Effect of total hydroalcholic extract of Nigella sativa and its n-hexane and ethyl acetate fractions on ACHN and GP-293 cell lines

AbstractMedicinal plants are noted for their many advantages including the ability to treat diseases such as cancer. In this study, we examined the antitumor effect of the medicinal plant Nigella sativa on the morphology, survival, and apoptosis of ACHN (human renal adenocarcinoma) and GP-293 (normal renal epithelial) cell lines. From a hydroalcoholic extract of N. sativa, n-hexane and ethyl acetate fractions were extracted. Cells were treated with various concentrations of total hydroalcholic extract and n-hexane and ethyl acetate fractions; cell viability, morphological changes, and apoptosis were then determined. Results were presented as mean ± standard error of the mean (SEM). One-way analysis of variance (ANOVA) was applied for the statistical analysis of the data. The total extract and the fractions in a dose- and time-dependent manner reduced the cell viability in ACHN with no effect on the GP-293 cell line. In addition, the total extract resulted in more morphological changes in the ACHN cells compared to the GP-293 cells. The effect of the total extract in inducing apoptosis after 48 hours in the ACHN cell line was greater than in GP-293. In addition, the effect of the two fractions was lower than the total extract at all used concentrations. Therefore, the effect of total extract and n-hexane and ethyl acetate fractions of N. sativa on cell viability and apoptosis in the ACHN cell line is greater than in the GP-293 cell line. However, the effect of the total extract is higher than either of the two fractions on their own

Effects of Zataria multiflora Extract and Carvacrol on Doxorubicin-Induced Oxidative Stress in Rat Brain

Background: Due to the antioxidant effects of Zataria multiflora (ZM) and Carvacrol (CAR) in various problems and the prominent role of the ROS in neurotoxicity induced by Doxorubicin (DOX), this study was designed to investigate the effects of ZM hydroalcoholic extract and CAR on DOX-induced oxidative stress in rat brain. Methods: 24 male rats were randomly divided into four groups including: 1)Control ,2)Doxorubicin (DOX) that received DOX via a tail vein on the first day of the study, 3,4) ZM+DOX and CAR+DOX which received ZM and CAR by gavage for 28 consecutive days. Brain tissue removed for redox markers evaluation. Results: MDA level in the DOX group was significantly increased compared to control group while in treated groups did not show any significant changes in comparison with the DOX group. Also, Thiol content in DOX group showed significant reduction compared to control group. Thiol contents in treated groups showed no significant difference compared to DOX group. Catalase (CAT) activity, an antioxidant enzyme, in the DOX group were significantly decreased compared to control group and increased in treated rats in comparison with the DOX group. Activity of Superoxide dismutase (SOD), an antioxidant enzyme, in the DOX group was significantly reduced compared to control group and increased in treated rats in comparison with the DOX group. Conclusion: The present study showed that ZM hydroalcoholic extract and CAR could inhibit DOX induced oxidative stress of the brain mainly with effect on the enzymatic antioxidant defense system

Protective effects of long-term administration of Ziziphus jujuba fruit extract on cardiovascular responses in L-NAME hypertensive rats

Objective: Ziziphus jujuba stimulates the release of nitric oxide (NO).  Because NO is involved in cardiovascular regulations, in this study the effects of hydroalcoholic extract of Z. jujuba on cardiovascular responses in acute NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats were evaluated. Materials and Methods: Rats were divided into 6 group (n=6): 1) saline, 2) L-NAME received (10mg/kg) intravenously, 3) sodium nitroprusside (SNP) (50µg/kg)+L-NAME group received SNP before L-NAME and 4-6) three groups of Z. jujuba (100, 200 and 400mg/kg) that treated for four weeks and on the 28th day, L-NAME was injected. Femoral artery and vein were cannulated for recording cardiovascular responses and drug injection, respectively. Systolic blood pressure (SBP), Mean arterial pressure (MAP) and heart rate (HR) were recorded continuously. Maximal changes (∆) of SBP, MAP and HR were calculated and compared to control and L-NAME groups. Results: In L-NAME group, maximal ΔSBP (L-NAME: 44.15±4.0 mmHg vs control: 0.71±2.1 mmHg) and ΔMAP (L-NAME: 40.8±4.0 mmHg vs control: 0.57±1.6 mmHg) significantly increased (p0.05). All doses of Z. jujuba attenuated maximal ∆SBP and ∆MAP induced by L-NAME but only the lowest dose (100 mg/kg) had significant effects (ΔSBP: 20.36±5.6 mmHg vs L-NAME: 44.1±4.0 mmHg and ΔMAP: 20.8±4.5 mmHg vs L-NAME: 40.8±3.8 mmHg (p0.05). Conclusion: Because long-term consumption of Z. jujuba extract, especially its lowest dose, attenuated cardiovascular responses induced by L-NAME, we suggest that Z. jujuba has potential beneficial effects in prevention of hypertension induced by NO deficiency

