Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793010420200701The effects of onion (Allium cepa L.) dried by different heat treatments on plasma lipid profile and fasting blood glucose level in diabetic rats3253331406610.22038/ajp.2019.14066ENTaha Gökmen UlgerAnkara University Graduate School of Health Sciences, 06080 Ankara, Turkey0000-0002-7751-9789Funda Pınar ÇakirogluAnkara University Faculty of Health Sciences, 06080 Ankara, TurkeyJournal Article20180904<strong>Objective:</strong> This study aims to evaluate the effects of onion (Allium cepa L.) against hyperglycaemia and dyslipidemia and determine possible changes in these effects due to different heat treatments applied to onion.<br /> <strong>Materials and Methods:</strong> 32 male Wistar-albino rats were divided into 4 groups as follows: the groups C and DC were fed with standard rat diet; the DLO group was fed with rat diet including 5% onion powder dried at -76°C in a lyophilizator, and the DFO group was fed with rat diet including 5% onion powder dried at 80°C in a furnace. Diabetes was induced in DC, DLO and DFO groups by injection of streptozotocin (45 mg/kg).<br /> <strong>Results:</strong> A decreasing tendency was observed in fasting blood glucose (FBG) values of DLO group during the experiment period and it was found that the 6th and 8th weeks values were significantly lower than the 1st and 2nd weeks values (p<0.05).On the other hand, no statistical difference was observed in the FBG values measured at different weeks in the DFO group. Significant differences were also observed among the groups in terms of plasma lipid values. DLO group was determined to have lower levels of triglyceride (p<0.001), LDL cholesterol and total cholesterol and higher levels of HDL cholesterol (p <strong>Conclusion:</strong> Lyophilized onion powder may be protective against hyperglycaemia and dyslipidemia arising from diabetes. However, the heat treatments applied to onion affect this protective role negatively.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793010420200701Role of natural products in mitigation of toxic effects of methamphetamine: A review of in vitro and in vivo studies3343511444710.22038/ajp.2020.14447ENMohammad MoshiriMedical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0003-0389-2270Ali RoohbakhshPharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranMehdi TalebiDepartment of community and Family Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranMilad IranshahiBiotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.Leila EtemadPharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.Journal Article20190724<strong>Objective:</strong> Methamphetamine (METH) increases dopamine, norepinephrine and serotonin concentrations in the synaptic cleft, and induces hyperactivity. The current management of acute METH poisoning relies on supportive care and no specific antidote is available for treatment. The main objective of this review was to present the evidence for effectiveness of the herbal medicine in alleviating the adverse effects of METH abuse.<br /> <strong>Materials and Methods:</strong> Literature search was performed using the following electronic databases: MEDLINE, Scopus, PubMed and EMBASE.<br /> <strong>Results:</strong> Plant-derived natural products ginseng and sauchinone reduced METH-induced hyperactivity, conditioned place preference and neurological disorder. <em>Garcinia kola</em> decreased METH-induced hepatotoxicity, raised METH lethal dose, and restored the METH-impaired cognitive function. Repeated administration of baicalein resulted in attenuation of acute binge METH-induced amnesia via dopamine receptors. <strong> </strong>Activation of extracellular-regulated kinase in the hypothalamus by levo-tetrahydropalmatine facilitated the extinction of METH-induced conditioned place preference and reduced the hyperactivity. Other herbal medicine from various parts of the world were also discussed including hispidulin, silymarin, limonene, resveratrol, chlorogenic acid and barakol.<br /> <strong>Conclusion:</strong> Based on the current study, some natural products such as ginseng and levo-tetrahydropalmatine are promising candidates to treat METH abuse and poisoning. However, clinical trials are needed to confirm these finding.