Iranian Journal of Pharmacology and Therapeutics
Volume:5 Issue: 1, 2006

The worldwide incidence, morbidity and mortality of asthma are increasing dramatically. It is one of the most common disorders encountered in clinical medicine in both children and adults. It affects approximately 5% of the adult population in the western world and its reported incidence is increasing vigorously in many developed nations. A network of a novel mediator known as ‘pleiotropic cytokines’ regulates the intermittent airway inflammation, bronchial smooth muscle hyperreactivity and bronchoconstricion underlying asthma. Preclinical and clinical data suggest that, the pathophysiological features of asthma are thought to result from the aberrant expansion of cytokines and chemokines. Cytokines are small extracellular signaling protein produced by different cells and possesses a wide spectrum of biological activities due to their redundancy and pleiotropic properties. They are critical to the functioning of both innate and adaptive immune responses. Cytokines and their receptors exhibit very high affinity for each other. Because of this high affinity, picomolar concentrations of cytokines can mediate a biological effect. The major groups of cytokines are lymphokines, proinflammatory cytokine, inhibitory cytokines and growth factors. Pathophysiology of asthma is still poorly understood and its cause remains unknown. On this basis, this review will concentrate on the synthesis, release and functional role of each cytokine in the pathophysiology of asthma.

Nootropic acitivity of calyces of Hibiscus sabdariffa Linn. was studied in mice. Elevated plus maze and passive avoidance paradigm were employed to evaluate learning and memory parameters. Scopolamine (0.4 mg/kg, i.p.) was used to induce amnesia in mice. The aqueous extracts of calyces of Hibiscus sabdariffa (HS-100 and 200 mg/kg, p.o.) significantly attenuated amnestic deficits induced by scopolamine (0.4 mg/kg, i.p.) and natural aging. HS (100 and 200 mg/kg) decreased the transfer latencies and increased step down latencies significantly in the aged mice and scopolamine induced amnesic mice as compared with Piracetam (200 mg/kg, i.p.). To delineate the possible mechanism through which H. sabdariffa elicits the anti-amnesic effects, we studied its influence on central cholinergic activity by estimating the whole brain acetylcholinesterase activity. H. sabdariffa significantly decreased acetyl cholinesterase activity in mice. The results indicate that, the aqueous extract of calyces of H. sabdariffa might prove to be a useful memory restorative agent in the treatment of dementia seen in elderly. The underlying mechanism of action can be attributed to its anti acetylcholinesterase property.

The aqueous extract of leaf of Aegle marmelos (Bael) at the dose 50 mg/100 g body weight resulted a significant diminution in the activities of testicular key steroidogenic enzymes along with low levels of plasma testosterone and relative wet weights of sex organs in respect to control without any significant alteration in general body growth. Germ cells numbers in different generation at stage VII of seminiferous epithelial cell cycle were diminished significantly after the treatment of the above extract. The above mentioned dose did not exhibit any toxicity in liver and kidney. Therefore, it may be predicted that the aqueous extract of leaf of Aegle marmelos has a potent antitesticular effect at a specific dose.

Herbal medicine development against the non-communicable disease like diabetes is one of the thrust area of research in the field of global medicine. Here we have studied the separate and composite methanolic extract of seed of Eugenia jambolana and root of Musa paradisiaca for the management of streptozotocin-induced diabetes mellitus. We have measured the fasting blood glucose level and glycogen content in liver as well as in skeletal muscle. Hyperglycemia and hyperlipidemia are two important characters of diabetes mellitus. Hyperlipidemia developed in these experimental diabetic rats was assessed by quantification of total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) and triglyceride (TG) in serum. We noted that after treatment of methanolic extract of above plant parts in separate as well as in composite manner in streptozotocin-induced diabetic rat resulted a significant remedial effect on blood glucose level as well as in the quantity of liver and skeletal muscle glycogen. Serum insulin level that was diminished in streptozotocin-induced diabetic state was recovered significantly after the co-administration of extract of above plant parts. Serum lipid profile was also corrected significantly in streptozotocin induced diabetic rats after the composite extract co-administration. The recovery in all the above-mentioned parameters was more effective when we use the composite extract in comparison to the separate extract of above plant parts. None of the extract has any metabolic toxicity induction in general. So the composite extracts of above plant parts have some remedial effects against streptozotocin-induced diabetic state.

The present study was carried out to evaluate the antimicrobial and antioxidant activities of methanol extract of Careya arborea (MECA) stem barks (Myrtaceae) in various in-vitro systems. Antimicrobial activities of MECA were carried out using disc diffusion methods with Gram positive and Gram negative bacteria and some fungal species. MECA showed broad-spectrum antimicrobial activity against all tested microorganisms. Antioxidant and free radical scavenging activities of MECA was assessed by using 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH), superoxide anion radical, nitric oxide radical and hydroxyl radical scavenging assays. The antioxidant activity of MECA increased in a concentration dependent manner. In DPPH radical scavenging assay the IC50 value of the extract was found to be 132.25 mg/ml. MECA was found to inhibit the nitric oxide radicals generated from sodium nitroprusside. The IC50 value was found to be 72.54 mg/ml, whereas the IC50 value of curcumin was 20.4 mg/ml. Moreover, the MECA was found to scavenge the superoxide generated by phenazine methosulphate (PMS) / nicotinamide adenine dinucleotide (NADH)- nitroblue tetrazolium (NBT) system. MECA was also found to inhibit the hydroxyl radical generated by Fenton''s reaction, where the IC50 value of MECA was found to be more than 1000 mg/ml and for catechin the IC50 value was found to be 5 mg/ml. The results obtained in the present study indicate that the MECA can be a potential source of natural antimicrobial and antioxidant agents.

