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Introduction: Honeysuckle (Lonicera japonica) is an ornamental flowering plant with numerous traditional medicinal uses. It has been claimed to have anti-spasmodic activities, but only limited studies have been done to support this. The objective of this research was to investigate anti-spasmodic effect of L. japonica flower extract on uterus contractions. Methods: Hydroalcoholic extract was prepared using the maceration technique. In addition, chloroform and ethyl acetate fractions were prepared using a solvent in solvent fractionation technique. Essential oils were collected using the hydro-distillation technique. Rat isolated uterus was suspended in an organ bath and contracted with oxytocin, acetylcholine (ACh), KCl, or application of electrical field stimulation (EFS). The relaxant effects of the extract, its fractions, and nifedipine were examined on uterine contrition induced by the above-mentioned stimuli. Results: Nifedipine in a concentration-dependent manner inhibited uterine contraction induced by oxytocin, KCl, ACh, and EFS. L. japonica flower extract also exhibited an inhibitory effect on the isolated rat uterus. Comparison of the hydroalcoholic extract with its chloroform and ethyl acetate fractions showed that the chloroform fraction was the most potent and the ethyl acetate the weakest part of the plant with antispasmodic activity. The relaxant effect of essential oil had close similarities to that of chloroform extract. Conclusion: Lipophilic compounds isolated by the chloroform partition of crude hydroalcoholic extract of L. japonica flower exhibited the most antispasmodic activity. Ethyl acetate partition of the same extract exhibited the least activity. Therefore, it can be concluded that the spasmolytic constituents of L. japonica flower reside in chloroform partitioning. The nonpolar essential oils may also have a contribution.

Introduction: Pharmacological studies confirm antispasmodic activities of chamomile (Matricaria chamomilla) extract on intestinal smooth muscles and it has been suggested that chamomile increases uterus tone, but so far there is no scientific studies which support this assumption. Therefore, this study was designed to determine spasmodic and spasmolytic activities of M. chamomilla extracts on rat isolated uterus. Methods: Hydro-alcoholic extract of M. chamomilla was prepared by maceration technique. Flavonoids rich extract was prepared by liquid in liquid extraction technique. The spasmodic effects of the extracts were assessed on spontaneously contracting rat uterus. The myorelaxant effect of M. chamomilla extracts was validated on isolated uterus contractions induced by KCl, acetylcholine (ACh), electrical field stimulation (EFS) and oxytocin. Results: Hydro-alcoholic extract of M. chamomilla (0.8 and 1.6 mg/mL) enhanced spontaneous movement of rat isolated uterus smooth muscle suspended in an organ bath. On the other hand, flavonoids rich fraction only diminished uterus contractile activities. Flavonoids rich extract of the plant at bath concentration ranges of 40 μg/mL to 400 μg/mL attenuated uterus response to ACh, KCl, EFS and oxytocin. The hydro-alcoholic extract of M. chamomilla at higher concentration ranges (250 μg/mL to 1.5 mg/mL) inhibited uterus contractions induced by the above spasmogens. Conclusion: The present study confirms both spasmodic and spasmolytic activities M. chamomilla hydro-alcoholic extract. Therefore, medicinal use of the crude extract of M. chamomilla may initiate uterus contraction which could increase risk of spontaneous miscarriage or premature parturition.

Introduction: Dracocephalum kotschyi is a native Iranian plant with antispasmodic activities on smooth muscles such as ileum and uterus. However, so far antispasmodic effect of D. kotschyi on tracheal smooth muscle has not been reported. Therefore, the objective of this research was to investigate antispasmodic activity of D. kotschyi extract and two of its components luteolin and apigenin on rabbit tracheal contraction in vitro. Methods: Rabbits were euthanized by carbon dioxide and the trachea was dissected and immersed in a Tyrode’s solution. Tracheal rings were prepared and mounted vertically in an organ bath at 37°C and gassed continuously with O2. The tracheal ring preparations were contracted with acetylcholine (ACh) and KCl. The isotonic tension was recorded before and after addition of aminophylline, apigenin, luteolin or flavonoids rich extract of D. kotschyi. Flavonoids rich extract were prepared from D. kotschyi using solvent-solvent fractionation technique. Results: Standard drug aminophylline, prevented tracheal ring preparation contracted with ACh. Cumulative addition of aminophylline also attenuated tonic contraction induced by KCl on tracheal smooth muscle. D. kotschyi extract at concentration ranges of 32-512 μg/mL in a concentration dependent manner inhibited KCl and ACh induced tracheal contraction. Apigenin and luteolin (range 16–512 μg/mL) relaxed KCl and ACh-induced contraction of tracheal smooth muscle in vitro in a concentration-dependent manner. Conclusion: This study demonstrated that D. kotschyi extract is a relaxant of tracheal smooth muscle. The relaxant effect of D. kotschyi extract could be due to its flavonoids component such as apigenin and luteolin.

