Based on epidemiological evidences، cardiac glycosides such as digoxin have been recently proposed as an anticancer drug. However، the outcomes are controversial and even application of digoxin as an anticancer agent is doubtful. Hence، in the present study، the anticancer properties of digoxin and its potential mechanisms have been investigated in a liver cancer cell line i.e. HepG2. hep G2 cell line was cultivated in RPMI-1640 with %15 FBS and 2µM digoxin for 6، 12، 24 and 48 hours. Apoptosis was detected in the cells treated with digoxin using in situ cell detection kit. Furthermore، the cells were stained by Giemsa to study the occurrence of senescence following administration of digoxin. Expression of HIF- α was determined by RT-PCR after the cells exposed to digoxin as well. Our findings revealed that digoxin induces apoptosis in a time dependent manner. A significant number of apoptotic cells were observed after 48hours exposure to digoxin (P<0.05). It seems that digoxin elicits senescence in hepG2 cell line in time dependent manner as well. Following digoxin treatment، down regulation of HIF1-α was considerably detected in the liver cancer cell line. Again، the result was prominent after 48hrs. Our findings strongly suggest that digoxin exerts its antitumor properties through inducing of apoptosis، cellular senescence and changing of HIF1- α gene profile. Due to cytotoxic effects of digoxin on the cells، it would be essential to determine the minimum toxicity dose and the drug mechanisms before its application in clinics for the patients.

Seeds of Ocimum basilicum (Basil) have many phytochemical components with anti- inflammatory and antioxidant property like its leaves. Aim of this study was to determine anti-inflammatory effect of O. basilicum seeds extract (OBSE) and mucilage (OBSM) on acetic acid-induced colitis in rats. Three doses of OBSE and OBSM (100، 200، and 400 mg/kg) were administered orally to separate groups of male Wistar rats، 2 h before ulcer induction (acetic acid 4%) and continued for 5 days. Normal saline (5 ml/kg) and dexamethasone (1 mg/kg) were administered in control and reference groups، respectively. All rats were sacrificed 24 h after the last dose (at sixth day) and tissue injuries were assessed macroscopically، pathologically and for myeloperoxidase (MPO) activity. All three doses of OBSM and OBSE reduced ulcer score، area and index as well as weight of wet colonic tissue compared to the control group significantly. In addition، OBSM (at three doses) and OBSE (400 mg/kg) were statistically effective in attenuation of mucosal inflammation severity and extent، crypt damage، total colitis index، and mono-amino oxidase (MPO) activity compared with controls. While both fractions were effective in amelioration of colitis in rats، OBSM was more effective than OBSE especially with greater doses (200، 400 mg/kg). It seems that mucilage form of O. basilicum could exert more protection against oxidative stress and inflammatory mediators in colitis tissue suggesting a suitable candidate for colitis prevention or treatment as alternative or complementary therapy.

This study was carried out to test the activity of the methanol-water (20:80 V/V) extract of the leaves of Urtica dioica L. on the DNA and sperms in Rat. The antioxidant activity of the extract was tested using two systems: the β-carotene spray method and measuring the coupled oxidation of β-carotene and linoleic acid. The rats were treated with the extract at 100، 500، and 1000 mg/kg body weight، and the extracted DNA from white blood cells. The results showed the presence of good antioxidant activity in the extract through the appearance of 3 positive bands (Rf= 0.4، 0.94، 0.96) that kept the yellow color of β-carotene. This activity was also confirmed from the ability of the extract to keep the of absorbance (at 470 nm) stable، relatively high، and close to the positive control curve for BHT that shows antioxidant activity when using the coupled oxidation of β-carotene and linoleic acid. Treating the rats with the extract at concentrations of 100 and 500 mg/kg did not have the effect on the DNA، while the third concentration (1000 mg/kg) caused DNA destruction. This was clear from the appearance of DNA smear with a molecular size approximately 0.3-20.5 Kbps. The study of the effect of the extract on rat sperm، the result shows different abnormalities in sperm، especially in high dose.

