Publications by authors named "Zahra Lorigooini"

30 Publications

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Epigenetic targeting of cancer stem cells by polyphenols (cancer stem cells targeting).

Phytother Res 2021 Feb 22. Epub 2021 Feb 22.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Epigenetic alterations are one of the main factors that disrupt the expression of genes and consequently, they have an important role in the carcinogenicity and the progression of different cancers. Cancer stem cells (CSCs) are accountable for the recurrence, metastasis, and therapeutic failure of cancer. The noticeable and specific pathways in CSCs can be organized by epigenetic mechanisms such as DNA methylation, chromatin remodeling, regulatory RNAs, among others. Since epigenetics modifications can be changed and reversed, it is a possible tool for cancer control and treatment. Epigenetic therapies against CSCs are emerging as a very new strategy with a good future expectation to treat cancer patients. Phenolic compounds are a vast group of substances with anticarcinogenic functions, antiinflammatory, and antioxidative activities. It seems these characteristics are related to neutralizing CSCs development, their microenvironment, and metabolism through epigenetic mechanisms. In the current work, the types of epigenetic changes known in these cells are introduced. In addition, some studies about the use of polyphenols acting through a variety of epigenetic mechanisms to counteract these cells will be reviewed. The reported results seem to indicate that the use of these phenolic compounds may be useful for CSCs defeat.
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http://dx.doi.org/10.1002/ptr.7059DOI Listing
February 2021

Limonene through Attenuation of Neuroinflammation and Nitrite Level Exerts Antidepressant-Like Effect on Mouse Model of Maternal Separation Stress.

Behav Neurol 2021 29;2021:8817309. Epub 2021 Jan 29.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Methods: Mice were randomly divided into experimental groups as follows: the control group received normal saline and MS groups received normal saline, limonene (10 and 20 mg/kg), L-NAME (10 mg/kg), L-arginine (L-arg) (75 mg/kg), limonene (10 mg/kg) plus L-NAME, and limonene (20 mg/kg) plus L-arg. Behavioral tests including the forced swimming test (FST), open field test (OFT), and splash test were performed. Finally, serum and hippocampal nitrite levels as well as the expression of inflammatory genes (IL-1 and TNF-) in the hippocampus were measured.

Results: We showed that MS caused depressive-like behavior. Treatment of MS mice with limonene reduced the duration of immobility time in FST and increases the grooming activity time in the splash test. Limonene also reduces serum and brain nitrite levels and reduces the expression of IL-1 and TNF- in the hippocampus. We found that L-NAME potentiated the effects of a subeffective dose of limonene.

Conclusion: We concluded that the antidepressant-like effects of limonene are probably mediated through inhibition of neuroinflammation and attenuation of nitrite levels in the hippocampus.
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http://dx.doi.org/10.1155/2021/8817309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864762PMC
January 2021

Auraptene exerts protective effects on maternal separation stress-induced changes in behavior, hippocampus, heart and serum of mice.

Int Immunopharmacol 2021 Apr 5;93:107436. Epub 2021 Feb 5.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Early life stress is associated with various complications. Auraptene has significant antioxidant and anti-inflammatory effects. This study aimed to assess the probable underlying mechanisms that mediate changes in the behavior, hippocampus, heart and serum in the mouse model of maternal separation (MS) stress. We evaluated the possible protective effects of auraptene in these changes focusing on inflammatory response and oxidative state. Mice were treated with auraptene (5, 10, and 50 mg/kg). In addition, anxiety-like behaviors were evaluated using behavioral tests; including open field test (OFT) and elevated plus maze (EPM). Hippocampus and heart samples were assessed histopathologically. Levels of malondialdehyde (MDA) and antioxidant capacity, as well as nitrite levels, were measured in serum, heart, and hippocampal tissues. Moreover, gene expression of inflammatory markers (Il-1β and Tlr-4) was evaluated in the heart and hippocampus. Results showed that auraptene reversed the negative effects of MS on behavior (increased time spent in central zone of the OFT and time and entries to the open arms of the EPM). Auraptene mitigated adverse effects of MS on the hippocampus (increased diameter and decreased percentage of dark neurons in the CA3 area). Accordingly, auraptene decreased MDA and nitrite levels and increased the antioxidant capacity in serum, and hippocampal samples. However, we observed different effects for different doses of auraptene in the heart samples. We concluded that MS is associated with anxiety-like behavior and cellular/molecular modifications in the heart, hippocampus and serum. We found that auraptene exerted protective effects against these negative effects of MS in mouse.
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http://dx.doi.org/10.1016/j.intimp.2021.107436DOI Listing
April 2021

Effect of Curcuma zedoaria hydro-alcoholic extract on learning, memory deficits and oxidative damage of brain tissue following seizures induced by pentylenetetrazole in rat.

Behav Brain Funct 2020 Oct 6;16(1). Epub 2020 Oct 6.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background: Previous studies have shown that seizures can cause cognitive disorders. On the other hand, the Curcuma zedoaria (CZ) has beneficial effects on the nervous system. However, there is little information on the possible effects of the CZ extract on seizures. The aim of this study was to investigate the possible effects of CZ extract on cognitive impairment and oxidative stress induced by epilepsy in rats.

Methods: Rats were randomly divided into different groups. In all rats (except the sham group), kindling was performed by intraperitoneal injection of pentylenetetrazol (PTZ) at a dose of 35 mg/kg every 48 h for 14 days. Positive group received 2 mg/kg diazepam + PTZ; treatment groups received 100, 200 or 400 mg/kg CZ extract + PTZ; and one group received 0.5 mg/kg flumazenil and CZ extract + PTZ. Shuttle box and Morris Water Maze tests were used to measure memory and learning. On the last day of treatments PTZ injection was at dose of 60 mg/kg, tonic seizure threshold and mortality rate were recorded in each group. After deep anesthesia, blood was drawn from the rats' hearts and the hippocampus of all rats was removed.