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793010420200701The effect of “mavizˮ on memory improvement in university students: A randomized open-label clinical trial3523641444310.22038/ajp.2020.14443ENReza MirheidaryDepartment of Iranian Traditional Medicine, Faculty of Medicine, Shahed University, Tehran, Iran0000-0002-5923-507XSeyyed Saeed EsmaeiliDepartment of Iranian Traditional Medicine, Faculty of Medicine, Shahed University, Tehran, Iran0000-0002-0171-5644Mohammad Reza ShaeiriDepartment of Clinical Psychology, Faculty of Humanities, Shahed University, Tehran, Iran0000-0002-2037-3475Mohammad Gholami FesharakiDepartment of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran- Iran0000-0001-9531-1642Journal Article20190227<strong>Objective:</strong> Numerous studies demonstrated the effect of grape on memory improvement. According to Iranian traditional medicine, “mavizˮ as a specific type of dried grapes can effectively improve memory. However, there is no reported clinical trial on the effect of “mavizˮ on memory improvement in humans. Hence, this study was conducted to investigate “mavizˮ effect on memory in university students.<br /> <strong>Materials and Methods:</strong> This randomized open-label clinical trial was conducted on a total number of 53 students of Shahed University, Tehran, Iran, from November 2017 to February 2018. The participants were randomly allocated into an intervention group (receiving “mavizˮ, 25 g in the morning for 4 weeks) or a control group (who did not take “mavizˮ). The Digit Span Task and the N-Back Task were used for the measurement of working memory at the pre- and post-intervention stages.<br /> <strong>Results:</strong> According to the results, no significant differences were found between the two groups regarding age, gender, marital status, and initial working memory test scores. “mavizˮ consumption produced a highly significant improvement in total working memory score in the Digit Span Task (5.18 vs. 2.35, p<0.001) and Acoustic Memory Span (1.29 vs. 0.62, p=0.021). Moreover, “mavizˮ consumption significantly increased the percentage of true responses in the N-Back Task and reduced the mean reaction time in the first level of the task.<br /> <strong>Conclusion:</strong> “mavizˮ consumption was improved working memory in young healthy adults.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793010420200701Ginger (Zingiber officinale Roscoe) extract can improve the levels of some trace elements and total homocysteine and prevent oxidative damage induced by ethanol in rat eye3653711433010.22038/ajp.2019.14330ENAbolfazl AkbariDepartment of Physiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran0000-0002-1577-4346Khadijeh NasiriDepartment of Exercise Physiology, Faculty of Sport Science, University of Mazandaran, Babolsar, IranMojtaba HeydariPoostchi Ophthalmology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0001-9612-0936Journal Article20190421<strong>Objective: </strong>Acute and chronic ethanol consumption cause oxidative stress and ginger improves suchconditions. In this study, the protective effects of ginger were studied on indices of oxidative stress, total homocysteinelevel and the level of the some of the oxidative stress-associated trace elements against toxicity induced by ethanol in rat eye.<br /> <strong>Materials and Methods:</strong>Twenty-four adult male Sprague-Dawley rats were randomly allocated into four groups and treated daily for 28 days as follows: group I: control;group II: ginger (1g/kg/day ginger extract by oral gavage); group III: ethanol (4g/kg/day ethanol by oral gavage) and group IV: ginger+ethanol. At the end of the experimental period, eye tissue sera were used for determination of different parameters. Furthermore, <em>in vitro</em> antioxidant potential and total phenol content of ginger extract were determined.<br /> <strong>Results: </strong>In ethanol group, significant changes in oxidative stress markers and levels of homocysteine and some trace elements, compared to other groups, were observed (p <strong>Conclusion: </strong>It can be concluded that ginger extract has protective effects against toxicity induced by ethanol in the eye of male rat.