Date، Phoenix dactylifera، is a commonly used food in arid and semiarid regions of the world including Iran. Date seeds، are low-cost agriculture by-products and used for several medicinal uses and animal food، however، there are no records on its likely toxic effects. To investigate the safety of P. dactylifera، we investigated its acute and sub-chronic toxicity in Wistar rats in both sexes. Animals were treated with four different single doses (5g/kg) of P. dactylifera extract oral gavage (per oral، p.o.)، and checked for symptoms of toxicity two weeks after dispensation. In the sub-chronic toxicity study، P. dactylifera seeds were administered in three different doses (500، 1000، 1500 mg/kg) through 45 days. Fatality، clinical symptoms، body weight alteration، gross findings، organ weights، hematological and biochemical criteria، and histological specifications were screened all along the study. We found no fatality or morbidity in clinical manifestations، corpse weight، or necropsy evidence in none of the rats in the acute study. Regarding the outcome of the sub-chronic assay، a meaningful decline in urea concentration in male animals and no significant differences observed in other hematological criteria in both sexes. No significant histopathological difference in lung and heart tissue of different groups were observed but there are kidney cortex congestion and hepatocyte focal degeneration in female and male rats taking elevated doses (1500 mg/kg) of palm kernel extract، respectively. Analyses of the obtained results with the information of signs، behaviour، and health monitoring could lead to the conclusion that the no observed adverse effect level of P. dactylifera was defined to be 1000 mg/kg for male and female rats.

The antiproliferative effect of dichloromethane extract of Artemisia aucheri (A. aucheri) has been demonstrated previously on human cancerous cell lines. In the current study، further fractionation was carried out on the dichloromethane extract of A. aucheri and their cytotoxic effects were evaluated on three human cancer cell lines; SKNMC، MCF-7، and A2780. Cell viability was determined by MTT assay and activation of caspases was evaluated by spectrophotometry. Quantitative real time RT-PCR was used to evaluate the genes expression. Detection of DNA fragmentation was carried out by flow cytometry. The obtained results showed that fractions 5 and 7 (F5 and F7) have a potent cytotoxic effect، especially against MCF-7 cells. F5 and F7 also induced apoptosis through the DNA fragmentation and mitochondrial membrane potential (MMP) disruption in MCF-7 cells. The caspase-3، 9 enzyme activities were also increased after exposure to F5 and F7. Moreover، caspase-8 activity increased significantly after exposure to F7 but not F5. The level of mRNA expressions of Bax and Smac/DIABLO was increased after exposure to both fractions. A detectable decrease was also observed in the mRNA expression of Bcl-2 after exposure to F7. No change was observed in the level of mRNA expressions of tumor suppressor P53 after exposure to F7. Therefore، the cell cycle arrest and apoptosis induced by F7 could probably be mediated through a p53-independent mechanism. Taken together، these observations demonstrated that the cytotoxic effect of F5 and F7 on MCF-7 cells is likely exerted via apoptotic cell death.

Acrylamide (ACR) monomer is an effective neurotoxicant، which damages the central and peripheral nervous systems in humans and animals. It also has broad applications in different industries. Grape seed extract (GSE) possesses antioxidant properties. The present study was designed to evaluate the beneficial effects of GSE against ACR-induced neurotoxicity in both in vitro and in vivo. In our in vitro study، the effect of different concentrations of GSE on ACR toxicity (IC50) in PC12 cells was evaluated using MTT assay. Moreover، in another experiment، the effect of GSE on neural toxicity induced by ACR was evaluated in rats. Pretreatment with GSE (10-100 µM) significantly decreased ACR induced cytotoxicity. In Wistar rats، exposure to ACR (50 mg/kg IP for 11days)، significantly induced severe gait abnormalities but treatment with GSE (12.5 mg/kg) reduced ACR induced neurotoxicity in animals. After that، rats were sacrificed and malondialdehyde (MDA) as a marker of lipid peroxidation and GSH content were determined in brain tissue. ACR induced lipid peroxidation and increased level of MDA، while reduced GSH level. Treatment with GSE significantly reduced level of MDA and increased GSH content in cerebral cortex (p<0.001). The results suggest that the neuroprotective effect of GSE in this model in part، may be due to its ability to scavenge free radicals and its effective recovery of the antioxidative defense system.

This study evaluated the anti-atherosclerosis effect of aqueous extract and polysaccharide-enriched fraction of Prosopis farcta on adhesion and inflammatory cascades in vascular endothelial cells and related molecular mechanisms. Cellular toxicities of LPS، plant extract and polysaccharide-enriched fraction were analyzed in vitro using the MTT method. The ROS accumulation، mRNA expression of ICAM1 and VCAM1، and COX activity were measured in HUVEC cells. These results revealed a new underlying mechanism for anti-atherosclerosis effect of P. farcta and polysaccharide-enriched fraction by attenuating inflammatory cascade mediated by COX expression، modulating expression of cell-adhesion molecules including VCAM-1 and ICAM-1، and diminishing oxidative stress agents.

