IRANIAN JOURNAL OF PHARMACOLOGY AND THERAPEUTICS (IJPT)
Year:2008 | Volume:7 | Issue:1|Papers Count:22

gases, such as NO and CO, play important roles both in normal physiology and in diseases. In recent years, interest has been directed towards other naturally-occurring gases, notably H2S, which is produced n body by three enzymes, namely cystathionine beta synthase (CBS), cystathionine gamma lyase (CSE) nd 3-Mercaptopyruvate sulfurtransferase (MST), present in mitochondria and/or cytosols where main ubstrate is L-cysteine. Recent studies have shown that vascular tissues generate measurable amount of 2S. NO is considered as inducer for H2S. H2S has gained importance as a neuromodulator and a asorelaxant factor and as the first endogenous gaseous ATP dependant K+ channel opener. It potenti-tes LTP by enhancing NMDA induced inward current.H2S induces vasorelaxation, inhibits insulin secre-ion and also has a role in inflammation. H2S also appear to have a role in neuroendocrine fuction be-ause it plays an important role in control of the hypothalamus-pitutary-adrenal axis, inhibit stimulated elease of corticotrophin-releasing hormone. H2S has been found to be decreased in patient with Alz-eimer’s disease and higher concentrations are found in patients with Down’s syndrome. It has a role in evelopment of hypertension, suggesting its role in CNS and CVS disorders. H2S it is well known toxic as with the smell of rotten eggs, is now proposed as a physiologically important molecule.

In this study, the binding of amlodipine (a Calcium channel Blocker) and arsenic (metalloid) to bovine serum albumin (BSA) was studied by equilibrium dialysis(ED) method in order to have an insight into their binding chemistry to BSA. Free amlodipine concentration was increased due to addition of arsenic which reduced the binding of the compounds to BSA. However, the free fraction was not increased to a level as it was expected from direct competitive displacement. The free amlodipine concentration was increased according to increasing the amlodipine concentration when only the BSA was present. When the binding sites were blocked by sufficient amount of arsenic, the increment of free concentration of amlodipine was prominent. When no arsenic was added, the free concentration of amlodipine was only 6.6% to 10.3%; whereas this release was 7.65% to 13.65% when arsenic was added with an increasing concentration from 1x10-5M to 12x10-5M. This suggests that in the presence of arsenic, the amlodipine is slowly displaced from its high affinity binding site.

The present study appraised the hepatoprotective activity of aqueous extract of Camellia sinensis leaves and its possible mechanism of action. Liver damage was induced by intraperitoneal administration of car bon tetrachloride/olive oil (50 % v/v, 0.5 ml/kg ) in male Wistar rats (150-220g) once daily for 7 days and the extent of damage was studied by assessing biochemical parameters such as alanine amino trans ferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), total protein and albumin in serum and concentrations of lipid peroxides (LPO), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in liver. The aqueous extract of Camellia sinensis (100 mg and 200 mg/Kg) were ad ministered orally to the animals with hepatotoxicity induced by carbon tetrachloride and its effects on bio chemical parameters were compared with those in animals treated with vitamin E (100 mg/Kg). Histopa thological studies were also done. Camellia sinensis 100 and 200mg/kg results in significant reduction in serum hepatic enzymes and liver lipid peroxide which were increased by carbon tetrachloride. There was significant increase in serum total protein, albumin and liver GSH, SOD and CAT when compared to those in rats treated by carbon tetrachloride. The antioxidant activity of Camellia sinensis (100 and 200mg/Kg) were comparable with the effects of vitamin E (100mg/Kg). Histopathological changes (con gestion of central vein, centrilobular necrosis and sinusoidal congestion) induced by carbon tetrachloride were reduced to a moderate extent in Camellia-sinensis-treated rats. Taking together, Camellia sinensis protectes the liver from carbon-tetrachloride-induced damage. Probable mechanism of its action is its anti-oxidant property.