Introduction: Lavender (Lavandula angustifolia Mill) is a herbal medicine widely used for gastrointestinal (GI) disorders. However, its pharmacological action on isolated ileum has not been studied. In this research effect of hydroalcoholic extract of L. angustifolia on isolate ileum contractions was studies and compared with loperamide. Methods: Hydroalcoholic extract of the plant was prepared by percolation method. The total flavonoid contents were assessed by colorimetric technique. A portion of rat ileum was suspended in an organ bath containing Tyrode’s solution. The tissue was kept under 1 g tension at 37°C and continuously gassed with O2. The tissue was stimulated with KCl (80 mM), acetylcholine (ACh, 2 μM) and electrical field stimulation (EFS). Effect of the L. angustifolia extract was studied on ileum contractions and compared with that of loperamide. Results: The yield of hydroalcoholic extract was 17% with total flavonoid content of 185 μg/mL in the stock solution. Loperamide in concentration dependent manner inhibited ileum contractile response to KCl, ACh and EFS. Hydroalcoholic extract of L. angustifolia (8-512 μg/mL) concentration dependently inhibited ileum contraction induced by KCl (IC50 = 88 ± 21 μg/mL), ACh (IC50 = 119 ± 251 μg/mL) and EFS (IC50 = 87 ± 33 μg/mL). The vehicle had no significant effect on ileum contractions. Conclusion: From this study it was concluded that L. angustifolia extract at microgram concentration shows an inhibitory effect on rat ileum smooth muscle. Therefore, isolation and identification of active ingredients are recommended.

AIM The phase III MPACT trial (N = 861) demonstrated superior overall survival (OS) with first-line nab-paclitaxel plus gemcitabine versus gemcitabine alone (median, 8.7 months vs 6.6 months; hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.62-0.83; P

Introduction: Aerial parts of Dracocephalum kotschyi have been used as antispasmodic agents in Iranian traditional medicine. Recent pharmacological studies confirmed antispasmodic activity of D. kotschyi extract. The objective of this research was to investigate antispasmodic activities of apigenin and luteolin to find out if they are responsible for the spasmolytic activity of hydroalcoholic extract of D. kotschyi. Methods: Aerial parts of D. kotschyi were extracted with ethanol. Antispasmodic effect of hydroalcoholic extract of D. kotschyi, apigenin and luteolin were examined on KCl and/or acetylcholine (ACh)-induced contractions in rat isolated ileum. Results: Hydroalcoholic extract of D. kotschyi concentrations-dependently inhibited KCl and ACh induced contractions with IC50 values of 41 ± 10 μg/mL and 133 ± 19 μg/mL, respectively. Apigenin concentrations-dependently inhibited KCl and ACh induced contractions with IC50 values of 57 ± 12 μM and 80 ± 18 μM, respectively. Luteolin concentrations-dependently inhibited KCl induced contractions with IC50 values of 68 ± 14 μM. Loperamide reduced both KCl and ACh induced contraction with IC50 values of 189 ± 44 nM and 82 ± 20 μM, respectively. Conclusion: In this study apigenin and luteolin were identified as two active ingredients responsible for antispasmodic activities of D. kotschyi extract.

