Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice

Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7–9, 10–12 or 13–15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study.None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females.However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13–15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed.The results of this study have important implications for the widespread use of this drug.     

Mutation and selection explain why many eukaryotic centromeric DNA sequences are often A + T rich

We have used chromosome engineering to replace native centromeric DNA with different test sequences at native centromeres in two different strains of the fission yeast Schizosaccharomyces pombe and have discovered that A + T rich DNA, whether synthetic or of bacterial origin, will function as a centromere in this species. Using genome size as a surrogate for the inverse of effective population size (N_e) we also show that the relative A + T content of centromeric DNA scales with N_e across 43 animal, fungal and yeast (Opisthokonta) species. This suggests that in most of these species the A + T content of the centromeric DNA is determined by a balance between selection and mutation. Combining the experimental results and the evolutionary analyses allows us to conclude that A + T rich DNA of almost any sequence will function as a centromere in most Opisthokonta species. The fact that many G/C to A/T substitutions are unlikely to be selected against may contribute to the rapid evolution of centromeric DNA. We also show that a neo-centromere sequence is not simply a weak version of native centromeric DNA and suggest that neo-centromeres require factors either for their propagation or establishment in addition to those required by native centromeres.     

Lack of micronuclei formation in bone marrow of rats after oral exposure to thiocyclam insecticide

In this study, a nereistoxin analogue insecticide, thiocyclam, was administered to adult male albino rats by gavage dose of 135, 270 and 540 mg/kg b.w. repeated for 5 days at 24 h intervals. Control animals received only water. Thiocyclam was tested for its potential to cause genotoxic effects in rat bone marrow cells using an in vivo micronucleus assay. After 24 h of the last treatment, rats from all dose levels were sacrificed. Bone marrow cells were collected and assayed for the presence of micronuclei. Thiocyclam did not cause any increase in the incidence of micronucleated polychromatic erythrocytes in rats bone marrow at any of the dose levels. The polychromatic erythrocytes/normochromatic erythrocytes (PCE:NCE) ratio was found to be in the range from 0.50 ± 0.11 to 0.55 ± 0.02. The results of this study demonstrate that the effect of thiocyclam is not significant in the rat in vivo micronucleus assay.     

Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors

Inhaled prostanoids and phosphodiesterase (PDE) inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor), motapizone (PDE3 inhibitor) or 8-Methoxymethyl-IBMX (PDE1 inhibitor) synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within <20 min, without significant changes in blood gases or systemic hemodynamics. Infusion of 8-Methoxymethyl-IBMX, motapizone and sildenafil caused each a dose-dependent decrease in pulmonary artery pressure, with sildenafil possessing the highest efficacy and at the same time selectivity for the pulmonary circulation. When combining a per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone) with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of P_PA reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor.     

Potent Inhibition of Pseudogymnoascus destructans,the Causative Agent of White-Nose Syndrome in Bats,by Cold-Pressed,Terpeneless, Valencia Orange Oil

The causative agent of White-nose Syndrome (WNS), Pseudogymnoascus destructans, has been shown to be fatal to several species of bats in North America. To date, no compounds or chemical control measures have been developed which eliminates the growth of the fungus in the environment or in affected animals. In the current study, we evaluated the activity of cold-pressed, terpeneless orange oil (CPT) against multiple isolates of P. destructans in vitro. For all assays, a modified Kirby-Bauer disk diffusion assay was used. Standardized spore suspensions were prepared, adjusted to a specific optical density, and used to plate fungal lawns. Plates were incubated at either 15°C or 4°C for up to 6 months and checked at regular intervals for growth. Once controls had grown, zones of inhibition were measured (mm) on test plates and compared to those obtained using current antifungal drugs. All P. destructans isolates were completely inhibited by 100% CPT (10 μL) at 1 month of incubation regardless of temperature (4°C and 15°C). Complete inhibition persisted up to 6 months following a single exposure at this concentration. Of the standard antifungals, only amphotericin B demonstrated any activity, resulting in zone diameters ranging from 58 mm to 74 mm. CPT, at the highest concentration tested (100%), had no significant effect against a variety of other environmental organisms including various filamentous fungi, bacteria and aerobic actinomycetes. Given that CPT is relatively non-toxic, the possibility exists that the all-natural, mixture could be used as an environmental pre-treatment to eradicate P. destructans from bat habitats. Additional studies are needed to assess any undesirable effects of CPT on bat behavior and health and overall impacts on other members of the interconnected ecosystem(s).     