It is over several decades that ultrasound is used to enhance the transdermal drug delivery (phonphore sis). The mechanism of the enhancement is not fully understood and the ability of ultrasound on the en hancement for some drugs is unclear. The effect of continuous wave 870 KHz ultrasound at intensity of 1 W/cm2 for 15 minutes on transdermal absorption of piroxicam from solution and gel formulations in hair less rat skin was studied. Exposure to ultrasound increased the rate of diffusion from gel and solution of piroxicam to 10 and 3 times higher than that in skins not exposed to ultrasound. We strongly believe that the lower diffusion of piroxicam from the solution is caused by extra-bubbles generated by ultrasound. It can be suggested that cavitation activity and its negative surface charges play a dominant rule in phono phoresis.

Gum of Butea monosperma is used to treat microbial and fungal infections in folk medicine. To validate this use, the in- vitro antimicrobial activity of petroleum ether and alcoholic extract of Butea monosperma gum was evaluated against various microbial strains such as Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Salmonella typhimurium, Pseudomonas aeuriogenosa, Escherichia coli, Candida albicans and Saccharomyces cerevisiae by using disc diffusion method. Minimum inhibitory concentration (MIC) was determined by agar dilution technique. Both extracts showed significant inhibition against reference gram positive bacteria and fungal strains. MIC value of petroleum ether extract against gram positive and fungal strains was 300 mg / ml and that of alcoholic extract was 200 mg / ml. Neither extract showed inhibitions against gram negative bacteria.

Treatment of diseases with natural remedies is gaining popularity because of fewer side effects. A sys temic and scientific investigation of aqueous extract of Euphorbia tirucalli for its antioxidant and hepato protective potential against carbon-tetrachloride-induced hepatic damage in rats was carried out. Antioxi dant property was assessed by using reducing property, superoxide anion scavenging and hydroxyl radi cal scavenging property. Hepato-protective property was assessed by measuring the extent of reversal of enhanced biochemical markers of hepatitis, like sSerum glutamate pyruvate transaminase, serum gluta mate oxaloacetate transaminase, alkaline phosphatase ALP, biluribin, cholesterol, triglycerides and also by estimating the tissue glutathione (GSH) levels and the extent of reduction in the tissue lipid peroxide tion. The aqueous extract has demonstrated dose-dependant invitro antioxidant property (at 20 mg, 40 mg, 60 mg, 80 mg, 100 mg) in all the models of the study. Similarly, aqueous extract of Euphorbia tirucalli at the doses of 125mg/kg and 250mg/kg produced significant hepatoprotective effect by decreasing the serum enzymes, bilirubin, cholesterol, triglycerides and tissue lipid peroxidation, while it significantly increased the levels of tissue GSH in a dose-dependant manner. From the present study, it may be concluded that the test extract possesses antioxidant and hepatoprotective properties. The hepatoprotective property may be attributed to its antioxidant potential.

The antioxidant activity of the melia azedarach was investigated in rats with ethanol-induced erythrocyte damage. Chronic administration of ethanol (20% w/v, 2 g/kg.p.o., daily for four weeks) increased the level of lipid peroxidation (LPO), decreased the activity of superoxide dismutase (SOD) and catalase and reduced the content of glutathione (GSH). The concurrent treatment of ethanol-administered rats with melia azedarach (500mg/kg, p.o.) prevented the ethanol-induced changes and the effect was compared with combination of vitamin E and C. It can, therefore, be suggested that the leaves of melia azedarach posses an erythrocyte protective activity against drug-induced oxidative stress.

