DARU, Journal of Pharmaceutical Sciences
Volume:15 Issue: 4, Winter 2007

Abstract: Stachys schtschegleevii Sosn. (commonly known as "Poulk" and "Sonbeleh Arasbarani") and Stachys inflate Benth. ("Sonbeleh Arghavani") are most widely used for medicinal purposes. Stachys schtschegleevii Sosn.(Lamiaceae) is widespread in North West of Iran and have been used traditionally to treat infections, asthma, rheumatic and other inflammatory disorders. In the present studies the anti-inflammatory activity of hydro-alcoholic extracts of both flowering and sterile tops of S. schtschegleevii were investigated. The methanolic extract of the sterile aerial parts was partitionated between chloroform, ethyl acetate and n-butanol. The column chromatography (CC) on silica gel was used to fractionate the ethyl acetate extract and the anti-inflammatory effects of each main fraction were evaluated by carrageenan-induced rat paw oedema assay. The reversed-phase preparative HPLC was used to isolate compounds from the active fractions and their structure (1-3) were elucidated by spectroscopic means. The ethyl acetate portion was fractionated into 11 major fractions. the most prominent anti-inflammatory effect was observed with fractions 8 to 10 of the ethyl acetate portion. Fraction 8 abolished considerably the mean maximal responses of inflammation from 87.003.5% in control to 61.107.2% (p<0.001) and 62.103.6% (p<0.001) in 15 and 30 mg/kg fraction-treated groups, respectively. Preparative-HPLC analyses of fractions 5 and 8-10 led to the isolation and identification of three major compounds, chrysoeriol 7-O-β-[6"-(p- coumaroyl)]-glucoside (1), apigenin 7-O-β-[6"-(p- coumaroyl)]-glucoside (2), and acteoside (3). It seems that caffeic acid derivatives such as acteoside may be implicated in anti-inflammatory effect of Stachys schetschegleevii Sosn.

Dark neurons are generated in vivo as an acute or delayed consequence of several pathological situations and lesions. The present study was designed to evaluate whether inflammatory pain induces formation of dark neurons in the dorsal horn of rat spinal cord. Since NO and JNK pathway are involved in the mechanisms of pain generation and degenerative neuronal alteration, their roles were also considered. Histological procedures were employed for detection of dark neurons following induction of inflammatory pain. On the fifth day; following daily injections of 5% formalin, numbers of dark neurons increased significantly. Acute and chronic administration of 1% or 2.5% formalin did not induce any remarkable neuronal alteration in the dorsal horn of lumbar spinal cord. Daily intrathecal administration of quercetin (inhibitor of JNK pathway) 100µg/rat, or PTIO (NO scavenger) 30µg/rat before injection of 5% formalin, led to a reliable reduction of formation of dark neurons. Results indicate that induction of inflammatory pain for longer periods may result in a serious central disorder, and administration of neutralizers or inhibitors of NO and JNK may exert neuroprotective effects

Because of confusion to gastric cancers arising at the gastro-esophageal junction, true esophageal adenocarcinoma was thought to be unusual. Esophageal adenocarcinoma (EAC) is becoming more common worldwide with increasing incidences.

Overexpression of decoy receptor (DcR) 3 protein, - a recently discovered member of the tumor necrosis factor receptor super-family, was examined in 60 esophagogastrectomy specimens containing areas of Barrett esophagus (n = 27), low-grade dysplasia (n = 40), high-grade dysplasia or carcinoma in situ (n = 33), and esophageal adenocarcinoma (EAC; n = 42) with immunohistochemical analysis. All cases were retrieved from the pathology files of Damanhour national medical institute hospital.

The results of this study revealed more overexpression of DcR3 in high-grade dysplasia or carcinoma in situ and EAC than in benign esophageal mucosa (both P < 0.0001), Barrett esophagus (both P < 0.001), and low-grade dysplasia (P < 0.01 and P = 0.033, respectively) significantly. Low-grade dysplasia also showed significant overexpression of DcR3 compared with benign esophagus (P < 0.05) but not with Barrett esophagus (P > 0.05). DcR3 overexpression seems negatively correlated with the grade of EAC.

Results of this study suggest that overexpression of DcR3 protein might be an aid in the diagnosis of high-grade dysplasia or carcinoma in situ and EAC and also might serve as a potential therapeutic target.