Results: Statistical analysis of the data showed that the CZ extract significantly increased the tonic seizure threshold and reduced the pentylenetetrazol-induced mortality and the extract dose of 400 mg/kg was selected as the most effective dose compared to the other doses. It was also found that flumazenil (a GABA receptor antagonist) reduced the tonic seizure threshold compared to the effective dose of the extract. The results of shuttle box and Morris water maze behavioral tests showed that memory and learning decreased in the negative control group and the CZ extract treatment improved memory and learning in rats. The CZ extract also increased antioxidant capacity, decreased MDA and NO in the brain and serum of pre-treated groups in compared to the negative control group.

Conclusion: It is concluded that the CZ extract has beneficial effects on learning and memory impairment in PTZ-induced epilepsy model, which has been associated with antioxidant effects in the brain or possibly exerts its effects through the GABAergic system.
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http://dx.doi.org/10.1186/s12993-020-00169-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542381PMC
October 2020

Possible involvement of NMDA receptor in the anxiolytic-like effect of caffeic acid in mice model of maternal separation stress.

Heliyon 2020 Sep 3;6(9):e04833. Epub 2020 Sep 3.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background And Aim: Anxiety disorders are one of the most common psychiatric disorders worldwide. Common anti-anxiety medications are associated with several side effects. Caffeic acid (CA) is a phenolic compound with several pharmacological effects. The aim of this study was to investigate the anxiolytic-like effect of CA in maternally separated (MS) mice focusing on the possible involvement of the NMDA receptor.

Materials And Methods: In this study, we used the MS paradigm (as a valid animal model of anxiety) in male mice and examined their anxiety-like behavior in postnatal day (PND) 45. The animals were divided into 12 experimental groups. Mice treated with CA alone and in combination with the NMDA receptor agonist/antagonist and then using open field (OFT) and elevated plus maze (EPM) anxiety-like behavior was assessed. Finally, the expression of NMDA receptor subtypes was assessed in the hippocampus using RT- PCR.

Results: Finding showed that CA exerted anxiolytic -like effects in the OFT and EPM tests. We showed that administration of effective dose of NMDA significantly reversed the anxiolytic-like effect of effective dose of CA and co-administration of ketamine (a NMDA receptor antagonist) significantly potentiated the effect of sub-effective dose of CA. Furthermore, ketamine enhanced the CA-reducing effect on NMDA receptors in the MS mice.

Conclusion: Our finding demonstrated that, probably at least, NMDA receptors are involved in the anxiety-like properties of CA in MS mice.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481568PMC
September 2020

Ginkgo biloba attenuated hepatotoxicity induced by combined exposure to cadmium and fluoride via modulating the redox imbalance, Bax/Bcl-2 and NF-kB signaling pathways in male rats.

Mol Biol Rep 2020 Sep 12;47(9):6961-6972. Epub 2020 Sep 12.

Pharmaceutical Science Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Aim of this study was to investigate the efficacy of Ginkgo Biloba (G.B) hydro-ethanolic extract against hepatotoxicity induced by combined exposure to cadmium (Cd) and fluoride (F) in Wistar rats. Animals were exposed to F (30 mg/L) + Cd (40 mg/L), F + Cd plus G.B (50,100 and 200 mg/kg), G.B (200 mg/kg), F + Cd plus Vit C(1000 mg/L) in drinking water for 42 days. Significant raise in liver enzymes and histopathological changes were observed in F + Cd treated rats. F + Cd exposure enhanced protein and glutathione oxidation, lipid peroxidation and decreased superoxide dismutase activity. F and Cd combination also caused mitochondrial dysfunction, swelling and mitochondrial membrane potential collapse in liver isolated mitochondria. Up-regulation of inflammatory genes (TNF-α, IL-1β and NF-kB) and pro-apoptotic Bax as well as down-regulation of anti-apoptotic Bcl-2 were detected after co-exposure to F and Cd. Interestingly, G.B alleviated F + Cd induced liver oxidative stress, mitochondrial damage and prevented inflammation and apoptosis. Furthermore, decrease in serum liver enzymes and improvement of histopathologic lesions were observed in G.B treated rats. This study explored the potential beneficial role of G.B on F + Cd combined hepatotoxic effects via considering its possible antioxidant, anti-inflammatory, mitochondrial protection and anti-apoptotic effects.
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http://dx.doi.org/10.1007/s11033-020-05755-2DOI Listing
September 2020

Diosgenin NMDA Receptor Exerted Anxiolytic-like Effect on Maternally Separated Mice.

Curr Pharm Des 2021 ;27(3):440-445

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background And Aim: Anxiety is one of the most common psychiatric disorders that lead to the disruption of daily life and also the quality of life. Routine medications have many side effects and cause physical dependence and psychosocial addiction. Diosgenin is a phytosteroid found in a number of herbs. The present study aimed to investigate the anxiolytic-like effect of diosgenin in the maternal separation model in male mice focusing on the role of NMDA receptors.

Materials And Methods: Maternal separation (MS) paradigm was performed daily (3 h) from postnatal day (PND) 2-14. Male mice were treated with different doses of diosgenin to find effective and sub-effective doses. In the next step, mice were treated with an effective dose of diosgenin plus NMDA and or a sub-effective dose of diosgenin plus ketamine (NMDA antagonist). Valid behavioral tests for the evaluation of anxiety-like behavior were performed. Then, mice were euthanized, the hippocampus was dissected out and gene expression of NMDA receptors (NR2a and NR2b subunits) was assessed.

