Iranian Journal of Pharmaceutical Sciences

Ketotifen is a potent, safe and long acting antihistamine that is effective in treatment of asthma and its use is believed to causes weight gain and drowsiness.
Cyproheptadine, an antihistamine, has anticholinergic and antiserotonergic effects, and causes increases of the appetite and weight gain. In this study the effects of different doses of ketotifen and/or cyproheptadine on the appetite and weight changes in mice is evaluated. Sixty four male mice were divided in 8 groups and received the following drug regimens for 45 days. Control group, normal saline (10 ml/kg, s.c.), three groups of cyproheptadine (5, 10, 20 mg/kg, s.c.), three groups of ketotifen (8, 16, 32 mg/kg, s.c.), and one group cyproheptadine (5 mg/kg, s.c.) combined with ketotifen (8 mg/kg, s.c.). Weight changes caused by above drug regimens were recorded every 2 days and average of food intake was recorded every day for 45 days. The results showed that the high dose of ketotifen (32 mg/kg, s.c.) increased weight, significantly, but its low dose (8 mg/kg, s.c.) decreased weight significantly. Cyproheptadine (5 mg/kg, s.c.) caused significant increase in weight gain and stimulated appetite, but its high dose of (20 mg/kg, s.c.), decreased the appetite and weight. Co-administration of cyproheptadine and ketotifen decreased the appetite, significantly. The results showed that different doses of cyproheptadine and ketotifen have different effects on the appetite and weight gain in mice, and possibly different mechanisms of action.

The pharmacokinetic properties of amoxicillin and clavulanic acid when used alone or in combination may be different and show interaction between these two agents that might decrease the absolute bioavailability of clavulanic acid. In an open, randomized, replicated Latin square under fasting condition, pharmacokinetics of new formulations of amoxicillin/clavulanic acid were compared with a reference formulation after single dose administration in 15 healthy male volunteers. Subjects were given equal molar doses of new suspension formulations of amoxicillin/clavulanic acid (312 mg/5 ml or 156 mg/5 ml) or Augmentin® (312 mg/5 ml) as the reference product. The wash-out period was one week between the administrations of these antibacterial agents. Blood samples were collected exactly before and after drug administration of each of the formulations at different time points up to 6 h. The concentrations of the antibiotics in plasma were measured by validated HPLC methods. Three formulations exhibited a similar mean C max of about 7.5±1.6 mg/l after Tmax of about 75±25 min. for amoxicillin and Cmax of about 2.5±0.6 mg/l after Tmax of about 61±15 min. for clavulanic acid. The AUC0-inf (total area under the curve) for amoxicillin was about 1278±172 g.min/ml and it was about 354±66 g.min/ml for clavulanic acid. There were no significant differences in pharmacokinetic parameters among these formulations. Pharmacokinetic parameters of amoxicillin and clavulanic acid found in this study were similar to previously
published data. The two generic formulations investigated in this study proved to be bioequivalent with brand-name Augmentin® with regard to the pharmacokinetic parameters Cmax, AUC0-t, AUC0-inf and Tmax. Moreover, the parametric confidence intervals (90%) for the ratio of the Cmax, Tmax, AUC0-t, and AUC0-Q values lie between 0.8-1.2 based on log transformed values. We may conclude that the two new formulations are bioequivalent with the reference suspension and could be considered equally effective in medicinal practice. Moreover, there were no interaction in pharmacokinetic parameters between amoxicillin and clavulanic acid. No serious adverse event was observed with the studied drugs.

The goal of this study was to evaluate the effects of quercetin and ACTH injection on prevention of development of morphine tolerance and dependence in mice. In this study different groups of mice received morphine (40 mg/kg, i.p.) plus quercetin (5, 10, 25 mg/kg, ip), ACTH (1, 2.5, 5 IU/mice, i.p.), or combination of quercetin (5 mg/kg) and ACTH (1 IU/mice) once a day for four days. Tolerance was assessed by administration of morphine (9 mg/kg) and using hot plate test on the fifth day. It was found that pretreatment with quercetin or ACTH decreased the degree of tolerance. Co-administration of quercetin and ACTH before morphine did not decrease the tolerance, significantly. From these results it may be concluded that administration of quercetin or ACTH alone could prevent the development of tolerance to the analgesic effects of morphine. These effects may be related to as nitric oxide inhibitor (eNOI) behavior of quercetin and the ability of morphine and their receptors in the control of the secretion of CRH.

