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PMID:  Int J Ophthalmol. 2018 ;11(2):189-195. Epub 2018 Feb 18. PMID: 29487805Abstract Title:  Anti-fibrotic effect of rosmarinic acid on inhibition of pterygium epithelial cells.Abstract:  AIM: To investigate the anti-fibrosis effect of rosmarinic acid (RA) in pterygium epithelial cells (PECs) to determine if RA is a potent agent for treating pterygium.METHODS: The PECs (1×10cells/mL) were treated with 100µmol/L of RA for 1, 3 and 6h. After RA treatment, the cell viability was determined by staining with acridine orange/DAPI and analysisa NucleoCounter NC-3000. The protein expression levels of type I collagen, transforming growth factor beta-1 (TGF-β1), TGF-β type II receptor (TGF-βRII), p-Smad1/5, p-Smad2, p-Smad3, and Smad4 of the cell lysates were measured by Western blot analysis.RESULTS: The cell viability of PECs was significantly decreased after RA treatment (

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Posted: June 25, 2018, 4:55 pm
PMID:  Cell Stress Chaperones. 2018 Apr 7. Epub 2018 Apr 7. PMID: 29627902Abstract Title:  Rosmarinic acid and siRNA combined therapy represses Hsp27 (HSPB1) expression and induces apoptosis in human glioma cells.Abstract:  High expression of Hsp27 in glioma cells has been closely associated with tumor cell proliferation and apoptosis inhibition. The aim of the present study was to asses the effects of rosmarinic acid (RA) on Hsp27 expression and apoptosis in non-transfected and transfected human U-87 MG cells. The effect of rosmarinic acid was compared to quercetin, which is known to be a good Hsp27 inhibitor. In order to block the expression of Hsp27 gene (HSPB1), transfection with specific siRNAs was performed. Western blotting technique was used to assess the Hsp27 expression, and caspase-3 colorimetric activity assay was performed to determine apoptosis induction. According to the results, it was found that RA and quercetin effectively silenced Hsp27 and both agents induced apoptosis by activating the caspase-3 pathway. Eighty and 215 μM RA decreased the level of Hsp27 by 28.8 and 46.7% and induced apoptosis by 30 and 54%, respectively. For the first time, we reported that rosmarinic acid has the ability to trigger caspase-3 induced apoptosis in human glioma cells. As a result of siRNA transfection, the Hsp27 gene was silencedby ~ 50% but did not cause a statistically significant change in caspase-3 activation. It was also observed that apoptosis was induced at a higher level as a result of Hsp27 siRNA and subsequent quercetin or RA treatment. siRNA transfection and 215 μM RA treatment suppressed Hsp27 expression level by 90.5% and increased caspase-3 activity by 58%. Herein, we demonstrated that RA administered with siRNA seems to be a potent combination for glioblastoma therapy.

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Posted: June 25, 2018, 4:34 pm
PMID:  Neurochem Int. 2018 Apr 13 ;118:1-13. Epub 2018 Apr 13. PMID: 29655652Abstract Title:  Protective role of rosmarinic acid on amyloid beta 42-induced echoic memory decline: Implication of oxidative stress and cholinergic impairment.Abstract:  In the present study, we examined whether rosmarinic acid (RA) reverses amyloidβ (Aβ) induced reductions in antioxidant defense, lipid peroxidation, cholinergic damage as well as the central auditory deficits. For this purpose, Wistar rats were randomly divided into four groups; Sham(S), Sham + RA (SR), Aβ42 peptide (Aβ) and Aβ42 peptide + RA (AβR) groups. Rat modelof Alzheimer was established by bilateral injection of Aβ42 peptide (2,2 nmol/10 μl) into the lateral ventricles. RA (50 mg/kg, daily) was administered orally by gavage for 14 days after intracerebroventricular injection. At the end of the experimental period, we recorded the auditory event related potentials (AERPs) and mismatch negativity (MMN) response to assess auditory functions followed by histological and biochemical analysis. Aβ42 injection led to a significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and 4-Hydroxy-2-nonenal (4-HNE) but decreased the activity of antioxidant enzymes (SOD, CAT, GSH-Px) and glutathione levels. Moreover, Aβ42 injection resulted in a reduction in the acetylcholine content and acetylcholine esterase activity. RA treatment prevented the observed alterations in the AβR group. Furthermore, RA attenuated the increased Aβ staining and astrocyte activation. We also found that Aβ42 injection decreased the MMN response and theta power/coherence of AERPs, suggesting an impairing effect on auditory discrimination and echoic memory processes. RA treatment reversed the Aβ42 related alterations in AERP parameters. Inconclusion, our study demonstrates that RA prevented Aβ-induced antioxidant-oxidant imbalance and cholinergic damage, which may contribute to the improvement of neural network dynamics of auditory processes in this rat model.