Results: MS provokes anxiety-like behaviors in the open field test (OFT) and elevated plus maze (EPM) test. Diosgenin significantly mitigated the negative effects of MS. Co-administration of NMDA attenuated anxiolyticlike effect of the effective dose of diosgenin, while ketamine potentiated the anxiolytic effect of sub-effective dose of diosgenin. Furthermore, MS increased the expression of the NMDA receptor in the hippocampus which to some extent modulated with diosgenin.

Conclusion: Diosignin has an anxiolytic-like effect on MS mice which at least, in part, mediated through NMDA receptors.
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http://dx.doi.org/10.2174/1381612826666200717083211DOI Listing
January 2021

Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors.

Behav Neurol 2020 7;2020:4813616. Epub 2020 Jun 7.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Methods: Mouse neonates were exposed to MS paradigm 3 hours daily from postnatal days (PND) 2 to 14. The control and MS mice were divided separately into 16 groups ( = 8) (8 groups for each set) including mice that received normal saline, mice that received rutin at doses of 10, 50, and 100 mg/kg, mice that received NMDA at a dose of 150 mg/kg, mice that received ketamine (NMDA antagonist) at a dose of 0.25 mg/kg, mice that received NMDA antagonist plus a subeffective dose of rutin, and mice that received NMDA plus an effective dose of rutin. Forced swimming test (FST) was performed. Afterwards, the hippocampus was evaluated in cases of histopathological changes as well as expression of NR2A and NR2B genes.

Results: Rutin significantly reduced immobility time in the FST. The expression of NR2A and NR2B subunits of NMDA receptor in MS mice was significantly higher than that in the control group. Rutin significantly decreased the expression of NR2B and NR2A subunits in the hippocampus. The CA3 diameter and percentage of dark neurons in the hippocampus of MS mice significantly decreased and increased, respectively, which partially reversed following rutin administration.

Conclusion: Rutin, partially, through a neuroprotective effect on the hippocampus exerted antidepressant-like effect. We concluded that NMDA receptors, at least in part, mediated the beneficial effect of rutin.
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http://dx.doi.org/10.1155/2020/4813616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296444PMC
June 2020

Possible Involvement of N-methyl-D-aspartate Receptor (NMDA-R) in the Antidepressant- like Effect of Trigonelline in Male Mice.

Curr Pharm Des 2020 ;26(39):5067-5071

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background And Aim: Depression is a mood disorder with high global prevalence. Depression is associated with a reduction in the hippocampal volume and change in its neurotransmitters function. Trigonelline is an alkaloid with neuroprotective activity. The aim of this study was to investigate the possible role of N-methyl-Daspartate (NMDA) receptor in the antidepressant-like effect of trigonelline, considering histopathological modifications of the hippocampus.

Methods: 60 Naval Medical Research Institute (NMRI) male mice were divided into 6 groups including group 1 (normal saline), groups 2, 3 and 4 (trigonelline at doses of 10, 50 and 100 mg/kg), group 5 (effective dose of trigonelline plus NMDA agonist) and group 6 (sub-effective dose of trigonelline plus NMDA antagonist). Forced swimming test (FST) was used to assess depressive-like behavior. Hippocampi were separated under deep anesthesia and used for histopathological evaluation as well as NMDA receptor gene expression assessment.

Results: Trigonelline at doses of 10, 50 and 100 significantly reduced the immobility time in the FST in comparison to the control group. The administration of the sub-effective dose of trigonelline plus ketamine (an NMDA receptor antagonist) potentiated the effect of the sub-effective dose of trigonelline. In addition, co-treatment of an effective dose of trigonelline with NMDA mitigated the antidepressant-like effect of trigonelline. Trigonelline at doses of 50 and 100 mg/kg significantly increased the diameter of the CA1 area of the hippocampus.

Conclusion: Trigonelline showed an antidepressant-like effect in mice, probably via attenuation of NMDA receptor activity and an increase in the CA1 region of the hippocampus.
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http://dx.doi.org/10.2174/1381612826666200610181259DOI Listing
January 2020

and rutin, as its major compound: investigating their effect on spatial memory and passive avoidance memory in rats.

Pharm Biol 2020 Dec;58(1):447-453

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

There are numerous pharmacological activities for and its bioactive constituent, rutin, on learning and memory. This study aimed to examine the effect of and rutin on memory in rats. In this study animals were treated with the hydroalcholic extract of and rutin by IP injection for 10 days. Behavioural and biochemical tests as well as HPLC analysis and antioxidant activity of extract have been evaluated. extract and rutin significantly increased learning and improved spatial memory, as well as secondary latency; moreover, there were significant increases in the serum and brain antioxidant capacity as well as the level of TBARS in serum and brain tissues. Results also showed that has significant DPPH radical scavenging effect (IC: 159.17 ± 1.56 μg/mL). The HPLC analysis of extract showed that caffeic acid (19.92 ± 0.01), rutin (40.15 ± 0.01), and apigenin (0.84 ± 0.01) mg/g of dry extract are the main components of the extract. Regarding the effects of . extract and rutin on animal brain cells, memory function, and learning, additional studies, including clinical trials, might be beneficial in producing natural supplementary drugs from this herb.
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http://dx.doi.org/10.1080/13880209.2020.1762669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301720PMC
December 2020

Ferulic acid through mitigation of NMDA receptor pathway exerts anxiolytic-like effect in mouse model of maternal separation stress.

