Propolis add-on therapy alleviates depressive symptoms; A randomized placebo-controlled clinical trial.

Almost half of the treatments with common antidepressants are failed or result in a relapse of symptoms after cessation. Moreover, the antidepressants side effects rationalize the use of complementary medicine as an adjunctive therapy. This study aimed to evaluate the efficacy and safety of propolis in complementary therapy of depressive disorder. Chromatography technics were used to detect propolis components. A double-blind, randomized, placebo-controlled trial was designed, and 54 participants were randomly assigned to receive either propolis or Placebo for 6 weeks. Treatment was defined as a decrease in 17-item Hamilton Depression Scale (HAMD-17) and Beck depression inventory (BDI). On D42, there was a significant reduction in HAMD score in the propolis group compared with the placebo group (p < .0001). HAMD score significantly decreased in the propolis group from 20.92 ± 3.77 on D0 to 10.03 ± 5.55 on D42, and BDI score was improved from 29.25 ± 3.06 on D0 to 14.17 ± 4.86 on D42. Our findings confirmed that complementary treatment of propolis with SSRIs could safely attenuate symptoms of moderate-severe MDD. These antidepressant effects might result from the rich phenolic acids and flavonoids content of Azerbaijan propolis.

Efficacy and safety of Sophora alopecuroides var. alopecuroides seed extract for opioid detoxification: A randomized, double-blind, and placebo-controlled clinical trial.

The seeds of Sophora alopecuroides L. var. alopecuroides (S. alopecuroides) have alleviated morphine withdrawal in mice. Therefore, in this study, the alkaloid composition of S. alopecuroides extract was determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analysis. Moreover, 50 abstinent opium addicts consumed three 400 mg extract capsules once daily and 50 other patients took placebo for 8 days. At the baseline and days 3 and 8, the clinical opiate withdrawal scale (COWS) was used to assess withdrawal symptoms. At the baseline and Day 8, the patients' blood levels of serum glutamate oxaloacetate transferase; serum glutamate pyruvate transferase; alkaline phosphatase; total, direct, and indirect bilirubins; creatinine and blood urea nitrogen; complete blood count; and prothrombine time were measured. The groups' parameter values were also compared. Sophocarpine, matrine, and sophoramine were the major alkaloids constituting, respectively, 32.85, 26.55, and 6.91% of the extract. The extract decreased the COWS score at Days 3 and 8 significantly compared with the placebo (p < .001). The extract did not significantly affect the blood parameters' values compared with the placebo (p > .05). There was no adverse drug effect. In conclusion, the extract reduces the acute opioid withdrawal symptoms and seems to have good safety and tolerability.

In vivo and in vitro evaluation of the effects of Urtica dioica and swimming activity on diabetic factors and pancreatic beta cells.

BACKGROUND: Urtica dioica (UD) has been identified as a traditional herbal medicine. This study aimed to investigate the effect of UD extract and swimming activity on diabetic parameters through in vivo and in vitro experiments. METHODS: Adult WKY male rats were randomly distributed in nine groups: intact control, diabetic control, diabetic + 625 mg/kg, 1.25 g/kg UD, diabetic + 100 mg/kg Metformin, diabetic + swimming, diabetic + swimming 625 mg/kg, 1.25 g/kg UD, and diabetic +100 mg/kg Metformin + swimming. The hearts of the animals were punctured, and blood samples were collected for biochemical analysis. The entire pancreas was exposed for histologic examination. The effect of UD on insulin secretion by RIN-5F cells in 6.25 or 12.5 mM glucose dose was examined. Glucose uptake by cultured L6 myotubes was determined. RESULTS: The serum glucose concentration decreased, the insulin resistance and insulin sensitivity significantly increased in treated groups. These changes were more pronounced in the group that received UD extract and swimming training. Regeneration and less beta cell damage of Langerhans islets were observed in the treated groups. UD treatment increased insulin secretion in the RIN-5F cells and glucose uptake in the L6 myotubes cells. CONCLUSIONS: Swimming exercises accompanied by consuming UD aqueous extracts effectively improved diabetic parameters, repaired pancreatic tissues in streptozotocin-induced diabetics in vivo, and increased glucose uptake or insulin in UD-treated cells in vitro.

