IRANIAN JOURNAL OF PHARMACOLOGY AND THERAPEUTICS (IJPT)
Year:2007 | Volume:6 | Issue:2|Papers Count:16

N-Phthaloyl GABA was administrated daily (50mg/Kg body weight-i.p) to Wistar rats for 21 days and cir-cadian rhythms of thiobarbituric acid reactive substances (TBARS) and antioxidants such as reduced glu-tathione (GSH), catalase (CAT) and superoxide dismutase (SOD) were studied under constant light (LL) conditions. Delayed acrophase of TBARS and advanced acrophase of antioxidants (GSH, CAT and SOD) were found in experimental groups as compared with control rats. LL-exposed rats showed increased mesor of TBARS and decreased mesor of antioxidants. Administrations of GABA reversed all the changes to the near normal. Since GABA is being involved in conveying dark information to clock, exoge-nous administration of P-GABA might reduce the photic information received by the clock. The exact mechanism is still unclear and further research is needed to elucidate the mechanism(s) involved.

Effects of Pongamia pinnata, an indigenous plant used in Ayurvedic Medicine in India on the temporal variations of circulatory lipid peroxidation products and antioxidants in ammonium chloride-(AC)-induced hyperammonemic rats has been studied. Experimental rats were divided into control, AC-treated, those treated with AC + ethanolic leaf extract of P. pinnata (PPEt), and PPEt-treated. The characteristics of 24 h rhythms (acrophase, amplitude and mesor) of lipid peroxidation products (thiobarbituric acid reactive sub stances - TBARS) and antioxidants (reduced glutathione (GSH), glutathione peroxidase (GPx), superox ide dismutase (SOD) and catalase (CAT)) were analyzed. Elevated lipid peroxidation (increased mesor of TBARS) associated with decreased activities of antioxidants (decreased mesor of GPx, GSH, SOD and CAT) were found in hyperammonemic rats. Differences were also found in amplitude and 'r' values between the hyperammonemic rats and other experimental groups. These alterations clearly indicate that temporal redox status could be modulated by PPEt during hyperammonemic conditions, which may also play a crucial role in disease development.

The present study was undertaken to investigate the beneficial effects of widely-prescribed lipid lowering drugs, pitavastatin, atorvastatin and simvastatin 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors in cognitive dysfunctions of mice. Intra-cerebroventricular (ICV)-Streptozocin-(STZ)- and high-fat diet (HFD)-induced amnesia served as interoceptive memory models where as, Morris watermaze served as an exteroceptive model in the present study. A total of 13 groups, comprising seven mice in each group were used in this investigation. Day 4 Escape latency time (ELT) recorded during acquisition trials conducted from day 1 to day 4, in water-maze was taken as an index of acquisition, where as mean time spent in target quadrant during retrieval trial on day 5, was taken as an index of retrieval (memory). ICV-STZ-(3 mg kg-1 i.p.), and HFD-treated (for 90 days) mice showed an impairment of acquisition as well as retention on water maze task as reflected by significant increase in ELT on day 4 and decrease in time spent in target quadrant on day 5. Pitavastatin (5 mg kg-1), atorvastatin (5 mg kg-1) and simvastatin (5 mg kg-1) significantly attenuated ICV-STZ- and HFD-induced amnesia. These results highlight the ameliorative role of statins in experimental amnesia with possible involvement of their cholesterol- dependent as well as cholesterol independent actions.

The aim of the present study is to evaluate the effect of ethanolic extract of leaves of Leptadenia reticulate leaves (LELR) against Dalton’s Ascitic Lymphoma (DAL) in Swiss Albino mice. DAL cells were injected intraperitoneally (106 cells) to the mice. Two days after cells injection the animals were treated with 200 mg/kg of LELR for 8 days. Five-fluorouracil (20 mg/kg) was used as reference drug. On day 11, cancer cell number, packed cell volume, decrease in tumour weight of the mice, increase in life span and hematological parameters were evaluated and compared with the same parameters in control. A significant increase in the life span and a decrease in the cancer cell number and tumour weight were noted in the tumour-induced mice after treatment with LELR. The hematological parameters were also normalized by LELR in tumour-induced mice. These observations are suggestive of the protective effect of LELR against Dalton’s Ascitic Lymphoma (DAL).