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Posted: June 25, 2018, 4:16 pm
PMID:  Food Funct. 2018 May 23 ;9(5):2796-2808. PMID: 29691532Abstract Title:  Black rice anthocyanin-rich extract and rosmarinic acid, alone and in combination, protect against DSS-induced colitis in mice.Abstract:  The aim of this study was to investigate the effect of black rice anthocyanin-rich extract (BRAE) and rosmarinic acid (RA), alone and in combination, on dextran sulfate sodium (DSS)-induced colitis in mice. Results showed that administration of BRAE and RA, alone and in combination, significantly decreased the disease activity index (DAI) and the histological score of colons in DSS-induced colitis mice. Moreover, the administration of BRAE and RA, alone and in combination, not only reduced myeloperoxidase (MPO) and nitric oxide (NO) levels, but also inhibited the expression of pro-inflammatory mediators including interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Our results showed that BRAE decreased the histological score and TNF-α mRNA expression in a dose-dependent manner, while BRAE + RA dose-dependently attenuated the histological score and mRNA expression of IL-6. However, the benefits of RA were not dose-dependent within the dose range of 25-100 mg kg-1. The combination of BRAE and RA showed better inhibitory effect on the NO content and iNOS mRNA expression than BRAE or RA given alone, and was the most effective in ameliorating DSS-induced colitis at 100 mg kg-1. Notably, the BRAE and RA combination exhibited additive interactions in reducing MPO and NO levels, as well as the expression of some pro-inflammatory mediators (IL-6, IL-1β and iNOS), especially at 100 mg kg-1. In conclusion, dietary BRAE and RA, alone and in combination, alleviate the symptoms and inflammation of DSS-induced colitis in mice, and may provide a promising dietary approach for the management of inflammatory bowel disease.

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Posted: June 25, 2018, 4:11 pm
PMID:  Biomed Pharmacother. 2018 Jun ;102:884-893. Epub 2018 Apr 5. PMID: 29710544Abstract Title:  The inhibitory effect of rosmarinic acid on overexpression of NCX1 and stretch- induced arrhythmias after acute myocardial infarction in rats.Abstract:  The incidence of arrhythmias is the main cause of high mortality after myocardial infarction (AMI). The aim of the present study was to determine whether the rosmarinic acid (RA) could reduce the stretch-induced arrhythmias (SIAs) related to overexpression of NCXafter AMI. Adult male Sprague-Dawley rats were randomly allocated into six groups: Sham, MI (100 mg/kg of isoproterenol (Iso), subcutaneously, on two consecutive days), RA (30 mg/kg, orally, 14 days), and RA (10, 15 and 30 mg/kg, 14 days) + I. MI induction was performed on the 13th and 14th days of the study period. Forty-eight hours after the first injection of Iso, the parameters of hypertrophy, plasma levels of malondialdehyde (MDA) and lipid profile were evaluated. Using Langendorff apparatus, the isolated hearts were transiently stretched for 5 s with three different end-diastolic volumes (ΔV = 0.05, 0.1 and 0.2 mL). Cardiac function parameters were measured for 30 s, and ventricular arrhythmias were recorded for 3 min after each stretch. Finally, the levels of cardiac troponin-I and NCXmRNA expression were examined. The rats of MI group showed a significant increase in hypertrophy index, MDA, triglyceride and cholesterol (P 

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Posted: June 25, 2018, 3:47 pm
PMID:  J Ethnopharmacol. 2018 Aug 10 ;222:201-207. Epub 2018 May 9. PMID: 29751125Abstract Title:  Anti-inflammatory activities and potential mechanisms of phenolic acids isolated from Salvia miltiorrhiza f. alba roots in THP-1 macrophages.Abstract:  ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Salvia miltiorrhiza f. alba (Lamiaceae) (RSMA) are used as the Danshen, a traditional Chinese medicine, to treat the vascular diseases at local clinics, especially for the remedy of thromboangiitis obliterans (TAO) more than 100 years. Phenolic acids are one of the major effective constituents of RSMA, and some studies have linked phenolic acids with anti-inflammatory functions.AIM OF THE STUDY: The purpose of this research was to isolate phenolic acids from RSMA and investigate their anti-inflammatory effects and potential mechanisms.MATERIALS AND METHODS: Nine already known compounds were obtained from RSMA. Their structures were elucidated through the spectroscopic analysis and comparing the reported data. The anti-inflammatory effects and potential mechanisms were investigated in LPS-stimulated THP-1 cells, using salvianolic acid B (SalB) as the positive control. The enzyme-linked immunosorbent assays (ELISA) were used to determine the secretory protein levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). And quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the mRNA levels of these inflammatory cytokines. The expression of TLR4, p65, p-p65, IκBα, and p-IκBα were measured using western blot.RESULTS: All these compounds, except for rosmarinic acid (5) and isosalvianolic acid (6) for IL-6 protein levels, rosmarinic acid-o-β-D-glucopyranoside (3) for IL-6 mRNA, and rosmarinic acid-o-β-D-glucopyranoside (3), rosmarinic acid (5) and isosalvianolic acid (6) for TNF-α mRNA levels, remarkably inhibited the production of TNF-α, IL-1β, and IL-6 at the concentration of 5 and 25 μM in the mRNA and protein levels. Lithospermic acid (7) showed the strongest inhibitory effect among them and was similar to that of SalB. In particular, lithospermic acid (7) and SalB markedly downregulated the expressions of TLR4, p-p65, and p-IκBα induced by LPS in THP-1 macrophages.CONCLUSIONS: All the phenolic acids displayed anti-inflammatory properties and the potential mechanisms involved the TLR4/NF-κB signal pathway. Results of this study indicate that phenolic acids may be effective constituents of RSMA to treat vascular diseases associated with inflammation.

