Rheumatoid arthritis: current therapeutics compendium.

Rheumatoid arthritis is a common chronic inflammatory disease with substantial economic, social, and personal costs. Its pathogenesis is multifactorial and complex. The ultimate goal of rheumatoid arthritis treatment is stopping or slowing down the disease progression. In the past two decades, invention of new medicines, especially biologic agents, revolutionized the management of this disease. These agents have been associated with an improved prognosis and clinical remission, especially in patients who did not respond to traditional disease-modifying anti-rheumatic drugs (DMARDs). Improvement in the understanding of the rheumatoid arthritis pathogenesis leads to the development of novel biologic therapeutic approaches. In the present paper, we summarized the current therapeutics, especially biologic agents, available for the treatment of rheumatoid arthritis.

Applying Vasopressin-Pre-Conditioned Human Adipose Mesenchymal Stem Cells Improves Heart Condition after Transplantation into Infarcted Myocardium.

Transplantation of H-AdMSCs may improve heart function after MI. AVP is a neurohypophyseal hormone that reduces cardiovascular damage. This study investigated the role of AVP preconditioning in the survival of MSCs and their effect on myocardial repair in the MI rats. H-AMSCs were isolated and incubated for 3 days. The expression of oxytocin and vasopressin receptors was evaluated by Real-time-PCR. Forty male Wistar rats were divided into 4 groups: control, sham, ASC and AVP-ASC. Ischemia was established by ligation of LAD coronary artery. Electrocardiography, fibrosis, angiogenesis, and apoptosis in myocardium were determined after 7 days. Results showed that preconditioned MSCs significantly increased cardiac function when compared with group that received non-preconditioned MSCs. This was associated with significantly reduced fibrosis, increased vascular density, and decreased resident myocyte apoptosis. Results indicate that AVP preconditioned MSCs can be consider a novel approach to management of MI.

Investigation of the effect of 8 weeks of high-intensity interval training and berberine supplementation on some echocardiography and electrocardiogram indices following myocardial ischemia-reperfusion in rats.

BACKGROUND: Myocardial ischemia leads to left ventricular (LV) dysfunction and cardiac arrhythmia. The present research was conducted with the aim to explore echocardiography changes and electrocardiogram parameters of the hearts of rats with ischemia-reperfusion injury (IRI). METHODS: The study subjects included 50 male Wistar rats) 8-10 weeks), which were divided into 5 groups (1: trained, 2: supplemented, 3: combined (training and supplementation), 4: sham, and 5: control). High-intensity interval training ý(HIIT) was performed for 8 weeks, 5 sessions per week. Rats belonging to groups 2 and 3 received 10 mg/kg berberine. Finally, after 48 hours, electrocardiogram and echocardiography were performed on all rats. Moreover, myocardial ischemia was performed by descending coronary artery ligation for 30 minutes. RESULTS: There were significant differences between the 5 groups in terms of the volumes and dimensions of LV end-systolic dimension (LVSD), LV end-diastolic dimension (LVDD)ý, fractional shortening cardiac output, ejection fraction (EF), stroke volume (SV), ventricular tachycardia (VT), and ventricular ectopic beats (VEBs) episodes, duration of VTs, and ECG parameters (P ≤ 0.05). CONCLUSION: Berberine supplementation and HIIT, as preconditioning agents, can possibly prevent the elevation of EF and fractional shortening, the reduction of cardiac output and SV, and arrhythmia improvement after myocardial IRI. Finally, these changes result in increased LV function and decreased mortality in rats with myocardial IRI.

Up-regulation of chemokine receptor type 4 expression in the ischemic reperfused heart by alcoholic extract of Cichorium intybus rescue the heart from ischemia injury in male rat.