J Basic Clin Physiol Pharmacol 2020 May 6. Epub 2020 May 6.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background Experiencing early-life stress plays an important role in the pathophysiology of anxiety disorders. Ferulic acid is a phenolic compound found in some plants which has several pharmacological properties. N-methyl-D-aspartate (NMDA) receptors are involved in the pathophysiology of mood disorders. In this study we aimed to assess the anxiolytic-like effect of ferulic acid in a mouse model of maternal separation (MS) stress by focusing on the possible involvement of NMDA receptors. Methods Mice were treated with ferulic acid (5 and 40 mg/kg) alone and in combination with NMDA receptor agonist/antagonist. Valid behavioral tests were performed, including open field test (OFT) and elevated plus maze test (EPM), while quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate gene expression of NMDA subunits (GluN2A and GluN2B) in the hippocampus. Results Findings showed that treatment of MS mice with ferulic acid increased the time spent in the central zone of the OFT and increased both open arm time and the percent of open arm entries in the EPM. Ferulic acid reduced the expression of NMDA receptor subunit genes. We showed that administration of NMDA receptor agonist (NMDA) and antagonist (ketamine) exerted anxiogenic and anxiolytic-like effects, correspondingly. Results showed that co-administration of a sub-effective dose of ferulic acid plus ketamine potentiated the anxiolytic-like effect of ferulic acid. Furthermore, co-administration of an effective dose of ferulic acid plus NMDA receptor agonist (NMDA) attenuated the anxiolytic-like effect of ferulic acid. Conclusions In deduction, our findings showed that NMDA, partially at least, is involved in the anxiolytic-like effect of ferulic acid in the OFT and EPM tests.
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http://dx.doi.org/10.1515/jbcpp-2019-0263DOI Listing
May 2020

The effect of atmospheric pressure cold plasma on the inactivation of in sour cherry juice and its qualitative properties.

Food Sci Nutr 2020 Feb 20;8(2):870-883. Epub 2020 Jan 20.

Medical Plants Research Center Basic Health Sciences Institute Shahrekord University of Medical Sciences Shahrekord Iran.

One of the nonthermal methods is the atmospheric pressure cold plasma (APCP). In this study, the effect of cold plasma on the reduction of bacteria and qualitative properties of sour cherry juice, including total phenolic content (TPC), total anthocyanin content (TAC), and vitamin C, were investigated. Independent variables included plasma exposure time (1, 5, and 9 min), applied field intensity (25, 37.5, and 50 kV/cm), feeding gas oxygen content (0%, 0.5%, and 1%), and sample depth (0.5, 1, and 1.5 cm). The results show that increased oxygen content in argon has the greatest effect on the reduction of bacteria, and plasma exposure decreased 6 logarithmic periods of bacteria in sour cherry juice. Optimization results showed when all bacteria were eliminated by plasma, TPC remained unchanged, and TAC and vitamin C decreased by 4% and 21%, respectively, while thermal methods increased TPC by 23% and decreased TAC and vitamin C by 26% and 77%, respectively. These results indicate that, compared with conventional thermal methods, sour cherry juice pasteurization using APCP has little effect on the juice qualitative properties, and this method can serve as a suitable alternative to conventional thermal methods.
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http://dx.doi.org/10.1002/fsn3.1364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020306PMC
February 2020

Oral acute and sub-acute toxic effects of hydroalcoholic Terminalia chebula Retz and Achillea wilhelmsii extracts in BALB/c mice.

Biomedicine (Taipei) 2019 Dec 21;9(4):25. Epub 2019 Nov 21.

Department of Pathology, School of Veterinary Medicine, Islamic Azad University, Shahrekord, Iran.

Background: This study examined the acute and sub-acute toxic effects of Terminalia chebula and Achillea wilhelmsii extracts on the murine model.

Methods: In both phases, mice were assigned to intervention and control groups. At the end of study, the liver, kidney, and heart tissues were collected for histopathological studies.

Results: In the acute phase of the study, the safe dose was ≤5000 mg/kg for both extracts. In sub-acute phase, LD50 (95% CI) of Achillea wilhelmsii extract was determined ≥5000 mg/kg and that of Terminalia chebula extract 2754.436 (2438-3114) mg/kg. The highest dose of T. chebula extract induced few histopathological changes.

Conclusion: It will be useful to gain information on the minimum lethal doses of T. chebula and A. wilhelmsii to adopt safe doses of the two plants.
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http://dx.doi.org/10.1051/bmdcn/2019090425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6870277PMC
December 2019

Trigonelline through the Attenuation of Oxidative Stress Exerts Antidepressant- and Anxiolytic-Like Effects in a Mouse Model of Maternal Separation Stress.

Pharmacology 2020 18;105(5-6):289-299. Epub 2019 Oct 18.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran,

Depression and anxiety are common psychiatric disorders accounting for social and economic burdens. Previous studies have shown that oxidative stress and oxidant/antioxidant imbalance are involved in the pathophysiology of psychiatric disorders. Experiencing early-life adversities (like maternal separation [MS] stress) provoked psychiatric disorders. Trigonelline (TRG) is a pyridine alkaloid that has various pharmacological effects including hypoglycemic, neuroprotective and memory-improving properties. To investigate the antidepressant- and anxiolytic-like effects of TRG focusing oxidative stress, we applied the MS paradigm to male mice at postnatal day (PND) 2-14 (3 h daily, 9-12 a.m.) and investigated the behaviors at PND 45-47. Using valid behavioral tests including a forced swimming test (FST), splash test, open field test (OFT) and elevated plus maze (EPM), we investigated behavioral modifications. Additionally, we examined the effects of MS and TRG treatment on the level of malondialdehyde (MDA), nitric oxide (NO) and also antioxidant capacity in the brain and serum. Our results showed that MS provoked depressive- and anxiety-like behaviors in the FST, OFT, EPM and splash test, which are associated with an increase in MDA and NO levels as well as a decrease in antioxidant capacity in the brain and serum samples. Findings determined that TRG significantly reversed the negative effects of MS on behavior that is accompanied by a decrease in MDA and NO as well as an increase in antioxidant capacity. Findings of the present study showed that beneficial effects of TRG may be, at least partially, mediated via the reduction of oxidative stress and an increase of antioxidant capacity.
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http://dx.doi.org/10.1159/000503728DOI Listing
February 2021

Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer.

