Research in Pharmaceutical Sciences
Volume:7 Issue: 3, Aug 2012

Carum copticum from Apiaceae family has several biological effects including analgesic, anti-inflammatory, anxiolytic and antispasmodic activities. This study was designed to evaluate its effect on suppression of naloxone-induced morphine withdrawal signs. Hydroalcoholic and polyphenolic extracts were prepared according to the standard methods. Male mice (25-30 g) were made dependent by subcutaneous injection of increasing doses (30-90 mg/kg) of morphine. Withdrawal syndrome was elicited by naloxone (5 mg/kg, i.p.) and number of jumpings and also presence of ptosis, hyperventilation, piloerection, tremor and diarrhea were evaluated during a 30 min period started immediately after naloxone injection. The hydroalcoholic extract at doses of 1 and 2g/kg and the polyphenolic extract at doses of 0.5, 1 and 2 g/kg significantly (P<0.05) inhibited jumpings. Both extracts inhibited tremor significantly (P<0.01). Also the maximum applied dose of the extracts significantly (P<0.05) reduced ptosis. These results clearly show that Carum copticum is effective in suppression of morphine withdrawal and further studies are needed to find out the responsible constituents and also the mechanism of their actions.

One of the emerging therapeutic strategies for targeted treatment of most cancers is the use of immunotoxins which are fusion proteins consisted of a targeting and a toxic moieties. We previously showed that the recombinant A254-GMCSF fusion protein selectively kills acute myeloblastic leukemia cells which harbor a large number of granulocyte-macrophage colony stimulating factor (GMCSF) receptors. Since further in vitro and preclinical studies require large amounts of this fusion protein free from any troublesome material like lipopolysacharide, we selected the insect cell expression system. Thus, the coding sequences of the A254-GMCSF and its truncated form, A247-GMCSF, were cloned and expressed by Sf9 cells. Subsequently, specific cytotoxicity of the purified proteins was evaluated on GMCSF receptor positive cell lines. SDS-PAGE and Western blot analysis of the expressed A254GMCSF and A247GMCSF fragments revealed bands of about 60 kD which were larger than the theoretically predicted size of about 47 kD. Deglycosylation analysis showed that these proteins are N-glycosylated by the insect cells. However, any other post-translation modification of the proteins by insect cells could be the reason for higher molecular weight of the fragments. Cytotoxicity assays showed specific killing activity of these proteins on HL60 and U937 cell lines with IC50s ranging 2-2.5 µg/ml. These IC50 values are much higher than those obtained from bacterially expressed A254-GMCSF (80 ng/ml) which could be due to any modification performed by insect cells on the fusion proteins.

Several species of Prangos are traditionally used as emollient, carminative, tonic, anti-flatulent, anthelmintic and anti-thrombotic agents. Osthole, a coumarin isolated from Prangos, are believed to be responsible for some of its effects. In this research, relaxant effects of Prangos ferulacea extract and osthole on rat uterus contraction induced by KCl, acetylcholine (ACh), oxytocin and electrical field stimulation (EFS) was investigated and compared with atropine and salbutamol. P. ferulacea acetonic extract concentration-dependently relaxed uterine contraction induced by KCl (IC50=13 ± 0.81 mg/ml), ACh (IC50=12 ± 1.38 mg/ml), oxytocin (IC50=16 ± 3.14 mg/ml) and EFS (IC50=11 ± 1.5 mg/ml). However, the extract at lower concentration (2.5 µg/ml) potentiated the EFS response. Osthole only had inhibitory effect on rat uterus and its relaxant effect was observed at lower concentration in comparison with P. ferulacea extract. Osthole in a similar way inhibited the response to KCl (IC50=4 ± 0.13 mg/ml), ACh (IC50=4 ± 0.8 mg/ml), oxytocin (IC50=4 ± 0.8 mg/ml) and EFS (IC50=1.± 0.5 mg/ml). Our results demonstrated that osthole acted directly on uterus smooth muscle to induce relaxation, whereas P. ferulacea caused both contraction and relaxation of rat uterine smooth muscle. The relaxation of osthole might be mediated through Ca2+ channel blocking activity as it inhibited the response to KCl. Mechanisms other than Ca2+ channel blocking appeared to be responsible for ACh relaxation effect of osthole.

In this study antibacterial, antifungal and cytotoxic effects of some new 2,3-disubstituted 4(3H)-quinazolinone derivatives have been evaluated. The in vitro antibacterial and antifungal tests of new synthesized compounds were performed using MABA method against six strains of bacteria (three Gram-positive and three Gram-negative) and three strains of fungi. Also Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC) tests were performed. All synthesized compounds indicated mild antibacterial effects especially against Gram-negative bacteria. The most sensitive bacteriumwas E. coli. All strains of tested fungi were sensitive to the synthesized compounds mostly at 32 μg/ml and there was no significant differences in the sensitivity of the tested compounds. MBC and MFC data indicated that tested compounds act as bactriostatic and fungistatic agents. Cytotoxic activity of the compounds was screened at 1, 10 and 100 µM concentrations against HeLa cells using the MTT colorimetric assay. While the synthesized compounds did not show significant cytotoxic activities, compounds 7a3 and 7a4 reduced cell viability to about 50% at 100 µM concentration. The present study revealed that most of the new synthesized compounds possess good antifungal effects and they could be considered as valuable candidates for further structural modification to design more potent antifungal agents.