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Posted: June 25, 2018, 2:27 pm
PMID:  Iran J Pharm Res. 2018 ;17(Suppl):89-100. PMID: 29796033Abstract Title:  Effect of(Lemon balm) on Sexual Dysfunction in Women: A Double- blind, Randomized, Placebo-controlled Study.Abstract:  Hypoactive sexual desire disorder (HSDD) is the most prevalent female sexual dysfunction (FSD) and its bio-psychosocial multifactorial etiology justifies its multifaceted treatment. In Persian Medicine (PM), the weakness of the main organs (heart, brain and liver) is one of the important causes of lack of sexual desire; hence, their strengthening is a priority during treatment.is one of the medicinal plants with tonic characteristics for the main organs in PM and was used for treatment in this study. The aim of the present study was to evaluate the efficacy and safety ofin the improvement of HSDD in women. Eighty nine (89) eligible women suffering from decreased sexual desire were randomly assigned to groups. The participants received medication (500 mg of aqueous extract of) or placebo 2 times a day for 4 weeks. Changes in scores of desire, arousal, lubrication, orgasm, satisfaction and pain were evaluated at the end of 4 weeks of treatment using the Female Sexual Function Index (FSFI) questionnaire in the two groups. Forty three participants completed the study. The increase in desire (

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Posted: June 25, 2018, 2:17 pm
PMID:  Can J Physiol Pharmacol. 2018 May 28. Epub 2018 May 28. PMID: 29806983Abstract Title:  A high omega-3 fatty acid diet rapidly changes the lipid composition of cardiac tissue and results in cardio-protection.Abstract:  The present study was designed to ascertain the effects of 3 diets with different omega-3/6 fatty acid ratios on infarct size and the modifications that these diets induce in the lipid composition of cardiac tissue. Sprague-Dawley rats were fed omega-3/6 fatty acid diets with 1:1, 1:5 or 1:20 ratios for at least 10 days, followed by occlusion of the left anterior descending artery for 40 min and 24 h of reperfusion. Infarct size was significantly smaller in the 1:1 group compared to the other groups. Significantly higher concentrations of the omega-3 fatty acids eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid were found in the 1:1 and other groups. Omega-6 polyunsaturated fatty acid levels were similar between groups, although they were higher in the 1:5 and 1:20 groups compared to the 1:1 group. Margaric acid concentrations were higher in the 1:1 group than in both other groups. Docosahexaenoic acid levels in cardiac tissue and infarct size were significantly correlated with no other significant links being apparent. In conclusion, the present study indicated that a 1:1 omega-3/6 fatty acid ratio protected against ischemia and was associated with increased omega-3 fatty acid composition of cardiac tissue.

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Posted: June 25, 2018, 1:56 pm
PMID:  J Neurogastroenterol Motil. 2018 Jun 4. Epub 2018 Jun 4. PMID: 29879761Abstract Title:  The Protective Effect ofL. in Visceral Hypersensitivity in Rat Using 2 Models of Acid-induced Colitis and Stress-induced Irritable Bowel Syndrome: A Possible Role of Nitric Oxide Pathway.Abstract:  Background/Aims: The aim of present study is to estimate the effects ofL. (MO) on visceral hypersensitivity (VH), defecation pattern and biochemical factors in 2 experimental models of irritable bowel syndrome (IBS) and the possible role of nitric oxide.Methods: Two individual models of IBS were induced in male Wistar-albino rats. In the acetic acid model, the animals were exposed to rectal distension and abdominal withdrawal reflex, and the defecation patterns were determined. In the restraint stress model, the colons of rats were removed and the levels of TNF-α, myeloperoxidase, lipid peroxidation, and antioxidant powers were determined. Rats had been treated with MO, L-NG-nitroarginine methyl ester (L-NAME), aminoguanidine (AG), MO + AG, or MO + L-NAME in the mentioned experimental models.Results: Hypersensitive response to rectal distension and more stool defecation in control rats have been observed in comparison to shams. MO-300 significantly reduced VH and defecation frequency in comparison to controls. VH and defecation pattern did not show significant change in AG + MO and L-NAME + MO groups compared to controls. Also, significant reduction in TNF-α, myeloperoxidase, TBARS, and an increase in antioxidant power in MO-300 was recorded compared to controls. AG + MO and L-NAME + MO groups showed a reverse pattern compared to MO-300.Conclusions: MO can ameliorate IBS by modulating VH and defecation patterns. Antioxidant and anti-inflammatory properties along with its effect on the nitrergic pathway seems to play important roles in its pharmacological activity.

