فهرست مطالب alireza garjani

 Atherosclerosis is a complicated cascade of inflammatory processes, oxidative stress, and apoptosis, making it the most prevalent cardiovascular disease. The onset and progression of cardiovascular diseases are greatly influenced by oxidative stress. Targeting oxidative stress is an effective strategy for treating such diseases. Marrubiin is a bioactive furan labdane diterpenoid acts as a strong antioxidant to protect against oxidative damage. This study aimed to investigate the protective effects of marrubiin against oxidative stress and apoptosis in a cellular model of the vascular system.

 Human umbilical vein endothelial cells were treated with varying concentration of marrubiin and its IC50 value was determined. The antioxidant potential of marrubiin was assessed by measuring the intracellular level of glutathione (GSH) using a colorimetric technique. Since apoptosis plays a significant role in the plaque rupture, the study also evaluated the protective effects of marrubiin on the expression of key genes involved in apoptotic pathways.

 Cells treated with marrubiin showed increased GSH levels compared to cell therapy control cells, indicating marrubiin’s ability to counteract the effects of TNF-α’s on GSH levels. Furthermore real-time PCR analysis demonstrated that marrubiin upregulated Bcl-xl while downregulating caspase3 and Nox4 in treated cells. These findings suggest that marrubiin protects against apoptosis and oxidative stress.

 Based on our findings, marrubiin is recommended as a preventive/therapeutic treatment for diseases caused by elevated intracellular reactive oxygen species levels in cardiovascular diseases.

In many diabetic patients, spermatogenesis complications are frequent causing infertility problems.This study aimed to demonstrate the effect of Forskolin on male reproductive dysfunction caused by type 2 diabetes.

In this experimental study, type 2 diabetes was induced by a high-fat diet (HFD) for onemonth and then a low single dose injection (35 mg/kg) of streptozotocin (STZ) in Wistar rats. After 72 hours, rats withmore than 200 mg/dl of blood glucose were considered type 2 diabetic rats. Forty rats (200-250 g) were divided intofour groups (n=10) including group 1 (G1): rats with normal diet and buffer citrate (STZ solvent) injection, group 2(G2): control type 2 diabetic rats with HFD and STZ injection, group 3 (G3): type 2 diabetic rats received phosphatebuffer saline (PBS) as Forskolin solvent, and group 4 (G4): Forskolin treated diabetic rats (10 mg/kg) for 1 month.

In comparison to control group, in diabetic groups (G2 and G3) some parameters are increased significantly:The blood glucose (P=0.00078), testicular malondialdehyde (MDA) level and body weight (P=0.00009) and Baxgene expression (P=0.00007). Unlike, some parameters are decreased significantly: The serum level of testosterone(P=0.0009), testicular superoxide dismutase (SOD, P=0.00007) and glutathione peroxidase (GPX) levels (P=0.00008),sperm concentration (P=0.00008), motility (P=0.00009), normal morphological sperm (P=0.00008) and Bcl-2 geneexpression (P=0.00009). However, in Forskolin treated group (G4) the parameters stayed close to control values thatwas significantly (P=0.00007) higher than in G2 and G3 groups. Therefore, treatment with Forskolin significantlyimproved these abnormal changes in Forskolin-treated group.

Our study demonstrates that Forskolin is an effective antidiabetic agent, which significantly improvessperm concentration, testosterone levels, and antioxidant activity in diabetic rats.

Myocardial infarction (MI) is the leading cause of death among cardiovascular diseases. Reperfusion, the most harmful phase, is accompanied byinflammatory, oxidative, andapoptotic cascades in cardiomyocytes, impairing thehemodynamic and histologic status of the cardiac tissue. The Scrophularia genus is well known for the cardioprotective effects of its species, showing beneficial impacts on blood pressure and arrhythmias in previous studies.

Regarding the mechanisms involved in MI and the cardioprotective effects of the Scrophularia genus, in this study, we evaluated the cardioprotective effects of Scrophularia atropatana on MI.

