Theoretical investigation of cyclooxygenase inhibition property of several non-steroidal anti-inflammatory drugs by density functional theory calculations and molecular docking studies

Understanding the geometry and electronic properties of non-steroidal anti-inflammatory drugs [NSAIDs] and the nature of their interactions with human cyclooxygenase-2 [COX-2] is important in the development and design of novel NSAIDs. In this paper, B3LYP/6-311++G [d,p] level of theory was applied to assess the acidity of NSAIDs in the gas phase. Subsequently, the role of intramolecular hydrogen bond on acidity of these compounds was confirmed by means of natural bond orbital [NBO] and quantum theory of atoms in molecules analyses [QTAIM]. Furthermore, by applying the polarized continuum model [PCM] at the B3LYP/6-311++G[d,p] level, the pK[a] value of NSAIDs in aqueous solution was calculated. The maximum error was found to be less than 0.1 pK[a] unit in comparison with the experimental value. This protocol can be used as a tool to predict pK[a] values of NSAIDs in future studies. In the last step, attempts have been made to generate a functional model of the structure of human COX-2 enzyme by means of homology modeling to gain more insight into the nature of interactions between NSAIDs and the active site of this COX-2 enzyme by docking studies. In addition, a mean binding energy for each drug was estimated based on its ionization ratio

Validated spectrophtometric method for determination of tamsulosin in bulk and pharmaceutical dosage forms

In this study a sensitive, simple and accurate spectrophotometric method was suggested for determination of tamsulosin in bulk powder and pharmaceutical dosage form based on the formation of an ion-pair complex between the drug and bromocresol green in a buffer solution at pH 3.5. The formed yellow color complex was extracted with chloroform and measured at 415 nm. The optimum reaction conditions such as pH, reagent amount, extracting solvent and the stoichiometry of the ion-pair complex were investigated. Under the optimized conditions, the Beer's law was obeyed in the concentration range of 1-160 mg/mL with acceptable correlation coefficient [r2 > 0.9997] and precision [CV < 3%] and accuracy [error < 2%]. The proposed method was successfully used for the determination of tamsulosin in pharmaceutical capsule with no-significant interferences of excipients

Screening of 20 commonly used Iranian traditional medicinal plants against urease

Infection with Helicobacter pylori is the most common cause of stomach and duodenal ulcers. About more than 80% of people are infected with H. pylori in developing countries. H. pylori uses urease enzyme product "ammonia" in order to neutralize and protect itself from the stomach acidic condition and urease enzyme activity has been shown to be essential to the colonization of H. pylori. Inhibitory activity of 20 traditional medicinal plants were examined and evaluated against Jack bean urease activity by Berthelot reaction to obtains natural sources of urease inhibitors. Each herb was extracted using 80% aqueous methanol, then tested its IC[50] value was determined. Eight of the whole 20 studied plants crude extracts were found the most effective with IC[50] values of less than 100 micro g/mL including Laurus nobilis, Zingiber officinale, Nigella sativa, Angelica archangelica, Acorus calamus, Allium sativum,Curcuma longa, and Citrus aurantium extracts, from which most potent urease inhibitory was observed for Zingiber officinale, Laurus nobilis, and Nigella sativa with IC[50] values of 48.54, 48.69 and 59.10 micro g/mL, respectively

Methanolic extract of African mistletoe (Viscum album) improves carbohydrate metabolism and hyperlipidemia in streptozotocin-induced diabetic rats

