ABSTRACT
Eugenia jambolana (Jamun) fruit has been reported to give soothing effect on human digestive system. Present study includes the effect of ethanolic extract of seeds of E. jambolana (EJE) against gastric ulcers induced by 2 h cold restraint stress (CRS), aspirin (ASP, 200 mg/kg, 4 h), 95% ethanol (EtOH, 1 ml/200 g, 1 h) and 4 h pylorus ligation (PL) in rats. To ascertain the mechanism of action of EJE, its effect was studied on mucosal offensive acid-pepsin secretion, lipid peroxidation (LPO, free radical) and defensive mucin secretion, cell proliferation, glycoprotein and glutathione (GSH, an antioxidant). Acute and subacute toxicity studies were also conducted for the safety profile of Eugenia jambolana. EJE 200 mg/kg, when administered orally for 10 days in rats was found to reduce the ulcer index in all gastric ulcer models. It tended to decrease acid-pepsin secretion, enhanced mucin and mucosal glycoprotein and decreased cell shedding but had no effect on cell proliferation. It showed antioxidant properties indicated by decrease in LPO and increase in GSH levels in the gastric mucosa of rats. Acute toxicity study indicated LD50 to be more than 10 times (>2000 mg/kg) of the effective ulcer protective dose while subactue toxicity study (>1000 mg/kg) indicated no significant change in the general physiological and haematological parameters, liver and renal function tests. The result of the present study indicates that E. jambolana seed has gastro-protective properties mainly through promotion of mucosal defensive factors and antioxidant status and decreasing lipid peroxidation.
Subject(s)
Anti-Ulcer Agents/administration & dosage , Plant Extracts/administration & dosage , Plants, Medicinal/chemistry , Seeds/chemistry , Stomach Ulcer/drug therapy , Syzygium/chemistry , Administration, Oral , Animals , Anti-Ulcer Agents/adverse effects , Anti-Ulcer Agents/isolation & purification , Aspirin , Cell Proliferation/drug effects , Cold Temperature , Disease Models, Animal , Dose-Response Relationship, Drug , Ethanol/chemistry , Female , Lipid Peroxidation/drug effects , Male , Mice , Plant Extracts/adverse effects , Plant Extracts/isolation & purification , Rats , Rats, Wistar , Stomach Ulcer/chemically induced , Stomach Ulcer/metabolism , Stress, PhysiologicalABSTRACT
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
Various 6-substituted benzothiazolyl-2-thiosemicarbazones were synthesized and screened for anticonvulsant activity in maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. The 6-methyl benzothiazolyl-2-thiosemicarbazones showed anticonvulsant activity in both mice i.p. and rat oral MES screen. The 6-nitro benzothiazolyl thiosemicarbazone derivative 1a emerged as the most promising one with anti-MES activity in mice i.p., rat i.p. and rat p.o. evaluations. All the compounds exhibited lesser or no neurotoxicity compared to phenytoin. The isatinimino derivatives had shown better activity when compared to the benzylidene or acetophenone derivatives.
Subject(s)
Anticonvulsants/toxicity , Seizures/drug therapy , Thiosemicarbazones/toxicity , Animals , Anticonvulsants/chemical synthesis , Anticonvulsants/therapeutic use , Convulsants/toxicity , Drug Evaluation, Preclinical , Male , Mice , Motor Activity/drug effects , Pentylenetetrazole/toxicity , Rats , Rats, Sprague-Dawley , Seizures/chemically induced , Structure-Activity Relationship , Thiosemicarbazones/chemical synthesis , Thiosemicarbazones/therapeutic useABSTRACT
The phenyl (thio) semicarbazide derivatives of phthalimido pharmacophore were synthesized and evaluated for their anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed using intraperitoneal (i.p.), maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ) and subcutaneous strychnine (sc STY)-induced seizure threshold tests in mice. Compound 2c afforded protection in all the three screens. Compounds except 1d, 2a and 2d showed no neurotoxicity up to 300 mg/kg. Compounds 1a, 1b, 2c, 2d, 2g and 2i were found to show oral MES activity. The compounds exhibited CNS depression and behavioral despair side effects, lesser than the conventional antiepileptic drugs.