In vivo effects of allogeneic mesenchymal stem cells in a rat model of acute ischemic kidney injury

Objective(s): Renal ischemia-reperfusion injury (IRI) as a severe condition of acute kidney injury (AKI) is the most common clinical problem with high mortality rates of 35-60% deaths in hospital. Mesenchymal stem cells (MSC) due to unique regenerative characteristics are ideal candidates for the treatment of the ischemic injuries. This work is focused on the administration of MSC to IRI-induced AKI Wistar rats and evaluating their significance in AKI treatment. Material and Methods: Animals underwent surgical procedure and AKI was induced by 40 min bilateral renal pedicle clamping. Immediately after reperfusion, 2×106 rat bone marrow derived MSCs were injected via intra-parenchymal or intra-aortic route. Results: Animals subjected to AKI after days 1 and 3 showed significant increase in the serum creatinine and blood urea nitrogen (BUN) concentration along with a declined glomerular filtration rate (GFR) when compared with non-ischemic animals. On the other hand, treated animals showed a significant enhanced regeneration as compared to ischemic animals in both administration route groups. Conclusion: According to the results concluded from the renoprotective effects of MSC in IRI/AKI, MSCs could be considered as promising therapeutic approach for AKI in clinical applications

Doxorubicin-induced renal inflammation in rats: Protective role of Plantago major

Objective: The aim of the present study was to evaluate the possible protective effect of Plantago major (P. major) extract against doxorubicin (DXR)-induced renal inflammation in rats. Materials and Methods: 80 male albino rats were randomly divided into 8 groups as follows: control, DXR, Ext (extract) 600, Ext1200, dexamethasone+DXR, vitamin E+DXR, Ext600+DXR, and Ext1200+DXR. Duration of the study was 35 days and DXR was intravenously injected on the 7th day of the experiment. Tumor necrosis factor-alpha (TNF-α) production and monocyte chemoattractant protein-1 (MCP-1) expression levels were assessed in the left kidney. Serum creatinine concentration and osmolarity were determined on the 1st, 14th, 21st, 28th and 35th days of the experiment. Results: DXR caused a significant increase in renal expression of MCP-1 and TNF-α production compared to control animals. Administration of dexamethasone, vitamin E and P. major extract significantly improved the expression of these inflammatory mediators compared to DXR group. Compared to day 1 in DXR group, serum osmolarity showed a significant increase on days 21, 28 and 35. Also, on these days, serum osmolarity in DXR group was significantly higher than that on the same days in control group. In Vit E+DXR and Ext 1200+DXR groups, there was no significant changes in serum osmolarity among different days of the study. However, in these groups, serum osmolarity on days 21, 28 and 35 showed a significant decrease compared to the same days in DXR group. Conclusion: Present results suggest that hydroethanolic extract of P. major protected renal tissue against DXR–induced renal inflammation

Effects of dichloromethane and N-butanol fractions of Nigella sativa on ACHN and GP-293 cell line morphology, viability, and apoptosis