Phytother Res 2019 Nov 12;33(11):2849-2861. Epub 2019 Aug 12.

Zabol Medicinal Plants Research Center, Zabol University of Medical Sciences, Zabol, Iran.

Silymarin is a complex extract isolated from the plant Silybum marianum, widely known for its prominent antioxidant and hepatoprotective effects, although increasing evidences have reported extraordinary antiproliferative and apoptotic abilities. As a result, several signaling pathways involved in cell cycle control, cell proliferation, and cell death have been deconvoluted as critical mechanisms. In this regard, cyclin and cyclin-dependent pathways have been the most studied ones. Following that, apoptotic pathways, such as p53, Akt, STAT-3, Ras, and caspases pathways, have been extensively studied, although other mechanisms involved in inflammation and angiogenesis have also been highlighted as silymarin-likely targets in cancer therapy. Therefore, the main challenge of this review is to discuss the diverse molecular mechanisms for silymarin antiproliferative and apoptotic effects; most of them largely studied in various types of cancers so far. Clinical trials and combination therapies related to silymarin application in cancer prevention and treatment are presented as well.
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http://dx.doi.org/10.1002/ptr.6470DOI Listing
November 2019

Comparing the Effect of Intranasal Lidocaine 4% with Peppermint Essential Oil Drop 1.5% on Migraine Attacks: A Double-Blind Clinical Trial.

Int J Prev Med 2019 5;10:121. Epub 2019 Jul 5.

Medicinal Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background: Prevalence of migraine, as a chronic neurovascular disorder, was approximately 10.3 and 23.1% among men and women, respectively, mostly in people younger than 40 years old. Migraine is prevalent in different geographic areas worldwide. The present study was designed to compare the impact of intranasal lidocaine 4% and peppermint essential oil drop 1.5% on migraine attacks.

Methods: In this double-blind, parallel, randomized controlled trial, 120 adult patients with a diagnosis of migraine based on the International Headache Society criteria were treated with intranasal lidocaine drop 4% or peppermint essential oil drop 1.5% or placebo. Patients expressed their symptoms 5 and 15 min after dripping, and if they still had a headache after 15 min, they were given the second dose. Patients with a second dose of medication, 15 min later recorded their headache rate. All patients recorded their symptoms after 30 min. Symptoms of the patients were followed by a researcher through the phone and in-person after 2 months. Then, the questionnaires were filled.

Results: In the present study, there was a significant difference among groups in headache intensity after treatment ( < 0.001). In 40% of the patients in the peppermint oil and lidocaine groups, the intensity of headache decreased. In the placebo group, fewer patients responded highly to the treatment, whereas 41.5% of patients in the lidocaine group and 42.1% of patients in the peppermint oil group responded to the treatment considerably.

Conclusions: Concerning the findings of the present study, nasal application of peppermint oil caused considerable reduction in the intensity and frequency of headache and relieved majority of patients' pain similar to lidocaine. On the basis of findings of this study, it can be concluded that nasal menthol, such as lidocaine, can be used to relieve migraine headaches.
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http://dx.doi.org/10.4103/ijpvm.IJPVM_530_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647908PMC
July 2019

Comparative study of the effect of Thymus daenensis gel 5% and diclofenac in patients with knee osteoarthritis.

Biomedicine (Taipei) 2019 Jun 24;9(2). Epub 2019 May 24.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background: Osteoarthritis is a syndrome characterized by joint pain and reduced performance and efficien- cy in patient. Thymus daenensis has been used since old times for the treatment of bone and joint deformities and pain in traditional medicine.

Purpose: This study was conducted to examine traditional usages and pharmacological features of T. daen- ensis with respect to the effect of the plant in patients with osteoarthritis.

Methods: 120 patients with osteoarthritis were divided into 3 groups. Patients in each group were treated by 5% Thymus daenensis gel, 1% diclofenac gel, or placebo for 6 weeks, along with oral celecoxib capsules. Patients were assessed in different intervals, based on the VAS score for assessment of pain in the joint and different dimensions of WOMAC questionnaire.

Results: Pain level (P < 0.005), stiffness during the day (P < 0.05), morning stiffness (P < 0.05) and physi- cal performance (P < 0.05) were significantly different among the groups.

Conclusions: Thymus daenensis gel improves the symptoms in patients equal and without significant difference than diclofenac group. It can be argued that its use can produce a satisfactory effect on patients with osteoarthritis due to its low cost, easy access, the plant's natively occurring in Iran.
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http://dx.doi.org/10.1051/bmdcn/2019090209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533939PMC
June 2019

Implication of NMDA-NO pathway in the antidepressant-like effect of ellagic acid in male mice.

Neuropeptides 2019 Aug 26;76:101928. Epub 2019 Apr 26.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Depression is one the common psychiatric disorders through the world. Nitric oxide (NO) and N-methyl-d-aspartate receptor (NMDA-R) are involved in the pathophysiology of depression. Previous studies have been reported various pharmacological properties for ellagic acid (EA). We aimed to evaluate possible involvement of NMDA-NO pathway in the antidepressant-like effect of EA. To do this, we used relevant behavioral tests to evaluate depressive-like behavior. In order to find effective and sub-effective doses of agents, mice treated with EA (6.25, 12.5, 25, 50 and 100 mg/kg), L-NAME (5 and 10 mg/kg), L-arg (25 and 50 mg/kg), NMDA (75 and 150 mg/kg) and ketamine (0.25 and 0.5 mg/kg). Furthermore, mice were treated with combination of sub-effective dose of EA plus sub-effective doses of L-NAME and/or ketamine as well as treated with effective dose of EA in combination of effective doses of L-arg and/or NMDA. Level of NO and gene expression of NR2A and NR2B subunits of NMDA-R were assessed in the hippocampus. Results showed that EA dose dependently provoked antidepressant-like effects and also decreased the hippocampal NO level as well as expression of NMDA-Rs. Co-administration of sub-effective doses of L-NAME or ketamine with sub-effective dose of EA potentiated the effect of EA on behaviors, NO level as well as NMDA-Rs gene expression in the hippocampus. However, co-treatment of effective dose of EA with effective doses of L-arg or NMDA mitigated effects of EA. In conclusion, our data suggested that NMDA-NO, partially at least, are involved in the antidepressant-like effect of EA.
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http://dx.doi.org/10.1016/j.npep.2019.04.003DOI Listing
August 2019

Depression and Treatment with Effective Herbs.