Asthma is a chronic inflammatory disorder of the airways. The available treatment options have major limitations owing to low efficacy, associated adverse events and compliance issues. Therefore, the health burden of bronchial asthma is increasing globally at an alarming rate, providing a strong impetus for the development of new therapeutics. Onosma bracteatum (O. bracteatum) is known traditionally in Ayurveda to possess anti-asthmatic activity. Hence, the present investigation was undertaken to evaluate the effect of aerial parts of O. bracteatum on bronchial hyperreactivity by various in vivo and in vitro experimental models. Experimental models studied were total and differential cell estimation in bronchoalveolar lavage fluid (BALF), estimation of histamine release from lungs, in vitro studies on tracheal strip and histopathological studies of egg albumin-sensitized guinea pigs. Treatment with ethanolic extract of O. bracteatum (5 mg/kg, p.o., for 15 days) significantly decreased the total and differential leukocyte count in bronchoalveolar lavage fluid (BALF), and also blocked histamine release from chopped lung tissues of sensitized guinea pigs. Ethanolic extract of O. bracteatum (5 mg/kg, p.o., for 15 days) prevented the potentiation of the responses of histamine and acetylcholine which resulted in a significant decrease in pD2 value of histamine and acetylcholine in guinea pig tracheal strip. Histopathological changes induced by egg albumin were also significantly reduced by the treatment with ethanolic extract of O. bracteatum (5 mg/kg, p.o., for 15 days). These results suggest that O. bracteatum decreases bronchial hyperresponsiveness by decreasing the infiltration of inflammatory mediators like eosinophils, neutrophils in BALF, inhibiting histamine release from lungs of sensitized guinea pigs and by decreasing airway inflammation.

Methanol extract of dried leaves of Momordica charantia Linn (Cucurbitaceae) was investigated for anxiolytic, antidepressant and anti-inflammatory activities in animal models. Anxiolytic activity of methanol extract of dried leaves of Momordica charantia Linn was tested by elevated plus maze test. The results showed a significant anxiolytic effect comparable, with diazepam in all the tested doses. Behavior despair test was used to assess antidepressant activity of methanol extract of M. charantia Linn leaves. The extract treatment showed antidepressant effect by decreasing mobility time of subjected rats to forced swimming dose of 300 mg/kg extract, the swimming behaviour of the animals was comparable to the standard drug imipramine. The anti-inflammatory activity was studied by Carrageenin-induced edema in rats and 60 % oedema inhibitions was observed with 300 mg/kg methanol extract of dried leaves of Momordica charantia Linn, which was nearly equivalent to that of 10 mg/kg of indomethacin.

Morinda citrifolia (Noni) has been traditionally used for bone and wound healing. The present study was carried out to investigate the effect of Morinda citrifolia leaves on experimental wounds and lipid peroxide levels in rats. Effect of aqueous extract of leaves of Morinda citrifolia (200 mg/kg) on excision, resutured incision and dead space wound models were studied. Changes in blood malondialdehyde (MDA) levels and histopathological studies were also carried out. There was a significant increase (p<0.0001) in wound contraction rate, tensile strength, granuloma breaking strength, collagen content, dry granuloma weight (p<0.01) and hydroxyproline content. A significant decrease (p<0.0001) in epithelialisation period and MDA levels in Morinda citrifolia leaf extract treated group were observed when compared to control group. From the results, it may be concluded that the M. citrifolia aqueous leaves enhances the wound healing and possess antioxidant activity.

The unilateral or bilateral lesions of the Substantia nigra pars compacta (SNc) by chemical neurotoxins such as 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are main method for generating the parkinson's animal models. But these neurotoxins are expensive, dangerous, difficult to use and inaccessible conveniently due to the international economical sanctions in Iran. The present study was designed to find a new animal model for Parkinson's disease. Forty eight animals were included in this study and divided into six groups. One group was selected as the control and also two groups as the sham of the SNc lesion. Other groups were subjected to lesion of SNc by 6-OHDA, MPTP and electrical lesion. Using histological studies and Murprogo’s method precision, the effectiveness of the electrical lesion was compared with that of chemical lesions. Our results showed the same extent of lesion was provided with electrical insult and neurotoxins. Due to the technical convenience, low cost, accessibility and the same potency of electrical- and neurotoxins-induced lesion, this model can be used as an alternative method for creating the Parkinson's models.