Effect of dexamethasone prodrug on inflamed temporomandibular joints in juvenile rats

IntroductionJuvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ.MethodsJoint inflammation was initiated by injecting two doses of complete Freund’s adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague–Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 mg of P-DEX intra-articularly (n = 9), (2) 15 mg of P-DEX into the tail vein (n = 7), or (3) nothing in addition to CFA (n = 8). The rats were killed 28 days later and measured by radiography for ramus height (condylar superior to gonion inferior [CsGoInf]), by micro-computed tomography for condylar width (CW) and bone volume/standardized condylar volume (BV/CV), and by histology for retrodiscal inflammatory cells. Inflammation targeting of systemic P-DEX was confirmed by IVIS infrared dye imaging. Inflammation and bone growth were compared between groups using analysis of variance and Pearson’s correlations.ResultsCFA caused a significant reduction in CsGoInf (p < 0.05), but neither route of P-DEX administration had an effect on CsGoInf or CW at CFA injection sites. BV/CV was significantly reduced in both inflamed and control condyles as a result of either steroid application (p < 0.05). The inflammatory infiltrate was overwhelmingly lymphocytic, comprising 16.4 ± 1.3 % of the field in CFA alone vs. <0.01 % lymphocytes in contralateral controls (p < 0.0001). Both P-DEX TMJ (10.1 ± 1.2 %) and systemic P-DEX (8.9 ± 1.7 %) reduced lymphocytes (p < 0.002). The total area of inflammatory infiltrate was significantly less in the systemic injection group than in the group that received CFA injections alone (2.6 ± 1.5 mm² vs. 8.0 ± 1.3 mm²; p = 0.009), but not in the group that received intra-articular P-DEX (8.8 ± 1.2 mm²).ConclusionsHigh-dose systemic administration of inflammation-targeting P-DEX is more effective than an intra-articular injection in reducing TMJ inflammation, but both routes may affect TMJ bone density.     

Factors influencing seed germination of medicinal plant Salvia aegyptiaca L. (Lamiaceae)

Salvia aegyptiaca is a xerophytic perennial herb belongs to the Lamiaceae family commonly used for medicinal purposes. Laboratory experiments were carried out to assess the effects of temperature and salinity on seed germination and recovery responses after transferring to distilled water. Temperatures between 10 and 40 °C seem to be favourable for the germination of this species. Germination was inhibited by either an increase or decrease in temperature from the optimum (30 °C). The highest germination percentages were obtained at 0 mM NaCl; however, the increase of solution osmolalities progressively inhibited seed germination. The germination rate decreased with an increase in salinity for most of tested temperatures, but comparatively higher rates were obtained at 30 °C. Salt stress decreased both the percentage and the rate of germination. An interaction between salinity and temperature yielded no germination at 300 mM NaCl. By experimental transfer to distilled water, S. aegyptiaca seeds that were exposed to moderately saline conditions recovered and keep their ability to germinate mostly at low temperatures. At 300 mM NaCl, germination recovery decreased with increasing temperature and it was completely inhibited at 40 °C.     

Therapeutic effects of Typha elephantina leave’s extract against paracetamol induced renal injury in rabbits

Present study focuses on ameliorative potential of Typha elephantina leave’s aqueous (TE.AQ) extract against Paracetamol (PCM) induced toxicity in rabbits. We fed the male rabbits with 300 mg PCM in alone and in combination with TE.AQ at different doses i.e. (100, 200 and 300 mg/kg body weight) or silymarin (100 mg/kg) daily for 21 days. PCM in alone significantly (P < 0.5) increased serum urea, uric acid, creatinine, total protein, albumin, globulin and blood urea nitrogen. Serum sodium, potassium and magnesium level were high. The glutathione, radical scavenging activity and Thiobarbituric acid reactive substances were significantly reduced. Treatment with TE.AQ at dose rate 300 mg/kg body weight and Silymarin significantly ameliorated all the parameters when compared with PCM administered group. The 100 and 200 mg of TE.AQ showed no significant effects. The histopathological examination confirmed the therapeutic potential of TE.AQ. These results established the presence of natural antioxidants in Typha elephantina leaves.     