Hydroalcoholic extract of Myrtus communis can alter anxiety and sleep parameters: a behavioural and EEG sleep pattern study in mice and rats.

CONTEXT: Myrtus communis L. (Myrtaceae), myrtle, is an evergreen shrub with strong antibacterial, anti-inflammatory, antihyperglycemic and antioxidant activities. Also, it is used as a sedative-hypnotic plant in Iranian traditional medicine. OBJECTIVE: This study evaluates the effect of 80% ethanolic extract of M. communis leaves on sleep and anxiety in mice and rats. MATERIALS AND METHODS: Male NMRI mice were subjected to open field, righting reflex, grip strength and pentylentetrazole-induced seizure tests. Male Wistar rats were used to evaluate the alterations in rapid eye movement (REM) and non-REM (NREM) sleep. They were treated with 25-400 mg/kg doses of the extract intraperitoneally. RESULTS: The applied doses (50-200 mg/kg) of M. communis extract increased vertical (ED50 = 40.2 ± 6.6 mg/kg) and vertical and horizontal activity (ED50 = 251 ± 55 mg/kg), while treatment with 200 and 400 mg/kg attenuated muscle tone significantly compared to vehicle treated animals (p < 0.001 for all) in a dose-independent manner. Also, a significant hypnotic and not anticonvulsant effect was observed when animals were treated with 200 mg/kg of the extract (p < 0.01). In this regard, electroencephalography results showed that REM sleep time was decreased (2.4 ± 0.5%), while total and NREM sleep times were increased significantly compared to the control group of mice (82.5 ± 7.6%). DISCUSSION AND CONCLUSION: The data show the anxiolytic and muscle relaxant effect of the extract without anticonvulsant activities. The anxiolytic, myorelaxant and hypnotic effects without effect on seizure threshold are in line with the effect of a alpha 2 GABA receptor agonist.

Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

Autism is a neurodevelopmental disorder that causes significant impairment in socialization and communication. It is also associated with ritualistic and stereotypical behaviour. Recent studies propose both hyper-and hypoglutamatergic ideologies for autism. The objective of this study was to assess the effects of memantine plus risperidone in the treatment of children with autism. Children with autism were randomly allocated to risperidone plus memantine or placebo plus risperidone for a 10-wk, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/d and memantine was titrated to 20 mg/d. Children were assessed at baseline and after 2, 4, 6, 8 and 10 wk of starting medication protocol. The primary outcome measure was the irritability subscale of Aberrant Behavior Checklist-Community (ABC-C). Difference between the two treatment arms was significant as the group that received memantine had greater reduction in ABC-C subscale scores for irritability, stereotypic behaviour and hyperactivity. Eight side-effects were observed over the trial, out of the 25 side-effects that the checklist included. The difference between the two groups in the frequency of side-effects was not significant. The present study suggests that memantine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N10; www.irct.ir).

Antioxidant and neuroprotective effects of Scrophularia striata extract against oxidative stress-induced neurotoxicity.

In this study, the neuroprotective effect of Scrophularia striata Boiss (Scrophulariaceae) extract, a plant growing in northeastern of Iran, against oxidative stress-induced neurocytotoxicity in PC12 was evaluated. The PC12 cell line pretreated with different concentrations (10, 50, 100, and 200 µg/ml) of the extract and then treated with H2O2 to induce oxidative stress and neurotoxicity. Survival of the cells, reactive oxygen species (ROS) generation, and apoptosis were measured using MTT assay, fluorescent probe 2',7'-dichlorofluorescein diacetate, and annexin V/propidium iodide, respectively. Moreover, the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) was used to evaluate the antioxidant capacity of the plant extract. Phytochemical assay by thin layer chromatography showed that the main components, including phenolic compounds, phenyl propanoids and flavonoids, were presented in the S. striata extract. The extract in concentrations of 50-200 µg/ml protected PC12 cells from H2O2-induced toxicity. The survival of the cells at concentration of 200 µg/ml was 64 % compared to that of H2O2 alone-treated cells (48 %) (p < 0.001). The extract also dose-dependently reduced intracellular ROS production (p < 0.001). Moreover, the extract showed antioxidative effects and decreased apoptotic cells. Collectively, these findings indicated the ability of S. striata to decrease ROS generation and cell apoptosis and also suggest the presence of the neuroprotective agents in this plant.