Abstract: Background and the purpose of the study: Angiotensin II (Ang II) other than acting as a vasopressor hormone has pro-inflammatory properties. Since angiotensin-converting enzyme)ACE), is present in inflamed synovial membrane, in this study the effect of enalapril in modulation of inflammation and cytokine production in experimental induced chronic arthritis was investigated. Chronic joint inflammation was induced by antigen-induced arthritis method in rabbits and enalapril was given orally (7.5mg/kg/day) two weeks before (prophylaxis group) or two weeks after (treatment group) induction. Serum of arthritis''s ACE activity was measured by HPLC, pro-inflammatory cytokines, IL-1β & IL-8 were measured in synovial fluid, and histology of knee joints was assessed in both groups. Results revealed that enalapril reduced ACE activity in serum significantly (P=0.004), had no effect on IL-8 of synovial fluid and reduced the IL-1β production (P<0.05). Histological results revealed a significant reduction in villous hyperplasia and pannus formation (P<0.05 in both groups). While in prophylaxis group no bone erosion was observed and the cartilage was either intact or slightly invaded by synoviocytes, in non-treated group the cartilage was mostly invaded. Enalapril reduces production of pro-inflammatory cytokine IL-1β and severity of joint damage in chronic arthritis and may have therapeutics benefits in inflammatory joint diseases

Abstract: In Iranian ancient medical books, the therapeutic effects of Satureja hortensis on respiratory diseases have been reported. In order to verify these reports, the relaxant effect of aqueous-ethanolic extract of Satureja hortensis on guinea pig trachea was examined. The relaxant effects of 6 cumulative concentrations of extract (0.15, 0.3, 0.45, 0.6, 0.75 and 0.9 g %) in comparison with saline and 4 cumulative concentrations of theophylline (0.15, 0.3, 0.45, and 0.6 mM) by their effects on precontracted tracheal chains of guinea pig by 10 µM methacholine (group 1) or 60 mM KCl in two different conditions including: non-incubated tissues (group 2) and incubated tissues with 1 µM propranolol, 1 µM chlorpheniramine and 1 µM atropine (group 3, for each group n=6) were examined. In group 1, the extract and theophylline showed concentration dependent relaxant effects compared to that of saline (p<0.05 to p<0.001). In group 2, three last concentrations of theophylline and four higher concentrations of extract showed significant relaxant effects compared to that of saline (p<0.05 to p<0.001). The effects of four lower concentrations of extracts in groups 1 and 2 were significantly lower than those of theophylline (p<0.05 p<0.001). In group 3, the extract did not show any significant relaxant effect. There were significant correlations between the relaxant effects and concentrations of extract and theophylline in groups 1 and 2 (p<0.001 for all cases). These results showed a potent relaxant effect of Satureja hortensis on guinea pigs trachea which was comparable to that of theophylline.

Background and the purpose of the study: The rhizomes of Drynaria quercifolia have antibacterial properties and are used traditionally for the treatment of cough, tuberculosis and typhoid fever. In the present study an attempt was made to isolate microbiologically active constituents from the rhizome of D. quercifolia and to determine their antibacterial and toxicological effects. Bioassay-guided investigations was employed for isolation of the active constitute of the rhizome of Drynaria quercifolia J. Smith. Disc diffusion technique and serial tube dilution technique were used to determine in vitro antibacterial activity and MIC, respectively. Sub-acute toxicities (body weight, hematological, biochemical and histopathological) were studied in albino mice upon 14 days treatment. Result and major Bioassay-guided investigations led to isolation of 3,4-dihydroxybenzoic acid whose in vitro antibacterial activity, minimum inhibitory concentration (MIC) and sub-acute toxicities were studied. The 3,4-dihydroxybenzoic acid showed significant antibacterial activity against four Gram-positive and six Gram-negative bacteria. The MIC values of 3,4-dihydroxybenzoic acid against these bacteria ranged from 8 to 64 µg/mL. In sub-acute toxicities studies 3,4-dihydroxybenzoic acid showed no significant effect in comparison to that of control group. In addition, acetyl lupeol was isolated from rhizome of this plant whose in vitro antibacterial activity was insignificant. Isolation of 3,4-dihydroxybenzoic acid and acetyl lupeol are the first report from this plant.