Isoproterenol (ISO) injections (100 mg/kg, sc, 24-hour intervals) were used to induce MI in rats. In intervention groups, two hours after the first ISO injection, 5, 10, and 20 mg/kg S. atropatana extract was administered by gavage (24-hour intervals) for three days. Cardiac hemodynamic parameters were measured by placing a catheter into the right carotid artery and the left ventricle. Total antioxidant status (TAS), malondialdehyde (MDA) and lactate levels, and histopathologic changes were evaluated.

Induction of MI was accompanied by declined median arterial pressure (MAP), left ventricular systolic pressure (LVSP), and total antioxidant status (TAS) levels. In contrast, the heart rate, left ventricle end-diastolic pressure (LVEDP), malondialdehyde (MDA), and lactate levels were elevated in the MI group. Scrophularia atropatana treatment increased the MAP, LVSP, and TAS levels and significantly reduced the heart rate, LVEDP, MDA, and lactate levels. Also, S. atropatana treatment prevented histopathologic changes post-MI.

The improving effects of S. atropatana on MI injuries suggest its potential as a complementary cardioprotective medication.

The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19.

This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality.

Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (P = 0.014) and 4.9% vs. 23.9% (P ≤ 0.001), respectively). Admission time characteristics were the same for both groups except for diabetes and hyperlipidemia, which were significantly different between the two groups. Observations of naproxen consumption on endpoints, duration of hospitalization, and the levels of spO2 did not show any significant differences between the intervention and the control group. The adjusted OR for intubation in the intervention group versus the control group was 0.21 [95% CI, 0.04-0.99 (P = 0.047)].

In this trial, metformin consumption had no effect on mortality and ICU admission rates in non-diabetic patients. However, metformin improved COVID-19 complications in diabetic patients who had been receiving metformin prior to COVID-19 infection, and it significantly lowered the intubation rates.

4-Phenyl butyric acid (4-PBA) is a chaperone-mediated autophagy (CMA) inducer, which eliminates unnecessary and damaged cellular components through lysosomal enzymes. It could reduce misfolded and unfolded proteins produced after myocardial infarction (MI) and can improve cardiac function. We aimed to investigate the effect of 4-PBA on isoproterenol-induced MI in rats. 

Isoproterenol (100 mg/kg) was injected subcutaneously for two consecutive days simultaneous with an intraperitoneal (IP) injection of 4-PBA at 20, 40, or 80 mg/kg at 24-hr intervals for five days. On day 6, hemodynamic parameters, histopathological changes, peripheral neutrophil count, and total anti-oxidant capacity (TAC) were evaluated. The expression of autophagy proteins was measured by using western blotting. 4-PBA significantly improved post-MI changes in hemodynamic parameters.

Histological improvement was found in 4-PBA 40 mg/kg (P<0.05). The neutrophil count in the peripheral blood significantly decreased in the treatment groups compared with isoproterenol. Furthermore, 4-PBA at 80 mg/kg significantly increased the serum TAC compared with isoproterenol (P<0.001). Western blotting showed a significant decrease in the P62 level (P<0.05) of 40 and 80 mg/kg 4-PBA treated groups.

This study demonstrated that 4-PBA could have a cardio-protective effect against isoproterenol-induced MI, which can be due to autophagy modulation and oxidative stress inhibition. Obtaining effective results in different doses shows the need for an optimum degree of cell autophagic activity.

Toll-like receptors (TLRs) are essential receptors of the innate immune system, playing a significant role in cardiovascular diseases. TLR4, with the highest expression among TLRs in the heart, has been investigated extensively for its critical role in different myocardial inflammatory conditions. Studies suggest that inhibition of TLR4 signaling pathways reduces inflammatory responses and even prevents additional injuries to the already damaged myocardium. Recent research results have led to a hypothesis that there may be a relation between TLR4 expression and 5' adenosine monophosphate-activated protein kinase (AMPK) signaling in various inflammatory conditions, including cardiovascular diseases. AMPK, as a cellular energy sensor, has been reported to show anti-inflammatory effects in various models of inflammatory diseases. AMPK, in addition to its physiological acts in the heart, plays an essential role in myocardial ischemia and hypoxia by activating various energy production pathways. Herein we will discuss the role of TLR4 and AMPK in cardiovascular diseases and a possible relation between TLRs and AMPK as a novel therapeutic target. In our opinion, AMPK-related TLR modulators will find application in treating different immune-mediated inflammatory disorders, especially inflammatory cardiac diseases, and present an option that will be widely used in clinical practice in the future.