Memantine add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized, double-blind, placebo-controlled study.

We aimed to evaluate the efficacy of memantine add-on in the treatment of primary negative symptoms of patients with stable schizophrenia. In a double-blind placebo-controlled clinical trial, 40 patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were stabilized on risperidone for a minimum of 8 weeks were randomized to either memantine (20 mg) or placebo in addition to risperidone, 6 mg/d, for eight weeks. Assessment was done using the Positive and Negative Syndrome Scale at baseline, week 4, and week 8. The Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale at baseline and week 8 were used to assess depression and extrapyramidal symptoms, respectively. All 40 patients had at least one postbaseline measurement, and 38 patients completed the trial. Patients in the memantine group showed a significantly greater improvement on negative subscale than the placebo group at end point (P < 0.001). The same effect was observed for the total score (P < 0.001) and the general psychopathology subscale score (P = 0.002). There was no significant difference in reduction of positive symptoms score between the 2 groups (P = 0.757). Changes in the Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale scores and frequency of adverse effects did not differ between the 2 groups. Our study showed that memantine is a tolerable and efficacious add-on treatment for primary negative symptoms of schizophrenia.

Aspirin for treatment of lithium-associated sexual dysfunction in men: randomized double-blind placebo-controlled study.

OBJECTIVES: The aim of the present study was to assess the effect of aspirin on lithium-related sexual dysfunction in men with stable bipolar affective disorder (BAD). METHODS: In a randomized, double-blind, placebo-controlled study, 32 men with stable BAD who had been on lithium maintenance therapy randomly received aspirin (240 mg/day) or placebo for six weeks. The International Index for Erectile Function (IIEF) was used to assess sexual symptoms at baseline, Week 3, and Week 6. Depressive and mania symptoms and plasma lithium concentrations were assessed at baseline and Week 6. Side effects were assessed using a checklist. RESULTS: Thirty patients (15/group) completed the study. Baseline and endpoint lithium concentrations and mania and depressive symptoms did not differ significantly between the two groups. Significant effects of time × treatment interaction were observed for total score [Greenhouse-Geisser: F(1.410,39.466) = 6.084, p = 0.010] and erectile function [Greenhouse-Geisser: F(1.629,45.602) = 7.250, p = 0.003]. By Week 6, patients in the aspirin group showed significantly greater improvement in the total (63.9% improvement from the baseline) and erectile function domain (85.4% improvement from the baseline) scores than the placebo group (14.4% and 19.7% improvement from the baseline, p-values = 0.002 and 0.001, respectively). By Week 6, 12 (80%) patients in the aspirin group and three (20%) patients in the placebo group met the criteria of minimal clinically important change [χ(2) (1) = 10.800, p = 0.001]. Other IIEF domains also showed significant improvement at the end of the trial. The frequency of side effects was similar between the two groups. CONCLUSION: Aspirin effectively improves lithium-related sexual dysfunction in men with stable BAD.

Protective effects of Scrophularia striata in Ovalbumin-induced mice asthma model.

BACKGROUND: Scrophularia striata Boiss. (Scrophulariaceae) is a plant growing in the northeastern part of Iran and being used as a traditional herb for various inflammatory disorders.This study was designed to investigate the protective effects of the Scrophularia striata extract in Ovalbumin (OVA) induced-asthma mice model. METHODS: OVA-sensitized mice were intrapritonealy treated with two doses (100 and 200 mg/kg) of the extract on days 8 to 14 separately. Broncoalveolar lavage fluids (BALF) was collected 48 h after the final OVA challenge and then the number of eosinophils and other inflammatory cells were assessed by direct microscopic counting. In addition, total immunoglubolin (Ig) E and OVA-specific IgE levels in serum, IL-4 and IL-5 cytokines in BALF were determined by Enzyme-Linked Immunosorbent Assay. Moreover, phytochemical assay by thin layer chromatography (TLC) and the 2, 2 diphenyl-1-picrylhydrazyl (DPPH) were used to evaluate the main compounds and the antioxidant capacity of the plant extract, respectively. RESULTS: The results showed that the main components; including flavonoids, phenolic compounds and phenyl propanoids were presented in the S. striata extract. In addition, the treatment with extract significantly reduced the number of inflammatory cells and suppressed T-helper 2 (Th2) cytokines including IL-4 and IL-5 in BALF. Also, total IgE and OVA-specific IgE levels in the serum decreased. CONCLUSION: Collectively, it is concluded that the extract has the potential to modulate the Th2 cytokines and could be used as immunomodulatory agent in the treatment of allergic asthma.