Archolaemus janeae (Gymnotiformes,Teleostei): First insights into karyotype and repetitive DNA distribution in two populations of the Amazon

Archolaemus, one of the five genera of Neotropical freshwater fish of the family Sternopygidae (Gymnotiformes), was long considered a monotypic genus represented by Archolaemus blax. Currently, it consists of six species, most of them occurring in the Amazon region. There are no cytogenetic data for species of this genus. In the present study, we used classical cytogenetics (conventional staining and C‐banding) and molecular cytogenetics (probes of telomeric sequences and multigenic families 18S rDNA, 5S rDNA, and U2 snDNA) to study the karyotype of Archolaemus janeae from Xingu and Tapajós rivers in the state of Pará (Brazil). The results showed that the two populations have identical karyotypes with 46 chromosomes: four submetacentric and 42 acrocentric (2n = 46; 4m/sm + 42a). Constitutive heterochromatin occurs in the centromeric region of all chromosomes, in addition to small bands in the interstitial and distal regions of some pairs. The 18S rDNA occurs in the distal region of the short arm of pair 2; the 5S rDNA occurs in five chromosome pairs; and the U2 snDNA sequence occurs in chromosome pairs 3, 6, and 13. No interstitial telomeric sequence was observed. These results show karyotypic similarity between the studied populations suggesting the existence of a single species and are of great importance as a reference for future cytotaxonomic studies of the genus.     

Physical Properties of Mitochondrial Lipids from Lycopersicon hirsutum

Mitochondrial lipids from Lycopersicon hirsutum undergo a broad thermal transition beginning well below 0°C and ending at approximately 25°C. Differential thermal analysis of mitochondrial lipids isolated from ecotypes of L. hirsutum that differ in chilling sensitivity indicates that these lipid preparations have physically similar properties. This was confirmed by electron-spin-resonance experiments, although this technique failed to detect the broad transition detected by differential thermal analysis. No quantitative differences were observed between the percentages of individual lipid classes (based on polar head group) or between the fatty acid compositions of mitochondrial lipids from the two ecotypes investigated. These results suggest that the observed differences between the responses of these ecotypes to prolonged exposure to 5°C may not be related to differences between the physical properties of their mitochondrial lipids.     

Protective effect of l-carnitine against acrylamide-induced DNA damage in somatic and germ cells of mice

Recent findings of acrylamide (AA) in many common foods have sparked renewed interest in assessing human health hazards. AA was evaluated by the International Agency for Research on Cancer as probably carcinogenic to humans. For this reason, the aim of this study is to evaluate the potential genotoxic effect of AA using chromosomal aberration analysis and micronucleus (MN) test in mouse bone-marrow cells and morphological sperm abnormalities. The result of the present work indicated that treatment with a single dose of 10, 20, or 30 mg/kg b.wt. of AA for 24 h and the repeated dose of 10 mg/kg b.wt. for 1and 2 weeks induced a statistically significant increase in the percentage of chromosomal aberrations and micronuclei in bone- marrow cells. These percentages reduced significantly in all groups treated with AA and the protective agent l-carnitine. Also the results indicated that the dose 10, 20 and 30 mg/kg b.wt. of AA induced a statistically significant percentage of morphological sperm abnormalities compared with the control group. Such effect reached its maximum (7.24 ± 0.61) with the highest tested dose which reduced to (4.02 ± 0.58) in the group treated with the same dose of AA and l-carnitine. In conclusion, the results confirm the protective role of LC against the mutagenicity of AA.     

FACTORS AFFECTING THE PRODUCTION OF CHROMOSOME ABERRATIONS BY CHEMICALS

In the present paper, the results of a study on the influence of temperature, hydrogen ion concentration, and oxygen tension on the production of chromosome aberrations in Vicia root tips by maleic hydrazide (MH), di-(2, 3-epoxypropyl)ether (DEPE), and 8-ethoxycaffeine (EOC), are described. Variations in the hydrogen ion concentration of the treatment solutions did not significantly influence the effect of EOC and DEPE. In contrast, the MH effect was considerably diminished by raising the pH from 4.7 to 7.3. A marked increase in the frequencies of aberrations produced by DEPE and MH was obtained by raising the temperature from 3° to 25°C. The effect of EOC increased with rising temperature up to 12°C. With a further rise in temperature the effect of EOC decreased, so that at 25°C. it was of about the same magnitude as at 3°C. The effect of EOC was completely inhibited, and that of MH partly so, when during the treatment (1) oxygen was excluded from the solution, (2) respiration was inhibited by azide or cyanide, or (3) phosphorylation was uncoupled from respiration by 2, 4-dinitrophenol (DNP). Pretreatments with DNP had a similar effect, but posttreatments did not influence the frequencies of aberrations. The effect of DEPE was unchanged by anoxia. Pre- or posttreatments with DNP did not change the total number of aberrations produced by DEPE, but the appearance of the effect was considerably delayed. The results are discussed.     