Medication errors are the second most common cause of adverse patient safety incidents and the single most common preventable cause of adverse events in medical practice. Given the high human fatalities and financial burden of medication errors for healthcare systems worldwide, reducing their occurrence is a global priority. Therefore, appropriate policies to reduce medication errors, using national data and valid statistics are required. The primary objective of this study was to provide a national ‘characteristic profile’ of medication error-associated adverse drug reactions (ADRs), which are also known as preventable ADRs (pADRs). A retrospective study of pADR reports submitted to the national pharmacovigilance center (PCV) within Iran’s Food and Drug Administration was conducted over a 2-year period (2015-2017). Preventability Method (P-Method), which is a standardized tool developed and recommended by the World Health Organization (WHO), was used for preventability assessment. The results of the analyses revealed that while the number of pADRs increased from year one to two (601 to 630), their proportion out of all ADRs per year decreased (7.32% to 6.44%). The percentage of pADRs was higher in females (61.01%) and adults (83.27%), and the highest number of reports were received by nurses (71.57%). Having ‘a documented hypersensitivity to an administered drug or drug class’ was the most common preventable factor in both years (61.23% and 54.29% respectively), and ‘anti-infectives used systemically’ were the medication class which primarily contributed to both serious (53.29%) and non-serious pADRs (39.19%). The specific characteristics of medication errors associated with ADRs from this study, especially the preventable criteria which led to their occurrence, can help devise more specific preventative policies.

Introduction: Zataria multiflora Boiss. is an indigenous herbal plant found in many parts of Iran. This herb is traditionally used as a remedy for treating gastrointestinal disorders including diarrhea. Despite the existence of few pharmacological evidences which support the antispasmodic action of Z. multiflora in vitro, there is no scientific report about therapeutic efficacy of Z. multiflora in animal models. The objective of this research was to investigate the antispasmodic activity of hydroalcoholic and hexane extracts of Z. multiflora on intestinal peristaltic movement as well as assessment of its antidiarrheal action in mice. Methods: Dried leafy branches of Z. multiflora were coarsely powdered and subjected to extraction by ethanol or hexane in a percolator apparatus. Antispasmodic activity of Z. multiflora in vivo was assessed by investigating effect of the extracts on intestinal charcoal meal transit. The antidiarrheal activity of Z. multiflora extracts was evaluated by castor oil and magnesium sulfate‑induced diarrhea. The inhibitory effects of the extracts were compared with the standard drug loperamide. Results: The antispasmodic activity of Z. multiflora (20 & 40 mg/kg) hydroalcoholic and hexane extracts was confirmed by a reduction in the distance traveled by charcoal meal alongside the small intestine. Z. multiflora extracts (20 & 40 mg/kg) also significantly attenuated the castor oil and magnesium sulfate‑induced diarrhea. Loperamide was more efficacious in reducing number of total stools in both models of diarrhea. Conclusion: The obtained results have established a pharmacological evidence for the folkloric use of the Z. multiflora as an antidiarrhoeal and spasmodic agent.

Background Retrospective studies show improved outcomes in colorectal cancer patients if taking statins, including overall survival, pathological response of rectal cancer to preoperative chemoradiotherapy (pCRT), and reduced acute and late toxicities of pelvic radiation. Major tumour regression following pCRT has strong prognostic significance and can be assessed in vivo using MRI-based tumour regression grading (mrTRG) or after surgery using pathological TRG (pathTRG). Methods A double-blind phase 2 trial will randomise 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 18+ sites in New Zealand and Australia. Patients will receive simvastatin 40 mg or placebo daily for 90 days starting 1 week prior to standard pCRT. Pelvic MRI 6 weeks after pCRT will assess mrTRG grading prior to surgery. The primary objective is rates of favourable (grades 1–2) mrTRG following pCRT with simvastatin compared to placebo, considering mrTRG in 4 ordered categories (1, 2, 3, 4–5). Secondary objectives include comparison of: rates of favourable pathTRG in resected tumours; incidence of toxicity; compliance with intended pCRT and trial medication; proportion of patients undergoing surgical resection; cancer outcomes and pathological scores for radiation colitis. Tertiary objectives include: association between mrTRG and pathTRG grouping; inter-observer agreement on mrTRG scoring and pathTRG scoring; studies of T-cell infiltrates in diagnostic biopsies and irradiated resected normal and malignant tissue; and the effect of simvastatin on markers of systemic inflammation (modified Glasgow prognostic score and the neutrophil-lymphocyte ratio). Trial recruitment commenced April 2018. Discussion When completed this study will be able to observe meaningful differences in measurable tumour outcome parameters and/or toxicity from simvastatin. A positive result will require a larger RCT to confirm and validate the merit of statins in the preoperative management of rectal cancer. Such a finding could also lead to studies of statins in conjunction with chemoradiation in a range of other malignancies, as well as further exploration of possible mechanisms of action and interaction of statins with both radiation and chemotherapy. The translational substudies undertaken with this trial will provisionally explore some of these possible mechanisms, and the tissue and data can be made available for further investigations. Trial registration ANZ Clinical Trials Register ACTRN12617001087347. (www.anzctr.org.au, registered 26/7/2017) Protocol Version: 1.1 (June 2017).