Falcaria vulgaris is a member of Umbelliferae family and is used for treatment of stomach disorders in the folk medicines of the west of Iran. This study was designed to evaluate the gastroprotective effect of F. vulgaris extract on ethanol (%50) induced gastric ulcers in rat. Thirty five young white male rats were divided to five groups (7rats/ group).Three case groups received plant extract (50, 100, 150 mg/kg) and control negative and positive groups received distilled water and ranitidine respectively. Animals were killed and their stomachs were removed and macroscopic and microscopic ulcer index were determined. Data were subjected to one way ANOVA followed by Dennett''s t-test. The results indicated that hydro alcoholic extract of F. vulgaris (50,100,150 mg/kg) significantly decreased the ulcer index (p < 0.05) and these doses of extract exerted macroscopic curative ratios of 66.9%, 76.9% and 80.25% respectively. F. vulgaris extract has gastroprotective effect on ethanol-induced ulcer in rat.

The chloroform extract of Andrographis paniculata roots was tested for its antihyperglycemic activity in alloxan induced diabetic rats using chronic and acute studies. The blood glucose lowering activity was determined after oral administration at doses of 50, 100 and 150 mg/kg body weight in acute study. Where as in case of chronic study blood glucose, protein, albumin and creatinine levels were estimated after 4 weeks of treatment at the dose of 300 mg/kg. Significant reductions in blood glucose levels were observed in both acute and chronic studies. The extract significanly inhibited the induction of albuminuria, proteinemia and uremia. The present study clearly indicated a significant antidiabetic activity with the chloroform extract of A. paniculata roots and supports the traditional usage of the plant by Ayurvedic physicians for the control of diabetes. Also the extract is useful in preventing the incidence of long-term complication, diabetic nephropathy.

Triphala'' is an age old commonly used Ayurvedic powdered preparation in Indian systems of medicine. This well known formulation is made by combining Terminalia chebula, Terminalia belarica and Emblica officinalis, in equal proportions based on the observation of Ayurvedic Formulary of India (AFI). The formulation is prescribed in the first line treatment of many aliments and is used as laxative, detoxifying agent and rejuvenator. To establish its clinical validity the present work was undertaken to evaluate its therapeutic potentials and adverse effects. The Triphala formulation was standardized by HPTLC (High Performance Thin Layer Chromatography), using Gallic acid as a marker and was subjected to clinical studies. After proper screening 160 patients of age between 16 - 52 years were selected for 45 days clinical study. The effectiveness of trial drugs were judged on the basis of the subjective and objective parameters. It was observed that the amount, frequency and consistency of stool were improved in Triphala treated group. The changes of odor, mucous, flatulence, belching and abdominal pain where also taken into account. The well being was assessed on the basis of the parameters like concentration, appetite, thirst, sleep, hyperacidity in arbitrary scoring system. Triphala was found to have good laxative property, help in management of hyperacidity and also improve appetite. No adverse effect was observed in the treated group when compared to normal patients. Triphala can be used effectively in the treatment of constipation and other gastric problems.

The present investigation was carried out to determine the efficacy and safety of Lepidium sativum (L. sativum) (Garden Cress, Fam: Cruciferae) in patients of bronchial asthma. L. sativum seed powder was given at a dose of 1 gm thrice a day orally to 30 patients of either sex in the range of 15-80 years with mild to moderate bronchial asthma without any concurrent medication. The respiratory functions (FVC, FEV1, FEF25-75% and MVV) were assessed using a spirometer prior to and after 4 weeks of treatment. Efficacy of the drug in improving clinical symptoms and severity of asthmatic attacks was evaluated by interviewing the patient and by physical and hematological examination at the end of the treatment. 4 weeks treatment with the drug showed statistically significant improvement in various parameters of pulmonary functions in asthmatic subjects. Also significant improvement was observed in clinical symptoms and severity of asthmatic attacks. None of the patient showed any adverse effect with L. sativum. The results of the present study suggest the usefulness of L. sativum seeds in patients with bronchial asthma.