Zearalenone induces chromosome aberrations in mouse bone marrow: preventive effect of 17β-estradiol, progesterone and Vitamin E

The cytogenetic effect of zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, was evaluated in vivo, in mouse bone marrow cells, by assessing the percentage of cells bearing different chromosome aberrations. The studies included different conditions for animal treatment, as follows: (1) single intraperitoneal (ip) injection, (2) repeated ip injections, (3) pre-treatment for 24 h with Vitamin E (Vit E), and (4) pre-treatment for 4 h with 17β-estradiol (17β-Est) or progesterone (Prog). ZEN induced different types of chromosome aberrations, which was concentration-dependent (2–20 mg/kg bw). These doses corresponded to 0.4–4% of the LD₅₀ in the mouse. Interestingly, when the dose of ZEN (40 mg/kg) was fractionated into four equivalent doses (4 × 10 mg/kg bw), into three doses (15 + 10 + 15 mg/kg bw), or into two equivalent doses (2 × 20 mg/kg bw), given every 24 h, the percentage of chromosome aberrations increased significantly. This finding suggests that ZEN proceeds by reversible binding on receptors that could become saturated, and that it damages the chromosomes in a ‘hit and go’ manner. Furthermore, pre-treatment of animals with 17β-estradiol or progesterone significantly decreased the percentage of chromosome aberrations, suggesting that (i) these hormones bind to the same cytoplasmic receptors transported into the nucleus to elicit DNA damage, (ii) they may play a role in preventing chromosome aberrations induced by ZEN. Similarly, Vit E prevented these chromosome aberrations indicating that Vit E, previously reported to prevent most of the toxic effects induced by ZEN, may also bind to the same receptors.     

Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial

BackgroundSarilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-6 receptor complex. In the MOBILITY phase III randomized controlled trial (RCT), sarilumab + methotrexate (MTX) treatment resulted in clinical improvements at 24 weeks that were maintained at 52 weeks in adults with rheumatoid arthritis (RA), who have inadequate response to MTX (MTX-IR). These analyses indicate the effects of sarilumab + MTX versus placebo on patient-reported outcomes (PROs) in this RCT.MethodsPatients (n = 1197) were randomized to receive placebo, sarilumab 150 or 200 mg subcutaneously + MTX every 2 weeks for 52 weeks; after 16 weeks, patients without ≥20 % improvement from baseline in swollen or tender joint counts on two consecutive assessments were offered open-label treatment. PROs included patient global assessment of disease activity (PtGA), pain, health assessment questionnaire disability index (HAQ-DI), Short Form-36 Health Survey (SF-36), and functional assessment of chronic illness therapy-fatigue (FACIT-F). Changes from baseline at weeks 24 and 52 were analyzed using a mixed model for repeated measures. Post hoc analyses included percentages of patients reporting improvements equal to or greater than minimal clinically important differences (MCID) and normative values in the FACIT-F and SF-36. Pearson correlation between observed PRO scores and clinical measures of disease activity was tested at week 24.ResultsBoth doses of sarilumab + MTX vs placebo + MTX resulted in improvement from baseline by week 24 in PtGA, pain, HAQ-DI, SF-36 and FACIT-F scores (p < 0.0001) that was clinically meaningful, and persisted until week 52. In post hoc analyses, the percentages of patients with improvement equal to or greater than the MCID across all PROs were greater with sarilumab than placebo (p < 0.05), with differences ranging from 11.6 to 26.2 %, as were those reporting equal to or greater than normative scores.ConclusionsIn this RCT in patients with MTX-IR RA, sarilumab + MTX resulted in sustained improvement in PROs that were clinically meaningful, greater than placebo + MTX, and complement the previously reported clinical efficacy and safety of sarilumab.