Urease inhibitory activities of ß-boswellic acid derivatives.

BACKGROUND AND THE PURPOSE OF THE STUDY: Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative. METHODS: 4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-ß-boswellic acid; 2, 3-O-acetyl-11-hydroxy-ß-boswellic acid; 3. 3-O- acetyl-11-keto-ß-boswellic acid and 4, 11-keto-ß-boswellic acid. Their inhibitory activity on Jack bean urease were evaluated. Docking and pharmacophore analysis using AutoDock 4.2 and Ligandscout 3.03 programs were also performed to explain possible mechanism of interaction between isolated compounds and urease enzyme. RESULTS: It was found that compound 1 has the strongest inhibitory activity against Jack bean urease (IC50 = 6.27 ± 0.03 µM), compared with thiourea as a standard inhibitor (IC50 = 21.1 ± 0.3 µM). CONCLUSION: The inhibition potency is probably due to the formation of appropriate hydrogen bonds and hydrophobic interactions between the investigated compounds and urease enzyme active site and confirms its traditional usage.

Coumarin compounds of Biebersteinia multifida roots show potential anxiolytic effects in mice.

BACKGROUND: Traditional preparations of the root of Biebersteinia multifida DC (Geraniaceae), a native medicinal plant of Irano-Turanian floristic region, have been used for the treatment of phobias as anxiolytic herbal preparation. METHODS: We utilized the phobic behavior of mice in an elevated plus-maze as a model to evaluate the anxiolytic effect of the plant extract and bio-guided fractionation was applied to isolate the active compounds. Total root extract, alkaline and ether fraction were administered to mice at different doses 30 and 90 min prior to the maze test. Saline and diazepam were administered as negative and positive controls, respectively. The time spent in open and closed arms, an index of anxiety behavior and entry time, was measured as an index of animal activity. RESULTS: The total root extract exhibited anxiolytic effect which was comparable to diazepam but with longer duration. This sustained effect of the crude extract was sustained for 90 min and was even more after injection of 45 mg/kg while the effect of diazepam had been reduced by 90 min. The anxiolytic effect factor was only present in the alkaline fraction and displayed its effect at lower doses than diazepam while pure vasicinone as the previously known alkaloid did not shown anxiolytic effect. The effect of the alkaline fraction was in a dose dependent manner starting at 0.2 mg/kg with a maximum at 1.0 mg/kg. Bio-guided fractionation using a variety of chromatographic methods led to isolation and purification of three coumarin derivatives from the bioactive fraction, including umbelliferone, scopoletin, and ferulic acid. CONCLUSION: For the first time, bio-guided fractionation of the root extract of B. multifida indicates significant sustained anxiolytic effects which led to isolation of three coumarin derivatives with well-known potent MAO inhibitory and anti-anxiety effects. These data contribute to evidence-based traditional use of B. multifida root for anxiety disorders.

Anti-hyperglycemic and anti-hypercholesterolemic effects of Aloe vera leaf gel in hyperlipidemic type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial.