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793010420200701Ethanolic extract of Iris songarica rhizome attenuates methotrexate-induced liver and kidney damages in rats3723831408410.22038/ajp.2019.14084ENHesam MoodiDepartment of Anatomical Sciences, Birjand University of Medical Sciences, Birjand, IranMehran HosseiniCellular and Molecular Research Center, Department of Anatomical Sciences, Birjand University of Medical Sciences, Birjand, Iran0000-0002-6793-2035Mohammad Reza AbediniCellular and Molecular Research Center, Department of Pharmacology, Birjand University of Medical Sciences, Birjand, IranMahsa Hassanzadeh-TaheriStudent Research Committee, Birjand University of Medical Sciences, Birjand, Iran0000-0001-8648-4322Mohammadmehdi Hassanzadeh-TaheriCellular and Molecular Research Center, Department of Anatomical Sciences, Birjand University of Medical Sciences, Birjand, Iran0000-0002-9193-0056Journal Article20190724<strong>Objective:</strong> The long-term sequelae of methotrexate (MTX) remain the major cause of concern for both patients and therapists. Therefore, new approaches to decrease MTX side effects are needed. The study was carried out to evaluate the effects of <em>Iris songarica</em> Schrenk (IS) rhizome extract against MTX-induced hepatic and renal injuries in rats.<br /> <strong>Materials and Methods:</strong> Forty male Wistar rats were randomly divided into five groups (n=8) including control, MTX, IS50, IS150 and IS300. Control and MTX groups were only treated orally with saline; whereas, IS50, IS150 and IS300 groups were treated with IS extract at three different doses (50, 150, and 300 mg/kg, respectively). Besides, the MTX and experimental groups were received a single dose of MTX (20 mg/kg) intraperitoneally on day 4. On the ninth day, animals were sacrificed, blood transaminases, urea and creatinine were assessed and the concentration of malondialdehyde (MDA) and the activity of super-oxide dismutase (SOD) were determined in both liver and kidney tissues. Moreover, hepatic and renal damages were evaluated histopathologically.<br /> <strong>Results:</strong> MTX by increasing oxidative stress (MDA) and decreasing antioxidant capacity (SOD) induced hepatic and renal damages as confirmed by biochemical and histological parameters analyses. However, treatment with IS caused significant improvements in hepatic and renal histological architectures and SOD activity (p<0.01) along with reducing liver enzymes, urea, creatinine and MDA (p<0.01).<br /> <strong>Conclusion:</strong> The results of the present study showed that IS extract through antioxidant and probably anti-inflammatory activities, could effectively limit MTX-induced hepatic and renal injuries in rats.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793010420200701Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines3843971437210.22038/ajp.2019.14372ENSeyed Ali HashemiDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.0000-0002-7991-1194Seyedeh Zahra BathaieDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran0000-0000-2529-045xMohammad Ali MohagheghiCancer Research Center of Cancer Institute, Imam Khomeini Hospital, Tehran University of Medical Science, Tehran, Iran.Journal Article20190713<strong>Objective:</strong> Inhibition of lipid metabolism in breast cancer has been suggested as an effective approach for cancer therapy. Saffron-derived crocetin (Crt) and crocin (Cro) with the known anticancer activity, have shown hypolipidemic effect in diabetes and atherosclerosis. Here, we investigated the effect of Crt/Cro on lipid content in breast cancer.<br /> <strong>Materials and Methods:</strong> A multi-model approach involving <em>in vivo, in vitro </em>and<em> in silico </em>studies was applied. The 4T1-induced breast cancer in mice was used to investigate the effect of Crt/Cro on cholesterol (Chl) and triglyceride (TG) levels in serum and tumor tissues. The Chl/TG levels were also assessed in the cytosol of MDA-MB-231 and MCF-7 breast cancer cell lines 6, 12 and 24 hr after Crt/Cro treatment. The interaction between Crt/Cro and hydroxymethylglutaryl coenzyme A reductase (HMGCR) was also computed by docking analysis.<br /> <strong>Results: </strong>Crt reduced both serum (p=0.003) and tumor (p=0.011) Chl and TG (p=0.001) levels in mice. Cro reduced TG levels in tumor (p=0.014) and serum (p=0.002) and Chl level in tumor (p=0.013) tissues. Crt reduced both Chl and TG in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Cro reduced both Chl and TG in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Crt binds to the active site of HMGCR with higher affinity (ΔG<sup>0</sup>=-6.6 kcal/mol) than simvastatin (ΔG<sup>0 </sup>=-6.0 kcal/mol).<br /> <strong>Conclusion:</strong> Crt and Cro effectively decreased Chl/TG content in the sera of tumor bearing mice, in breast tumors and breast cancer cell lines. Crt showed a higher hypolipidemic potential than Cro. <em>In silico</em> analysis indicated Crt binding in the HMGCR active site.