Curr Pharm Des 2019 ;25(6):738-745

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Depression is a common psychiatric disease and one of the main causes of disability worldwide. In spite of certain developments in this field, chemical and synthetic drugs used for the treatment of depression disrupt the treatment process due to numerous side effects and high cost. Today, the goal of using a potential method for treating depression involves the use of medicinal and phytochemical plants, which have many therapeutic benefits. Studies have shown that medicinal plants affect the nervous system and exert antidepressant effects in various ways, including synaptic regulation of serotonin, noradrenaline and dopamine, and inflammatory mediators. In this study, depression as well as the factors and mechanisms involved in its development are first addressed, and then medicinal plants effective in the treatment of depression along with their mechanisms of actions are reported.
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http://dx.doi.org/10.2174/1381612825666190402105803DOI Listing
February 2020

Inflammatory responses bridge comorbid cardiac disorder in experimental model of IBD induced by DSS: protective effect of the trigonelline.

Inflammopharmacology 2019 Dec 28;27(6):1265-1273. Epub 2019 Mar 28.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Pathogenesis of the inflammatory bowel disease (IBD) involves the combination of immunological and inflammatory factors. IBD is associated with several extra-intestinal manifestations. The exact underlying bridge between the probable cardiac diseases in IBD patients is undetermined. Trigonelline is an alkaloid with several therapeutic potential properties. In this study, we aimed to assess the probable underlying mechanisms of this comorbidity as well as protective effect of trigonelline focusing inflammatory response and oxidative state in mouse model of colitis. Dextran sodium sulfate (DSS) was used for induction of colitis in mice. Trigonelline (10, 50 and 100 mg/kg) was administrated via intraperitoneal rout (i.p.) for 14 continuous days. Heart, intestine and serum samples were taken for assessment of total antioxidant capacity, malondialdehyde (MDA), gene expressions of inflammatory markers including tumor necrosis factor alpha (Tnf-α), interleukin 1-beta (Il/1β), toll- like receptor 4 (Tlr4) as well as for evaluation of histopathological alterations. Results demonstrated that trigonelline effectively attenuated the cellular/molecular and histopathological adverse effects of colitis in the intestine and heart tissues. In this regards, we found that trigonelline decreased the MDA level, attenuated the expression of Tnf-α, Il/1β and, Tlr4 as well as modulated the histopathological alterations in the intestine. Furthermore, trigonelline increased the antioxidant capacity in the related experimental groups. We concluded that IBD (colitis) is associated with comorbid cellular/molecular modifications in the heart and for the first time, we found that trigonelline has potential therapeutic effects (at least partially) to attenuate the cardiac manifestations of the colitis.
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http://dx.doi.org/10.1007/s10787-019-00581-wDOI Listing
December 2019

The effect of Fisch. & C.A.Mey extract on the viability and the proliferation of MDA-MB-231 cell line.

Biosci Rep 2019 01 11;39(1). Epub 2019 Jan 11.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

Some medicinal herbs and compounds are known to target cancer cells, but the success of them as anticancer compounds depends to a large extent on their ability to activate pathways that kill cancer cells by arresting cell cycle and inducing apoptosis. The aim of the present study was to determine the anticancer effects of on the breast cancer cells to reveal the underlying mechanism of its anti-breast cancer properties. In this experimental study, triple negative breast cancer cell line (MDA-MB-231) was cultivated in RPMI-1640 medium. Hydroalcoholic extract (70:30) of aerial parts of the plant was prepared. The cultured cells were treated with different concentrations (0-1000 μg/ml) of extract for 24 and 48 h. Toxicity of the extract on MDA-MB-231 cells was examined using MTT (3-[4,5-dimethyl-2-thiazolyl]-2, 5 diphenyl tetrazolium bromide) test. The Annexin V-FITC Apoptosis Detection Kit was used to evaluate apoptosis and necrosis. Flow cytometry technique was employed to differentiate different phases of the cell cycle in the cells. Data were analyzed by GraphPad Prism and SPSS software. After 24 and 48 h, the IC50 values were respectively 76.78 (95% CI = 60.75-97.05; = 0.8588) and 59.71 (95% CI = 46.25-77.09; = 0.8543) μg/ml for The extract exhibited antiproliferative effects against MDA-MB-231 cells in a dose-dependent manner. Annexin V-FITC/PI assay confirmed that the extract was able to induce apoptosis in MDA-MB-231 cells. Moreover, treatment with the extract resulted in cell cycle arrest at G1 phase. Therefore, could induce apoptosis and cycle arrest in the MDA-MB-231 cell line. It might be a good resource of natural products for producing anti-breast cancer drugs.
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http://dx.doi.org/10.1042/BSR20181538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328893PMC
January 2019

Medicinal Plants and Atherosclerosis: A Review on Molecular Aspects.