Angiogenesis is the formation of new blood capillaries، and it is important for physiological processes such as growth and development and pathological conditions such as tumor growth and metastasis. Angiogenesis inhibition is considered very useful in the prevention and treatment of cancer. Matrix metalloproteinases (MMPs) are a family approximately consists of 28 zinc-dependent content endopeptidase which degrade the extracellular matrix (ECM) and play an important role on angiogenesis development and tumor metastasis. Therefore، inhibition of MMPs prevents the angiogenesis. The expression and levels of MMP-2 and MMP-9 is increased in many human tumors، including ovarian، breast and prostate tumors. In this study، cytotoxic effects of (Z)-3-((5-(benzylthio)-4H-1،2،4-triazol-3-yl)imino)-5-haloindolin-2-one derivatives 1a-1l were evaluated in MCF-7 (human breast adenocarcinoma) cell line by MTT assay. Then، the potency of the tested of some synthesized compounds was evaluated on supernatants activities and levels of MMP-2 and MMP-9 by gelatin zymography and ELISA methods. Among the tested compounds، 1j، 1l and 1k had the greatest cytotoxicity against MCF-7 cell line compared to the positive (sunitinib) and negative (DMSO) controls. Moreover، our observations indicated that the compounds 1j، 1l and 1k decreased the supernatants activities of MMP-2 and MMP-9 more than others and all of the tested compounds considerably decreased the supernatants levels of MMP-9. Finally، our findings suggest that the tested derivatives are probably able to inhibit macromolecules like MMPs which have essential role in angiogenesis pathway.

Morinda citrifolia fruit have been used treatment numerous diseases such as dysentery، heart diseases، AIDS، cancers and others. The aim of this study was to determine the antibacterial and antioxidant activities of anthraquinones fractions from the fruits of Morinda citrifolia. Well diffusion assay، minimum inhibitory concentration and the minimum bactericidal concentration were used to test antibacterial activity against Staphylococcus aureus، Escherichia coli، Bacillus cereus، Pseudomonas aeruginosa MRSA and Helicobacter pylori. DPPH radical scavenging activity and Superoxide dismutase activity assays were used to evaluate their antioxidant activity. LC-MS analysis was used to identify anthraquinones and SEM studies that revealed mode of action. Anthraquinones fraction from the fruit of M. citrifolia exhibited significant at P value < 0.05 inhibition against the test of bacteria including MRSA and H. pylori. Anthraquinones fractions from the fruit have high level 91.40% with significant at P value < 0.05 of antioxidant activities compared compare with control. LC-MS analysis of anthraquinones of the M. citrifolia identified specific compounds in this fraction. SEM results of these substances showed significant morphological changes of cell wall، membrane and destruction of bacterial cell. It could be concluded that the anthraquinones of the part of this plant had a good antibacterial and antioxidant effects. The results suggest the anthraquinones from M. citrifolia fruit can be a new source of antimicrobials against pathogenic bacteria and antioxidant source.

Allium Jesdianum Boiss (Allium) has many pharmacological beneficial effects. However، its protective effects against hepatotoxicity induced by carbon tetrachloride (CCl4) have not been explained. The present study was undertaken to investigate the protective effects of Allium on liver oxidative stress in male mice treated to CCl4. Forty-two male mice were randomly divided into six groups. Control group، sham group، CCl4 group، Allium 500 mg/kg + CCl4، Allium 1000 mg/kg + CCl4، Allium 2000 mg/kg + CCl4. Results showed that CCl4 significantly increased serum levels of alanine aminotransferase، aspartate aminotransferase، lipid peroxidation and decreased catalase activity and glutathione level، and also caused inflammation، coagulative necrosis، degeneration of hepatocytes، fatty change، and dilated sinosouids in liver tissue. While administration of Allium at the all doses used significantly altered all examined endpoints that induced by CCl4. Overall، our findings suggest that Allium possesses hepatoprotective effects against CCl4-induced hepatotoxicity by suppressing oxidative stress and improving the antioxidative defense system.