Colitis is an inflammatory disease of the intestine with unknown etiology involving multiple immune, genetic, and environmental factors. We were interested to examine the effect of total extract from Dracocephalum Kotschyi (D. kotschyi) Boiss. on the experimental colitis. D. kotschyi hydroalcoholic extract (10, 20, and 40 mg/kg) or apigenin (5, 10, and 20 mg/kg) were administered orally 2 h prior to induction of colitis which was induced by intrarectal administration of acetic acid (4%) in rats. Prednisolone (4 m/kg) was used as the standard drug for comparison. Biochemical evaluation of inflamed colon was performed by measuring myeloperoxidase (MPO) activity. After 5 days treatment, mucosal ulceration was evaluated. Intrarectal instillation of acetic acid caused significant inflammatory reactions as indicated by macroscopic and microscopic changes. The activity of MPO increased in vehicle treated groups while recovered to normal level by pretreatment of animals with D. kotschyi extract, apigenin, or prednisolone. D. kotschyi and apigenin-treated groups showed significantly lower score values of macroscopic and microscopic characters when compared with the vehicle-treated negative control group. The beneficial effect of apigenin was comparable with that of prednisolone. This research has shown the anti-inflammatory potential of D. kotschyi extract and apigenin in experimentally induced colitis.

Hyperlipidemia is associated with increased risk of atherosclerosis; therefore, control of this risk factor is very important in preventing atherosclerosis. Cucumber (Cucumis sativus) seed is used traditionally as a lipid-lowering nutritional supplement. The aim of this study was to evaluate the effect of cucumber seed extract on serum lipid profile in adult patients with mild hyperlipidemia. In a randomized double-blind placebo-controlled clinical trial, hyperlipidemic patients with inclusion criteria were randomly and equally assigned to either Cucumis or placebo groups and used one medicinal or placebo capsule, respectively, once daily with food for 6 wk. Body mass index (BMI) as well as fasting serum levels of total cholesterol, triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) were measured for all patients pre- and post-intervention and finally the changes were compared between the groups. Twenty-four patients in Cucumis group and 23 patients in placebo group completed the study. Cucumis seed extract resulted in significant reduction of total cholesterol (P = 0.016), LDL-C (P < 0.001), TG (P < 0.001), and BMI (P < 0.001) as well as significant increase of HDL-C (P = 0.012) compared to placebo. In conclusion, the consumption of C. sativus seed extract with daily dose of 500 mg results in desirable effects on serum lipid profile in adult hyperlipidemic patients. Therefore, cucumber seed could be considered as a food supplement for treatment of dyslipidemia.

Dracocephalum kotschyi Boiss. is a traditional medicine with antispasmodic activities. The objective of this research was to study antispasmodic activities of hydroalcoholic extract of D. kotschyi on rat isolated uterus contractions for comparison with isolated ileum. Hydroalcoholic extract was obtained from aerial part of D. kotschyi using percolation method. A portion of rat ileum or uterus was suspended in Tyrode′s solution at 37 °C and gassed with O 2 . Effect of D. kotschyi extract was assessed on ileum or uterus contractions induced by KCl (80 mM), acetylcholine (ACh, 500 nM), electrical field stimulation (EFS) or oxytocin (0.0005 IU/mL). The extract of D. kotschyi concentration-dependently inhibited ileum responses to KCl (IC 50 = 65 ± 18 μg/mL), ACh (IC 50 = 102 ± 18 μg/mL) and EFS (IC 50 = 117 ± 29 μg/mL). The extract of D. kotschyi also concentration-dependently inhibited uterus responses to KCl (IC 50 = 453 ± 64μg/mL), ACh (IC 50 = 58 ± 9 μg/mL), EFS (IC 50 = 22 ± 3 μg/mL) as well as oxytocin (IC 50 = 70 ± 11 μg/mL). From this experiment it was concluded that D. kotschyi extract possesses antispasmodic activities on both smooth muscle of ileum and uterus. In comparison, the extract was more effective inhibitor of ACh and EFS responses in rat uterus than on the ileum. On the other hand, the extract was a more potent inhibitor of KCl response on rat ileum. However, the extract was found to be a potent inhibitor of oxytocin-induced contraction of rat uterus. These results indicate that D. kotschyi extract may contain components that might be useful lead compounds for prevention of uterus spasm.