Curr Pharm Des 2018 ;24(26):3123-3131

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Atherosclerosis is an inflammatory vascular disease that is characterized by progressive accumulation of cholesterol in the arterial walls and it is a major cause of cardiovascular disease. Issues related to the side effects of synthetic drugs have in recent times, led to the misuse of drugs, a lack of patient consultations, and consequently, a disruption in meticulous disease control. Therefore, a new insight into medicinal plants has recently emerged and much research has been conducted on these herbs in an attempt to prepare novel naturally based drugs. The aim of this review article was to scrutinize the molecular mechanisms of medicinal plants possessing effectiveness against atherosclerosis. To conduct the review, electronic searches were performed to retrieve potentially relevant publications, indexed within internet databases and reference textbooks concerning the effects and underlying molecular mechanisms of plants or their constituents used to treat atherosclerosis. Overall, medicinal plants facilitate atherosclerosis treatment through a variety of mechanisms which include the regulation of expression of inflammatory factors, stimulation of peroxisome proliferator-activated receptors (PPARs), inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), promotion of ATP-binding cassette transporter A1 (ABCA1) as well as ATP-binding cassette transporter G (ABCG), facilitation of adiponectin activity, reduction of sterol regulatory element-binding proteins (SREBPs) and antioxidant activity. An increased perception of these herbal mechanistic links is an important prelude to the design of novel plant based drugs.
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http://dx.doi.org/10.2174/1381612824666180911121525DOI Listing
October 2019

Immunosuppression-lipid Metabolism Interplay and Medicinal Plants in Atherosclerosis: A Review.

Curr Pharm Des 2018 ;24(24):2789-2793

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Atherosclerosis is a chronic arterial disease responsible for the majority of vascular-related deaths throughout the world. Immune cells and inflammation in conjunction with hyperlipidemia play a key role in atherosclerosis development. Regarding the low efficacy of the synthetic drugs and also the associated negative side effects which can adversely influence health-related quality of life, looking for natural, affordable and non-toxic substances seem necessary. Plant-derived natural products play a critical role in the prevention and treatment of atherosclerosis. In this review, we aimed to outline the most important medicinal herbs effective for atherosclerosis through the impact on immune system.
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http://dx.doi.org/10.2174/1381612824666180829105309DOI Listing
October 2019

Medicinal Plants with Multiple Effects on Diabetes Mellitus and Its Complications: a Systematic Review.

Curr Diab Rep 2018 08 13;18(10):72. Epub 2018 Aug 13.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Purpose Of Review: This systematic review describes evidence concerning medicinal plants that, in addition to exerting hypoglycemic effects, decrease accompanying complications such as nephropathy, neuropathy, retinopathy, hypertension, and/or hyperlipidemia among individuals with diabetes mellitus (DM).

Recent Findings: Studies on the antidiabetic mechanisms of medicinal plants have shown that most of them produce hypoglycemic activity by stimulating insulin secretion, augmenting peroxisome proliferator-activated receptors (PPARs), inhibiting α-amylase or α-glucosidase, glucagon-like peptide-1 (GLP-1) secretion, advanced glycation end product (AGE) formation, free radical scavenging plus antioxidant activity (against reactive oxygen or nitrogen species (ROS/RNS)), up-regulating or elevating translocation of glucose transporter type 4 (GLUT-4), and preventing development of insulin resistance. Not only are medicinal plants effective in DM, but many of them also possess a variety of effects on other disease states, including the complications of DM. Such plants may be appropriate alternatives or adjuncts to available antidiabetic medications.
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http://dx.doi.org/10.1007/s11892-018-1042-0DOI Listing
August 2018

A screening of growth inhibitory activity of Iranian medicinal plants on prostate cancer cell lines.

Biomedicine (Taipei) 2018 Jun 28;8(2). Epub 2018 May 28.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background: Prostate cancer has been known as one of the most common malignancy in the men and it is therefore very important to prevent and treat this cancer. In this study, the anticancer effects of 20 species of medicinal plants in Iran, especially those grown in Chaharmahal and Bakhtiari province, were investigated on prostate cancer cell lines to identify potential natural alternatives for the development of prostate cancer anticancer drugs.

Methods: The plants were gathered from Chaharmahal va Bakhtyari and their aerial parts extracted through maceration method using ethanol 70%. Anti-proliferative activity of extracts on PC-3, DU145 and HDF cell lines was evaluated by MTT assay 48 hours after treatment.

Results: Euphorbia szovitsii Fisch. & C.A.Mey. and Achillea wilhelmsii had anti-proliferative activity more than other plants on PC-3. Also IC50s for Urtica dioica, Euphorbia szovitsii Fisch. & C.A.Mey. and Medicago sativa were lower amount among the examined plants on Du-145.

Conclusion: According to our result, Euphorbia szovitsii Fisch. & C.A.Mey., U. dioica and Medicago sativa with good anti-proliferative activity can serve as an effective source of natural products to develop new antiprostate cancer drugs.
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http://dx.doi.org/10.1051/bmdcn/2018080208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992925PMC
June 2018

Tricin isolated from potentiated the effect of docetaxel on PC3 cell proliferation: role of miR-21.

Nat Prod Res 2019 Jun 15;33(12):1828-1831. Epub 2018 Feb 15.

b Medicinal Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences , Shahrekord , Iran.

For more effectiveness and overcoming the drug resistance Chemotherapy agents, the combination treatment is raised. Flavonoids with different anti-cancer effects are an appropriate choice as lead compounds. Over expressed MiR-21 in prostate cancer is associated with metastasis and drug resistance to chemotherapy with Docetaxel. In this study, the anticancer effect of 4', 5, 7-Trihydroxy-3', 5'-dimethoxyflavone (Tricin) was investigated with Docetaxel on PC3 cell line. Tricin was initially isolated from the by column chromatography and recrystallization method. The chemical structure of isolate was elucidated by spectroscopic techniques. IC of Tricin and Docetaxel were assessed 117.5 ± 4.4 μM and 0.1 ± 0.02 nM by MTT assay, respectively. Analysis of results indicates the synergistic effect of combination therapy on decreased proliferation. MiR-21 in treated cells with Tricin significantly decreased compared to control cells. So, Tricin can be effective in the reduction of metastasis and drug resistance of Docetaxel.
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http://dx.doi.org/10.1080/14786419.2018.1437439DOI Listing
June 2019

Study of Combined Ultrasound-microwave Effect on Chemical Compositions and Count of Rose Aromatic Water.

