid/toxicity , Animals , Aspirin/toxicity , Catalase/metabolism , Chromatography, Thin Layer/methods , Cold Temperature , Duodenal Ulcer/etiology , Female , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Glutathione/metabolism , Ligation/adverse effects , Lipid Peroxidation/drug effects , Male , Methanol/chemistry , Nitric Oxide/metabolism , Pepsin A/metabolism , Phytotherapy , Plant Extracts/chemistry , Pylorus/surgery , Rats , Restraint, Physical/adverse effects , Stomach Ulcer/etiology , Superoxide Dismutase/metabolismABSTRACT
Standardized aqueous extract of Neem (Azadirachta indica) leaves (AIE) has been reported to show both ulcer protective and ulcer healing effects in normal as well as in diabetic rats. To study the mechanism of its ulcer protective/healing actions, effects of AIE (500 mg/ kg) was studied on various parameters of offensive acid-pepsin secretion in 4 hr pylorus ligation, pentagastrin (PENTA, 5 microg/kg/hr)-stimulated acid secretion and gastric mucosal proton pump activity and defensive mucin secretion including life span of gastric mucosal cells in rats. AIE was found to inhibit acid-pepsin secretion in 4 hr pylorus ligated rats. Continuous infusion of PENTA significantly increased the acid secretion after 30 to 180 min or in the total 3 hr acid secretion in rat stomach perfusate while, AIE pretreatment significantly decreased them. AIE inhibited the rat gastric mucosal proton pump activity and the effect was comparable with that of omeprazole (OMZ). Further, AIE did not show any effect on mucin secretion though it enhanced life span of mucosal cells as evidenced by a decrease in cell shedding in the gastric juice. Thus, our present data suggest that the ulcer protective activity of AIE may be due to its anti-secretary and proton pump inhibitory activity rather than on defensive mucin secretion. Further, acute as well as sub acute toxicity studies have indicated no mortality with 2.5 g/kg dose of AIE in mice and no significant alterations in body or tissues weight, food and water intake, haematological profile and various liver and kidney function tests in rats when treated for 28 days with 1 g/kg dose of AIE.
Subject(s)
Azadirachta , Gastric Mucosa/metabolism , Peptic Ulcer/prevention & control , Phytotherapy , Plant Leaves , Animals , Azadirachta/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Gastric Acid/metabolism , Gastric Mucosa/pathology , Mucins/metabolism , Pentagastrin/toxicity , Peptic Ulcer/chemically induced , Peptic Ulcer/metabolism , Peptic Ulcer/pathology , Phytotherapy/methods , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Proton Pumps/metabolism , RatsABSTRACT
Asparagus racemosus (AR) is a herb used as a rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.
Subject(s)
Abnormalities, Drug-Induced/etiology , Asparagus Plant/chemistry , Fetal Development/drug effects , Medicine, Ayurvedic , Teratogens/toxicity , Abnormalities, Drug-Induced/embryology , Animals , Body Weight/drug effects , Female , Fetal Resorption/chemically induced , Litter Size , Male , Plant Extracts/toxicity , Plant Roots/chemistry , Pregnancy , Rats , Rats, Inbred StrainsABSTRACT
Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems.
Subject(s)
Antioxidants/metabolism , Free Radicals/metabolism , Glycoproteins/metabolism , Musa/chemistry , Stomach Ulcer/metabolism , Stomach Ulcer/pathology , Animals , Cell Proliferation , Diabetes Mellitus, Type 2 , Female , Glutathione/metabolism , Male , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Rats , Stomach Ulcer/chemically induced , Stomach Ulcer/prevention & control , Streptozocin/pharmacology , Sucralfate/therapeutic useABSTRACT
The standardized methanolic extract of leaves of O. sanctum (OSE; eugenol content 5%) given in doses of 50-200 mg/kg, orally, twice daily for five days showed dose-dependent ulcer protective effect against cold restraint stress induced gastric ulcers. Optimal effective dose (100 mg/kg) of OSE showed significant ulcer protection against ethanol and pyloric ligation-induced gastric ulcers, but was ineffective against aspirin-induced ulcers. OSE significantly healed ulcers induced by 50% acetic acid after 5 and 10 days treatment OSE (100 mg/kg) significantly inhibited the offensive acid-pepsin secretion and lipid peroxidation and increased the gastric defensive factors like mucin secretion, cellular mucus, and life span of mucosal cells and had antioxidant effect, but did not induce mucosal cell proliferation. The results indicate that the ulcer protective and healing effects of OSE may be due to its effects both on offensive and defensive mucosal factors.
