Gestational exposure to silymarin increases susceptibility of BALB/C mice fetuses to apoptosis

Background: silymarin is a flavonolignan that has been the subject of research to evaluate the beneficial properties for decades. Silymarin has been known for its potent cytoprotective, hepatoprotective and antioxidant activities. The goal of the present study was to gain a deeper understanding of possible molecular mechanisms of apoptosis of the injuries induced by silymarin on BALB/c mice fetuses

Methods: the present experimental study was carried out in virgin female BALB/c mice. The animals were divided randomly into 4 groups. Three test groups were injected intraperitoneally with silymarin at doses of 50, 100 and 200mg/kg/day during gestational days 6-15. The control group received the solvent by the same route at equivalent volume. Western blot analysis was conducted to determine the levels of caspase-3 and caspase-8 in fetal heart, kidney, lungs and brain tissue

Results: the results of this study showed that silymarin administration during organogenesis at doses of 50, 100 and 200 mg/kg can significantly increase the protein levels of caspase-3 and 8 in heart, kidneys and brain tissues of mice fetuses compared with control group [p<0.001]. Silymarin exposure could not change the level of apoptotic markers in fetal lung tissue

Conclusion: according to the results, programmed cell death, especially via the intrinsic pathway, plays a pivotal role in the pathogenesis of silymarin-induced malformations in some tissue including heart, kidneys and brain. More studies are needed to determine other molecular mechanisms underlying silymarin- induced embryo toxicity

Cytotoxic and apoptotic potential of rheum turkestanicum janisch root extract on human cancer and normal cells

Rheum turkestanicum Janischew. [Polygonaceae] is a plant that grows in central Asia and in north-east of Iran. Traditionally, people use roots of/?, turkestanicum as an anti-diabetic and anti-hypertensive as well as anticancer agent. In this study the cytotoxicity and apoptogenic properties of ethyl acetate [EtOAc], [-hexane and H[2]O extracts from Rheum turkestanicum Janischew. [Polygonaceae] root were determined against HeLa and MCF-7 cell lines and human blood lymphocytes. Malignant and non-malignant cells were cultured in RPMI1640 medium and incubated with different concentrations of plant extracts. Cell viability was measured by MTS assay. Apoptotic cells were evaluated using PI staining of DNA fragmentation by flow cytometry [sub-G 1 peak]. The degree of DNA fragmentation was analyzed using agarose gel electrophoresis based on the formation of inter-nucleosomal units. The expression of apoptosis-related protein Bax and PARP cleavage were detected by Western blotting. EtOAc and w-hexane extracts decreased cell viability in malignant but not in non-malignant cells, as a concentration and time dependent manner. EtOAc extract induced a sub-G 1 peak in flow cytometry histogram of treated cells compared to the control. DNA fragmentation indicating apoptotic cell death was involved in R. turkestanicum induced toxicity and cleaved PARP fragment was also detected. In conclusion, this is the first report on the cytotoxic effects of R. turkestanicum in which apoptosis played an important role. However, further evaluations are needed to fully understand the possible anti-tumor properties

Evaluation of nitric oxide or opioid receptors involvement in antinociceptive properties of silymarin

It has been shown that Silybum marianum or its extracts have hepatoprotective, antioxidant, anticancer, anti-inflammatory and anti-diabetic effects. Nitric oxide [NO] plays an important role in neurotransmission, neuroprotection, neurotoxicity and pathological pain, as a neurotransmitter or neuromodulator in the central nervous system. Therefore, this experiment was performed in order to assess the analgesic effects of single and multiple-dosed ip administration of silymarin and the probable role of nitric oxide or opioid receptors using tail flick assay. Based on our results, only silymarin 100 mg/kg showed analgesic properties. Since naloxone did not change silymarin's analgesic effects, it is concluded that opioid receptors are not involved. Although in the presence of L-arginine, analgesic effect of silymarin remained intact, but it is not possible to strongly determine the involvement of nitric oxide pathway here. Based on our results, the difference between anti nociceptive properties of single and multiple-dosed treatment of silymarin 100 mg/kg is not significant. It is concluded that silymarin exert its analgesic effects via other mechanisms. Inhibiting 5-lipooxygenase and neutrophil chemotaxis to inflammation location could be the probable ways of silymarin's action

Effect of curcumin on doxorubicin-induced cytotoxicity in H9c2 cardiomyoblast cells

