Saeed Samarghandian

Apoptosis, an important mechanism that contributes to cell growth reduction, is reported to be induced by Crocus sativus (Saffron) in different cancer types. However, limited effort has been made to correlate these effects to the active ingredients of saffron. The present study was designed to elucidate cytotoxic and apoptosis induction by safranal, the major coloring compound in saffron, in a human prostate cancer cell line (PC-3). PC-3 and human fetal lung fibroblast (MRC-5) cells were cultured and exposed to safranal (5, 10, 15, and 20 μg/ml). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to assess cytotoxicity. DNA fragmentation was assessed by gel electrophoresis. Cells were incubated with different concentrations of safranal, and cell morphologic changes and apoptosis were determined by the normal inverted microscope, Annexin V, and propidium iodide, followed by flow cytometric analysis, respectively. MTT assay revealed a remarkable and concentration-dependent cytotoxic effect of safranal on PC-3 cells in comparison with non-malignant cell line. The morphologic alterations of the cells confirmed the MTT results. The IC50 values against PC-3 cells were found to be 13.0 ΁ 0.07 and 6.4 ΁ 0.09 μg/ml at 48 and 72 h, respectively. Safranal induced an early and late apoptosis in the flow cytometry histogram of treated cells, indicating apoptosis is involved in this toxicity. DNA analysis revealed typical ladders as early as 48 and 72 h after treatment, indicative of apoptosis. Our preclinical study demonstrated a prostate cancer cell line to be highly sensitive to safranal-mediated growth inhibition and apoptotic cell death. Although the molecular mechanisms of safranal action are not clearly understood, it appears to have potential as a therapeutic agent.

Honey is reported to contain various compounds such as antioxidants. Chrysin is a natural and biologically active compound extracted from honey. It possesses antioxidant properties and promotes cell death by perturbing cell cycle progression. We focused on the possible role that chrysin may act as a potential anticancer agent, and tested its biological activity and possible mechanisms in the human lung adenocarcinoma epithelial cell line. Antiproliferative effect of honey and chrysin were determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay; DNA fragmentation was determined by gel electrophoresis assay; apoptosis was detected by flow cytometer; apoptosis-related gene expression was detected by reverse transcription polymerase chain reaction assay; and activation of caspase-3 and caspase-9 were evaluated by a colorimetric assay; Bax and Bcl-2 protein expression were also analysed by western blotting. The results revealed that the cell viability decreased in a concentration- and time- dependent manner in the malignant cells treated with honey and chrysin in comparison with the nonmalignant cells. The IC50 values of honey against A549 cells were determined 15 ± 0.05% and 8 ± 0.05 % after 48 and 72h, respectively. The IC50 dose of chrysin was determined to be 49.2 ± 0.6 and 38.7 ± 0.8 μM at 48 and 72 h, respectively. Reactivity with Annexin V fluorescence antibody and propidium iodide showed that chrysin induced apoptosis in the lung cancer cells (p<0.001). Moreover, chrysin treatment resulted in the activation of caspase-3 and - 9 and an increase in the Bax/Bcl-2 ratio (p<0.01). Bax protein expression was increased but Bcl-2 protein expression decreased in chrysin-treated cells .Chrysin inhibits the growth of the lung cancer cells by inducing cancer cell apoptosis via the regulation of the Bcl-2 family and also activation of caspase-3 and -9, which may, in part, explain its anticancer activity. This study shows that chrysin could also be considered as a promising chemotherapeutic agent and anticancer activity in treatment of the lung cancer cells in future.

Methods: Monolayer cultures of ARPE19, RGC5, and CEC were used. Bevacizumab (0.008–2.5 mg/ml), diluted in culture medium, was added to cells that were growing on cell culture dishes. Cellular proliferative activity was monitored by 5′-bromo-2′-deoxyuridine ...