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Posted: June 25, 2018, 1:44 pm
PMID:  Evid Based Complement Alternat Med. 2018 ;2018:7860456. Epub 2018 May 16. PMID: 29887909Abstract Title:  A Comparative Study ofLeaves and Stems Ethanolic Extracts in terms of Antioxidant, Cytotoxic, and Antiproliferative Potential.Abstract:  L. has attracted an increased interest in recent years due to its multiple pharmacological effects. This study aimed to compare twoethanolic extracts, obtained from leaves and stems, with regard to their antioxidant activity, total phenolic content, and cytotoxic effects.ethanolic extracts showed a very good antioxidant activity in the DPPH test, correlated with the content in total phenols: higher in the case offrom leaves extract (32.76 mg GAE/g) and lower forfrom stems extract (8.4 mg GAE/g). The lemon balm extracts exerted a cytotoxic effect on breast cancer cells (MDA-MB-231) even at low concentrations (100 g/mL), whereas, in the case of healthy HaCat cells,leaves extract only displayed cytotoxicity at much higher concentrations (500 and 1000 g/mL) andstems extracts were highly cytotoxic (starting at 100 g/mL). In addition, the extracts exerted inhibitory effects on cell migration and proliferation. These results provide information that confirms the high potential ofas a source of chemopreventive agents. Moreover, these data can be considered a solid background for furtherstudies involving mice bearing breast tumors.

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Posted: June 25, 2018, 1:31 pm
PMID:  Clin Nutr ESPEN. 2018 Aug ;26:47-52. Epub 2018 May 19. PMID: 29908682Abstract Title:  The effects of Melissa officinalis supplementation on depression, anxiety, stress, and sleep disorder in patients with chronic stable angina.Abstract:  BACKGROUND: Despite advances in the treatment of cardiovascular diseases in recent decades, patients experience high levels of depression, anxiety, stress, and insomnia. Since the calming effect of Melissa officinalis (MO) has been known, this study aimed to determine the effects of MO supplementation on depression, anxiety, stress, and sleep disturbances in patients with chronic stable angina (CSA).METHODS: In this double-blind placebo-controlled clinical trial, 80 patients with CSA were divided randomly into two groups (taking 3 g MO supplement or placebo daily for 8 weeks). The shortened 21-item version of the depression, anxiety and stress scale (DASS-21) test and Pittsburgh sleep quality index were done before and after the intervention.RESULTS: At the end of the study, the intervention group receiving MO capsules had a significant reduction in scores of depression, anxiety, stress, and total sleep disturbance, compared with the placebo group (P 

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Posted: June 25, 2018, 12:20 pm
PMID:  Food Funct. 2018 Jun 20 ;9(6):3134-3142. PMID: 29790547Abstract Title:  Melissa officinalis L. ethanolic extract inhibits the growth of a lung cancer cell line by interfering with the cell cycle and inducing apoptosis.Abstract:  Melissa officinalis is a plant from the family Lamiaceae, native in Europe particularly in the Mediterranean region. Given our interest in identifying extracts and compounds capable of inhibiting tumor cell growth, and given the antioxidant content and the high consumption of Melissa officinalis in Portugal, this study aimed to test the tumor cell growth inhibitory activity of five different extracts of this plant (aqueous, methanolic, ethanolic, hydromethanolic and hydroethanolic) in three human tumor cell lines: MCF-7, AGS and NCI-H460. All extracts decreased cell growth in all cell lines in a concentration-dependent manner. The ethanolic extract was the most potent one, presenting a GI50 concentration of approximately 100.9μg mL-1 in the NCI-H460 lung cancer cells. This extract was characterized by LC-DAD-ESI/MS regarding its phenolic composition, revealing rosmarinic acid as the most abundant compound. The GI75 concentration of this extract affected the cell cycle profile of these cells. In addition, both the GI50 and the GI75 concentrations of the extract induced cellular apoptosis. Moreover, treatment of NCI-H460 cells with this extract caused a decrease in pro-caspase 3 and an increase in p53 levels. This study emphasizes the relevance of the study of natural products as inhibitors of tumor cell growth.