Trial registration

ClinicalTrials.gov. NCT01061736. February 2, 2010     

A test for meiotic drive in hybrids between Australian and Timor zebra finches

Meiotic drivers have been proposed as a potent evolutionary force underlying genetic and phenotypic variation, genome structure, and also speciation. Due to their strong selective advantage, they are expected to rapidly spread through a population despite potentially detrimental effects on organismal fitness. Once fixed, autosomal drivers are cryptic within populations and only become visible in between‐population crosses lacking the driver or corresponding suppressor. However, the assumed ubiquity of meiotic drivers has rarely been assessed in crosses between populations or species. Here we test for meiotic drive in hybrid embryos and offspring of Timor and Australian zebra finches—subspecies that have evolved in isolation for about two million years—using 38,541 informative transmissions of 56 markers linked to either centromeres or distal chromosome ends. We did not find evidence for meiotic driver loci on specific chromosomes. However, we observed a weak overall transmission bias toward Timor alleles at centromeres in females (transmission probability of Australian alleles of 47%, nominal p = 6 × 10^–5). While this is in line with the centromere drive theory, it goes against the expectation that the subspecies with the larger effective population size (i.e., the Australian zebra finch) should have evolved the more potent meiotic drivers. We thus caution against interpreting our finding as definite evidence for centromeric drive. Yet, weak centromeric meiotic drivers may be more common than generally anticipated and we encourage further studies that are designed to detect also small effect meiotic drivers.     

Radiation Resistance and Injury of Yersinia enterocolitica

The D values of Yersinia enterocolitica strains IP134, IP107, and WA, irradiated at 25°C in Trypticase soy broth, ranged from 9.7 to 11.8 krad. When irradiated in ground beef at 25 and −30°C, the D value of strain IP107 was 19.5 and 38.8 krad, respectively. Cells suspended in Trypticase soy broth were more sensitive to storage at −20°C than those mixed in ground beef. The percentages of inactivation and of injury (inability to form colonies in the presence of 3.0% NaCl) of cells stored in ground beef for 10 days at −20°C were 70 and 23%, respectively. Prior irradiation did not alter the cell's sensitivity to storage at −20°C, nor did storage at −20°C alter the cell's resistance to irradiation at 25°C. Added NaCl concentrations of up to 4.0% in Trypticase soy agar (TSA) (which contains 0.5% NaCl) had little effect on colony formation at 36°C of unirradiated Y. enterocolitica. With added 4.0% NaCl, 79% of the cells formed colonies at 36°C; with 5.0% NaCl added, no colonies were formed. Although 2.5% NaCl added to ground beef did not sensitize Y. enterocolitica cells to irradiation, when added to TSA it reduced the number of apparent radiation survivors. Cells uninjured by irradiation formed colonies on TSA when incubated at either 36 or 5°C. More survivors of an exposure to 60 krad were capable of recovery and forming colonies on TSA when incubated at 36°C for 1 day than at 5°C for 14 days. This difference in count was considered a manifestation of injury to certain survivors of irradiation.     

Assessment of pharmacological activities of two medicinal plant of Bangladesh: Launaea sarmentosa and Aegialitis rotundifolia roxb in the management of pain,pyrexia and inflammation

Background

The current study aims at evaluating the analgesic, anti-pyretic and anti-inflammatory properties of methanolic extract of the stem, bark and leaves of Launaea sarmentosa and Aegialitis rotundifolia roxb.

Results

The AELS and AEAR extract presented a significant (***p < 0.001) dose dependent increase in reaction time in writhing method and showed inhibition of 63.1% and 57.1% respectively at the doses of 400 mg/kg body weight while standard drug showed (P < 0.001) inhibition of 69.23%. In tail immersion method, AELS and AEAR showed maximum time of tail retention at 30 min in hot water i.e. 6.93 sec and 6.54 sec respectively at highest doses of 400 mg/kg body weight than lower dose while standard pentazocine showed reaction time of 7.62 sec. The AELS and AEAR extract also exhibited promising anti-inflammatory effect as demonstrated by statistically significant inhibition of paw volume by 32.48% and 26.75% respectively at the dose of 400 mg/kg body weight while the value at the dose of 200 mg/kg body weight were linear to higher dose at the 3^rd hour of study. On the other hand, Standard indomethacin inhibited 40.13% of inflammation (***P < 0.001). In Cotton-pellet granuloma method, AELS and AEAR extract at the dose of 400 mg/kg body weight exhibited inhibition of inflammation of 34.7% and 29.1% respectively while standard drug showed (P < 0.001) inhibition of 63.22%. Intraperitoneal administration of AELS and AEAR showed dose dependent decrease in body temperature in brewer’s yeast induced hyperthermia in rats at both doses. However, AELS significantly decreased body temperature (***p < 0.001) at 400 mg/kg compared to control.

Conclusions

Present work propose that the methanolic extract of Launaea sarmentosa and Aegialitis rotundifolia roxb possesses dose dependent pharmacological action which supports its therapeutic use in folk medicine possibly mediated through the inhibition or blocking of release of prostaglandin and/or actions of vasoactive substances such as histamine, serotonin and kinins.