Diabetes mellitus type 2 with dyslipidemia is a common disease. Previous studies suggest that aloe (Aloe vera L.) leaf gel may positively affect the blood glucose and lipid levels in dyslipidemic type 2 diabetic patients. Thus, in this randomized double-blind placebo-controlled clinical trial with hyperlipidemic (hypercholesterolemic and/or hypertriglyceridemic) type 2 diabetic patients aged 40 to 60 years not using other anti-hyperlipidemic agents and resistant to daily intake of two 5 mg glyburide tablets and two 500 mg metformin tablets, the efficacy and safety of taking aloe gel (one 300 mg capsule every 12 hours for 2 months) combined with the aforementioned drugs in treatment of 30 patients were evaluated and compared with the placebo group (n = 30). The aloe gel lowered the fasting blood glucose, HbA1c, total cholesterol, and LDL levels significantly (p = 0.036, p = 0.036, p = 0.006, and p = 0.004, respectively) without any significant effects on the other blood lipid levels and liver/kidney function tests (p > 0.05) compared with the placebo at the endpoint. No adverse effects were reported. The results suggest that aloe gel may be a safe anti-hyperglycemic and anti-hypercholesterolemic agent for hyperlipidemic type 2 diabetic patients.

Bioassay-guided Isolation of Flavonoids from Caesalpinia bonduc (L.) Roxb. and Evaluation of Their Cytotoxicity.

Cancer is one of the most important causes of death all around the world. Screening plants and their secondary metabolites as cytotoxic agents is one of the common methods for identifying new compounds used in chemotherapy and inhibition cancer process. Caesalpinia bonduc (L.) Roxb. from the Fabaceae family was used for improving wound, fever, tumor, hydrocele, hernia, smallpox, toothache, inflammation, and as astringent, anthelmintic, antidiabetic, and antimalarial agent in traditional medicine. A bioassay-guided study of this species led to the isolation of three flavonoids. At first, the cytotoxicity of methanol extract of aerial parts (leaves and stems), seeds, and legumes of this plant was tested against MCF-7 and PC-3 by MTT assay. The methanol extract of legumes showed better inhibitory activities (IC50 < 500 µg/mL). As a result, this extract was selected for fractionation. In the next step, the ethyl acetate (EtOAc) fraction was selected for phytochemical analysis based on the inhibitory activity (IC50 = 170 ± 0.9 µg/mL). In this way, total phenol content (625 ± 7.2 GAE/g extract) and antioxidant activity (IC50 = 6.1 ± 0.3 µg/mL) was compared by BHT (IC50 = 13.5 ± 0.7 µg/mL). Finally, three compounds including, quercetin-3-methyl ether (1), kaempferol (2), and kaempferol-3-O-α-L-rhamnopyranosyl-1→2)-ß-D-xylopyranoside (3) were isolated from EtOAc fraction, and all isolated compounds were tested for their cytotoxicity and compound 1 showed better inhibitory activity than other two compounds. This study suggests that Caesalpinia bonduc could be considered for further investigations as a natural source of biological compounds.

Flavonoids, cinnamic acid and phenyl propanoid from aerial parts of Scrophularia striata.

No phytochemical investigation regarding Scrophularia striata Boiss. (Scrophulariaceae) has been performed, although several reports about other Scrophularia species have been published. The inhibitory effects of aerial parts of S. striata on matrix metalloproteinase expression elaborate a new approach to treat variety of malignant and inflammatory disorders. Five known compounds, including cinnamic acid, three flavonoids (quercetine, isorhamnetin-3-O-rutinoside and nepitrin) and one phenyl propanoid glycoside (acteoside 1) were isolated from S. striata Boiss. by chromatographic techniques and the structures of compounds were characterized by spectroscopic methods. This is the first report regarding the isolation of these compounds from S. striata.

Process optimisation for green synthesis of zero-valent iron nanoparticles using Mentha piperita.

The potential of Mentha piperita in the iron nanoparticles (FeNPs) production was evaluated for the first time. The influences of the variables such as incubation time, temperature, and volume ratio of the extract to metal ions on the nanoparticle size were investigated using central composite design. The appearance of SPR bands at 284 nm in UV-Vis spectra of the mixtures verified the nanoparticle formation. Incubating the aqueous extract and metal precursor with 1.5 volume ratio at 50°C for 30 min leads to the formation of the smallest nanoparticles with the narrowest size distribution. At the optimal condition, the nanoparticles were found to be within the range of 35-50 nm. Experimental measurements of the average nanoparticle size were fitted well to the polynomial model satisfactory with R2 of 0.9078. Among all model terms, the linear term of temperature, the quadratic terms of temperature, and mixing volume ratio have the significant effects on the nanoparticle average size. FeNPs produced at the optimal condition were characterised by transmission electron microscopy, thermogravimetry analysis (TGA), and Fourier-transform infrared spectroscopy. The observed weight loss in the TGA curve confirms the encapsulation of FeNPs by the biomolecules of the extract which were dissociated by heat.