OBJECTIVES: Cichorium intybus is used in traditional medicine for various diseases including heart disease. This study aimed at evaluating the chemokine receptor type 4 up-regulation and cardioprotective effects of hydroalcoholic extract of C. intybus in a rat model of ischemic reperfusion. METHODS: Animals in four groups of eight rats each received vehicle or one of three doses of C. intybus (50, 100 or 200 mg/kg/d) for 14 days. Then they were subjected to 30 min of ischemia followed by 7 days of reperfusion. At the end of the experiment, blood specimens were prepared for serum assays. The level of myocardium chemokine receptor type 4 was also measured using RT-PCR. KEY FINDINGS: Cichorium intybus (CI-50) improved infarct size, episodes of the ventricular ectopic beat, ventricular tachycardia, and duration of ventricular tachycardia, QTc shortening. It also stabilized the ST segment changes and increased heart rate during ischemia. The blood pressure decreased in CI-50 group in comparison to the control and CI-200 group. C. intybus increased serum superoxide dismutase and reduced lactate dehydrogenase activity, Cardiac Troponin I and malondialdehyde levels. C. intybus led to an increase in the expression of chemokine receptor type 4. CONCLUSIONS: These findings suggest that C. intybus administration before ischemia is able to induce cardioprotective effect against ischemic reperfusion injury, probably through chemokine receptor type 4 over-expression and antioxidant activity.

Cardioprotective activity of ethanolic extract of Echinophora cinerea against aluminum phosphide poisoning in rats.

Rice tablet, also known as aluminum phosphide (ALP), is a nonorganic material used as an insecticide and rodenticide in the storage and transportation of grains. Phosphine gas, released from the chemical material, in contact with humidity and weak acid, can induce poisoning and death. This study was conducted to investigate the effect of ethanol extract of Echinophora cinerea leaves on ALP poisoning in heart in rats. In this study, factors such as blood pressure, heart rate, electrocardiography, and biochemical biomarkers of oxidative stress of cardiac tissue were evaluated. The use of Echinophora extract at a dose of 200 mg per/kg primarily improved bradycardia, hypotension, and cardiac conduction. Echinophora extract at a dose of 400 mg could protect body against oxidative stress. It seems that Echinophora extract has significant clinical positive effects that can be employed in treatment protocols of acute poisoning associated with ALP. PRACTICAL APPLICATIONS: Administration of the Echinophora cinerea extract can improve bradycardia, hypotension, and conduction disturbances of the heart caused by poisoning with rice tablet. E. cinerea extract also can increase the levels of antioxidant enzymes and protect the body against oxidative damage caused by poisoning with rice tablet. Therefore, Echinophora extract has significant clinical positive effects that can be used in treatment protocols of acute poisoning associated with aluminum phosphide.

A Review on the Most Important Medicinal Plants Effective in Cardiac Ischemia-Reperfusion Injury.

Ischemia, referring to reduction and restriction of perfusion to myocardial tissue which involves coronary artery through the formation of misplaced clots and thrombosis, is one of the most important cardiovascular diseases. Plant-based compounds help to improve or prevent disease by affecting the factors involved in the disease. This review was conducted to report the medicinal plants and factors effective in cardiac ischemiareperfusion (I/R) injury to supplement the knowledge about this disease and its prevention and treatment using certain medicinal plants and their active compounds. For this purpose, medicinal plants and their potential antioxidant activities, effects on lipid levels and plaque formation, atherosclerosis and development of cardiovascular diseases and ischemia were reviewed. METHODS: To conduct this review, relevant articles published between 1983 and 2018 were retrieved from the Google Scholar, PubMed, Scientific Information Database, Web of Science, and Scopus using search terms antioxidant, ischemia, reperfusion, heart, infarct, inflammation, cholesterol and medicinal plants. Then, the eligible articles were reviewed. RESULTS: The active compounds of plants, including phenolic compounds, flavonoids, and antioxidant compounds, can be effective on certain pathogenic factors particularly in decreasing cholesterol and blood pressure, preventing an increase in free radicals and ultimately reducing blood clots and vascular resistance to reduce and prevent ischemic disease and its harmful effects. CONCLUSION: Medicinal plants discussed in this article seem to be able to prevent cardiac damage and the disease progression via affecting the factors that are involved in ischemia.

Cardioprotective Effect of Ethanolic Leaf Extract of Melissa Officinalis L Against Regional Ischemia-Induced Arrhythmia and Heart Injury after Five Days of Reperfusion in Rats.