There is an ever-growing need to develop green, non-toxic, and eco-friendly procedures for synthesis and assembly of nanoparticles (NPs) with the desired morphologies and sizes. The hydroalcoholic extract of Persian oak leaves [Quercus brantii Lindl. (Fagaceae)] contains high content of phenolic and flavonoid compounds with strong antioxidant activities, and it seems that this plant can be considered a good candidate for metal nanoparticle synthesis.The potential of Q. brantii leaves in the production of silver NPs and the effect of the extract ethanol concentration on the produced NPs were studied.Quercus brantii leaves were freshly collected, air-dried at room temperature, powdered, and sieved. Hydroalcoholic extracts (70% and 96%) were prepared by percolation of the plant powder. The reaction mixtures contained (final concentrations): AgNO3 (1 mM) as the substrate, plant extract as the biocatalyst, and phosphate buffer (pH = 7, 100 mM) as the reaction medium. Silver ions were determined using atomic absorption analysis. Particle size distribution of NPs was analyzed using Nano-Zeta Sizer (Malvern Instruments Ltd, Malvern, UK). Samples for TEM were prepared by drop-coating the silver nanoparticle suspensions onto carbon-coated copper grids.Hydroalcoholic extract (96%) of Q. brantii successfully produced quite small (as small as 0.83 nm and the mean size of 6 nm), spherical, and poly-dispersed NPs with low aggregates. The conversion was fast and completed in 5 h.This plant and the extraction method seem to be quiet attractive for industrial scale production of NPs.

Hairy roots induced by Agrobacterium rhizogenes are distinguished by their high growth rate, genetic stability, and lateral branching. Datura metel is an important medicinal plant whose hairy roots are used for the production of atropine, a tropane alkaloid applied as an anticholinergic and parasympathetic agent. To increase the yield of atropine, biotic (Bacillus cereus and Staphylococcus aureus) and abiotic (AgNO3 and nanosilver) elicitors were added to the hairy root cultures of D. metel and then analyzed through high-performance liquid chromatography. All the elicitors influenced biomass accumulation and atropine production. Among the tested elicitors, nanosilver was most effective in enhancing the hairy roots' atropine content. To the authors' knowledge, the application of nanosilver for increasing tropane alkaloid production is reported for the first time here and could improve the atropine production of pharmaceutical industries.

Trichomoniasis is a common sexually transmitted disease (STD) caused by a protozoan parasite called Trichomonas vaginalis. This disease, with roughly 170 million new infected people worldwide per year, is associated with various problems such as pre-term delivery, high infant mortality or low birth weight. In addition, trichomoniasis increases patient susceptibility to HIV infection. The mainstay medication for trichomoniasis is metronidazole, but some resistant strains to this treatment have been identified. Moreover, treatment with metronidazole is associated with numerous side effects. Thus efforts to identify new alternative drugs in order to control trichomoniasis are vital. The use of medicinal herbs has gained widespread acceptance in both developing and non-developing societies because of owing to fewer side effects and better patient tolerance. In our search for alternative drugs in the treatment of trichomoniasis, we reviewed the effect of different plant extracts on Trichomonas vaginalis in vitro.

Using a bioassay-directed fractionation of Pycnocycla spinosa Decne. Ex Boiss. var. spinosa, a new polycyclic diterpenoid, 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene ( 1 ), two known compounds; vanillin ( 2 ) and isoacetovanilon ( 3 ), and a new phenolic compound, 6-(4-hydroxy-3-methoxyphenyl)-hexanoic acid ( 4 ) with inhibitory effects on KCl-induced smooth muscle contractions on the rat isolated ileum were obtained. Compound 1 , the most active of the series, which exerted potent antispasmodic activity with IC 50 value of IC 50 = 0.062 ± 0.011 μM, is likely the main active ingredient of the extract. The structures of the isolated compounds were established based on 13 C and 1 H NMR as well as 2D NMR, IR, HR-MS, and X-ray crystallographic methods.