Eryngium is a genus with 274 species, which belongs to the Umbelliferae family. The nine species of this genus are endemic to Iran. The existence of terpenoids, saponins, flavonoids, and steroid components in most Eryngium species is the reason behind their anti-inflammatory, anti-cancer, and especially, anti-diabetic effects among the well-known medicinal plants.

This study aimed to evaluate the effects of anti-diabetic features of Eryngium thyrsoideum and caucasicum on streptozotocin (STZ)-induced diabetic mice.

The extract of the plants’ dried samples was prepared by using 70% ethanol solvent and adopting the maceration method. The mice were divided into eight groups, and the mice with a high blood glucose of more than 200 mg/dL were assigned to diabetic groups. Diabetic animals received different doses of the extract orally or through intraperitoneal (IP) injection for eighteen days. The animals were anesthetized by IP injection of ketamine and xylazine, and serum samples were isolated.

The results showed that hydroalcoholic extract of E. thyrsoideum significantly reduced the blood sugar level in diabetic groups receiving the extract (oral and IP) in low (100 mg/kg) and high (300 mg/kg) doses. Overall, oral glucose tolerance decreased significantly after two hours. Coincidental management of STZ and 300 mg/kg of the extract consumed orally reduced the blood sugar level remarkably. Serum malondialdehyde (MDA) and serum insulin levels significantly decreased and increased, respectively, in the diabetic groups receiving low and high doses (oral and IP) of the E. thyrsoideum extract. In the case of E. caucasicum, no significant effect in terms of reducing blood sugar and other factors was observed.

In sum, receiving 100 mg/kg and 300 mg/kg of hydroalcoholic extract (oral and IP) decreased the blood sugar level, while receiving oral glucose tolerance, serum MDA, and serum insulin caused a significant increase.

Inflammation in the implant-abutment interface is one of the main factors that can reduce implant stability. Therefore, this study investigated the effect of chlorhexidine, tetracycline, saliva, and a dry environment on the interleukin IL-1β and interleukin IL-6 levels of the gingival groove fluid at the implant-abutment interface.

Twenty-four (10 men and 14 women) patients referred to the Faculty of Dentistry for implant treatment, who met the inclusion criteria, were examined. Four different materials were used in each implant, including 2% chlorhexidine, 3% tetracycline, saliva, and a dry medium. Each test material was placed inside the implant screw during the anchorage session, and the healing screw was closed. Patients were then sampled in three implantation sessions and one month after prosthesis delivery. Interstitial fluid groove was used for sampling after cleaning the mouth (half an hour after three minutes of thorough brushing). The data were analyzed with SPSS 20 using ANOVA and relevant post hoc tests.

There was a significant difference in the mean IL-6 and IL-1β levels between the four materials (P<0.05). IL-6β levels were similar in tetracycline and chlorhexidine but significantly higher than in saliva and the dry environment (P<0.05). IL-6 and IL-1β levels in the saliva were significantly higher than in the dry environment (P<0.05).

The use of tetracycline at the junction of implant and abutment reduces the inflammatory cytokines IL-6 and IL-1β.

Type 2 diabetes mellitus is a chronic metabolic disorder with prominent vascular injuries. In this condition, the levels of multiple pro- and anti-angiogenic factors have been shown to change. This study aimed to investigate the possible effect of metformin on proangiogenic factor, endocan levels, via the modulation of p-AMPK/AMPK axis in diabetic mice.

Mice were randomly assigned to one of 4 groups (n=6): Control (normal saline) and the diabetic group was injected streptozotocin and two groups were given 50 and 100 mg/kg metformin orally, once daily for two weeks after diabetes induction. Endocan protein levels were detected in the liver and kidneys by ELISA and immunofluorescence analysis. Phosphorylation of AMPK was assessed using western blotting. Histological examination was performed to follow the metformin effect on Von Willebrand factor expression and diabetes-related pathologies.