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Posted: June 25, 2018, 12:02 pm
PMID:  Biomed Pharmacother. 2018 Jun 1 ;105:334-349. Epub 2018 Jun 1. PMID: 29864622Abstract Title:  Proteomics analysis demonstrating rosmarinic acid suppresses cell growth by blocking the glycolytic pathway in human HepG2 cells.Abstract:  Rosmarinic acid (RA), isolated from herbal balm mint plants, has demonstrated potent anti-tumor properties against liver cancer. However, the precise underlying mechanisms remain unclear. This study aimed to investigate the molecular mechanisms of RA in HepG2 cells. RA anti-tumor activity was assessed using 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and Hoechst 33258 staining. Apoptosis and the cell cycle distribution were evaluated by flow cytometry. A proteomics approach was used to identify differentially expressed proteins following RA treatment in HepG2 cells, and quantitative reverse transcription-quantitative polymerase chain reaction was used to validate the results. Bioinformatics analysis was also implemented to further understand the identified proteins, and western blotting was used to analyze the associated proteins. Our results suggested that RA treatment significantly inhibits the viability of HepG2 cells. The MTT and LDH assays indicated dose-dependent decreases in cell proliferation following RA treatment. Hoechst 33258 staining and flow cytometry analysis showed that RA exhibits an apoptosis-inducing effect and induces cell cycle arrest in G1. The proteomics analysis successfully identified 16 differentially expressed proteins. Bioinformatics analysis indicated that the identified proteins participated in several biological processes and exhibited various molecular functions, mainly related to inactivation of the glycolytic pathway. Further western blotting analysis showed that RA could downregulate the expression of glucose transporter-1 and hexokinase-2, leading to the suppression of glucose consumption and generation of lactate and ATP. Taken together, our study found that RA exhibits significant cytotoxic effects by inhibiting cell proliferation and inducing apoptosis and cell cycle arrest, possibly by blocking the glycolytic pathway in human HepG2 cells.

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Posted: June 25, 2018, 11:48 am
PMID:  Sci Rep. 2018 Jun 19 ;8(1):9341. Epub 2018 Jun 19. PMID: 29921877Abstract Title:  Rosmarinic Acid Restores Complete Transparency of Sonicated Human Cataract Ex Vivo and Delays Cataract Formation In Vivo.Abstract:  Cataract, the leading cause of vision impairment worldwide, arises from abnormal aggregation of crystallin lens proteins. Presently, surgical removal is the only therapeutic approach. Recent findings have triggered renewed interest in development of non-surgical treatment alternatives. However, emerging treatments are yet to achieve full and consistent lens clearance. Here, the first ex vivo assay to screen for drug candidates that reduce human lenticular protein aggregation was developed. This assay allowed the identification of two leading compounds as facilitating the restoration of nearly-complete transparency of phacoemulsified cataractous preparation ex vivo. Mechanistic studies demonstrated that both compounds reduce cataract microparticle size and modify their amyloid-like features. In vivo studies confirmed that the lead compound, rosmarinic acid, delays cataract formation and reduces the severity of lens opacification in model rats. Thus, the ex vivo assay may provide an initial platform for broad screening of potential novel therapeutic agents towards pharmacological treatment of cataract.

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Posted: June 25, 2018, 11:39 am
PMID:  Dose Response. 2018 Apr-Jun;16(2):1559325818761455. Epub 2018 Apr 11. PMID: 29662431Abstract Title:  The Neuroprotective Effects of Thymoquinone: A Review.Abstract:  Thymoquinone (TQ), one of the main components active of, exhibited very useful biomedical effects such as anti-inflammatory, antioxidant, antimicrobial, antiparasitic, anticancer, hypoglycemic, antihypertensive, and antiasthmatic effects. There are several studies about pharmacological activities of TQ but its neuroprotection effects are not fully described. The literature search has indicated many studies pertaining to the effects of TQ in neurological problems such as epilepsy, parkinsonism, anxiety, and improvement of learning and memory, and so on. In addition, TQ protected brain cells from various injuries due to its antioxidant, anti-inflammatory, and apoptotic effects in cell line and experimental animal models. The present study has been designed to review the scientific literature about the pharmacological activities of TQ to the neurological diseases. This study purposed that although experimental studies indicated the beneficial effects of TQ against nervous system problems, better designed clinical trials in humans are needed to confirm these effects.

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Posted: June 24, 2018, 12:20 pm
PMID:  Front Neurol. 2018 ;9:236. Epub 2018 Apr 13. PMID: 29706929Abstract Title:  Neuromodulatory Effect of Thymoquinone in Attenuating Glutamate-Mediated Neurotoxicity Targeting the Amyloidogenic and Apoptotic Pathways.Abstract:  Overexposure of the glutamatergic N-methyl-d-aspartate (NMDA) receptor to the excitatory neurotransmitter l-glutamic acid leads to neuronal cell death by excitotoxicity as a result of increased intracellular Ca, mitochondrial dysfunction, and apoptosis. Moreover, it was previously reported that prolonged activation of the NMDA receptor increased beta-amyloid (Aβ) levels in the brain. Thymoquinone (TQ), the active constituent ofseeds, has been shown to have potent antioxidant and antiapoptotic effects. The aim of the present study was to explore the neuromodulatory effects of different doses of TQ (2.5 and 10 mg/kg) against apoptotic cell death and Aβ formation resulting from glutamate administration in rats using vitamin E as a positive control. Behavioral changes were assessed using Y-maze and Morris water maze tests for evaluating spatial memory and cognitive functions. Caspase-3, Lactate dehydrogenase, Aβ-42, and cytochromegene expression were determined. TQ-treated groups showed significant decreases in the levels of all tested biochemical and behavioral parameters compared with the glutamate-treated group. These findings demonstrated that TQ has a promising neuroprotective activity against glutamate-induced neurotoxicity and this effect is mediated through its anti-amyloidogenic, antioxidant, and antiapoptotic activities.