Many studies have been performed for treatment or prevention of pulmonary fibrosis. However, no effective treatment has been found yet. The aim of this study
was to investigate the effect of grape seed extract on bleomycin-induced lung fibrosis in rat. Hydroalcoholic extract of grape seed (Vitis vinifera) was prepared
using maceration method. NMRI rats weighing 250-300 g were given single intratracheal instillation of bleomycin (7.5 IU/kg=5 mg/kg) or saline. The experimental
groups were treated with a single dose of bleomycin followed by different doses of oral grape seed extract (100, 200, 400 mg/kg/day) or vitamin E (20 IU/kg) for two weeks, and then the animals were sacrificed and lungs were removed for histology and biochemical investigation. Histopathological examination of bleomycin-treated animals showed that bleomycin caused marked alveolar thickening associated with fibroblasts and myofibroblasts proliferation and collagen production in interstitial tissue leading to pulmonary fibrosis. Administration of grape seed extract reduced fibrotic damages in lung tissue in a dose-dependent manner. The effect of grape seed was comparable to that of vitamin E. Collagen and hydroxyproline contents of lung tissue were determined using spectrophotometric method. Lung weight, hydroxyproline and collagen amounts in bleomycin treated animals were significantly higher than in normal, vitamin E and grape seed treated groups. From this study, it can be concluded that grape seed extract may be able to diminish the fibrogenic effects of bleomycin on lung. This effect of grape seed can be attributed to active ingredients of the plant with anti-oxidant properties.

The search for indigenous natural antidiabetic agents is still ongoing. Securigera securidaca seeds are reputed in folk medicine for their value as an antidiabetic remedy, so the present study was carried out to investigate the hypoglycemic efficacy in both normal and streptozotocine (STZ)-induced diabetic rats. Hydroalcoholic extract of the seeds were administered orally with doses of 200, 400, and 800 mg/kg and intraperitoneally with a dose of 400 mg/kg to separated groups of male Wistar rats. The control and reference groups received oral vehicle (1 ml/kg) and glibenclamide (10 mg/kg, p.o.), respectively. Blood samples were collected at 0, 1, 2, 3, 4, and 8 h after treatment and blood glucose levels were determined using glucose oxidase method. Results indicated that hydroalcoholic extract of S. securidaca was not effective to lower blood glucose level both in normal and diabetic rats. Glibenclamide on the other hand, reduced blood level of glucose in diabetic rats and caused hypoglycemia in normal animals and the effect was time-dependent. It is concluded that seeds of S. securidaca were not effective to reduce blood glucose level in this animal model of diabetes.

Extracts derived from Viscum album have been shown to kill cancer cells in vitro. Some studies have noted that different species of this plant collected from around the world displayed cytotoxic effects in different extents. In the present study, we evaluated the effects of Iranian mistletoe extracts on five cancer cell lines. Plants growing on hornbeam tree (Carpinus betulus) were collected, air-dried and hydroalcoholic (MeOH-H2O with 2% acetic acid) and methanolic extracts were obtained using percolation. Also the plant juice was obtained by pressing. Cytotoxicity of the extracts on a panel of cancer cells (Hela, KB, MDA-MB-468, K562 and MCF- 7) were studied using colorimetric MTT assay. Results showed that plant juice was the most cytotoxic fraction on all cancer cells tested (IC50=0.0316 mg). The IC50 of hydroalcoholic and methanolic extracts were 0.1 and 0.316 mg, respectively. These results suggest that alkaloids and huge compounds like viscotoxin and lectins extracted by press or hydroalcoholic solvents were probably responsible for their cytotoxicity. Results also indicated that Hela cells were more resistant while KB cells were more sensitive to the cytotoxic effects of the extracts. It can be concluded that cytotoxicity of Iranian mistletoe extract on the cell lines tested closely depends on the host tree and extraction methods.

The influenza viruses are major etiologic agents of human respiratory infections, and inflict a sizable health and economic burden. This study examines the
antiinfluenza virus activity of hydroalcoholic extract of olive leaves (OLHE). Olive leaves were collected from gardens around the city of Shiraz, characterized, dried, ground to powder, and its hydroalcoholic extract was prepared. The influenza viruses were isolated from patients and characterized by standard antiinfluenza sera. Virucidal effects of OLHE (10-1 to 103 μg/ml) were examined in pretreatment, treatment and incubation protocols using quantal assay after incubation for 72 h. All experiments were performed three times in quadruplicates. Pretreatment of the cell line with OLHE for one hour followed by the addition of the virus was associated with virucidal effects (1 to 1000 μg/ml). OLHE added one hour after incubation of the virus with cell did not show antiviral effects. OLHE incubated with the virus for one hour, and then added to the cell line did have antiviral activity (1 to 1000 μg/ml). The findings indicate that antiviral activity of OLHE occurred extracellularly, probably by changing the properties of membrane of the virus, rather than that of the cell, to prevent the virus from attaching and penetrating the cell line.

Chemical constituents of the essential oil of flowers of Lavandula officinalis Chaix. growing in Isfahan, Iran, were studied by TLC and gas chromatography-mass
specrtometery (GC-MS) methods. Twelve components which constitute 94.8% of the examined oil were identified. The main constituents were linalool (34.1%), 1,8-
cineole (18.5%), borneol (14.5%), camphor (10.2%), terpinen-4-ol (4.5%), linalyl acetate (3.7%), α-bisabolol (3%), α-terpineol (2.2%) and (Z)-β-farnesene (2.2%).