Background. Removing tooth results in gingival bleeding. Several measures are taken to stop bleeding. In this study, the effect of green tea extract on cessation of bleeding and oozing after removing of mandibular molars was investigated.Methods. This was a randomized controlled clinical trial carried out on 62 patients who were referred for extraction of their mandibular molars. The volunteers were randomly and equally divided into treatment and control groups. In the first group, green tea extract-impregnated sterile gauze was used after removing the tooth while in the second group, green tea extract-free gauze was applied. Active bleeding and oozing monitoring was done every 5 minutes until cessation of bleeding and one hour after that, respectively. The results were compared usingt-test.Results. The mean ± SD of bleeding duration in green tea group was significantly lower than control group (5.87±1.76versus10.09±3.61minutes,P=0.001). In addition, the number of people with oozing one hour after surgery was significantly lower in the green tea group (6 versus 29 persons,P=0.001).Conclusion. This study showed that green tea extract contributes to significant decline in bleeding of the socket caused by tooth extraction as well as reduction of oozing.

Objective To evaluate the effect of aromatherapy with Lavandula angustifolia essential oil on post-tonsillectomy pain in pediatric patients. Methods This was a randomized controlled prospective clinical trial. In this study, 48 post-tonsillectomy patients aged 6-12 years were randomly assigned to two groups (24 patients in each group). After tonsillectomy surgery, all patients received acetaminophen (10-15 mg/kg/dose, PO) every 6h as necessary to relieve pain. The patients of the case group also inhaled lavender essential oil. The frequencies of daily use of acetaminophen and nocturnal awakening due to pain, and pain intensity (evaluated using visual analog scale [VAS]) were recorded for each patient for 3 days after surgery. Finally, the mean values of variables were compared between two groups separately for each post-operative day. Results The use of lavender essential oil caused statistically significant reduction in daily use of acetaminophen in all three post-operative days but had not significant effects on pain intensity and frequency of nocturnal awakening. Conclusion Aromatherapy with lavender essential oil decreases the number of required analgesics following tonsillectomy in pediatric patients.

Six labdanes (1-6) and four isopimaranes (7-10), including three new natural products (7, 9, and 10), were isolated from Platycladus orientalis, and their structures determined using 1D and 2D NMR methods, ion-cyclotron resonance HRMS, and optical rotation data. Relative configurations of all chiral centers in the isopimaranes were determined using NOESY experiments at 600 and 800 MHz. Specific optical rotation data were used to correlate absolute configurations. Compounds 1-9 and aframodial (11) were tested for their in vitro antiplasmodial activity and for their ability to induce changes of erythrocyte shape in order to obtain data about possible correlation between the two effects. All compounds tested exhibited weak (IC(50) > 25 microM) in vitro antiplasmodial effects against Plasmodium falciparum strain 3D7. At the same time, the compounds caused echinocytic or stomatocytic changes of the erythrocyte membrane curvature, indicative of their incorporation into the lipid bilayer, in the concentration region where the antiplasmodial activity was observed. The antiplasmodial effect of these compounds thus appears to be an indirect effect on the erythrocyte host cell. Weak or moderate antiplasmodial activity observed with many other apolar natural products, in particular those with amphiphilic structures, is also likely to be an indirect effect.

Traditional herbal medicines such as Ferula gummosa Boiss. have been used for treatment of intestinal disorders in Iran. To date no pharmacological evidence for their effectiveness has been reported. The aim of this study was to examine the relaxant effect of essential oil, hydro-alcoholic, etheric, petrolic and methanolic extracts of Ferula gummosa and two of its components, alpha-pinene and beta-pinene, on isolated rat ileum contractions induced by KCl and acetylcholine (ACh). Ferula gummosa essential oil (FGEO) and hydro-alcoholic, etheric, petrolic and methanolic extracts all inhibited the response to 80 mM KCl in a concentration-dependent manner and attenuated the maximum attainable response of the ACh concentration-response curve. Although the effect of etheric extract on ACh contractions was less than that of petrolic extract, the overall order of effectiveness on the weight basis was the etheric, petrolic, methanolic, and hydro-alcoholic extracts, and the essential oil, respectively. A mixture of etheric and petrolic extracts together had a similar effect on KCl response to etheric extract was used alone. Alpha-pinene and beta-pinene both exhibited inhibitory effect on the contraction of rat ileum, but the inhibitory effect of beta-pinene on KCl contraction was more pronounced. The inhibitory effect of a mixture of these two compounds was, however, less than the sum of their separate effects. When a mixture of alpha-pinene and beta-pinene together were examined on the ileum, without presence of the spasmogen, they initially caused contraction of the tissue, while neither of them used alone caused a noticeable contraction of the ileum. This study shows that Ferula gummosa essential oil and its various extracts are relaxant of rat isolated ileum and that at least part of their inhibitory effect is due to alpha-pinene and beta-pinene components. As the inhibition of contractile over-activity of the ileum is the basis of the treatment of some gastero-intestinal disorders such as diarrhea, Ferula gummosa may have clinical benefits for treatment of this condition.