ELISA assay showed an elevated levels of endocan in the renal and hepatic tissues of diabetic mice following treatment with metformin (p<0.05). Immunofluorescence and immunohistochemistry examination of kidneys showed that the increase of endocan protein coincided with the promotion of vWF factors in mice treated with metformin (p<0.05). We did not find endocan factor in hepatic tissue of diabetic mice pre- and post-treatment with metformin. Western blotting confirmed the phosphorylation of AMPK by metformin in kidneys (p<0.05), but these changes did not reach statistically significant levels in hepatic tissues (p>0.05).

Metformin could change the endocan levels during diabetic condition possibly by the modulation of p-AMPK/AMPK axis.

The present study examined the effects of high cholesterol and high oxidized-cholesterol diets on the myocardial expression of TLR4 and pro-inflammatory cytokine in rats.

Male Wistar rats were allocated into 6 groups and fed with a normal diet, cholesterol, and oxidized-cholesterol rich diets with or without isoproterenol-induced myocardial infarction. TLR4 and MyD 88 expression and levels tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured in the heart and serum.

Oxidized cholesterol-fed animals had higher serum levels of oxidized low-density lipoprotein (LDL) (263±13 ng/dL) than the cholesterol-fed animals (98±8 ng/dL; P<0.001). A high level of oxidized-LDL caused fibrotic cell formation and enhanced neutrophil infiltration in the absence of MI. Both cholesterol and oxidized-cholesterol upregulated TLR4 mRNA expression and increased TNF-α and IL-6 production in the hearts of rats with MI. In rats fed with oxidized-cholesterol the serum and myocardial levels of TNF-α (653±42 pg/mL, 1375±121 pg/100 mg, respectively) were higher than MI group (358±24 pg/mL, P<0.001 and 885±56 pg/100 mg, P<0.01). A significant correlation was seen between TLR4 expression and infarct size.

These findings suggest that cardiac TLR4 is preferentially upregulated by oxidized cholesterol in rats. Oxidized cholesterol may have a critical role in cardiac toxicity in the absence of pathological conditions.

Cynodon dactylon is a herbal medicine of interest in Iranian traditional medicine, which is used in cardiovascular diseases such as atherosclerosis and heart failure. The purpose of this study was to evaluate the effects of total extract of C. dactylon rhizomes on myocardial infarction and on post myocardial infarction (MI) heart tissue injuries.

Isoproterenol (100 mg/kg) was injected subcutaneously for two consecutive days for induction of MI in rats and C. dactylon extract was administered orally twice daily started before isoproterenol injection for 4 consecutive days.

Histopathological analysis showed a marked increase in myocardial necrosis in rats with MI (p<0.001). Treatment with C. dactylon (200 mg/kg) significantly (P<0.05) decreased myocardial necrosis. Hemodynamic variables were significantly suppressed in MI group and treatment with C. dactylon improved the hemodynamic parameters (P<0.05). Our electrocardiogram analysis demonstrated that C. dactylon with all doses increased R-Amplitude and R-R Interval (p<0.05, p<0.01) which were suppressed in MI group. Furthermore in treated groups with 100 and 200 mg/kg, P-R interval was also significantly increased in compared to MI group.

This study demonstrated that C. dactylon can improve hemodynamic and electrocardiogram parameters in isoproterenol-induced myocardial infarction and thereby suggest that it can be used as a cardioprotective agent in myocardial infarction.