Subject(s)
Anti-Ulcer Agents/therapeutic use , Gastric Mucosa/drug effects , Ocimum/chemistry , Ulcer/drug therapy , Administration, Oral , Animals , Anti-Ulcer Agents/administration & dosage , Catalase/metabolism , Cell Proliferation/drug effects , DNA/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Free Radicals/metabolism , Gastric Mucosa/enzymology , Gastric Mucosa/metabolism , Lipid Peroxidation/drug effects , Male , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Rats , Rats, Inbred Strains , Superoxide Dismutase/metabolism , Ulcer/etiologyABSTRACT
Oxidative stress is believed to initiate and aggravate many diseases including peptic ulcers and gastric carcinoma. We observed an increase in rat gastric mucosal lipid peroxidation (LPO) and superoxide dismutase (SOD) and a decrease in catalase (CAT) levels in cold restraint stress-induced gastric ulceration while, in clinical peptic ulceration and gastric carcinoma patients, an increase in serum LPO and a tendency to decrease in SOD and CAT levels were observed. The result thus, indicated a positive correlation between free radical-induced oxidative stress both in gastric and duodenal ulcers and gastric carcinoma.
Subject(s)
Antioxidants/metabolism , Oxidative Stress/physiology , Peptic Ulcer/metabolism , Stomach Neoplasms/metabolism , Animals , Catalase/blood , Cold Temperature , Duodenal Ulcer/etiology , Duodenal Ulcer/metabolism , Duodenal Ulcer/pathology , Female , Free Radicals/metabolism , Humans , Lipid Peroxidation/physiology , Male , Peptic Ulcer/etiology , Peptic Ulcer/pathology , Rats , Restraint, Physical , Stress, Psychological/complications , Stress, Psychological/physiopathology , Superoxide Dismutase/bloodABSTRACT
Gastric ulcers were induced in normal/NIDDM rats by various physical (2 hr cold restraint stress and 4 hr pylorus ligation) and chemical agents (ethanol, 1 ml/200 g, oral, 1 hr before; aspirin, 200 mg/kg, oral, 4 hr) and duodenal ulcers were induced by cysteamine (40 mg/200 g). Ulcer healing activity was studied in gastric ulcers induced by acetic acid (50%) and HCI (0.6 M). The result indicated that in both, normal and NIDDM rats, B. monniera extract (BME, 20-100 mg/kg) did not show any significant effect on blood glucose level, while A. indica (AIE, 250-1000 mg/kg) significantly decreased it. However, both BME (50 mg/kg) and AIE (500 mg/kg) showed significant anti-ulcer and ulcer-healing activities in normal and NIDDM rats. Further, the present results also indicated that the ulcer protective effects of BME was more pronounced in non-diabetic, while that of AIE was more in NIDDM rats. The anti-ulcer and ulcer-healing activities of BME and AIE may be due to their effects on various mucosal offensive and defensive factors, and correction of blood sugar level by AIE may help to have more ulcer protective effect in NIDDM rats.
Subject(s)
Azadirachta/chemistry , Bacopa/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Duodenal Ulcer/drug therapy , Phytotherapy , Stomach Ulcer/drug therapy , Acetic Acid/toxicity , Animals , Anti-Ulcer Agents/therapeutic use , Aspirin/toxicity , Cold Temperature , Diabetes Mellitus, Type 2/chemically induced , Dose-Response Relationship, Drug , Duodenal Ulcer/chemically induced , Ethanol/toxicity , Female , Male , Plant Extracts/therapeutic use , Rats , Stomach Ulcer/chemically induced , Wound Healing/drug effectsABSTRACT
Bacopa monniera Wettst. (syn. Herpestis monniera L.; Scrophulariaceae) is a commonly used Ayurvedic drug for mental disorders. The standardized extract was reported earlier to have significant anti-oxidant effect, anxiolytic activity and improve memory retention in Alzheimer's disease. Presently, the standardized methanolic extract of Bacopa monniera (bacoside A - 38.0+/-0.9) was investigated for potential antidepressant activity in rodent models of depression. The effect was compared with the standard antidepressant drug imipramine (15 mg/kg, ip). The extract when given in the dose of 20 and 40 mg/kg, orally once daily for 5 days was found to have significant antidepressant activity in forced swim and learned helplessness models of depression and was comparable to that of imipramine.