Background: Renal cell carcinoma (RCC) is among the top death-causing cancers. Medicinal herbs can also have beneficial effects on RCC treatment. In this project, we aimed to study the antitumor effect of dichloromethane and N-butanol fractions of hydroalcoholic extract of Nigella sativa (N. sativa) on the morphology, viability, and apoptosis of ACHN (human renal adenocarcinoma) and GP-293 (normal renal epithelial) cell lines. Materials and Methods: In this experimental study, N-butanol and dichloromethane fractions of N. sativa were obtained, and ACHN and GP293 cell lines were treated with various concentrations of dichloromethane (0–100 μg/mL) and N-butanol (0–12.5 μg/mL) fractions for 24, 48, and 72 hours. Then, morphological changes, viability, and apoptosis were investigated. Results: Our results indicated that dichloromethane and N-butanol fractions cause morphological changes and significant decreases in the percentage of live cells in the ACHN cell line, in a dose- and time-dependent manner. In the GP-293 cell line, however, a lower toxicity was observed in comparison with that found for ACHN. The results of flow cytometry showed an apoptotic effect of dichloromethane and N-butanol fractions on the ACHN cell line but a higher rate of apoptosis induction for the total extract compared to the two fractions in the renal cancer cell line compared to the normal cell line. Conclusion: Our findings demonstrated that these two fractions of N. sativa induce inhibitory effects on the ACHN cell line morphology and viability. These effects were lower than those induced by the total extract. In addition, the two fractions caused more marked effects in the renal cancer cell line compared with the GP-293 cell line

The Effects of Inactivation of Pedunculopontine Tegmental Nucleus by Cobalt (II) Chloride on Cardiovascular Responses in Hemorrhagic Hypotensive Rats

Introduction: Based on the evidence, the Pedunculopontine Tegmental nucleus (PPT) is involved in cardiovascular function regulation. In this study, the probable role of PPT on cardiovascular parameters in the hypotension induced by Hemorrhage (HEM) was evaluated.  Methods: The study rats were divided up into 5 groups: 1. Control (Saline); 2. Cobalt(II) chloride (CoCl2); 3. HEM; 4. Saline+HEM; and 5. CoCl2+HEM. Their right and left femoral arteries were cannulated for recording the cardiovascular responses and blood withdrawal, respectively. Saline and CoCl2 were microinjected into the PPT using the stereotaxic apparatus. Maximum changes of Systolic Blood Pressure (SBP), Mean Arterial Pressure (MAP), and the Heart Rate (HR) after the microinjection of CoCl2 in normal and Hemorrhage conditions were recorded. Changes of SBP, MAP, and HR were calculated over time at 5-min intervals and compared with those of the control and HEM groups using repeated measures ANOVA. The Independent sample t-test was used to compare the changes in cardiovascular parameters between the control and HEM groups at 0 and 20 min after Hemorrhage.  Results: The changes in SBP, MAP, and HR in the CoCl2 group were not significantly different from those in the control group. In the HEM group, the SBP and MAP changes significantly decreased (P<0.001) and HR changes significantly increased (P<0.001) compared to those parameters in the control group. In the CoCl2+HEM group, SBP and MAP changes were significantly attenuated compared to those in the HEM group (P<0.05) and HR changes induced by Hemorrhage decreased compared to that in the HEM group (P<0.01). Conclusion: Our results indicate that the PPT has no effects on normal cardiovascular parameters. However, it could modulate cardiovascular responses induced by Hemorrhage

Preventive effect of hydroalcoholic extract of Rosa damascena on cardiovascular parameters in acute hypertensive rats induced by angiotensin II