314 Background: The IMPaCT trial screened patients with advanced pancreas cancer for molecular targets and aimed to test molecularly guided therapy in a pilot randomized study, but closed in December 2015 having delivered personalized treatment to only 1 patient. A follow up analysis of the screened cohort provides insight into the clinical utilisation of targetable molecular results in pancreas cancer. Methods: IMPaCT screened for 3 genetic phenotypes matched to precision treatment: Her2 amplification (trastuzamab + gemcitabine), KRAS wildtype (erlotinib + gemcitabine) and DNA damage repair pathway defects (platinum-based). Previously recruited primary resected APGI participants known to be alive were also screened for these targets. The initial pilot protocol included randomisation, but after amendment in early 2015, became a single-arm study allowing one cycle of gemcitabine + nab-paclitaxel during screening. Results: A total of 101 potential patients were screened. This was enriched for patients with known targets where sequence data was available from primary pancreatectomy. 23 had one of the 3 molecular targets in this enriched population (4 Her2 amplified, 16 KRAS wt, 2 BRCA2, 1 ATM). The prospectively recruited de novo metastatic cohort (n = 63) had an actionable mutation detection rate of 14.3%. Of the 23 patients identified, 3 received personalised treatment off study, 1 on study, 3 are currently alive without recurrence, 1 is monitored for suspected recurrence, 2 developed second primary malignancies, 10 died or progressed prior to result and 3 decided not to use personalised treatment. The identification of a molecular target did not significantly affect overall survival. Conclusions: Although actionable molecular targets were detected, recruitment rates on the IMPaCT trial were low (1%). Follow up illustrates that these molecular results were incorporated into clinical care off trial or still have the potential to be utilised in another 6.9% of the cohort. Further follow up is planned for long term outcomes. Clinical trial information: ACTRN12612000777897.

Hydroalcoholic extract and essential oil of aerial parts of Pycnocycla caespitosa have spasmolytic activity on rat ileum contractions. The objective of this research was to separate fractions of total hydroalcoholic extract of P. caespitosa guided by their spasmolytic activity on rat uterus. Aerial parts of P. caespitosa were extracted with ethanol. The concentrated extract was subjected to column chromatography and thin layer chromatography (TLC) for isolation fractions, then one of the bioactive fractions was subjected to further isolation to find its active components. Five fractions were obtained (Fr.1-Fr.5) and their anti-spasmodic activities were examined on uterus contraction induced by KCl (80 mM) and compared with ritodrine. In addition, spasmolytic effect of Fr.4 (one of the bioactive fractions) was determined on rat uterus induced by oxytocin (0.0005 IU/mL) and compared with ritodrine. Hydroalcoholic extract of P. caespitosa (0.032-2 mg/mL) reduced the responses to KCl but the inhibitory effect was not complete with 2 mg/mL extract in the bath. Four fractions (Fr.1, Fr.2, Fr.3 and Fr.4) (32-500 μg/mL) inhibited rat uterus contractions on the uterus while Fr.4 was slightly more active than others (IC50 = 146 ± 23 μg/mL). Falcarindiol and isoacetovanillone were identified from Fr.4 using phytochemical methods including high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and TLC. In conclusion, in this research bioactivity guided technique was successfully used for separation of active fraction of P. caespitosa. Falcarindiol and isoacetovanillone were identified from the active fraction which inhibited both tonic and rhythmic contractile responses in rat isolated uterus.