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Posted: June 24, 2018, 12:14 pm
PMID:  Oxid Med Cell Longev. 2018 ;2018:1209801. Epub 2018 Mar 20. PMID: 29743967Abstract Title:  Neuropharmacological Potential and Delivery Prospects of Thymoquinone for Neurological Disorders.Abstract:  Thymoquinone (TQ) is an active ingredient isolated fromand has various pharmacological activities, such as protection against oxidative stress, inflammation, and infections. In addition, it might be a potential neuropharmacological agent because it exhibits versatile potential for attenuating neurological impairments. It features greater beneficial effects in toxin-induced neuroinflammation and neurotoxicity. In various models of neurological disorders, it demonstrates emergent functions, including safeguarding various neurodegenerative diseases and other neurological diseases, such as stroke, schizophrenia, and epilepsy. TQ also has potential effects in trauma mediating and chemical-, radiation-, and drug-induced central nervous system injuries. Considering the pharmacokinetic limitations, research has concentrated on different TQ novel formulations and delivery systems. Here, we visualize the neuropharmacological potential, challenges, and delivery prospects of TQ, specifically focusing on neurological disorders along with its chemistry, pharmacokinetics, and toxicity.

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Posted: June 24, 2018, 12:07 pm
PMID:  Biomed Pharmacother. 2018 Jun ;102:1152-1160. Epub 2018 Apr 5. PMID: 29710533Abstract Title:  Thymoquinone alleviates arsenic induced hippocampal toxicity and mitochondrial dysfunction by modulating mPTP in Wistar rats.Abstract:  Arsenic is a pervasive environmental pollutant that is found in ground waters globally and is related to numerous morbidities in the high-risk population areas in countries including Bangladesh, India, and the USA. Arsenic exposure has been ubiquitously reported for exacerbating free radical generation, mitochondrial dysfunction, and apoptosis by interfering with the mPTP functioning. Over the past decades, nutraceuticals with antioxidant properties have shown promising efficacy in arsenic poisoning. In the present study, we have examined, the protective efficacy of thymoquinone (TQ), an active component of seed oil of Nigella sativa with antioxidant and anti-inflammatory activity on arsenic-induced toxicity in hippocampi of Wistar rats. In our results, arsenic conditioning (10 mg/kg b.wt.; p.o.) for 8 days has caused a significant increase in intracellular ROS generation, mitochondrial dysfunction and apoptotic events. On the contrary pretreatment with TQ (2.5 and 5 mg/kg b.wt.; p.o.) inhibited arsenic-induced mitochondrial dysfunction such as lowering of mitochondrial membrane potential (Δψm). Our results indicated that the neuroprotective efficacy of TQ in arsenic-induced stress is mediated through or in part by inhibition of mPTP opening. Demonstration of neuroprotective action of TQ provides insight into the pathogenesis of arsenic-related neuropathological morbidities.

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Posted: June 24, 2018, 11:59 am
PMID:  Bratisl Lek Listy. 2018 ;119(5):312-316. PMID: 29749248Abstract Title:  Antiproliferative and antiapoptotic effect of thymoquinone on cancer cells in vitro.Abstract:  OBJECTIVES: Nigella sativa oil and thymoquinone were comparatively tested in vitro for their effects on human cancer cell lines (glioma,T98; prostate, LnCaP) as well as mouse embryonic fibroblast cell lines (3T3), and for the induction of apoptosis.METHODS: Individual cell lines were treated with thymoquinone and N. sativa oil for 24 and 48 hr. Survival rate with MTT, apoptosis with flow cytometry and caspase-9 mRNA enzyme levels with RT-PCR were determined in vitro.RESULTS: Application of respective concentrations of N. sativa oil (excluding 100μg/mL for 48 hr) did not change the number of tested cell lines, however, treatment with thymoquinone reduced the number of all cells significantly. Thymoquinone also exerted its apoptosis inducing effect through the activation of caspase-9.CONCLUSION: Differing with the type of cancer cells, thymoquinone posseses a strong contentration and time dependent survival reducing effect on cancer cells via apoptosis (Fig. 6, Ref. 22). Text in PDF www.elis.sk.