An imbalance between production of reactive oxygen species (ROS) and its elimination by antioxidant defense system in the body has been implicated for causes of aging and neurodegenerative diseases. This study was design to assess the changes in activities of antioxidant enzymes (superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase), lipid peroxidation and reduced glutathione (GSH) levels in the brain of 2, 10 and 20 month old rats, and to determine the effect of safranal on the status of selected oxidative stress indices in the 10 and 20 month old rats. The aged rats (10 and 20 months) were given intraperitoneal injections of safranal (0.5 mg/kg day) daily for one month. The results of this study demonstrated that aging caused significant increase in the level of lipid peroxidation as well decrease in the GSH level and activities of SOD and GST in the brain of aging rats. The results of this study showed that safranal ameliorated the increased lipid peroxidation level as well as decreased GSH content of the brain of 10 and 20 month old rats. In addition, safranal treatment to the 20 month old rats, which restored the SOD and GST activities. In conclusion, safranal can be effective to protect susceptible aged brain from oxidative damage by increasing antioxidant defenses.

The levels of corticosterone and noradrenalin as the two nociception modulators modify after stress condition. The propose of current study was to investigate the effect of chrysin on formalin-induced nociceptive behaviors and serum levels of corticosterone and noradrenalin in rats. Pain was induced by applying 20 μL of 5% formalin in distilled water in the subplantar of the right hind paw. Chrysin (50, 100 and 150 mg/kg, intraperitoneally (i.p.) was administered 60 min before formalin injection. Morphine (10 mg/kg, i.p.) was administered 30 min before formalin injection. The control group received the same volume of saline by i.p. injection 30 min before formalin injection. Chrysin treatment can significantly decrease formalin-induced pain in rat in a dose-dependent manner. Chrysin (150 mg/kg) significantly inhibit the first phase (P < 0.01), whereas, the all concentration of chrysin were affected on the later phase of formalin-induced pain (P < 0.05). Chrysin could significa...

Bisphenol A (BPA), an endocrine-disrupting chemical, has been considered as a possible risk factor for diabetes and its complications. However, the underlying mechanisms of BPA-induced diabetes are not clear. The present study was performed to evaluate the effects of BPA on the hyperglycemia, lipid abnormalities and oxidative stress. In this study, the mice were divided into three groups of six animals each: One group as a control (C) and two other groups which exposed to 0.5 and 2 mg/kg concentrations of BPA. BPA powder was dissolved in sterile extra virgin olive oil and injected intraperitoneally to the tested groups, while the control group only received pure olive oil for 4 weeks. After 4 weeks, the changes of glucose, lipid profile reduced, total protein, glutathione (GSH), malondialdehyde (MDA), total antioxidant status (TAS), catalase (CAT) and super oxide dismutase (SOD) were determined in serum and pancreas. The results indicated that BPA dose-dependently increased the leve...

Restraint stress may be associated with elevated free radicals, and thus, chronic exposure to oxidative stress may cause tissue damage. Several studies have reported that carvacrol (CAR) has a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CAR on restraint stress induced oxidative stress damage in the brain, liver, and kidney. For chronic restraint stress, rats were kept in the restrainers for 6 h every day, for 21 consecutive days. The animals received systemic administrations of CAR daily for 21 days. To evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) activities were measured in the brain, liver, and kidney. In the stressed animals that received vehicle, the MDA level was significantly higher (P < 0.001) and ...

This study evaluated whether crocin, a bioactive component of saffron, has a protective effect on kidney through reducing the oxidative stress and inflammatory response in aged rats. In this study the changes in activities of antioxidant enzymes, lipid peroxidation, glutathione (GSH) levels and the expression of pro-inflammatory cytokines in the serum and renal tissue were evaluated by ELISA and RT-PCR, respectively. The middle and aged rats were given intraperitoneal injections of crocin (10, 20, 30 mg/kg/day) for 4 weeks. After 4 weeks, animals were anesthetized with diethyl ether. The kidney samples were taken for biochemical analysis. The results revealed the aging was associated with a significant decrease in the activities of antioxidant enzymes, and GSH content with increase in lipid peroxidation level in kidney of the aged rats (p < 0.001). The increased levels of serum renal functional parameter, oxidative parameters (p < 0.01) and also pro-inflammatory cytokine level...