Abstract: Gabapentin has been recently considered as an analgesic in neurpathic pain through spinal site of action. In addition co-administration of low dose of morphine with gabapentin, is proposed not only to reduce side effects, tolerance, and dependency of morphine but also has some analgesic effects. In this study, the analgesic effect of intracerebroventricular (ICV) gabapentin and its effect on morphine antinociception were investigated in tail-flick test. An intraventricular cannula was surgically inserted into ventricle space of rat brain. The latency time was measured after microinjection of 100,300,600 and 1000 µg of gabapentin or normal saline (sham). After determination of subanalgesic dose of gabapentin (300µg), the combinational groups received subanalgesic and low dose of morphine (2 and 7 mg /kg) intraperitoneally, thirty minutes prior to gabapentin administration. Time response curve and Area Under the Curve (AUC), as antinociceptive index, were compared among the groups. Intraventricular gabapentin showed analgesic effects at 600 µg (ICV). The combination of subanalgesic doses of gabapentin (300 µg ICV) and morphine (2 mg /kg i.p) increased significantly time-response curve and AUC compared to other groups. In addition, the analgesic response following co-administration of gabapentin (300 µg ICV) and analgesic dose of morphine was increased significantly compared to the sham and gabapentin group. The results demonstrated that intraventricular gabapentin has analgesic effect in transient model of pain and enhances morphine antinociception through cerebral site of action.

Background and the purpose of the study: In continuation of our research program for new antitubercular agents, some hybrid compounds containing a 5-nitrohetrocyle and 1,3,4-thiadiazole ring havae been synthesized and their antituberculosis activity have been evaluated. QSAR studies were subsequently used to find the structural requirements for activity of this series of compounds. 2-(nitroaryl)-5-(nitrobenzylsulfinyl and sulfonyl)-1,3,4-thiadiazole derivatives, have been synthesized and evaluated against Mycobacterium tuberculosis H37Rv (ATCC27294) in BACTEC 12B medium using a broth micro dilution assay. The minimum inhibitory concentration (MIC) was determined for compounds that demonstrated ≥ 90% growth inhibition in the primary screening. A QSAR study was performed on percentage of inhibition of the corresponding compounds using multiple linear regressions. The predictive ability of the obtained model was verified by cross-validation and chance correlation. The final model showed that the calculated and predicted activities are in good agreement with their observed antituberculosis activities (R (cross-validation) = 0.87). Results and major Results of the biological assay showed that three compounds (8c, 9a, 10b) were antimycobacterial agents showing MIC value of 6.25 µg.ml-1.It was also concluded that all three active compounds belong to nitroimidazoles and sulfonyl compound 9a, was the most active analogue. The results of QSAR study demonstrated that electronic distribution is among the most important determining factors for activity in this series of compounds.

Background and the purpose of the study: A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of an allopurinol mouthwash in prevention and alleviation of the oral radiotherapy induced mucositis. An allopurinol suspension mouthwash having proper physical stability at least for 6 weeks was prepared. A total of 24 patients with oral, nasopharynx or hypopharynx cancer were enrolled in the study. They were randomly allocated to receive either an allopurinol suspension or normal saline as placebo that were identical in appearance. Patients were instructed to use the suspension as a mouthwash 3 times a day for 3 minutes after beginning of each radiotherapy cycle. Patients were graded on the basis of severity of their own symptoms on a weekly basis by using WHO scale. There were no differences in the severity of mucosits between the allopurinol and placebo-treated groups in first and second weeks of treatment (p =0.227, p = 0.121 respectively). In the third, fourth, fifth and sixth weeks, there were significant differences between two groups (p< 0.05 in each weeks separately).Major Result of this study support the hypothesis that an allopurinol mouthwash may prevents or alleviate oral mucositis induced by radiotherapy.

The purpose of this study was to evaluate the efficacy of Satureja khuzistanica Jamzad extract and its essential oil preparations in the treatment of recurrent aphthous stomatitis (RAS) to explain its folkloric use as analgesic and wound healer. 60 patients with minor aphthae were selected and randomly divided into three groups. Groups A and group B received topical preparations of S. khuzistanica extract and S. khuzistanica essential oil, respectively. Group C (control group) received hydroalcoholic solution as a placebo. The date of pain elimination and the duration of complete healing were recorded. Mean time of pain elimination showed significant differences (p = 0.0001) between groups A (3.40±0.50 days) and group B (3.20±0.41 days) with group C (5.70±1.12 days). The mean duration of complete healing also showed significant differences (p = 0.0001) between group A (5.90±1.24 days) and group B (6.85±1.30 days) in comparison to group C (10.40±1.66 days). No significant differences were found between groups A and group B regarding both mean of the duration of complete healing of lesions and mean time of pain elimination (p = 0.10 and 0.085 respectively). The results obtained for S. khuzistanica extract (group A) was similar to group B (received S. khuzistanica essential oil). The findings of this study revealed that S. khuzistanica extracts and S. khuzistanica essential oil preparation showed better effects in treatment of RAS than placebo. It was concluded that the S. khuzistanica is effective herbal medicine for the management of minor aphthae. Results of the present study may confirm the folkloric use of the plant.