The blood biochemical parameters were investigated in yak (Bos grunniens L) after intravenous admini stration of 5 mg/kg enrofloxacin. Blood samples were collected from the jugular vein daily for 5 days after the initiation of drug administration. Heparinized blood samples were collected for determination of mean corpuscular volume (MCV), erythrocyte sedimentation rate (ESR), hemoglubin (Hb) estimation and serum was collected for estimation of total protein, albumin, globulin, urea and blood glucose. Results of hematological and blood chemistry profile revealed that enrofloxacin did not change above mentioned parameters significantly. Therefore, the drug might be used safely in the yaks.

Major proportion of intracellular calcium (Ca2+) is achieved through opening of calcium channels present in the plasma membrane which play an important role in regulating neuromuscular coordination and release of neurotransmitters from nerve terminals. Blockade of these calcium channels adversely affects contractile process and release of neurotransmitters in majority of the neuromuscular preparations in vitro. In present study, the cumulative addition of verapamil (10-7-10-3 M) caused marked excitation in amplitude, baseline tension and frequency of spontaneous muscular activity of Gastrothylax crumenifer a rumen amphistome. Diltiazem (10-6-10-3 M) caused a significant and concentration-dependent increase in amplitude and frequency of spontaneous muscular activity of isometrically mounted rumen amphistome. It also caused significant rise in baseline tension at 10-5 to 10-3 M concentrations. Addition of nifedipine (10-7-10-3 M) elicited significant and concentration-dependent rise in amplitude and baseline tension, as compared to control values without significantly effecting frequency of spontaneous contraction

Hepatoprotective efficacy of propolis extract (honeybee hive product, 200 mg/kg, p.o.) was studied against biochemical and histopathological changes induced by carbontetrachloride (CCl4, 0.15 ml/kg, i.p.). Silymarin, a known hepatoprotective drug was used as positive control. Subchronic exposure to CCl4 for 3 weeks (5 days a week) caused sharp elevation in the activity of liver marker enzymes i.e., serum transaminases, alkaline phosphatase and lactate dehydrogenase. CCl4 administration significantly decreased blood glucose level and increased serum proteins. Tissue biochemistry revealed significant reduction in total protein and glycogen contents, activity of alkaline phosphatase and adenosine triphosphatase; and significant increase in acid phosphatase activity in liver and kidney. CCl4-induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances  (TBARS) formed as an index of lipid peroxidation. Hepatorenal glutathione level showed marked depletion, whereas lipid peroxidation was enhanced significantly. A 5-day treatment of propolis extract after toxicant administration reversed alterations in blood and tissue biochemical variables including liver function test and markers of oxidative stress almost as same as in silymarin-treated positive control. Histopathological studies of liver and kidney showed improved cellular architecture after propolis therapy and confirmed its hepatoprotective efficacy as a natural miracle.

Ceftizoxime is a common agent used in prophylaxis of infections after abdominal hysterectomy. Metronidazole could be used instead of ceftizoxime for this matter. To compare these two drugs, in a randomized clinical trial, 30 patients received metronidazole suppositories (1g) and 33 patients received intravenous ceftizoxime (1g) before surgery. There were not any significant demographic (age, weight, parity, hospitalization duration, pre-operation hemoglobin) differences between two groups. Also, the incision type and post-operation bleeding were the same in two groups. The complications after abdominal hysterectomy such as febrile morbidity, urinary tract infections and wound infections were not significantly different between two treatment groups. These results indicate that a single dose metronidazole has the same effect as ceftizoxime in infection prophylaxis of post-hysterectomy infection.