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Posted: June 24, 2018, 11:52 am
PMID:  J Neuroimmunol. 2018 Jul 15 ;320:87-97. Epub 2018 May 4. PMID: 29759145Abstract Title:  Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ -activated BV-2 microglia cells.Abstract:  Neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. Chronic activation of microglia induces the release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines. Additionally, chronic microglial activation has been implicated in several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Thymoquinone (TQ) has been identified as one of the major active components of the natural product Nigella sativa seed oil. TQ has been shown to exhibit anti-inflammatory, anti-oxidative, and neuroprotective effects. In this study, lipopolysaccharide (LPS) and interferon gamma (IFNγ) activated BV-2 microglial cells were treated with TQ (12.5 μM for 24 h). We performed quantitative proteomic analysis using Orbitrap/Q-Exactive Proteomic LC-MS/MS (Liquid chromatography-mass spectrometry) to globally assess changes in protein expression between the treatment groups. Furthermore, we evaluated the ability of TQ to suppress the inflammatory response using ELISArray™ for Inflammatory Cytokines. We also assessed TQ's effect on the gene expression of NFκB signaling targets by profiling 84 key genes via real-time reverse transcription (RT) PCR array. Our results indicated that TQ treatment of LPS/IFNγ-activated microglial cells significantly increased the expression of 4 antioxidant, neuroprotective proteins: glutaredoxin-3 (21 fold; p 

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Posted: June 24, 2018, 11:41 am
PMID:  Environ Toxicol Pharmacol. 2018 Jun ;60:216-224. Epub 2018 May 7. PMID: 29763882Abstract Title:  Thymoquinone influences the expression of genes involved in self-renewal and immunomodulatory potential of mouse bone marrow-derived mesenchymal stem cells in vitro.Abstract:  Thymoquinone (TQ) is an active ingredient of some medicinal herbs. Despite extensive studies on the biological and pharmacological properties of TQ, its effect on the characteristics of stem cells remains to be clarified. Therefore, this study was aimed to investigate the effect of TQ on viability, proliferation and immunomodulatory potential of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) in vitro. The BM-MSCs were isolated from young NMRI mice. The cytotoxic effect of TQ on the BM-MSCs was evaluated using MTT assay. Then, the effect of TQ on the proliferation of BM-MSCs and the mRNA expression of genes involved in self-renewal and immunomodulatory potential of MSCs was assessed by the cell counting and real-time PCR assays. Results showed that TQ reduces the number of BM-MSCs in a dose- and time-dependent manner. In addition, the half-maximal inhibitory concentration values of TQ on the BM-MSCs were 8μg/ml at 24h and 4 μg/ml at 48 and 72h after treatment. Furthermore, about 90% of the BM-MSCs were alive after treatment with concentrations ≤2 μg/ml of TQ for 24h. The results of cell counting assay indicated that TQ at concentrations of 1-2 μg/ml significantly enhanced the proliferation of BM-MSCs (P

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Posted: June 24, 2018, 11:27 am
PMID:  Exp Ther Med. 2018 Jun ;15(6):4987-4994. Epub 2018 Apr 16. PMID: 29904397Abstract Title:  Thymoquinone reduces spinal cord injury by inhibiting inflammatory response, oxidative stress and apoptosis via PPAR-γ and PI3K/Akt pathways.Abstract:  The present study used a mild contusion injury in rat spinal cord to determine that thymoquinone reduces inflammatory response, oxidative stress and apoptosis in a spinal cord injury (SCI) rat model and to demonstrate its possible molecular mechanisms. The rats in the thymoquinone group received 30 mg/kg thymoquinone once daily by intragastric administration from 3 weeks after surgery. Hematoxylin and eosin staining, Basso, Beattie and Bresnahan (BBB) scale and tissue water content detection were used in the present study to analyze the effect of thymoquinone on SCI. The activity of inflammatory response mediators, oxidative stress factors and caspase-3/9 was measured using ELISA kits. Furthermore, western blotting was performed to analyzed the protein expression levels of prostaglandin E2, suppressed cyclooxygenase-2 (COX-2) and activated peroxisome proliferator-activated receptorγ (PPAR-γ), PI3K and Akt. The results from the study demonstrated that thymoquinone increased Basso, Beattie and Bresnahan score and decreased water content in spinal cord tissue. Treatment with thymoquinone decreased inflammatory response [measured by levels of tumor necrosis factor α, interleukin (IL)-1β, IL-6 and IL-18], oxidative stress (measured by levels of superoxide dismutase, catalase, glutathione and malondialdehyde) and cell apoptosis (measured by levels of caspase-3 and caspase-9) in SCI rats. Thymoquinone treatment inhibited prostaglandin E2 activity, suppressed COX-2 proteinexpression and activated PPAR-γ, PI3K and p-Akt protein expression in SCI rats. These data revealed that thymoquinone reduces inflammatory response, oxidative stress and apoptosis via PPAR-γ and PI3K/Akt pathways in an SCI rat model.