OBJECTIVE@#To justify the use of African mistletoe (AM) Viscum album (V. album) in folkoric medicine to treat diabetes.@*METHODS@#In one experiment, the fasting blood glucose (FBG) levels of diabetic rats were monitored for 4 h. Diabetic rats were treated with AM at doses of 50 mg/kg (AM1) and 100 mg/kg (AM2), glibenclamide (GB) (positive control) and saline solution (SS). In another experiment, diabetic rats were treated with AM2, GB and SS daily for 3 weeks.@*RESULTS@#AM1 and AM2 elicited significant (P<0.05) hypoglycaemic effects within 4 h of extract administration. AM1 and AM2 decreased the FBG by 41% and 49%, respectively, at 2 h. AM2 was found to lower FBG by 51%, relative to baseline, which was comparable to GB at 3 h. In the second experiment, AM2 and GB significantly (P<0.05) decreased the FBG by 34% and 51%, respectively. This was followed by marked decrease in levels of HbA1C in AM2- and GB- treated diabetic rats. AM2 significantly (P<0.05) decreased the STZ-induced increase in levels of serum triglyceride, urea, lactate dehydrogenase, α-amylase and low-density lipoprotein-cholesterol. Furthermore, diabetic rats treated with AM2 had significantly (P<0.05) elevated high-density lipoprotein-cholesterol. In contrast, STZ administration produced insignificant (P<0.05) effect on the levels of serum creatinine and total bilirubin.@*CONCLUSIONS@#Extract of African mistletoe has anti-diabetic and anti-hyperlipidemic effects in STZ-diabetic rats. AM may find clinical application in the amelioration of diabetes-induced lipid disorders.

preliminary investigation of the jack-bean urease inhibition by randomly selected traditionally used herbal medicine

Helicobacter pylori [H. pylori] infection leads to different clinical and pathological outcomes in humans, including chronic gastritis, peptic ulcer disease and gastric neoplasia and even gastric cancer and its eradiation dependst upon multi-drug therapy. The most effective therapy is still unknown and prompts people to make great efforts to find better and more modern natural or synthetic anti-H. pylori agents. In this report 21 randomly selected herbal methanolic extracts were evaluated for their effect on inhibition of Jack-bean urease using the indophenol method as described by Weatherburn. The inhibition potency was measured by UV spectroscopy technique at 630 nm which attributes to released ammonium. Among these extracts, five showed potent inhibitory activities with IC[50] ranges of 18-35 microg/ mL. These plants are Matricaria disciforme [IC[50]:35 microg/mL], Nasturtium officinale [IC[50]:18 microg/mL], Punica granatum [IC[50]:30 microg/mL], Camelia sinensis [IC[50]:35 microg/mL], Citrus aurantifolia [IC[50]:28 microg/mL]

Effect of dexamethasone on striatal neurotransmissions in the rats subjected to Parkinson's disease animal model

The aim of this study was to evaluate the effects of dexamethasone on striatal dopaminergic, glutamatergic and gamma amino butyric acid [GABA] ergic neurotransmission in normal and parkinsonian rats. Dexamethasone [0.15, 0.30, 0.60 and 0.8 mg/kg] was administered to normal or parkinsonian rats [i.p.] followed by the analysis of the striatal neurotransmitters concentrations. Additionally, the effect of dexamethasone on the damaged Substantian nigra pars compata [SNc] neurons has been investigated. Dexamethasone resulted in decreased level of striatum glutamatergic-GABAergic and enhanced dopaminergic neurotransmission in normal and parkinsonian rats. In addition, acute treatment with dexamethasone did not improve the lesion at all. These findings suggest the new therapeutic mechanism of action for dexamethasone in Parkinson's disease animal model

Comparative study of zataria multiflora and anthemis nobelis extracts with myrthus communis preparation in the treatment of recurrent aphthous stomatitis

Recurrent aphthous stomatitis [RAS] is a prevalent and complicated disorder and its management is directed toward treatment of symptoms. The purpose of this study was to compare the efficacy of three herbal preparations in the management of RAS. One hundred and one out of 115 patients with minor aphthae were selected and randomly divided into four groups. Groups A, B and C received topical preparations of Zataria multiflora, Anthemis nobilis and a 50% [v/v] mixture of Zataria multiflora and Anthemis nobilis respectively. Groups D [positive control] received Myrthus communis [Myrtle, mouth rinse], which reported to be efficient in the management of RAS. The time of pain elimination and the duration of the thorough healing were recorded. Mean time of pain elimination showed significant differences [p<0.01] between groups A [3.00 +/- 1.14 day], C [3.08 +/- 1.84 days] and D [4.30 +/- 2.12 days] with group B [5.20 +/- 3.11 days]. The mean duration of healing also showed significant differences [p<0.03] between groups A [6.00 +/- 2.80 days], C [6.70 +/- 2.70 days] and D [7.60 +/- 3.10 days] with B [8.70 +/- 3.90 days]. No significant differences were observed between groups A and C with group D [positive control]. The result obtained for treatment with Z. multiflora [group A] was similar to that of group C, but better than M. communis [group D]. Findings of this study revealed that Z. multiflora extract showed better effects than M. communis which is reported to be effective in the treatment of RAS. It is concluded that the Z. Multiflora extract is an effective product for the management of minor aphthae