Trinitrobenzene sulfonic acid (TNBS)-induced colitis is one of the most common methods for studying inflammatory bowel disease in animal models. Several factors may, however, affect its reproducibility, rate of animal mortality, and macroscopic and histopathological outcomes. Our aim was to validate the main contributing factors to this method and compare the effects of different reference drugs upon remission of resultant colon injuries. TNBS was dissolved in 0.25 ml of ethanol (50% v/v) and instilled (25, 50, 100 and 150 mg/kg) intracolonically to the male Wistar rats. After determination of optimum dose of TNBS in male rats and assessment of this dose in female rats, they were treated with reference drugs including dexamethasone [1 mg/kg, intraperitoneally (i.p.) and 2 mg/kg, orally (p.o.)], Asacol (mesalazine, 100 mg/kg, p.o.; 150 mg/kg, enema) and hydrocortisone acetate (20 mg/kg, i.p.; 20 mg/kg, enema) which started 2 h after colitis induction and continued daily for 6 consecutive days. Thereafter, macroscopic and microscopic parameters and clinical features were assessed and compared in different groups. We found that the optimum dose of TNBS for the reproducibility of colonic damage with the least mortality rate was 50 mg/kg. Amongst studied reference drugs, hydrocortisone acetate (i.p.), dexamethasone (i.p. and p.o.) and Asacol (p.o.) significantly diminished the severity of macroscopic and microscopic injuries and could be considered effective for experimental colitis studies in rats. Our findings suggest that optimization of TNBS dose is essential for induction of colitis under the laboratory conditions; and gender exerts no impact upon macroscopic and histological characteristics of TNBS-induced colitis in rats. Furthermore, the enema forms of hydrocortisone and Asacol are not appropriate reference drugs.

A series of ortho-hydroxypyridine-4-ones were prepared in high yields and evaluated for antioxidant and iron chelating activities. N1-H hydroxypyridinones Va, Vb, and Ve were the best radical scavengers in DPPH free radical scavenging assay. Compound Vb was proved to be the most potent compound in hydrogen peroxide scavenging assay. All of the synthesized compounds had very close chelating ability, compounds containing N1-CH3 hydroxypyridinone ring were stronger chelating agents.

Standardization of induction of oxidative stress with Fenton mixture (FM) in isolated perfused rat kidney and the antioxidant effect of Terminalia arjuna bark in the isolated oxidatively stressed rat kidney has been evaluated. Six groups each containing eight isolated perfused rat kidneys were used for the present study and the oxidative stress was induced by perfusing the isolated kidneys with FM. The antioxidant effect of Terminalia arjuna at the dose of 250 and 500 mg/kg was evaluated in oxidative stress induced isolated kidneys. A significant (P<0.05) increase in lipid peroxidation, gluatamate pyruvate transaminase, glutamate oxaloacetate transaminase were observed in oxidative stress induced isolated kidney. On perfusion with extract, the oxidative stress was decreased with increasing in antioxidants while the marker enzymes were found to maintain the normal level. It was concluded from the present study that hydroalcholic extract of Terminalia arjuna bark at the dose of 250 and 500 mg/kg showed significant antioxidant potential in isolated perfused rat kidneys.

Increased exposure to estrogen has been associated with the risk of breast cancer. Substituted benzofuran derivatives with inhibitory effects on estrogen synthesis could be considered as a potential approach to reduce the risk of breast cancer. The study of cytotoxic effects of these compounds has suggested involvement of other mechanisms such as DNA damage. In the current study we have investigated genotoxic effects of some benzofuran derivatives on MCF-7 cell line. The MCF-7 cell line was exposed both to benzofuran phenylmethyl imidazole and its 4- fluoro, 4-chloro, 2-methoxy and 2-methyl derivatives for 2 h. The Comet assay was used to examine DNA damage due to this exposure. We also studied the DNA repair capacity after 2 h exposure to genotoxic concentrations of these compounds and their recovery were evaluated after 17 and 24 h, using the comet assay. The results indicated that genotoxic effects of these compounds appeared in concentrations of 10-8 to 10-6 M. The 4- fluoro and 4-chloro derivatives exhibited the highest genotoxicity and the unsubstituted benzofuran phenylmethyl imidazole had the lowest effect. The 4- fluoro, 4-chloro and 2-methyl derivatives were recovered after 24 h while 2-methoxy and the unsubstituted derivatives were recovered after 17 h. The results showed that these compounds are genotoxic and the concentration of tested benzofuran derivatives with genotoxic effects are not close to their enzyme inhibitory concentration. Moreover, our study shows that the DNA damages are repairable. Therefore, it seems that the investigated compounds have the potentials as therapeutic agents.

Water-distilled essential oil of Ferulago macrocarpa (Umbelliferae) fruits was analyzed using GC-MS for the first time. Forty-two components comprising 99.5% of the total oil were identified, of which bornyl acetate (40.8%), 2,3,6-trimethyl benzaldehyde (7.2%), δ-selinene (5.5%), 1,10-di-epi-cubenol (5.1%), germacrene D (3.5%), β-phellandrene (3.5%) and α-pinene (3.4%) were found to be the major components. The oil of F. macrocarpa fruits consisted of 15 monoterpene hydrocarbons (21.4%), 6 oxygenated monoterpenes (42.2%), 17 sesquiterpene hydrocarbons (22.4%) and one oxygenated sesquiterpene (5.1%). Three benzenoid derivatives also comprised 8.4% of the oil. Monoterpenes and sesquiterpenes comprised 63.6% and 27.5% of the F. macrocarpa fruits essential oil respectively; however, bornyl acetate (40.8%) was identified as the most abundant component of the oil.