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Posted: June 24, 2018, 10:50 am
PMID:  Avicenna J Phytomed. 2018 May-Jun;8(3):188-197. PMID: 29881705Abstract Title:  Thymoquinone recovers learning function in a rat model of Alzheimer's disease.Abstract:  Objective: Alzheimer's disease is a neurodegenerative disorder characterized by accumulation of amyloid beta in the hippocampus. In recent decades, herbal medicine has been widely used to treat many neurodegenerative disorders,as in comparison to conventional drugs, herbal remedies exert minimal side effects. Here, the effects of thymoquinone, as the main active component of, on passive avoidance memory in rat model of Alzheimer's disease, were evaluated.Materials and Methods: Hippocampal injection of amyloid beta (Aβ) was used to induce Alzheimer's disease in male Wistar rats, followed by intra peritoneal administrations of 5 and 10 mg/kg thymoquinone on a daily basis for 4 weeks. Animals were subjected to fear learning behavior in passive avoidance test and histopathological analysis of the hippocampus was done. Shuttle box test was used to evaluate the condition studying memory. Thioflavin-S and Hematoxylin and Eosine staining were done to confirm Aβ plaque formation and to evaluate the effect of thymoquinone on the pyramidal cells in the hippocampal CA1 region.Results: Amyloid beta caused cognitive dysfunction reflected by increasing initial and step-through latency along with plaque formation and degeneration of pyramidal cells in the hippocampus. Thymoquinone administration ameliorated this effect by significant reductions in plaque formation in CA1 region of the hippocampus and increased latency time. It also increased the number of surviving neurons in the hippocampus.Conclusion: It seems that thymoquinone improved learning function in a rat model of Alzheimer's disease. Thus, thymoquinone could be possibly used as an anti-neurodegenerative agent for protecting hippocampal neurons against neurotoxic effects of Aβ in patients with Alzheimer's disease.

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Posted: June 24, 2018, 10:31 am
PMID:  Avicenna J Phytomed. 2018 May-Jun;8(3):263-275. PMID: 29881712Abstract Title:  Early and late preventive effect ofon the bleomycin-induced pulmonary fibrosis in rats: An experimental study.Abstract:  Objective: Pulmonary fibhrosis is a disease of the connective tissues in the respiratory system.has been used for the treatment of pulmonary diseases like asthma. This study investigated the early and late preventive effect of methanolic extract ofon a bleomycin- induced pulmonary fibrosis model.Materials and Methods: This study was carried out using 52 rats. Pulmonary fibrosis was induced by a single endotracheal injection of bleomycin (5 mg/kg). Extract of(500 mg/kg per day) or methylprednisolone succinate (4 mg/kg per day) was injected intraperitoneally in two periods (i.e. days 1-14 as early preventive group and days 15-28 days as late preventive group). The lung tissues were histologically examined at the end of each period and inspected for the amount of hydroxyproline and biomarkers of oxidative stress.Results: The pulmonary inflammation and fibrosis were significantly decreased in groups treated with methylprednisolone andextract compared to bleomycin group in both early and late prevention groups (p

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Posted: June 24, 2018, 9:22 am
PMID:  Pestic Biochem Physiol. 2018 Jun ;148:16-21. Epub 2018 Mar 13. PMID: 29891368Abstract Title:  Protective role of thymoquinone against paraquat-induced hepatotoxicity in mice.Abstract:  Paraquat is a common and effective herbicide; although its poisoning could lead to severe oxidative organ damages and its main target organs are the lungs, kidneys, heart, and liver. Thymoquinone is the active ingredient of Nigella sativa which is traditionally used in herbal medicine; recent studies have shown that thymoquinone could inhibit oxidative stress. This study explores protective effects of thymoquinone on paraquat-induced hepatotoxicity in mice. Accordingly, adult male mice were randomly divided into nine groups for three continuous days intraperitoneal injection treatment: (1) control; (2) solvent; (3) 20 mg/kg vitamin E; (4) 20 mg/kg thymoquinone; (5) 20 mg/kg paraquat and Groups 6, 7, 8, and 9 received 20 mg/kg of vitamin E and 5, 10, and 20 mg/kg of thymoquinone, respectively. The last four groups, received 20 mg/kg paraquat just 24 h after pretreatments. We assessed serum liver enzymes activities, liver histopathology changes, oxidative (lipid peroxidation) and antioxidative (ferric reducing antioxidant power) potential, superoxide dismutase (SOD) and catalase activity, and total thiol groups content after administration of the poison and treatments. Pretreatment with 10 mg/kg thymoquinone inhibited, safely, the elevations in levels of liver function tests (LFTs) and lipid peroxidation, restored the activity of SOD, and ameliorated the histopathological alterations induced by paraquat. Eventually, our results indicate that thymoquinone performs its hepatoprotective role in mice by prevention of SOD suppression mediated by paraquat.

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Posted: June 24, 2018, 9:15 am
Content Was Refreshed: 25 Jun 2018 | 20:05:43
Last Modified: April 28, 2018