Effects of standardized hydro-alcoholic extract of Vaccinium arctostaphylos leaf on hypertension and biochemical parameters in hypertensive hyperlipidemic type 2 diabetic patients: a randomized, double-blind and placebo-controlled clinical trial.

OBJECTIVE: To study the blood pressure, lipid and glycemic effects and safety of Vaccinium arctostaphylos leaf in the hypertensive hyperlipidemic type 2 diabetic patients. MATERIALS AND METHODS: The patients took 350 mg standardized plant leaf hydro-alcoholic extract capsule (n=50) or placebo capsule (n=50) three times daily alongside conventional drugs for 2 months. At the baseline and endpoint, systolic and diastolic blood pressures and blood levels of fasting glucose (FG), 2-hr postprandial glucose (2hPPG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), LDL-C, triglyceride, HDL-C, SGOT, SGPT and creatinine were determined in both groups. To evaluate the extract safety, serum SGOT, SGPT and creatinine levels were tested; also, the patients were requested to report any adverse effects. RESULTS: FG, 2hPPG, HbA1c, TC, LDL-C, triglyceride and systolic and diastolic blood pressures were decreased, whereas HDL-C was increased significantly in the extract group compared to those of the placebo group at the endpoint (for all cases, p<0.05). The extract did not significantly influence other parameters and no adverse effects were reported. CONCLUSION: V. arctostaphylos leaf hydro-alcoholic extract as an adjunct to the conventional drugs has additional antihypertensive as well as anti-dyslipidemic and anti-hyperglycemic effects in hypertensive hyperlipidemic type 2 diabetic patients. Besides, the extract lacks hepatic, renal and patient-reported adverse effects.

Antifungal and antibacterial activities of Pentanema divaricatum and its active constituent.

The antimicrobial activity of ethanol and chloroform extracts of Pentanema divaricatum Cass. was studied using the conventional disk diffusion method. The extracts' highest antimicrobial activity was observed against Aspergillus niger. Bioassay-guided fractionation of the crude extract by preparative thin layer chromatography (PTLC) showed one antimicrobial fraction which was especially effective against Aspergillus niger. By conventional spectroscopy the active fraction was identified as 4alpha,5alpha-epoxy-10alpha,14H-1-epi-inuviscolide. This compound represented the most potent antimicrobial candidate, with MIC values of <25 microg/disk against A. niger strains and 200 microg/disk against Bacillus cereus and Staphylococcus aureus.

Anticancer potential of Ferula hezarlalehzarica Y. Ajani fraction in Raji lymphoma cell line: induction of apoptosis, cell cycle arrest, and changes in mitochondrial membrane potential.

BACKGROUND: Cancer is a major cause of mortality. The present study evaluates the antitumor effects of Ferula hezarlalehzarica Y. Ajani fractions on various cancer cell lines, including the Raji Burkitt's lymphoma cells. METHODS: We evaluated the cytotoxic activity of various fractions of F. hezarlalehzarica against tumor cell lines by the MTT assay. Annexin V-PE/7-AAD and cell cycle analysis were assessed by flow cytometry. Expressions of genes associated with cell death and proliferation (Bax, Bcl-2, Fas, and c-Myc) were determined using real-time PCR. Alteration in mitochondrial membrane potential (MMP) was examined by JC-1 dye staining. RESULTS: The hexane fraction of F. hezarlalehzarica showed the highest degree of cytotoxicity against Raji cells (IC50 = 31.6 µg/ml). Flow cytometry analysis showed that 200 µg/ml of the fraction induced apoptosis in >96% of Raji cells after 24 h. In cell cycle analysis, at the same concentration, the percentage of apoptotic cells in the sub G1phase increased to 95.25 ± 1.76% at 48 h of treatment. The fraction induced cell cycle arrestat the G0/G1phase. Exposure to 100 µg/ml of the fraction after 48 h increased the percentage of G0/G1 cells (76.3 ± 6.08%) compared to the negative control (<50%). Treatment with75µg/ml of fraction reduced the expressions of Bcl-2 (0.23 ± 0.008-fold) and c-Myc (0.68 ± 0.07-fold) and increased Bax (1.75 ± 0.31-fold) and Fas (5.02 ± 0.74-fold; p < 0.01). We observed a decrease in MMP (≈0.4, p < 0.05) at ≥100 µg/ml and this effect remained almost unchanged until 48 h. CONCLUSIONS: The F. hezarlalehzarica hexane fraction induced apoptosis in Raji cells by changing the expression of apoptosis-related genes, cell cycle distribution, and MMP. These data suggested a potential effectiveness of F. hezarlalehzarica for inducing cell death in lymphoma cells. Graphical abstract ᅟ.