Astragaloside IV (AST) is a saponin from the roots of Astragalus plants which has been widely used in traditional medicine to treat cardiovascular diseases. However, the effect of AST on myocardial infarction remains unknown. Thus, we aimed to investigate the cardio protective effects of AST on isoproterenol-induced myocardial infarction in rats. AST was isolated from the roots of Astragalus caspicus. Male Wistar rats were assigned to 5 groups of control, isoproterenol, and treatment with 2.5, 5 and 10 mg/kg AST given orally immediately before MI induction. Subcutaneous injection of isoproterenol (100 mg/kg) for two consecutive days was used to induce myocardial infarction. AST was given orally once daily for 4 days. On the fifth day hemodynamic and electrocardiographic parameters were assessed, and serum and tissue samples were used to evaluate histological and biochemical changes. To more assessment of the effects of AST on myocardium, we also used three doses of 0.1, 1 and 2 µM of AST in isolated heart model. In statistical analysis with one-way-ANOVA test, any differences between groups were considered significant at p<0.05. Isoproterenol injection caused ECG abnormality, hemodynamic depression and myocardium damage. While AST administration increased mean arterial blood pressure and heart rate and improved the left ventricular contractility. The peripheral neutrophil count, cardiac enlargement and cardiac ischemia was significantly decreased by AST. Also, histopathological evaluations showed that AST significantly diminished post MI necrosis and fibrosis in heart tissue and inhibited the inflammatory responses. The isolated heart studies hemodynamic factors showed no significant changes. Results showed that AST can protect heart against myocardial infarction by improving cardiac histology and ventricular contractility. Due to the lack of protection in the isolated heart, it is likely that the positive effects are more associated with the improvement of the oxidative stress markers in the systemic circulation, and the absolute effect on the isolated heart does not play an essential role in myocardium protection.

This study was carried out to boost the pharmacologic influence of carvedilol (CAR) (as a poorly water-soluble drug) by developing CAR-eudragit® RS100 (Eud) nanofibers and nanobeads benefiting an electrospraying approach. CAR-Eud nanoformulations with varying ratios (1:5 and 1:10) at total solution concentrations of 10 %, 15 % and 20 % w/v were formulated. The solution concentration remarkably impressed the size and morphology of the samples; in which, the nanobeads (mean diameter of 135.83 nm) were formed at low solution concentrations and high concentrations led to nanofibers (mean diameter of 193.45 nm) formation. DSC thermographs and PXRD patterns along with FTIR spectrum precisely showed CAR amorphization and no probable chemical interactions between CAR and Eud in the electrosprayed nanosystems. The in vitro release considerations demonstrated that the nanoformulations with the drug: polymer ratios of 1:10 and 1:5 depict rapid dissolution rate compared to the physical mixtures (PMs) and the pure drug. The in vivo studies in Wistar male rats suggested that the electrosprayed nanoformulation (1:10; 20 %) reduced the isoproterenol (ISO) induced elevation of heart rate, necrosis and accumulation of neutrophils in the heart tissue more efficient than the pure drug and PM. Our finding illustrated that the electrospraying as a profitable one-step procedure could be productively benefited to improve the physicochemical features and pharmacologic influences of CAR.

The editors of Pharmaceutical Sciences would like to thank all of our reviewers and particularly our top reviewers who have contributed to the journal in Volume 24 (2018)

Cardiovascular diseases (CVDs) is recognized as the leading cause of mortality worldwide. The increasing prevalence of such disease demands novel therapeutic and diagnostic approaches to overcome associated clinical/social issues. Recent advances in nanotechnology and biological sciences have provided intriguing insights to employ targeted Nanomachines to the desired location as imaging, diagnosis, and therapeutic modalities. Nanomedicines as novel tools for enhanced drug delivery, imaging, and diagnosis strategies have shown great promise to combat cardiovascular diseases.
In the current study, we intend to review the most recent studies on the nano-based strategies for improved management of CVDs.
A cascade of events results in the formation of atheromatous plaque and arterial stenosis. Furthermore, recent studies have shown that nanomedicines have displayed unique functionalities and provided de novo applications in the diagnosis and treatment of atherosclerosis.
Despite some limitations, nanomedicines hold considerable potential in the prevention, diagnosis, and treatment of various ailments including atherosclerosis. Fewer side effects, amenable physicochemical properties and multi-potential application of such nano-systems are recognized through various investigations. Therefore, it is strongly believed that with targeted drug delivery to atherosclerotic lesions and plaque, management of onset and progression of disease would be more efficient than classical treatment modalities.

Coronary artery disease is a leading cause of death worldwide. The present study has been designed to investigate efficacy of methanolic extract of Scrophularia subuphylla (S. subuphylla) on ischemia and reperfusion-induced myocardial injury in isolated rat heart.
The isolated male Wistar rat hearts (n= 5) were perfused by Krebs-Henseleit solution enriched with the extract (0, 1, 5, and 10 μg/ml), using the langendorff method. After 15 minutes stabilization, the hearts were subjected to 30 minutes regional ischemia and then 120 minutes reperfusion.
Administration of the extract did not improve any of cardiac markers of flow rate, heart rate and developed pressure. Number, percentage and duration of arrhythmias were not affected by any concentrations of the extract. However, the concentration of 1 and 5 µg/ml increased the VT duration compared to control group (P Generally, the methanolic extract of S. subuphylla at the doses which studied exhibited no protective effects against I/R-induced injures, which might be due to the high amount of cardiac glycosides with low therapeutic index.