Iran J Pharm Res 2018 ;17(Suppl2):146-160

Department of Mechanical Engineering of Biosystem, Shahrekord University, Iran.

Since the rose water is used in food, pharmaceutical, and cosmetic products, its microbiological control is necessary. Conventional pasteurization methods cause undesirable changes in taste, smell, medicinal properties and nutritional value with decreasing the amount of essential oil, because of high temperatures. In this study, the effects of the microwave power, temperature, ultrasound power, and ultrasonic exposure were evaluated during rose water pasteurization process on its chemical compositions and content. In order to determine the microbial inactivation by microwave and ultrasound, at a concentration of 2 × 10 per mL was inoculated to rose aromatic water. The results showed that each variable on the inactivation of and energy consumption per microbial reduction cycle had a significant effect. The optimum values of microwave power, temperature, ultrasound power, and ultrasound exposure time were obtained 326.24 W, 43.32 °C, 100 W and 4 min, respectively. The chemical composition assessment was done by GC/MS analysis. Phenethyl alcohol is one of the main components of rose water which was completely lost in the conventional pasteurization method, while in pasteurization process by combined method, it showed an acceptable decrease as compared with raw rose water. Furthermore, the proposed method caused minimal changes in the chemical compositions of the rose water as compared to the conventional heating methods.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447883PMC
January 2018

A Review of Botany and Pharmacological Effect and Chemical Composition of Species Growing in Iran.

Pharmacognosy Res 2017 Oct-Dec;9(4):305-312

Social Determinants of Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

This review was conducted to investigate the botany, phytochemistry, and pharmacological properties of species. The information of this review was obtained by searching for keywords , , pharmacological effects, and traditional and modern medicine in scientific articles and books published in search engines Scopus, Google Scholar, Science Direct, PubMed, and Web of Science. The traditional uses of and the existence of valuable phytochemicals in the plant have led to isolation and drug discovery of natural medicines such as antibiotic, analgesics, and anticancer drugs, and the beneficial effects of these plants can widely be used in healthcare.

Summary: species are medicinal and aromatic plants that are belong to Apiaceae family. This genus have four species in Iran. The botany, geographical distribution, traditional and pharmacological effects of genus were described. Also, the major chemical constituents of the essential oil and extract of different species of that have been reported. Overall, the existence of valuable phytochemicals purpose species as novel candidate to isolation and drug discovery of natural medicines such as antibiotic, analgesics, and anticancer drugs.
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http://dx.doi.org/10.4103/pr.pr_22_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717781PMC
December 2017

The effect of vaginal cream containing ginger in users of clotrimazole vaginal cream on vaginal candidiasis.

J Adv Pharm Technol Res 2017 Apr-Jun;8(2):80-84

Deputy of Research and Technology, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Vulvovaginal candidiasis is one of the most common infections of the genital tract in women that causes many complications. Therefore, we examined the clinical effect of ginger cream along with clotrimazole compared to vaginal clotrimazole alone in this study. This double-blind clinical trial was conducted on 67 women admitted to the Gynecology Clinic of Hajar Hospital with vaginal candidiasis. The patients were divided randomly into two groups of 33 and 34 people. The diagnosis was made according to clinical symptoms, wet smear, and culture. Ginger-clotrimazole vaginal cream 1% and clotrimazole vaginal cream 1% were administered to groups 1 and 2, respectively, once a day for 7 days and therapeutic effects and symptoms were evaluated in readmission. Data analysis was performed using SPSS version 22, -test and Chi-square. The mean value of variables itching ( > 0.05), burning ( > 0.05), and cheesy secretion ( < 0.05) in users of ginger-clotrimazole was less than the other group after the treatment. Recurrence in clotrimazole group was 48.5% and in ginger-clotrimazole group 51.2% during the 1-month follow-up with no significant difference. Study results showed that cream containing ginger and clotrimazole 1% was more effective and may be more useful than the clotrimazole to treat vaginal candidiasis.
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http://dx.doi.org/10.4103/japtr.JAPTR_176_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416660PMC
May 2017

Evaluation of Anti-Platelet Aggregation Effect of Some Allium Species.

Iran J Pharm Res 2015 ;14(4):1225-31

Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Epidemiologic studies show that the cardiovascular diseases are associated with multiple factors such as raised serum total cholesterol, increased LDL, increased platelet aggregation, hypertension and smoking. In-vitro studies have confirmed the ability of some plants of Allium species to reduce these parameters. Therefore, we evaluated anti-platelet aggregation effect of some Allium species (Allium ampeloprasum, A. hirtifolium, A. haemanthoides, A. vavillovi, A. atroviolaceum, A. jesdianum, A. shelkovnikovii) using arachidonic acid (AA) and adenosine diphosphate (ADP) as platelet aggregation inducers. The screening results for methanolic extract of Allium species showed that the maximum effect of anti-platelet aggregation was related to A. atroviolaceum. This extract inhibited the in-vitro platelet aggregation induced by AA and ADP with IC50 values of 0.4881 (0.4826-0.4937) mg/ml and 0.4945 (0.4137-0.5911) mg/ml respectively. These results support the hypothesis that the dietary intake of Allium could be beneficial for prevention of cardiovascular diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673951PMC
December 2015