Melissa officinalis has antioxidant and anti-inflammatory activities and is used in various diseases. Aim of the study: We investigated the role of M. officinalis extract (MOE) against ischemia-induced arrhythmia and heart injury after five days of reperfusion in an in-vivo rat model of regional heart ischemia. The leaf extract of M. officinalis was standardized through HPLC analysis. Adult male Sprague-Dawley rats (n = 32) were subjected to 30 min of ischemia by occlusion of the left anterior descending coronary artery followed by 5 days of reperfusion. The rats (n = 8 in each group) were randomized to receive vehicle or M. officinalis as follows: group I served as saline control with ischemia, groups II, III and IV received different doses of MOE- (25, 50 and 100 mg/kg, respectively), by oral gavage daily for 14 days prior to ischemia. Administration of M. officinalis significantly improved ischemia/reperfusion (I/R)-induced myocardial dysfunction by reduction of infarct size, also, during the ischemic period, ventricular tachycardia, and ventricular ectopic beats episodes decreased as compared with that of the control group. Stabilized ST segment changes and QTc shortening increased the R and T wave amplitudes and the heart rate during ischemia. The extract also caused significant elevations in serum superoxide dismutase (SOD) activity as well as a significant decrease in serum cardiac troponin I (CTnI), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels, 5 days after reperfusion. MOE-100mg/kg was the effective dose. Cinamic acid (21.81 ± 1.26 mg/gr) was the main phenolic compound of plant sample. The ethanol extract of M. officinalis was observed to exhibit cardioprotective effects against I/R injury, probably due to antioxidant properties. The results indicate that MOE has antioxidant and cardio-protective effects against ischemia-induced arrhythmias and ischemia-reperfusion induced injury as was reflected by reduction of infarct size and cardiac injury biomarkers. These data support the potential uses of M. officinalis in the treatment of heart ischemia- reperfusion disorders and even developing new anti- arrhythmias drugs after further investigations.

Late cardiac perconditioning by phenylephrine in an isolated rat heart model is mediated by mitochondrial potassium channels

The present study was designed to investigate the effect of early and late administration of phenylephrine during ischemia against regional ischemia-reperfusion injuries in an isolated rat heart model. All animals were randomly divided into experimental groups: (I) IR (Ischemic/ reperfusion): the hearts underwent 35 min of regional ischemia followed by 60 min of reperfusion; (II) 5HD-IR-0: the hearts were perfused for 5 min with 5HD (5-hydroxydecanoate, specific mKATP channel blocker, 100 µM) at the onset of regional ischemia; (III) 5HD-IR-20: the hearts were perfused for 5 min with 5HD 20 min after regional ischemia; (IV) PE-IR-10: the hearts were perfused for 5 min with phenylephrine 10 min after regional ischemia; (V) PE-IR-30: the hearts were perfused for 5 min with phenylephrine (100 µM) 30 min after regional ischemia; (VI) PE-5HD-IR-10 group: the hearts were perfused for 5 min with 5HD at the onset of regional ischemia after which phenylephrine was administrated as in group IV; and (VII) PE-5HD-IR-30: the hearts were perfused for 5 min with 5HD 20 min after the ischemia and then phenylephrine was administrated as in group V. The hemodynamic parameters were recorded throughout the experiment. Ischemia-induced arrhythmias, myocardial infarct size (IS), creatin kinase-MB isoenzyme (CK-MB), plasma lactate dehydrogenase (LDH) activities, and coronary blood flow (CBF) were measured in all animals. Perfusion of phenylephrine 30 min after the regional ischemia curtailed the myocardial infarct size, reduced CK-MB, and improved cardiac function and CBF. Administration of 5HD 30 min after the ischemia abolished cardioprotective effects of phenylephrine in the late phase. These results suggest the involvement of mKATP in the mechanism of phenylephrine-induced late preconditioning.

Protective effects of cinnamon bark extract against ischemia-reperfusion injury and arrhythmias in rat.