Background: Rosa damascena (R.D) is an aromatic plant with numerous therapeutic effects including cardiovascular effect. The mechanism cardiovascular effect of R.D is unclear and suggested mediated through renin–angiotensin system (RAS). Therefore, in this study, the role of hydroalcoholic extract of R.D on acute hypertension induced by AngII was evaluated. Methods: After anesthesia, femoral artery and vein of rats were cannulated for recording cardiovascular responses and drug injection, respectively. Systolic blood pressure (SBP), mean arterial blood pressure (MAP), and heart rate (HR) were recorded continuously by power lab software. Rats were divided into saline, AngII (50 ng/kg), AngII + Losartan (10 mg/kg), and three groups of R.D extract (250, 500, and 1000 mg/kg). Losartan and AngII were administered intravenously and the other ones intraperitoneal. In the R.D groups, 30 min after injection of the extract, AngII was injected and the maximum changes in SBP, MAP, and HR were calculated and compared to that in control and AngII groups. Results: Results show that AngII significantly increased SBP, MAP, and decreased HR than the control group which was blocked by losartan. SBP and MAP in R.D + AngII groups were significantly lower than AngII alone (P < 0.05 –P < 0.001). Only MAP in higher dose (1000 mg/kg) was significantly lower than low dose (250 mg/kg; P < 0.05). Two higher doses also significantly decreased bradycardia induced by AngII (P < 0. 01). Conclusions: The preventive effect of hydroalcoholic extract of R.D on cardiovascular parameters maybe is mediated by suppression of AngII activity

Role of the Nitrergic System of the Cuneiform Nucleus in Cardiovascular Responses in Urethane-Anesthetized Male Rats

Background: The presence of nitric oxide (NO) in the cuneiform nucleus (CnF) has been previously shown. In this study, NG-nitro-L-arginine methyl ester (L-NAME) (an inhibitor of NO synthase), L-arginine (L-Arg) (a precursor of NO), and sodium nitroprusside (SNP) (a donor of NO) were microinjected into the CnF and cardiovascular responses were investigated. Methods: Seventy male rats were divided into 7 groups (n=10 each): 1) saline, 2 and 3) L-NAME (30 and 90 nmol), 4 and 5) L-Arg (20 and 60 nmol), and 6 and 7) SNP (9 and 27 nmol). After anesthesia, the femoral artery was cannulated and cardiovascular parameters were recorded using a PowerLab system. Time course changes in mean arterial pressure (ΔMAP) and heart rate (ΔHR) were calculated and compared with those in the control group (repeated measures ANOVA). Maximum ∆MAP and ∆HR were also compared with those in the control group (independent sample t test). Results: ∆MAP with both doses of L-NAME (30: P=0.026 and 90: P=0.007) and ∆HR with the higher dose (P=0.034) were significantly higher than those in the control group. Maximal ∆MAP with both doses (P<0.01 and P<0.001, n=10) and maximal ∆HR with the higher dose (P<0.01) were significantly higher than those in the control group. Changes in L-Arg with both doses were not significantly higher than those in the control group (P=0.26, n=8). ∆MAP and ∆HR of SNP only with the higher dose were significantly lower than those in the control group (P=0.006 and P=0.035), and maximal responses with the higher dose were lower than those in the control group (∆MAP: P<0.01 and ∆HR: P<0.05, n=7). Conclusion: Our results showed that the nitrergic system of the CnF had an inhibitory effect on central cardiovascular regulation

Effect of hydro-alcoholic extract of Rosa damascena on cardiovascular responses in normotensive rat

Objective: Rosa damascena mill L. (R. damascena) is a well-known plant with fragrant effects. Several therapeutic effects of this plant on respiratory, gastrointestinal and nervous systems have been reported. It is also suggested to have beneficial effect on cardiovascular system especially blood pressure regulation. The present study was carried out to evaluate acute cardiovascular effect of hydro-alcoholic extract of R. damascena. Materials and Methods: Thirty-two male Wistar rats were randomly divided into four groups (n= 8 for each group). After anesthesia, a catheter was inserted into the femoral artery and blood pressure and heart rate (HR) were continuously recorded by a power lab system. Animals received three doses of hydro-alcoholic extract (250, 500, and 1000 mg/kg) via peritoneal (i.p). After 30 min, systolic blood pressure (SBP), mean arterial pressure (MAP) and HR were recorded and maximal changes were compared to control group. Results: Injection of all doses of the extract did not significantly change HR compare to control group. The SBP, dose dependently, was decreased by all doses of the extract and the maximal response was significant compared to saline group (p Conclusion: This study provides evidence of a hypotensive effect of hydro-alcoholic extract of R. damascena with no significant effect on HR. Therefore, R. damascena is suggested to have beneficial effect to control blood pressure. However, it needs to be more investigated