Iranian Journal of Pharmaceutical Sciences

Some studies have demonstrated the potential of herbal drugs for the treatment of various diseases associated with impaired vascular nitric oxide (NO). For diagnosis of the mechanism of these herbal plants, it seems necessary to evaluate the herbal extracts on the Endothelium cell. The aim of the study was to investigate the effect of extract of Trigonella foenum-graecum (T.foenum), Nigella sativa (NS), Allium sativum, and Cannabis sativa on nitric oxide (NO) production by the endothelial cells 3T3 cell line.Ground herbs suspended in water and methanol, were filtered and concentrated under pressure. Remaining contents were dried and obtained powder dissolved in water. The cell line was treated with plant extracts. The clarified supernatant of the culture was used for evaluation of quantitative changes in NO production using Griess test.Among the four extracts, only the group treated with T.foenum extract, significantly increased NO production compared to the control group. Also, NO concentration in other extract group was lower than T.foenum group. This study suggested that the T.foenum extract can significantly increase NO concentration in cell culture and the increase in nitric oxide production is because of the presence of diosgenin T.foenum extracted.

The leaves of Arum conophalloides (Araceae) were used in some west areas of Iran as a dessert. The aerial parts of the herb were collected from Sahneh Mountains, Kermanshah Province, west of Iran and was hydrodistilled by Clevenger-type apparatus. Composition of the essential oil was determined by GC and GC/MS. Totally, 18 components (92% of total essential oil) were identified. The oil contains mainlyΤ-muurolol (%25.4), Ionone (%12.6), nonanal (%17.7), Τ-cadinol (%8.9), Fitone (%7.9), and Methyl palmitate (%7.0). The chemical composition of essential oils from the herbs is being reported for the first time.

Plants from the genus Phyllanthus like Phyllanthus muellerianus have long been used in folk medicine for several ailments including fevers, toothache, dysmenorrhea, anemia, and paralysis. Despite these folkloric uses, there are little scientific data supporting the use of this plant in the management of pain. The purpose of this study is to evaluate the aqueous extract of the aerial parts of Phyllanthus muellerianus and its dominant secondary metabolite, geraniin for potential anti-nociceptive effects. The acetic acid-induced abdominal writhing and formalin–induced nociception tests were used to assess the anti-nociceptive effects of the aqueous extract and geraniin. Morphine and diclofenac were used as standard anti-nociceptive agents. The involvement of opioidergic, adrenergic, muscarinic, adenosinergic, serotonergic and nitric oxide pathways in the anti-nociceptive effects of the extract and geraniin were evaluated by selective antagonism of these pathways. Additionally, the effects of voltage-sensitive Ca2+ channels and ATP-sensitive K+ channels were also assessed by selective blockade with nifedipine and glibenclamide respectively.Oral administration of the aqueous extract (30, 100, 300 mg kg-1) and geraniin (3, 10, 30 mg kg-1) produced significant anti-nociceptive effects in both models of chemical nociception. The anti-nociceptive effects of both the extract and geraniin were not antagonized by L-NAME (10 mg kg-1), yohimbine (3 mg kg-1), atropine (5 mg kg-1), theophylline (5 mg kg-1), ondansetron (0.5 mg kg-1) glibenclamide (8 mg kg-1) or nifedipine (10 mg kg-1). Naloxone (2 mg kg-1), however, reversed the anti-nociceptive effects of only geraniin. In conclusion, the aqueous extract and geraniin obtained from the aerial parts of Phyllanthus muellerianus possess both peripheral and central anti-nociceptive effects in murine models of chemical nociception with the anti-nociceptive action of geraniin involving possibly the opioidergic pathways.

Sesbania grandiflora leaves are extensively used locally since ancient time as in traditional systems. Based on mainly folkloric use, we investigated to know the potential of Sesbania grandiflora leaves extracts through biological works in vivo and in vitro. The ethanolic extract of S. grandiflora leaves was partitioned into ethyl acetate soluble fraction (ESF), petroleum ether soluble fraction (PSF), carbon tetrachloride soluble fraction (CTSF), chloroform soluble fraction (CSF), and aqueous soluble fraction (AQSF). The extracts were evaluated for their thrombolytic, membrane stabilizing, antimicrobial and antidiarrhoeal activities and the results were compared with standard drugs; streptokinase for thrombolytic, acetyl salicylic acid for anti-inflammatory, kanamycin for antimicrobial activities and loperamide against diarrhoea. In thrombolytic investigation, among all partitionates, the ESF showed highest % of clot lysis (59.57%) as compared to (69.23%) and (3.07%) exhibited by the standard streptokinase and water. In case of membrane stabilizing study, ESF also significantly inhibited the haemolysis of human erythrocyte membrane both induced by hypotonic solution (64.30 ± 0.64%) and by heat (57.21 ± 0.69%), respectively as compared to (70.12 ± 26%) and (73.90 ± 0.29%) demonstrated by acetyl salicylic acid. In the antidiarrhoeal assay, the ethanolic extract (EE) inhibited the mean number of defecation by 24.97% and 41.05% at 200 mg/kg and 400 mg/kg body weight, respectively. In antibacterial activity, it was exhibited by the extracts being comparatively more prominent on the gram negative bacteria than the gram positive bacteria. Our study revealed that satisfactory amount of flavonoid and tannin presence showed a significant and positive correlation between total phenolic compound contents with pharmacological activities of S. grandiflora.