Resistance to drug such as metronidazole is one the commonest causes of treatment failure while eradicating Helicobacter pylori. Considering the safety of ketoconazole and fluconazole and their inhibitory activity on biosynthesis of fatty acids from cholesterol in cell membrane of H.pylori, the idea of their efficacy against H.pylori is raising. The aim of this study is to evaluate susceptibilities of metronidazole-resistant strains of H.pylori against two antifungal drugs, ketoconazole and fluconazole. In this prospective crosssectional study, 35 isolates of H.pylori from patients with digestive disorders were recruited. Plates were incubated microaerobically. Resistance to metronidazole, minimum inhibitory concentrations (MIC) of ketoconazole and fluconazole for H.pylori isolates were determined by two methods: disc diffusion and agar dilution. Disc diffusion method indicated that metronidazole resistance was seen in 11 strains out of 35. Ketoconazole and fluconazole MICs were 8 and 40mg/lit, respectively, which was confirmed by agar dilution method. Ketoconazole and fluconazole showed an excellent in vitro activity against the H.pylori isolates. However, in vivo activity of these drugs should be evaluated in controlled clinical trials.

A simple, sensitive and economically viable spectrophotometric method for the determination of corticos-teroids (predinsolone {PSL}, dexamethasone {DEX}, prednisone {PS}, betamethasone sodium phosphate {BEP} and hydrocortisone {HYD} has been developed. The method involves the oxidation of corticoster-oids by iron (III) and subsequent complexation of iron (II) with potassium hexacynoferrate (III), forming bluish green colored complex having the maximum absorbance at 780 nm. The method has been applied for the determination of above-mentioned corticosteroids in pharmaceutical formulations. The common excipients do not interfere with the proposed method. A statistical comparison of these results with those of reported method shows good agreement and indicates no significant difference in the precision. The precision of the method developed is implied from the values of standard deviation which are varying from 0.03% to 1.06%. These are remarkable in comparison to the existing visible spectrophotometric studies on steroids. . Recovery was found to be quantitative, and analysis to determine the mass per tablet was obtained with the variation of ±0.25% to 0.85% which implies the success of the method to get rid of the interference from excipients. The studies have shown that the method is fast, reproducible and accurate and can be used in the analysis of marketed formulations. The processed samples were stable up to 2hours minimizing the error in terms of fluctuating absorbance values.

The present work was designed to evaluate the in vitro lipid peroxidation inhibitory and antimicrobial activities of the methanol extract of Phyllanthus niruri (MEPN) (Family: Euphorbiaceous). Lipid peroxidation as measured by the optical density of the prepared solutions (10-320 μg/ml) and then the percent inhibi-ion was calculated. Ascorbate/FeSO4-induced per oxidation was inhibited by standard antioxidants such s L-ascorbic acid, quercetin and MEPN. Moreover, the percent inhibition of the methanol extract was increased in a concentration-dependent manner. IC50 value for the MEPN, L-ascorbic acid and quercetin or lipid per oxidation was found to be 62.5 mg/ml, 41 mg/ml and 19.75 mg/ml respectively. The antimicrobial activity of MEPN was determined by disc diffusion method with various gram-positive and gram-negative microorganisms. The MEPN showed strong antimicrobial activity against Bacillus pummel’s 8241, bacillus cereus, Escherichia Coli 54B and Vibrae Cholera at a concentration of 750 mg/ml/disc. However, its activity against Staphylococcus aureus ML 152 and Vibrae cholera 14035 was less significant. The ntimicrobial activity of the extract was compared with the standard drug, chloramphenicol at a concentra-ion of 10mg/ml/disc. The results obtained in the present investigation clearly suggest that MEPN can be a potential source of natural antioxidant and antimicrobial agent.