In spite of considerable development in contraceptive technology, search for female antifertility agent in plants continues to be a potential area of investigation. The ethanol extract of Crotalaria juncea seeds which showed promising antiovulatory activity in female albino rats was examined for the isolation of its active fractions. Two fractions were obtained using Thin Layer Chromatography (TLC) of the extract. Both fractions were subjected for testing their anti-ovulation activity and estrous cycle in rats. After preliminary trials, the fraction I (200mg/kg body weights) showed maximum antiovulatory activity when administered orally to the rats for 30 days. Decreased number of healthy follicles (Class I - ClassVI) and corpora lutea and increased number of regressing follicles (Stage IA, Stage IB, Stage IIA, Stage IIB) were observed in the ovary after 30 days treatment. The treatment caused an increase in the cholesterol level and acid/alkaline phosphatase activity and a decrease in protein and glycogen contents of the ovary. Estrous cycle was affected as a significant increase in estrus and metaestrus phases and a decrease in diestrus and proestrus phases in the treated groups during experimental period of 30 days were observed. These results suggest that a fraction of ethanolic extract of crotalaria juncea might be used as a contraceptive in the females.

Concern about the rising prevalence of antibiotics-resistant strains of pathogenic microorganisms has been expressed in the last three decades. However, intensive studies on extracts and biologically-active compounds isolated from medicinal plants have also doubled in the last decade. As a result of paucity of knowledge and folkloric claim on the leaves effectiveness in infectious disease treatments, we aimed to determine the antimicrobial activity of essential oils and lignans present in the crude Sesame radiatum leaves extracts. Ethanolic, Methanolic and Aqueous extracts of Sesame radiatum leaves were studied for their in-vitro antimicrobial activity against both Gram positive and Gram negative micro-organisms and Yeast using Agar diffusion method. The GC-MS phytochemical screening of methanolic extract showed the presence of carboxylic acids and phenolic groups in essential oils especially some of the most potent antioxidants like Sesamol, Sesamolin and Sesamin. Both the methanolic and ethanolic extracts have broad spectrum antimicrobial effect against all the tested micro-organisms except Streptococcus pneumoniae, Candida albicans and Staphylococcus aureus respectively, while the aqueous extract exhibited no inhibitory effect on Staphylococcus aureus and Streptococcus pneumoniae except on Candida albicans. The result confirmed the folkloric claims of the antimicrobial effectiveness of locally consumed Sesame leaves extracts especially against bacterial and common skin infection in many areas of the Country (Nigeria).

The activity of cytochrome p450 isozyme 3A4 (CYP3A4) enzyme and P-glycoprotein (P-gp) is modulated by grapefruit juice and herbal drugs. CYP3A4 is the major phase I drug metabolizing enzyme and P-gp is an ATP-dependent drug efflux pump that regulates the intestinal absorption of orally administered drugs. Honey is commonly consumed as a dietary supplement. However, its influence on human CYP3A4 and P-gp activity is not yet well documented. Therefore, we investigated the influence of a 10-day honey administration on CYP3A4 and P-gp activity in healthy volunteers using carbamazepine and digoxin as their probe drugs respectively. A within-group pharmacokinetic study was done in 12 healthy volunteers. They were administered single oral dose of carbamazepine (200 mg) and digoxin (0.5 mg) before and after 10 days of honey (10 ml twice daily) intake. Blood samples (5ml) were collected at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2, 4, 8, 12, 24, 48 and 72 h after drug administration. Concentration of carbamazepine and digoxin in plasma was measured by HPLC and RIA method respectively. Ten days of honey administration did not significantly alter the C max, Tmax and AUC(0-t) of carbamazepine (probe drug for CYP3A4) and digoxin (probe drug for P-gp). Our results suggest that honey may not significantly modulate the CYP3A4 enzyme and P-glycoprotein activity. The coadministration of honey with drugs may not result in significant drug interactions.