Metformin is one of the most popular drugs tested against nonalcoholic fatty liver disease (NAFLD). The present study aimed to investigate whether calcium-vitamin D3 cosupplementation will intensify the effect of metformin on the prevention of high-fat, high-fructose (HFFr) diet-induced hepatic steatosis.
Male wistar rats (210±16 g) were assigned into the following seven groups: a Control group to receive a standard chow and six HFFr-fed groups to receive diets containing either normal (0.5% calcium and 1000 IU/kg vitamin D3) or high amount of calcium and vitamin D3 (2.4% calcium and 10000 IU/kg vitamin D3) (CaD), in combination with gastric gavage administration of either saline or 25 or 200 mg/kg body weight/day metformin. After 60 days, rats were assessed with respect to their anthropometric, metabolic and hepatic parameters, as well as their hepatic AMP-activated protein kinase (AMPK) phosphorylation.
Metformin and CaD, either alone or in combination, caused a significant reduction in HFFr diet-induced high serum aspartate aminotransferase (AST), hepatic steatosis and lipid accumulation without effect on insulin resistance and AMPK phosphorylation. In addition, slightly (and non-significantly) better effects of the combination in ameliorating steatosis and hepatic cholesterol content were observed.
Taken together, our results suggest that metformin and CaD could protect against the onset of HFFr diet-induced NAFLD in an insulin and AMPK-independent manner, without any marked additional benefits of their combination.

Saturated fatty acids and high sugar consumption along with sedentary lifestyle increase. The prevalence of atherosclerotic cardiovascular disease.
In the present study, dietary high cholesterol and oxidized cholesterol implications after myocardial infarction induced by Isoproterenol compared with myocardial infarction subjects with normal diet were studied.
36 animals were allocated randomly in 6 groups; three groups were fed with standard, high-cholesterol or high-oxidized cholesterol diets for 14 weeks. The other three groups received the same diets as well as ISO to induce acute MI. Lipid profile, OxLDL and total antioxidant levels were measured in the serum. The myocardial CoQ10 content was analyzed using a validated RP-HPLC. The infarct size was determined using triphenyl tetrazolium chloride staining. Histological changes and necrosis were evaluated using microscopic analysis.
Malondialdehyde concentration and infarct size in all high fat-fed groups were increased compared to the control group, especially in the ISO-induced MI groups. The total antioxidant level was decreased in both ISO-induced MI treated groups. CoQ10 content of the myocardium in control group (4.45 ± 0.19 μg/100 mg) was significantly higher than cholesterol-fed (2.99 ± 0.05 μg/100mg, P Overall, we concluded that the expansion of the infarct size and reduction of the CoQ10 content in the rat’s myocardium occurred as a result of elevated level of high serum level of OxLDL rather than non-oxidized LDL.

Under the diabetic condition, sustained production of oxidative/nitrosative stress results in irreversible vascular injuries. A great number of diabetic pathologies, such as inefficient or aberrant neo-angiogenesis emerge following chronic hyperglycemic condition. Lack of enough data exists regarding hydroxychloroquine (HCQ) contribution on angiogenesis during diabetes mellitus.
To better address whether HCQ could blunt or exacerbate oxidative status and angiogenesis under high glucose condition (HCG), human umbilical vein endothelial cells (HUVECs) were exposed to 30 µM HCQ in combination with 30 mM glucose over a course of 72 hours. Viability was measured was evaluated by MTT assay. We used Griess method and TBARS assay to monitor changes in the levels of NO and MDA followed by flow cytometric analysis of ROS using DCFDA. To show the impact of HCQ on cell motility and in vitro angiogenic properties, we exploited routine scratch test and in vitro tubulogenesis, respectively.
Our data showed that HCQ diminished cell viability under 5 and 30 mM glucose contents. HCQ significantly decreased the total levels of nitric oxide (NO), malondialdehyde (MDA), and reactive oxygen species (ROS) in both sets of environments. Additionally, inhibitory effects were observed on cell migration after exposure to HCQ (P  In overall, results suggest that HCQ changes the oxidative/nitrosative status of HUVECs both in 5 and 30 mM conditions. HCQ is able to reduce migration and angiogenic activity of HUVECs irrespective of the glucose content.