Prenatal stress in rats results in structural, physiological and behavioral alterations that persist in adult-hood. Serotonin (5-HT) is an important neurotransmitter known to be involved in these prenatal stress-induced behavioral alterations. The aim of the study was to investigate the effects of interrupted synthesis of 5-HT and immobilization stress during different gestational period on brain serotonergic system of male and female neonatal (postnatal day 15) and adult rats (60 days old). Pregnant rats were subjected to re-straint stress three times daily for 45 min during day 3-14 (G 3-14) or day 14-21 (G 14-21) of pregnancy. Another group of pregnant rats were injected with the inhibitor of 5-HT synthesis, parachlorophenyla-lanine (p-CPA, 400 mg/kg/2ml, single dose, ip) on day 9 or 17 of pregnancy. Following sacrifice, tissue concentrations of 5-HT and its metabolite 5-hydroxy indole acetic acid (5-HIAA) were analyzed in whole brains of neonatal pups and in brainstem, hypothalamus, hippocampus, and frontal cortex of adults. Stress during G 14-21 days showed a significant reduction of 5-HT and 5-HIAA levels in early neonatal development but not later during adulthood. Decreases in whole brain concentrations of 5-HT and 5-HIAA were observed in p-CPA 9 and G 14-21 neonatal pups. The concentration of 5-HT was decreased in fron-tal cortex and hypothalamus of adult rats receiving p-CPA. Prenatal stress affects tissue concentrations of 5-HT and 5-HIAA in neonatal pups and adults and it is possible that such changes may underlie the re-ported behavioral deficits in offspring of stressed female rats. These data also provide evidence that the critical period for prenatal stress-induced changes in brain 5-HT neurons were between days 14-21 (during final trimester of pregnancy).

to determine the anticonvulsant activity of the leaf extract of Croton zambesicus in mice and rats, and in order to verify the traditional use of the plant in the treatment of epilepsy, the pentyleneterazole (PTZ) and he maximal electroshock seizure (MES) models were used for assessing the anticonvulsant effects of the aqueous leaf extract in mice and rats. In the PTZ test, the leaf extract (1000-2000 mg/kg p.o.) produced a significant (p<0.05) increase in the onset of seizures in rats and mice compared with the control group. The aqueous extract (1500 and 2000 mg/kg p.o.) produced some protection (42.9%) in rats, while 000 mg/kg p.o. of that produced significant protection (71.4%) against PTZ-induced convulsion in mice. n the MES test, the aqueous extract (500-1500 mg/kg p.o.) produced a significant (p<0.05) increase in the onset of seizures compared with the control group. At 1500 mg/kg p.o., the extract also produced sig-nificant protection (71.4%) against MES-induced convulsions in mice. The results obtained from this study indicate that the aqueous leaf extract of Croton zambesicus may be beneficial in both absence and tonic clonic seizures.

This study was designed to evaluate the hepatoprotective and antioxidant activity of methanol extract of Lippia nodiflora (MELN) in acute experimental liver injury induced by paracetamol (750mg/kg, b.w). MELN at the doses of 200 and 400mg/kg, p.o was administered for 7 days and biochemical parameters such as serum glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin and total proteins with enzymatic and non-enzymatic antioxidant level were recorded. MELN at both doses prevented the increase in liver weight when compared to hepatotoxin treated control. The higher dose (400 mg/kg) of Lippia nodiflora extract was found to be more effective than the lower dose (200 mg/kg) in paracetamol induced liver damage. MELN produced significant (p<0.001) hepatoprotective effect by decreasing the activity of serum enzymes such as SGOT, SGPT, ALP, bilirubin and lipid peroxidation while it significantly (p<0.001) increased the levels of total proteins, glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in a dose dependent manner. The activity of MELN was compared with standard drug silymarin (25mg/kg), which is a well-known natural anti-hepatotoxic drug and the potency of MELN is more or less the same as that of silymarin. It is con-cluded that the methanol extract of whole plant possesses good hepatoprotective activity probably by its antioxidative potential on hepatocytes.