Bio-guided fractionation and isolation of active component from Tragopogon graminifolius based on its wound healing property.

ETHNOPHARMACOLOGICAL RELEVANCE: Tragopogon graminifolius (T. graminifolius) from Asteraceae family has been used as a remedy in Persian traditional medicine for the treatment of various disorders such as wound healing. AIM OF THE STUDY: The purpose of this study is to investigate the compounds of T. graminifolius, which are responsible for its wound healing activity. MATERIALS AND METHODS: The experiment was performed in three phases; each phase consisted of fractionation of extracts followed by scratch assay. The results of the scratch assay were expressed using scratch closure index (SCI), representing the contraction of scratch. RESULTS: In phase I, Ethyl acetate fraction (E) showed the maximum SCI (61.7 ±â€¯3.5) that was selected for more fractionation in the next phase. In phase II, 12 fractions were obtained and labeled as fractions E- A to L, respectively. Based on the SCI of fractions, EF (SCI=68.9 ±â€¯0.6) was the most active fraction in phase II and selected for further fractionation in phase III. In phase III, 8 fractions were resulted by fractionation of EF and labeled as EF- 1-8. Fraction EF5 with the highest SCI (30.8 ±â€¯3.0) was the most effective fraction and Luteolin was the main component. Luteolin significantly improved viability of fibroblast cells and increased cell population that was accompanied by decreased cell apoptosis. Luteolin-induced cell number increase in the S and G2M phases of the cell cycle, further confirms the proliferative effect of this compound. CONCLUSION: The results showed that the total extract and fractions of T. graminifolius stimulate proliferation and migration of skin fibroblast cells and Luteolin is one of the active compounds responsible for these effects.

Evaluating the effect of Myrtus communis on programmed cell death in hydatid cyst protoscolices.

OBJECTIVE: To evaluate the possible involvement of programmed cell death strategy in hydatid cyst protoscolices following treatment with Myrtus communis (M. communis) as an herbal medicine. METHODS: Protoscolices were aseptically collected from sheep liver hydatid cysts. Evaluating the effect of M. communis extract on programmed cell death and increased activity of caspases 3, 8, and 9 in hydatid cyst protoscolices was conducted by treating the protoscolices with different concentration (5, 50, and 100 mg/mL) of M. communis extract at 37 °C and 5% CO2 for 4 h by using the Bradford test and ELISA commercial kits. RESULTS: The extract of M. communis at all concentrations led to initiation of programmed cell death in protoscolices and this effect, was only significant at 50 and 100 mg/mL concentrations, compared to the negative control (P < 0.05). Also, the activity of caspases 3, 8, and 9 in hydatid cyst protoscolices, was shown that the extract at all 3 concentrations could only increase the activity of caspases 3 and 9. Moreover, a significant increase in the activity of caspase 3 was only observed at concentrations 50 and 100 mg/mL by 37.00% and 66.19% while a significant increase in the activity of caspase 9 at the same concentrations was observed by 20.89% and 63.67%, respectively (P < 0.05). CONCLUSIONS: The extract of M. communis at different concentrations could increase the activity of caspases 3 and 9 and caused programmed cell death in hydatid cyst protoscolices however, this effect was significant at high concentrations of the extract.