Cinnamomum zeylanicum (cinnamon) is a plant with potent antioxidant activity and has been used in traditional medicine for improvement of heart function. The effects of cinnamon bark ethanolic extract were investigated against ischemia-induced arrhythmias and heart injury in an in vivo rat model of regional heart ischemia. The extract was also standardized, and its antioxidant activity was evaluated. Adult male Sprague-Dawley rats were subjected to 30 min of ischemia by occlusion of the left anterior descending coronary artery followed by 5 days of reperfusion. Thirty-two animals were randomized to receive daily oral administration of vehicle or C. zeylanicum bark extract (intragastric, 50, 100, or 200 mg/kg) 14 days before ischemia. C. zeylanicum was standardized through HPLC analysis. Administration of cinnamon bark extract significantly improved ischemia/reperfusion-induced myocardial injury as evidenced by reduction of the infarct size. Also, during the ischemic period, ventricular tachycardia and ventricular ectopic beats episodes decreased as compared with that of the control group. The extract stabilized the ST segment changes and QTc shortening, decreased R-wave amplitude, and increased heart rate during ischemia. The extract also caused significant elevations in serum superoxide dismutase and glutation proxidase activities as well as a significant decrease in serum cardiac troponin I, lactate dehydrogenase, and malondialdehyde levels, 5 days after reperfusion. In HPLC analysis, the amounts of Cinamic acid, Methyl eugenol, and Cinnamaldehyde were 8.99 ± 0.5, 13.02 ± 1.8, and 14.63 ± 1.1 mg/g, respectively. The results show that the ethanolic extract of cinnamon bark is able to protect the heart against ischemia-reperfusion injury probably due to its antioxidant properties. Hence, it might be beneficial in these patients and this remedy might be used for preparation of new drugs.

The Analgesic and Anti-Inflammatory Activity of Linum usitatissimum in Balb/c Mice.

Linum usitatissimum L is traditionally used for relief of pain and inflammation. In this study, the analgesic and anti-inflammatory effects of this plant were evaluated. Xylene test was used for anti-inflammatory evaluation in which 48 mice were randomly designated into 6 groups of 8 each including: control, dexamethasone as positive control (15 mg/kg), and experimental groups (42, 85, 170, and 340 mg/kg, respectively). For analgesic evaluation, 192 mice were randomly designated into 4 sets of 6 groups of 8 mice, including control, morphine as positive control, morphine plus naloxone, experimental groups (200 and 500 mg/kg extract), and extract along with naloxone group, which received 500 mg/kg. The analgesic activities were evaluated at 5, 15, 30, and 60 minutes, respectively, in each set. Both doses showed analgesic activity, the 200 mg/kg possessed higher effects ( P < .05). Naloxone reduced a section of its effect ( P < .001). The 170 mg/kg dose of the extract showed anti-inflammatory activity ( P < .05). The extract had phenolic, flavonoid, and flavonol compounds with antioxidant activity. Linum usitatissimum L dose dependently had analgesic activity partially like morphine and might be used as analgesic and anti-inflammatory agent.

CXCR4 expression is associated with time-course permanent and temporary myocardial infarction in rats.

OBJECTIVES: Experimental myocardial infarction triggers secretion of Stromal cell-derived factor1 and lead to increase in the expression of its receptor "CXCR4" on the surface of various cells. The aim of this study was to evaluate the expression pattern of CXCR4 in peripheral blood cells following time-course permanent and temporary ischemia in rats. MATERIALS AND METHODS: Fourteen male Wistar rats were divided into two groups of seven and were placed under permanent and transient ischemia. Peripheral blood mononuclear cells were isolated at different time points, RNAs extracted and applied to qRT-PCR analysis of the CXCR4 gene. RESULTS: Based on repeated measures analysis of variance, the differences in the expression levels of the gene in each of the groups were statistically significant over time (the effect of time) (P<0.001). Additionally, the difference in gene expression between the two groups was statistically significant (the effect of group), such that at all times, the expression levels of the gene were significantly higher in the permanent ischemia than in the transient ischemia group (P<0.001). Moreover, the interactive effect of time-group on gene expression was statistically significant (P<0.001). CONCLUSION: CXCR4 is modulated in an induced ischemia context implying a possible association with myocardial infarction. Checking of CXCR4 expression in the ischemic changes shows that damage to the heart tissue trigger the secretion of inflammatory chemokine SDF, Followed by it CXCR4 expression in blood cells. These observations suggest that changes in the expression of CXCR4 may be considered a valuable marker for monitoring myocardial infarction.