Ignoring two main characteristics of the concentration-response data, correlation between observations and presence of outliers, may lead to misleading results. Therefore, the special method should be considered. The present study was designed to apply the outlier robust nonlinear mixed estimation for effects of phenylephrine on rat corpus cavernosum strips. In this study, eight different doses of phenylephrine in eight experimental groups were used. Each group consisted of eight rats. The concentration–response curves to phenylephrine (0.1μM to 300μM) were obtained by the cumulative addition of phenylephrine to the chamber. Because of the existence of an outlier to achieve robust estimations, M-estimation method and Huber function as a dispersion function were used. Cumulative administration of phenylephrine (0.1μM - 300μM) caused concentration-dependent contractions in strips of rat corpus cavernosum (-Log EC50 was 5 ± 0.31, 95% CI= 5.92 to 4.21). The contraction of corpus cavernosum started in the concentration of 0.3 μM and then gradually increased in a dose-dependent manner till it reached a plateau in 100 μM. To consider the clustering feature of concentration-response data, the 4pl regression with a random term has been used. To estimate parameters, because of existence of an outlier in dataset, the robust procedure has been applied. The contraction of corpus cavernosum started in the concentration of 0.3 μM and then gradually increased in a dose-dependent manner till it reached a plateau in 100 μM.

Buthotus schach is one of the dangers scorpions in Iran that belong to the Buthidae family. Toxins are existing in venom scorpion, modulate the ion channels by blocking or opening the pore of the channel or by altering the voltage gating and useful as pharmacological tools. In the present study, we investigated the effects of venom and its obtained fractions by gel filtration on electrophysiological properties of magnocellular supraoptic of hypothalamus by using whole cell patch clamp. Our results shown indicated scorpion crude venom and its fraction effect on voltage gated sodium channels. A significant decrease was revealed in amplitude firing, in venom various concentration and some of the venom fractions. Also, a significant increase was shown in half width and rise time 10% to 90% actions potential firing. Previous evidence revealed a change in electrophysiological properties such as amplitude and rise time 10% to 90%, related to voltage gated sodium channels. Sodium channels toxins existed on scorpion venom caused modulate on sodium channels. In order to access bioactive components, six fractions were collected by gel chromatography techniques. After bath application of fractions, F2 and F3 components show the same effects than venom on electrophysiological properties of magnocellular supraoptic.

6- Mercaptopurine (6-MP) is widely used in clinic as an immunosuppressive for treatment of acute lymphocytic leukemia, Crohn's disease, and ulcerative colitis with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of 6-MP against isolated rat hepatocytes were searched in this study using ―Accelerated Cytotoxicity Mechanism Screening (ACMS)‖ techniques. The concentration of 6-MP required to cause 50% cytotoxicity in 2 hour at 37∘C was detected to be 400 μM. A significant increase in 6-MP induced cytotoxicity and reactive oxygen species (ROS) formation, % mitochondrial membrane potential (MMP), lysosomal damage were observed. The addition of chloroquine (lysosomotropic agent), L-carnitine (inhibitor of membrane permeability transition (MPT), Diphenyleneiodonium (DPI) as an inhibitor of production of superoxide, and H2O2 by mitochondria and Dimethyl sulfoxide (DMSO) as a radical scavenger decreased 6-MP-induced cytotoxicity, ROS formation, collapse of MMP, and lysosomal damage. Results from this study suggest that 6-MP -induced cytotoxicity in isolated rat hepatocytes due to ROS formation, mitochondrial and lysosomal damages that resulted in crosstalk toxicity between mitochondrial and lysosomal damage and finally cell death.

The aim of this investigation was to design and develop nanoemulsions (NEs) as novel ophthalmic delivery systems for brinzolamide (BZD). Phase behavior of quaternary systems composed of triacetin and CapryolTM 90 (selected oils, screened through the solubility studies), various surfactants (namely, Cremophor RH 40, Brij 35, Labrasol and tyloxapol), Transcutol P (as co-surfactant) and water at different surfactant/co-surfactant weight ratios (Rsm) was investigated by the construction of phase diagrams. Formulations were taken from the o/w NE region on the phase diagrams, depending on the extent of NE domain. The spontaneous emulsification method was used to prepare various formulations containing 0.4 wt% of the drug. The nanosized character of NEs was evaluated, the cumulative drug release from of the selected formulations was determined for a period of 6 h, using a dialysis sac technique and the release efficiency for NEs was calculated. The therapeutic efficacy of the selected BZD-loaded NEs to lower the IOP was assessed by the calculation of various pharmacodynamic parameters (ie., Emax, Tmax AUC0-6h). In all cases, the average size of the droplets was found to be less than 40 nm. In vitro release studies indicated that the release efficiency in most of the NEs was higher as compared to the BZD ophthalmic suspension. Comparison of the pharmacodynamics parameters confirmed the equivalent efficacy of most BZD formulations.