Doxorubicin [DOX], a widely used chemotherapeutic agent can give rise to serve cardiotoxicity by inducing apoptosis. Curcumin, the active compound of the rhizome of Curcuma longa L. has anti-inflammatory, antioxidant and anti-proliferative activities. Curcumin has been identified to increase cytotoxicity in several cancer cell lines in combination with DOX, but there is no study about its effect and DOX on normal cardiac cells. Therefore, in the present study, we evaluated the effect of curcumin on apoptosis induced by DOX in H9c2 rat heart-derived cells. Cell viability was determined by MTT assay. Also, activation of caspase-3 was evaluated by spectrophotometry. Quantitative real time RT-PCR was used to evaluate the expression of c-IAP1. Detection of intracellular DOX accumulation was performed by flow cytometry. No toxicity observed when the cells exposed for 1 hr to different concentrations of curcumin, but pretreatment of cells with curcumin increased cytotoxicity of DOX in a dose dependent manner. Analysis of caspase-3 activation showed that curcumin pretreatment increased caspase-3 activation. RT-PCR analysis clearly showed that curcumin significantly decreased mRNA gene expression of c-IAP1 compared to cells treated with DOX alone. Pretreatment of H9c2 cells with DOX and curcumin had no effect on the intracellular accumulation of DOX. Our observations indicated that subtoxic concentrations of curcumin sensitize H9c2 cells to DOX-induce apoptosis. These results suggest that the use of curcumin in combination with DOX in malignancy must be reevaluated

Protective effect of aqueous and ethanolic extracts of portulaca oleracea against cisplatin induced nephrotoxicity

Poriulaca oleracea L. is a herbaceous weed from portulacaceae family. It can be found in many parts of the world. Modern pharmacological studies have demonstrated that P. oleracea have antioxidant effects. The protective effect of aqueous and ethanolic extract of P. oleracea against cisplatin-induced renal toxicity was studied in rats. Single intraperitoneal injection of 4 mg/kg cisplatin was administrated to rats. After 5 days, blood urea nitrogen [BUN] and serum creatinine [Scr] concentration were determined. Effect of aqueous and ethanolic extracts, before and after cisplatin injection on BUN and Scr, as well as morphological renal damage, was evaluated. It was indicated that treatment with aqueous and ethanolic extracts of P. oleracea in the highest dose [0.8 and 2 g/ kg], 6 and 12 hr before cisplatin injection reduced BUN and Scr. Tubular necrotic damage was not observed either. Results suggest that P. oleracea extract may protect against cisplatin-induced renal toxicity and might serve as a novel combination agent with cisplan to limit renal injury

Antinociceptive effect of elaeagnus angustifolia fruits on sciatic nerve ligated mice

The role of Elaeagnus angustifolia fruit as an analgesic agent in acute pain has been proved earlier. In this study, the effects of aqueous extracts of three parts of this fruit [pericarp, medulla and seed] on chronic pain were investigated in mice. A partial nerve injury was made using a tight ligature around the sciatic nerve, then doses [0.5, 1, 1.5 g/kg, i.p.] of pericarp, medulla and seed extracts were injected in nerve ligated mice. The effect of different doses of three parts of this fruit on chronic pain was examined 14 days after sciatic nerve ligation using the hot-plate test. Controls received saline [5 ml/kg, i.p.] and imipramine [40 mg/kg]. In the hot plate test, intraperitoneal injection of different doses of three parts of this fruit showed considerable analgesic effect on nerve ligated mice that was dose dependent with duration of action of 120 min. Administration of the aqueous extracts of pericarp, medulla and seed of E. angustifolia fruit indicated significant analgesic effect on chronic pain in nerve ligated animals

Effect of Portulaca oleraceae L. extracts on the morphine dependence in mice

This study was initiated to investigate the effect of Portulaca oleraceae on morphine dependence in mice. Dependence was induced using the subcutaneous injections of morphine for 3 days. On the day 4, morphine injected 2 h prior to intraperitoneal injection of naloxone. The plant extracts ethanolic or aqueous administered 0.5 h before the final dose of morphine. The number of jumping during the 30 min period after naloxone injection was considered as a measure of withdrawal syndrome. Both extracts reduced the jumping episodes dose-dependently. The maximum effect was observed at doses of 0.28 g/kg and 1.4 g/kg for the aqueous and ethanolic extracts, respectively. Clonidine and extracts decreased the total activity in locomotion test. These findings indicated that Portulacea oleraceae extracts can decrease morphine dependence in mice