Background: Trichomonas vaginalis is considered one of the main causes of vulvovaginitis in women. Metronidazole with vast side effects is now the drug of choice for treatment of this infection. In an attempt to find an alternative drug, the effect of Eucalyptus camaldulensis on this parasite was shown in previous studies. In this investigation, the effect of different extracts of this plant on T. vaginalis in culture medium has been investigated. Materials and Methods: Five different extracts including total extract, diethyl ether, chloroform, ethyl acetate, and water fractions were prepared. The extracts were dried using vacuum rotary evaporator and then they were used for in vitro anti-trichomonas experiments. Results: Crude extract of E. camaldulensis showed 80% growth inhibition (GI) in a concentration of 12.5 mg/ml during 24 h. Diethyl ether extract in a concentration of 25 mg/ml showed 100% GI during 24 h. With ethyl acetate extract, 100% GI was detected with the minimum concentration of 12.5 mg/ml in the first 24 h. Finally, water extract in a concentration of 50 mg/ml showed 80% and 100% GI after 48 and 72 h, respectively. Conclusion: Ethyl acetate fraction is the extract which showed the highest percentage of GI (100%) with the least concentration (12.5 mg/ml) after 24 and 48 h.

Pycnocycla spinosa is an essential oil from a wild plant growing in central Iran. However, so far its pharmacological effects have not been studied. The aim of this study was to look for relaxant effects of the essential oil and hydro-alcoholic extract of P. spinosa on rat isolated ileum contractions induced by KCl and acetylcholine (ACh). P. spinosa essential oil (PSEO) and the hydro-alcoholic extract inhibited the response to 80 mM KCl in a concentration-dependent manner and attenuated the maximum attainable response of ACh concentration-response curve. Furthermore, in caster oil induced diarrhoea, the hydro-alcoholic extract had a dose-dependent anti-diarrhoeal effect. This study showed that P. spinosa essential oil and its hydro-alcoholic extract act as a relaxant of rat isolated ileum. As the inhibition of contractile over-activity of the ileum is the basis for the treatment of gastro-intestinal disorders such as diarrhoea, P. spinosa may have clinical benefits for treatment of this condition. Copyright © 2003 John Wiley & Sons, Ltd.

Hydroalcoholic extract of Pycnocycla spinosa was shown to have spasmolytic action in vitro and antidiarroheal effect in vivo. The hydroalcoholic extract of P. spinosa is composed of alkaloid-, flavonoid- and saponin-rich components. These components were separated by fractional separation technique. The pharmacological objective of this study was to look for relaxant effect of these components of hydroalcoholic extract of P. spinosa on rat isolated ileum contractions. The alkaloid-, flavonoid- and saponin-rich fractions of P. spinosa inhibited the response to 80 mM KCl in a concentration-dependent manner. The alkaloid-rich fraction was the most and saponin-rich fraction the least effective relaxant of ileum contractions. The alkaloid-rich fraction also inhibited the response to acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). From this study, it can be concluded that the antispasmodic action of hydroalcoholic extract of P. spinosa could be due to components in the alkaloid-rich fraction and to a lesser extent, to its flavonoid-rich fraction.

Background: Moringa peregrina (Forssk.) Fiori. is a tropical tree growing in southeast of Iran. All parts of this plant have nutritional uses and pharmacological activities. The present study was designed to evaluate the effect of hydroalcoholic extract from the leaves of M. peregrina in dexamethasone (Dex)-induced hypertension in rats. Materials and Methods: Male Wistar rats received Dex (30 μg/kg, subcutaneously; s.c.) or saline (as vehicle, 1 ml/kg, s.c.) for 14 days. In a prevention study, the rats received M. peregrina extract (100, 200 and 400 mg/kg, orally) for 4 days, followed by Dex for 14 days. In a reversal study, the animals received M. peregrina extract orally from day 8 to 14. The systolic blood pressure (SBP) was measured using tail-cuff method. The hydrogen peroxide (H 2 O 2 ) concentration and ferric reducing antioxidant power (FRAP) were assessed in plasma samples. Results: Dex significantly increased the SBP and the plasma H 2 O 2 and decreased the plasma FRAP value (P < 0.001). M. peregrina extract at a dose of 400 mg/kg prevented (P < 0.01) but did not reverse Dex-induced hypertension in rats. It also dose-dependently reduced the plasma H 2 O 2 concentration and improved the FRAP value upon Dex administration. Conclusions: The findings of the present study indicated the antioxidant and partially antihypertensive effects of the hydroalcoholic extract from the leaves of M. peregrina in Dex-induced hypertension. Further experiments on other fractions of the leaves and also other parts of this plant are suggested for better evaluation of its antihypertensive effect and finding its mechanisms of action.