The present investigation was undertaken to study the benefical effects of Coenzyme Q10 in streptozotocin (STZ)-induced type I diabetic rats. STZ-diabetes produced a significant increase in fasting glucose levels that was associated with decrease in serum insulin levels. STZ also produced hypercholesterolemia, hypertriglyceredemia, increase in lipid peroxidation and decrease in high density lipoprotein (HDL) levels. Treatment with Coenzyme Q10 produced a significant decrease in fasting glucose levels without affecting insulin levels. Coenzyme Q10 was also found to decrease significantly AUCglucose and no significant change in AUCinsulin values in STZ-diabetic rats. Treatment with Coenzyme Q10 also caused decrease in serum cholesterol, serum triglyceride levels and an increase in HDL levels. Coenzyme Q10 treatment also reduced lipid peroxidation in diabetic rats. The elevated blood pressure in diabetic rats was also lowered. Our data suggest that Coenzyme Q10 has beneficial effects in diabetes induced complications.

The aim of the present work was to develop a simple and rapid method for determination of theophylline (THP) and guaifenesin (GU) in syrup without involving any preparation operations like separation or masking. A HPLC and two spectrophotometric methods based on the derivation of the main spectra are described for the determination of THP and GU in combined pharmaceutical syrup form. The first derivative method can be applied only for THP and depends on the use of the second-order derivative spectra of the absorption spectrum of binary mixtures. The second derivative amplitudes at 291.6 nm were selected for the assay of THP. The second method is based on the use of the first derivative of the ratio-spectra obtained by dividing the absorption spectrum of binary mixtures by a standard spectrum of one of the compounds. The first derivative amplitudes at 286.3 and 231.7 nm were selected for the assay of THP and GU, respectively. Calibration curves were established at 5-40 mg/mL for GU and 20-70 mg/mL for THP. The proposed method was accurate with at least 99.5% recovery values and precise with coefficient of variation (CV) of 1.7% and 5.3% for THP and GU, respectively. Also a modified USP HPLC method was applied for determination of these two compounds in syrup. The results obtained by HPLC and derivative spectrophotometric methods applied to the same samples were compared together with selecting HPLC as a reference method for the developed spectrophotometric methods. The HPLC method was based on isocratic reversed-phase liquid chromatography by using C18 column with methanol: water (40:60, v/v) (pH 3.0) as mobile phase. Caffeine was used as an internal standard (IS) and the substances were detected at 280 nm. Calibration solutions used in HPLC were in the same range as spectrophotometric method and the detection and quantitation limits were found to be 6.9 and 20.1 mg/mL for THP and 3.7 and 11.1 mg/mL for GU, respectively. The proposed methods were successfully applied to the determination of the drugs in synthetic mixtures and commercially available syrup with a high recovery, good accuracy and precision.

Hyperphosphatemia has an important role in the development of secondary hyperparathyroidism and bone disease in patients with end-stage renal disease (ESRD). The most effective method of phosphate elimination lies with phosphate binders, the agent that more commonly used, calcium carbonate, is not an ideal binding agent. In this regard, calcium acetate has been reported to have more or at least a similar phosphate binding efficacy and less pronounced hypercalcemic effect. However, this subject is still a matter of controversy. This study was designed to compare the efficiency of these salts. Preparation of calcium acetate and comparison of the phosphate binding power and hypercalcemic effect of calcium acetate with that of calcium carbonate in hemodialysis patients. Thirty stable ESRD patients undergoing regular hemodialysis for mean 4.23 years (SD 3.63) were studied. Half of the patients were started on calcium acetate for a month. Then, after two weeks wash out period, they received calcium carbonate for a month. The others followed an inverse protocol. Results. 24 patients completed the study. A significant decrease in plasma phosphate levels was only observed after treatment with calcium acetate [6.65 mg/dL (SD 1.38) vs. 5.83 mg/dL (SD 1.55) p < 0.05]. Calcium acetate may be a better choice in handling of hyperphophatemia in ESRD patients and when calcium acetate is used, control of hyperphophatemia can be better achieved with a lower risk of hypercalcemia.

Meloxicam is a non steroidal anti-inflammatory drug, used in the treatment of rheumatoid arthritis and oestoarthritis. It is practically insoluble in water leading to poor dissolution, variations in bioavailability and gastric irritation on oral administration. In order to modulate its gastric side effect and to increase aqueous solubility, physical mixture and solid dispersion of the drug were prepared with polyethylene glycol 6000 and polyvinyl pyrrolidine. The analgesic, anti-inflammatory and ulcerogenic effects were assessed for physical mixture and solid dispersion in comparison with meloxicarn alone. The results indicate that both physical mixture and solid dispersion possess better analgesic and anti-inflammatory properties with less ulcerogenic potential as compared to pure meloxicam.

Tamoxifen is the drug of choice in the treatment of breast cancer. Recent reports show an increased incidence of endometrial carcinoma in patients taking tamoxifen. In this article, we report a case of malignant mixed mullerian tumor after tamoxifen use.

The importance of oxidase-positive, nonfermentative, Gram-negative bacilli in a variety of pathological processes is becoming increasingly important. Oligella urethralis is an organism which is normally isolated as a commensal from the genitourinary tract. We have described one case of urinary tract infection caused by this organism. This isolated organism is found to be resistant to quinolones, while relatively sensitive to a wide variety of antibiotics. These findings clearly indicate that this organism may be an opportunistic pathogen and that extensive application of quinolones may provide a selective pressure for the emergence of resistance. We believe that this is the firs report of isolation and quinolone resistance in Oligella in Iran.