Diabetes mellitus is a metabolic disorder in the endocrine system. This dreadful disease is found in all parts of the world and is becoming a serious threat to mankind health. There are lots of chemical agents available to control and to treat diabetic patients, but total recovery from diabetes has not been reported up to this date. Alternative to these synthetic agents, plants provide a potential source of hypoglycemic drugs and are widely used in several traditional systems of medicine to prevent diabetes. Several medicinal plants have been investigated for their beneficial use in different types of diabetes. The effects of these plants may delay the development of diabetic complications and correct the metabolic abnormalities using variety of mechanisms. A considerable number of plants were subjected to clinical trials and were found effective. Moreover, during the past few years many phytoconstituents responsible for antidiabetic effects have been isolated from hypoglycaemic plants. This paper focuses mainly on diabetes, plants used as antidiabetics in various traditional medicines, constituents isolated from these plants, various mechanisms through which herbs act against diabetes and few examples of antidiabetic formulations available in the market.

man depends heavily on various plant species for his survival. Indian traditional system of medicine is based on empirical knowledge of the observations and the experience over millennia and more than 5000 plants are used by different ethnic communities in India. During the last few decades there has been an increasing interest in the study of medicinal plants and their traditional use in different parts of India. The present communication constitutes a review on the medicinal properties, ethno medicinal uses and pharmacological activities of five common medicinal plants (Acalypha indica L., Achyranthes aspera L., Adha-toda vasica Medicus, Coriandrum saticum and Centella asiatica) used in Indian traditional medicine. these plants are known to contain various active principles of therapeutic value and to possess biological activity against a number of diseases.

Organ damage after reperfusion of previously viable ischemic tissues is defined as ischemia/reperfusion injury. The pathophysiology of ischemia/reperfusion injury involves cellular effect of ischemia, reactive oxygen species and inflammatory cascade. Protection against ischemia/reperfusion injury may be achieved by preconditioning or postconditioning. In this review, we discuss basic mechanisms involved in the pathophysiology of ischemia/reperfusion injury. Moreover, the pharmacology of preconditioning and postconditioning is delineated.

The aim of this study was to evaluate antitumour activity of the roots of Hibiscus tiliaceus Linn. against Dalton’s Ascitic Lymphoma (DAL) in Swiss albino mice. A significant enhancement of mean survival time (MST) of H. tiliaceus treated tumour bearing mice was found with respect to control group. H. tiliaceus treatment was found to enhance peritoneal cell counts. When these H. tiliaceus treated animals under-went intraperitoneal (i.p.) inoculation with DAL cells, tumour cell growth was found to be inhibited. The results indicated that, H. tiliaceus treated group were able to reverse the hematological parameters, pro-tein and Packed Cell Volume (PCV) consequent to tumour inoculation with in fourteen days after the transplantation.

Individual approaches to the diagnosis and management of penicillin allergy are practiced by clinicians. This cross-sectional survey of physicians was aimed at exploring their ways of dealing with diagnosis and management of penicillin G allergy. Of the 235 respondents, 63% believed patients’ self-reported history of penicillin allergy and avoided using penicillin G; 97% do so for patients whose allergic status was con-firmed with positive skin test results. Researchers insist on skin testing for patients claiming penicillin allergy and for those whose allergic status was confirmed with positive skin test results, before considering antibiotic substitution, in an attempt to minimize the development of multi drug resistant pathogens. Un-due concern about penicillin allergy may negatively influence the therapeutic outcome of rheumatic fever and syphilis. Repeated skin testing is recommended before each subsequent course of penicillin G, even in patients who have tolerated it before which was practiced by an appreciable number (89%) of our re-spondents. Epi cutaneous followed by intra dermal routes with major and minor determinants have been recommended for penicillin G skin testing. 100% of our respondents skin tested by intra dermal route alone, using penicillin G and its repository preparations before injecting the respective full dose preparations. Legal problems arising from serious clinical outcomes of penicillin allergy may pose a threat to the physician of losing self esteem in the society forcing him to be overcautious with its use. Educating both the public and health care providers is necessary in this regard.