Comparison of sucralfate and hydrocortisone enemas in treatment of active ulcerative proctitis; a double-blind randomized clinical trial

Sucralfate enema has been proposed and investigated in treatment of ulcerative proctitis, but its efficacy is still a matter of debate. Hydrocortisone enema is still an established drug in treatment of ulcerative proctitis. This study was designed to compare the effect of sucralfate enema with hydrocortisone enema. Patients with active sigmoidoscopic and histologic features of ulcerative proctitis were included. All patients had clinical manifestations of proctitis for at least four weeks prior to the study and had negative parasitic stool culture. The total of 25 patients entered the study. They were randomly divided in two groups; group I [n =14] and group II [n = 11] who received sucralfate and hydrocortisone enemas respectively for 4 weeks. Both groups had a significant improvement in clinical features, histologic activity and sigmoidoscopic evaluation in comparison with the baseline. Furthermore there was no significant differences between the two groups concerning mean changes of clinical, sigmoidoscopic, and histologic grading, after treatment. Considering the low cost and minimal adverse effects of sucralfate, and almost equal efficacy in comparison with hydrocortisone enema, its usage can be recommended

Anatomical and phytochemical study of Lilium Ledebourii Boiss, A rare endemic pecies in Iran

Lilium ledebourii [Baker] Boiss.[Liliaceae], locally named "Susan -e Chelcheragh" is a native and rare species grown on the heights of Damash region [ca. 2100 m] in Gilan province, north part of Iran.The microscopic and anatomical features and the composition of oils of flower and corm of this unique plant were studied. The microscopic study has shown the main characteristic elements of leaf, stem, corm and flower of this plant. The composition of essential oils of flower and corm were determined by coupled GC-MS analysis. The yields of oils of flower and corm were 0.71% and 1.65% [v/w] respectively. The major components of flower's oil were isopulegol [55.15%], pentacosane [18.1%], 3-methyltricosane [9.97%], tricosane [5.35%], 2-methylpentacosane [4.35%], docosane [4.28%] and linalool oxide [2.20%]. The components of corm's oil were almost fatty acids. No aromatic volatile compound was found in the corm oil. Primary qualitative phytochemical tests of stem, leaf, corm and flower showed positive results for alkaloid and flavonoid [one plus] in stem and for saponin [4 plus] in corm and [2 plus] in the flower. Tests for tannin in all parts were negative. Further phytochemical and botanical studies on this unique plant is of importance

Determination of ginkgolides A and B in ginkgo biloba leaves by HPLC using activated charcoal

Ginkgo biloba [GB] preparations are now among the leading herbal medicines that exert a broad spectrum of possible clinical applications. Several methods have been reported for quantification of ginkgolides of GB and its pharmaceutical preparations and the HPLC techniques are now considered to be the method of choice. However, most reported HPLC methods are not simple and their work-up procedure are inadequate. The present paper describes a simple and non-expensive method for extraction and determination of ginkgolides A and B in GB leaves and their phytopharmaceuticals. The method is based upon extraction of ginkgolides from aqueous solution by activated charcoal, followed by extraction with Methanol and injection of the Methanolic solution into chromatographic system. Ginkgolides were separated on an ODS column with a mobile phase of water-methanol [67:33 v/v] at a flow rate of 1.0 ml/min and were detected at 220 nm. The mean recoveries of ginkgolide A and B were 97 and 98.4%, respectively. This method is simple and can be used for routine analysis of GB extracts and phytopharmaceuticals preparations