Rosmarinic acid is a polyphenolic compound with considerable antioxidant activities. We aimed to investigate its cardioprotective effects against isoproterenol-induced myocardial infarction (MI) in rats.
Male Wistar rats were assigned to 5 groups of control, isoproterenol, and treatments with 10, 20, 40 mg/kg of rosmarinic acid. Myocardial infarction was induced by subcutaneous injection of isoproterenol (100 mg/kg) once daily for 2 days. Rosmarinic acid was injected intraperitoneally once daily for 4 days, from the day of isoproterenol injection. In the fifth day the animals were anesthetized and hemodynamic and electrocardiographic parameters were recorded. After collecting the blood samples, the hearts were removed, weighed immediately to measure the cardiac enlargement, and kept for further histological studies. Lactate dehydrogenase and malondialdehyde were measured in the heart tissues for evaluating the damages and lipid peroxidation, respectively.
Rosmarinic acid revealed a considerable antioxidant activity in vitro, with IC50 of 6.43µg/ml. Isoproterenol induced cardiac arrhythmias, myocardial damage and cardiac enlargement. Rosmarinic acid significantly reduced peripheral neutrophil percentage and inhibited isoproterenol-induced ST-segment elevation and R-amplitude depression in the infarcted hearts. It also significantly increased the mean arterial pressure and heart rate and decreased the left ventricular end diastolic pressure. The ventricular contractility was considerably improved by rosmarinic acid. Histopathological evaluations showed that rosmarinic acid significantly diminished the post-MI necrosis and fibrosis in the myocardium and inhibited the cardiac edematous.
It is deducible from the results that rosmarinic acid improves the cardiac performance and inhibits post-MI myocardial depression, probably due to its anti-oxidative activity.

The upward desire in using traditional medicine as a remedy for treatment of different diseases has led the scientists to be thoughtful on plants as alternative sources of conventional drugs.
Herein, anti-inflammatory effects of Marrubium vulgare methanolic extract was evaluated in carrageenan- induced paw edema in rats through examining paw thickness, histological studies and myeloperoxidase activity (MPO). The antioxidant activity of M. vulgare extract and its phenolic and flavonoids content were evaluated by folin-Ciocalteau, and aluminum chloride colorimetric assay, separately.
The results showed that M. vulgare alleviated paw inflammation as indexed by reduction paw thickness (p In the main, the observed anti-inflammatory and antioxidant properties of M. vulgare could be attributed to the high amounts of phenolic and flavonoid content identified in the extract.

Myocardial infarction is a common presentation of coronary artery disease and the leading cause of death worldwide. The present study was investigated potential resistance to ischemia-reperfusion (I/R) injuries following administration of methanolic (MeOH) extract of Scrophularia frigida (S. frigida) in isolated rat heart. Male Wistar rat hearts (n= 8-10) were isolated and allowed to equilibrate for 20 min, and then subjected to 30 min regional ischemia followed by 120 min reperfusion. In the control group, Krebs-Henseleit (K/H) solution was perfused, however in the treatment groups; K/H solution containing 1, 5, and 10 µg/ml of extract was infused. In addition, total phenol, total flavonoid content and antioxidant property were evaluated and extract was subjected to phytochemical analysis. Administration of extract improved the flow rate, developed pressure and max and min left ventricular dp/dt. Number and duration of VT significantly were reduced by all extract concentrations in ischemic phase. In reperfusion phase, significant decreases in single and total arrhythmias were seen. Furthermore, 5 and 10 µg/ml of the extract remarkably decreased the infarct size. An appropriate concentration of S. frigida extract exhibited a protective effect against I/R-induced injures, which might be due to the antioxidant activity of the iridoids and phenolics.