... Antitrypsin Levels in Burned Mice Kaoru Koike, Yotabo Shinozawa, Motoyasu Yamazaki, Tomoyuki Endo, Ryosuke Nomura, Juktchi Aiboshi,1 Saeed Samarghandian,1 ... severe burn injury by as much as 50%, and that low albumin levels often persist for many weeks (Moody et al ...

Honey is reported to contain various compounds such as antioxidants. Chrysin is a natural and biologically active compound extracted from honey. It possesses antioxidant properties and promotes cell death by perturbing cell cycle progression. We focused on the possible role that chrysin may act as a potential anticancer agent, and tested its biological activity and possible mechanisms in the human lung adenocarcinoma epithelial cell line. Antiproliferative effect of honey and chrysin were determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay; DNA fragmentation was determined by gel electrophoresis assay; apoptosis was detected by flow cytometer; apoptosis-related gene expression was detected by reverse transcription polymerase chain reaction assay; and activation of caspase-3 and caspase-9 were evaluated by a colorimetric assay; Bax and Bcl-2 protein expression were also analysed by western blotting. The results revealed that the cell viability decreased in a concentration- and time- dependent manner in the malignant cells treated with honey and chrysin in comparison with the nonmalignant cells. The IC50 values of honey against A549 cells were determined 15 ± 0.05% and 8 ± 0.05 % after 48 and 72h, respectively. The IC50 dose of chrysin was determined to be 49.2 ± 0.6 and 38.7 ± 0.8 μM at 48 and 72 h, respectively. Reactivity with Annexin V fluorescence antibody and propidium iodide showed that chrysin induced apoptosis in the lung cancer cells (p<0.001). Moreover, chrysin treatment resulted in the activation of caspase-3 and - 9 and an increase in the Bax/Bcl-2 ratio (p<0.01). Bax protein expression was increased but Bcl-2 protein expression decreased in chrysin-treated cells .Chrysin inhibits the growth of the lung cancer cells by inducing cancer cell apoptosis via the regulation of the Bcl-2 family and also activation of caspase-3 and -9, which may, in part, explain its anticancer activity. This study shows that chrysin could also be considered as a promising chemotherapeutic agent and anticancer activity in treatment of the lung cancer cells in future.

In this study, biochemical changes due to long term usage of morphine in rat's liver were assessed. Twenty male Wistar rats (180-220 g) were included and divided into two groups. Normal saline was given intraperitoneally in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4, 8, and 10 mg/kg/day in the first, second and the third ten days of the study, respectively. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and liver malondialdehyde (MDA) level as well as activities of superoxide dismutase (SOD), glutathione-s-transfrase (GST) and catalase (CAT) were measured. Serum levels of AST, ALT and LDH were significantly higher in the morphine group compared with the control group. The mean MDA level of liver was significantly higher in the morphine group compared with the control group (P < 0.05). The activities of SOD, GST and CAT were significantly lower in the morphine group compared with the control group (P < 0.01). Our findings pointed out the risk of hepatic damage due to long term usage of morphine via disturbance oxidant-antioxidant balance. Although morphine is showed to be effective in pain treatment, their toxic effects should be kept in mind during the chronic usage.

Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.

In this study, biochemical changes due to long term usage of morphine in rat's liver were assessed. Twenty male Wistar rats (180-220 g) were included and divided into two groups. Normal saline was given intraperitoneally in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4, 8, and 10 mg/kg/day in the first, second and the third ten days of the study, respectively. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and liver malondialdehyde (MDA) level as well as activities of superoxide dismutase (SOD), glutathione-s-transfrase (GST) and catalase (CAT) were measured. Serum levels of AST, ALT and LDH were significantly higher in the morphine group compared with the control group. The mean MDA level of liver was significantly higher in the morphine group compared with the control group (P < 0.05). The activities of SOD, GST and CAT were significantly lower in the morp...

Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with diabetes mellitus. Findings indicate that safranal has antioxidant properties. The aim of the present study was the evaluation of possible protective effects of safranal against oxidative damage in diabetic rats. In this study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, three safranal (0.25, 0.50, 0.75 mg/kg/day)-treated diabetic groups. Diabetes was induced by streptozotocin (STZ) in rats. STZ was injected intraperitoneally at a single dose of 60 mg/kg for diabetes induction. Safranal (intraperitoneal injection) was administered 3 days after STZ administration; these injections were continued to the end of the study (4 weeks). At the end of the 4-week period, blood was drawn for biochemical assays. In order to determine the changes of cellular antioxidant defense systems, antioxidant enzymes including gluta...

Our knowledge about a link between buprenorphine and hepatotoxicity is controversial. This study evaluated the effects of buprenorphine on the liver of young, adult, and aged rats. For this reason, young, adult, and aged rats received intraperitoneally 0.25, 0.5, and 1 mg/kg buprenorphine for 30 days. The present results revealed that the normal aging was associated with a significant decrease in the activities of antioxidant enzymes, and an increase in the liver lipid peroxidation, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities in the aged rats. This study also demonstrated that buprenorphine led to a significant increase in the serum activities of ALT, AST, and LDH as well as liver lipid peroxidation content with a decrease in the antioxidant enzymes in the liver of buprenorphine-treated aged rat versus the aged matched control animals. In conclusion, the present results demonstrate that buprenorphine deteriorated oxidative damage in the aged livers.

The efficacy of herbal medicine has been confirmed in treatment of diabetes mellitus (DM) by amelioration of oxidative stress. The present study was designed to investigate protective effects of Cichorium intybus extract (CIE) against oxidative damage in diabetic rats. In this study, the rats were divided into the control (C), diabetic (D), D + CIE- treated (125 mg/kg/day) groups. Male Sprague-Dawley rats aged 9 weeks (160 ± 15 g) were administered with streptozotocin (STZ, 60 mg/kg) intraperitoneally (ip) to induce experimental diabetes. From 3 days after STZ administration to the end of the study (4 weeks) the ethanolic extract of CIE was administered (i.p) to diabetic rats. Body weight and blood glucose were measured weekly. At the end of the 4-week period, blood was drawn for biochemical assay, in order to determine the changes of cellular antioxidant defense system, serum oxidative damage and serum lipid were measured profile. CIE injection to diabetic rats resulted in significant reduction in blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels and significant elevation high density lipoprotein cholesterol (HDL-C) level as well as increase in the body weight as compared with the rats treated with STZ alone. In the treated diabetic group, we also observed the significant increase in reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) with decline in malondialdehyde (MDA) level compared with the non-treated diabetic group. These results suggest that the Cichorium intybus extract has antioxidant properties and prevents diabetes complications by modulation of oxidative stress system.

Despite the wide spread of lead environmental pollution, the effect of this heavy metal on respiratory disease was not shown yet. In respect to increased oxidative stress is an important mechanism in the pathogenesis of respiratory disease, the present study was designed to examine the association between lead toxicity and lung disease via measuring oxidative stress biomarkers in bronchoalveolar lavage fluid (BALF) and lung tissue of rat. For this aim, 32 rats were divided into the following groups of eight animals each: control, three lead tested (received lead acetate in the drinking water for a period of 14 d at concentrations of 250, 500 and 1000 ppm) groups. At the end of the 2 week period, malondialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) contents were measured to assess free radical activity in the BALF and lung tissue. Superoxide dismutase (SOD) was also determined. A significant dose-dependent increase in the BALF supernatant and lung homogenate levels of MDA and NO with decrease GSH level and SOD activity were observed in the lead-treated groups compared with the control group (p < 0.05). Thus, lead acetate may be contributed to respiratory disorders via increased oxidative stress.

Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow coloring principle in turmeric, is a polyphenolic and a major active constituent. Besides anti-inflammatory, thrombolytic and anti-carcinogenic activities, curcumin also possesses strong antioxidant property. The neuroprotective effects of curcumin were evaluated in a weight drop model of cortical contusion trauma in rat. Male Wistar rats (350-400 g, n=9) were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and subjected to head injury. Five days before injury, animals randomly received an i.p. bolus of either curcumin (50 and 100 mg/kg/day, n=9) or vehicle (n=9). Two weeks after the injury and drug treatment, animals were sacrificed and a series of brain sections, stained with hematoxylin and eosin (H&E) were evaluated for quantitative brain lesion volume. Two weeks after the injury, oxidative stress parameter (malondialdehyde) was also measured in the brain. Curcumin (100 mg/kg) significantly reduced the size of brain injury-induced lesions (P<0.05). Neurological examinations (rotarod and inclined-plane tests) were performed on days 1, 3, 7 and 14 post-brain injury. Control injured rats had a significant neurological deficit during 2 weeks (P<0.001). The injury increased brain levels of the malondialdehyde by 35.6% and these increases were attenuated by curcumin (100 mg/kg). Curcumin treatment significantly improved the neurological status evaluated during 2 weeks after brain injury. The study demonstrates the protective efficacy of curcumin in rat traumatic brain injury model.

Conventional and newly emerging treatment procedures such as chemotherapy, catalytic therapy, photodynamic therapy and radiotherapy have not succeeded in reversing the outcome of cancer diseases to any drastic extent, which has led researchers to investigate alternative treatment options. The extensive repertoire of traditional medicinal knowledge systems from various parts of the world are being re-investigated for their healing properties Crocus sativus L., commonly known as saffron, is the raw material for one of the most expensive spice in the world, and it has been used in folk medicine for centuries. Chemical analysis has shown the presence of more than 150 components in saffron stigmas. The more powerful components of saffron are crocin, crocetin and safranal. Studies in animal models and with cultured human malignant cell lines have demonstrated antitumor and cancer preventive activities of saffron and its main ingredients, possible mechanisms for these activities are discussed. More direct evidence of anticancer effectiveness of saffron as chemo-preventive agent may come from trials that use actual reduction of cancer incidence as the primary endpoint. This review discusses recent literature data and our results on the cancer chemopreventive activities of saffron and its main ingredients.

The association between lead exposure and asthma is controversial. The effect of inhaled lead acetate on lung inflammation, tracheal responsiveness and immune components in guinea pigs after sensitization was examined in this study. Five groups of guinea pigs were randomly allocated to control (group C), sensitized (group S), and three test groups exposed to inhaled lead concentrations 0.1, 0.2 and 0.4M Pb after sensitization (n=6 for each group). The measured variables included tracheal responsiveness to methacholine and ovalbumin (OA); total and differential white blood cells (WBC) counts of lung lavage; serum cytokine levels (IFN-γ and IL-4); and lead concentration in lung tissue. Tracheal responsiveness to methacholine and OA; total and differential WBC counts; IL-4 and IFN-γ were significantly increased in sensitized animals compared to control group (p<0.05 to p<0.001). However, the ratio of IFN-γ/IL-4 were significantly decreased in group S (p<0.05). In addition, all measured parameters in animals exposed to highest lead concentration and most of them in animals exposed to medium lead concentration were significantly higher than group S, except for the IFN-γ and IFN-γ/IL-4 ratio, which were significantly decreased (p<0.05 to p<0.001). The lead concentration in lung tissues of all test animals was significantly higher than that of group C (p<0.001 for all groups). These results showed that lead acetate exposure can cause further increase in tracheal responsiveness to methacholine and OA, total and differential WBC count and IL-4, IFN-γ and IFN-γ/IL-4 ratio. Therefore, environmental exposure to lead may aggravate the severity of asthma.

Journal of Medicinal Plants Research Vol. 4(23), pp. 2551-2556, 4 December, 2010 Available online at http://www.academicjournals.org/JMPR ISSN 1996-0875 ©2010 Academic Journals ... Modulation of programmed cell death by honey bee in ... Saeed Samarghandian1*, ...