A review of plant-based compounds and medicinal plants effective on atherosclerosis.

Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications.

Antioxidant Activity and Teratogenicity Evaluation of Lawsonia Inermis in BALB/c Mice.

BACKGROUND AND AIM: Lawsonia inermis is a medicinal plant with abortive properties. There has been no scientific study to evaluate the teratogenicity of this plant. This study was performed to determine the antioxidant activity and the possible side effect of L. inermis hydroalcoholic extract on development of congenital abnormalities in BALB/c mice. MATERIALS AND METHODS: In this experimental study, 120 female mature BALB/c mice were assigned to four groups and after mating and confirming the vaginal plug, the animals in the first group (G1) were kept with no intervention, and the second (G2), third (G3) and fourth (G4) groups were intraperitoneally (ip) injected with respectively saline (0.3 ml), and 10 and 100 mg/kg of L. inermis extract (for 7 days). On the 19th day, caesarean section was performed on the mice and embryos were examined for abnormalities. Their height and weight were measured. Data were analysed by ANOVA and post-hoc least significant difference tests. RESULTS: There were significant differences between G3 and G4, and G1 (p<0.001); no significant difference was seen between G3 and G4. At 100 mg/kg dose of L. inermis, the parietal bones were absent in 90% of embryos and more extra ribs were observed in both G3 and G4 (p = 0.01). CONCLUSION: L. inermis may have teratogenicity and should be used cautiously during pregnancy.

A review on promising natural agents effective on hyperlipidemia.

Hyperlipidemia is a prevalent disease and a major component of the metabolic syndrome resulting from various factors. This disease increases morbidity and mortality when combined with other prevalent diseases such as diabetes mellitus, hypertension, and cardiovascular diseases. The side effects of the current lipid-lowering drugs have increased the tendency to move toward traditional and alternative treatments. Epidemiological observations indicate that using alternative treatments, consumption of medicinal plants, diet, and consumption of fruits have had satisfactory results on the effects of hyperlipidemia in many societies. It should be noted that in majority of societies, even developed countries, the tendency toward eating lipid-lowering medicinal plants has increased extensively. Using these plants especially when common remedies cannot control the disease is significant. Although consumption of medicinal plants by hyperlipidemic patients may show improvement in disease state, drug interaction and side effects may cause complications in disease control. Therefore, in this review, apart from introducing some of the reliable plants effective in inhibition and decrease of hyperlipidemia, the possibility of their intoxication and drug interaction is also presented.

In Vitro Impact of Hydro-alcoholic Extract of Rosa damascena Mill. on Rat Ileum Contractions and the Mechanisms Involved.

BACKGROUND: The petal's hydro-alcoholic extract of Rosa damascena Mill. on ileum contractions of Wistar rats and its possible mechanism were investigated. METHODS: Forty-eight male Wistar rats were divided into six groups. Ileum was placed adjacent to propranolol (1 µM), naloxone (1 µM) and L-NAME (100 µM) and also under the influence of different doses (2-8 mM) of calcium chloride. RESULTS: Cumulative extract of R. damascena Mill. (100, 500, and 1000 mg/L) decreased ileum contractions induced by KCl (60 mM) in a dose-dependent manner (P < 0.0001). Propranolol and naloxone significantly decreased the inhibitory effect of the extract on contractions induced by KCl (P < 0.001), but L-NAME was ineffective. Furthermore, calcium led to the contraction of depolarized tissue through KCI and this contractile effect decreased significantly induced by the cumulative concentrations of the extract (P < 0.001). CONCLUSIONS: The results indicate that R. damascena Mill. dose-dependently (100, 500, and 1000 mg/L) decreases ileum movements of the rat probably through stimulating the ß-adrenergic and opioid receptors and voltage-dependent calcium channels, and it may be used to treat digestive disorders.