The present study was aimed at elucidating the protective effect of ferulic acid (FA), a natural polyphenol, against nicotine-induced tissue damage, including damages to lung, liver and kidney of experimental rats. Female albino rats of Wistar stain were used for the experimental study. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg body weight (5 days a week, for 22 weeks) and FA was given simultaneously by intragastric intubations for 22 weeks. To establish the most effective protective support, we have used three different doses of FA (10, 20 and 40 mg/kg body weight). The levels of lipid peroxidative indices viz., thiobarbituric acid reactive substances and hydroperoxides, nitric oxide and protein carbonyl content in lung, liver and kidney of nicotine-treated rats increased significantly in nicotine-treated rats when compared to control, which were brought down to near normal in FA-treated groups. The body weight gain of rats and endogenous antioxidant status viz., superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione were found to be significantly decreased in lung, liver and kidney of nicotine-treated group, which were significantly increased in FA-administered groups. The dose 20 mg/kg body weight of FA was found to be more effective than the other two doses. Our data suggest that FA exerts its protective effect by modulating lipid peroxidation and augmenting antioxidant defense system in tissues.

The whole plant of Biophytum petersianum was extracted with a mixture of water- alcohol (1:1) to evaluate its relaxant effect on aorta rings. In isolated Wistar rat tissue, the hydro-ethanolic extract (0.1, 0.25 and 0.5 mg/ml) non-competitively antagonized calcium chloride and high-K+-induced aorta contractions in a concentration-dependent manner. Moreover, the inhibition of noradrenaline–induced contractions in the presence of extract (1 mg/ml) suggests that the extract has an effect on mobilization of intracellular calcium. These results indicate that hypotensive effect of Biophytum petersianum may result from inhibition of calcium influx via both voltage-and receptor-operated calcium channels.

The aim of this study is to determine the effect of the aqueous extract of the leaves of Eucalyptus globules on blood glucose level in fasted rats, and to find a new medical adjunct to anti-diabetes drugs. The aqueous extract of Eucalyptus was administered in various doses (150-400 mg/kg) orally. Blood glucose level was checked 2-6 h after treatment. The study showed that oral administration of the extract (250 mg/ kg) resulted in significant decrease in blood glucose level peaking at 4 hours, in a dose-dependent manner (p<0.0005). This effect declined after 6 hours of feeding in all the doses examined (150 , 250 , 400 mg/kg body weight).These data indicates that Eucalypyus globules represents an effective anti hyperglycemic adjunct for the treatment of diabetes and a potential source for the discovery of new orally active agent in future.

The present work is carried out to study the antioxidant potential of ethanolic extract of Alstonia scholaris Linn. (Apocynaceae) using various in vitro tests including 1, 1-diphenyl-2-picryl-hydrazil (DPPH.) free radical scavenging, metal ion chelating, hydrogen peroxide scavenging, superoxide anion radical scavenging, and ferric thiocyanate reducing ability. Ethanolic extract of Alstonia scholaris had significant (p<0.01) (DPPH.) free radical scavenging (63%), metal ion chelating (74.88%), hydrogen peroxide scavenging (72.28%), superoxide anion radical scavenging (67.66%) and significant (p<0.05) ferric thiocyanate reducing activities. These various antioxidant activities were compared to standard antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxy toluene (BHT), l- ascorbic acid and α-tocopherol. The results indicated that ethanolic extract of Alstonia scholaris Linn. Possessed antioxidant property. The results observed were comparable to antioxidant properties of BHA, BHT, lascorbic acid and α-tocopherol.

Reactive oxygen species (ROS) are generated via normal metabolic processes or as the products of exogenous insults. They are capable of damaging essential biomolecules and accelerating cancer, cardiovascular diseases and neurodegenerative diseases. In the present study, the antioxidant role of Terminalia chebula aqueous extract was evaluated against age-related oxidative stress in heart tissues of young and aged rats. Young and aged rats were treated with T. chebula aqueous extract at a dose of 200mg/kg body weight in 1.5ml sterile water orally for 4 weeks. Control young and aged rats were received sterile water only. In aged rats, the increased content of malondialdehyde (MDA) was observed. The antioxidants, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, reduced glutathione (GSH), vitamin C and E levels were decreased in heart tissues of aged control rats. Administration of T. chebula to aged rats prevented the depletion of SOD, CAT, GPx activities and GSH, vitamin C and E contents. Also, the level of MDA content was decreased in heart tissues. The results of the present study show that T. chebula aqueous extract modulates the activities of antioxidants and lipid peroxidation through the management of oxidant/antioxidant imbalance in rat heart tissues.