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793010420200701Grape seed extract alleviates radiation-induced damages in human blood lymphocytes3984061457510.22038/ajp.2020.14575ENReza Ghasemnezhad TarghiDepartment of Radiology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-5353-3159Valiallah SabaDepartment of Radiology, Faculty of Paramedicine, AJA University of Medical Sciences, Tehran, Iran0000-0001-5531-5171Journal Article20190314<strong>Objective:</strong> Ionizing radiation induces deleterious effects in the biological systems by producing free radicals. Grape Seed Extract (GSE) as a free radical scavenger could protect the body against the damages<em>.</em><br /> <strong>Materials and Methods:</strong> In this study, 12 healthy male volunteers were divided into Groups 1, 2, 3 and 4 and received 100, 300, 600 and 1000 mg GSE, respectively. Peripheral blood samples were collected from each volunteer 15 min before, and 1, 2, and 5 hr after GSE oral administration. Blood samples were then irradiated with 150 cGy of 100 kvp X-ray (Irradiated control group, was treated with only 1.5 Gy of X-rays). Cytogenic damages were detected by micronucleus assay.<br /> <strong>Results:</strong> Results showed that irradiation significantly increased the incidence of micronuclei (p <strong>Conclusion:</strong> Consumption of GSE before undergoing radiation protects human lymphocytes against X-rays by reducing radiation-induced genotoxicity.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793010420200701Role of the potassium channels in vasorelaxant effect of asafoetida essential oil4074161479110.22038/ajp.2020.41755.2401ENHassan EsmaeiliDepartment of heart, School of Medicine, Gorgan University of Medical Sciences, Gorgan, IranMansour EsmailidehajDepartment of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, IranSomayeh Entezari ZarchDepartment of Pharmacology, School of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, IranHossein AzizianDepartment of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, IranJournal Article20190713<strong>Objective:</strong> In a previous work, we showed that asafoetida essential oil (AEO), from oleo-gum resin of <em>Ferula asafoetida </em>L. from the Apiaceae family, has a vasodilatory effect. This effect was both endothelium-dependent and endothelium-independent. The present study was designed to determine whether potassium channels and intracellular calcium release contribute to AEO-induced vasodilation.<br /> <strong>Materials and Methods:</strong> Rats' thoracic aorta were isolated and denuded. Following induction of contraction by potassium chloride (60 mM), concentration-response curve was plotted by the cumulative addition of AEO (0.625-80 µl/l to the medium of rings. The vasodilatory effect of AEO was assessed before and after addition of phenylephrine and potassium channel blockers (including barium chloride (BC), 4-aminopyridine (4A) and glibenclamide (Gl)).<br /> <strong>Results:</strong> AEO relaxed the precontracted rings in a concentration-dependent manner (IC50=23 µl/l). All potassium channel blockers significantly attenuated the vasodilatory activity of AEO when they were added to rings medium before addition of KCl (p<0.01, 4A and Gl groups and p< 0.001, BC group vs. control group) but not after that. In contrast to K channel blockers, adding AEO before or after phenylephrine, the tension was reduced significantly (p <strong>Conclusion:</strong> The findings of this study indicated that the vasodilatory effect of AEO on denuded-endothelium aortic ring was mediated through activation of potassium channels and reduced intracellular calcium release.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793010420200701Anti-diarrhoeal activity of a polyherbal formulation in rats and elucidation of its cellular mechanisms4174271433910.22038/ajp.2019.14339ENSasikumar MuruganResearch and Development centre, Natural Remedies Pvt Ltd, Plot No. 5B, Veerasandra Indl. Area, 19th K.M. Stone, Hosur Road, Bangalore 560100, Karnataka, IndiaDivya PurusothamanResearch and Development centre, Natural Remedies Pvt Ltd, Plot No. 5B, Veerasandra Indl. Area, 19th K.M. Stone, Hosur Road, Bangalore 560100, Karnataka, IndiaEdwin Jothie RichardResearch and Development centre, Natural Remedies Pvt Ltd, Plot No. 5B, Veerasandra Indl. Area, 19th K.M. Stone, Hosur Road, Bangalore 560100, Karnataka, IndiaNehru Sai Suresh ChalichemResearch and Development centre, Natural Remedies Pvt Ltd, Plot No. 5B, Veerasandra Indl. Area, 19th K.M. Stone, Hosur Road, Bangalore 560100, Karnataka, IndiaBharathi BethapudiResearch and Development centre, Natural Remedies Pvt Ltd, Plot No. 5B, Veerasandra Indl. Area, 19th K.M. Stone, Hosur Road, Bangalore 560100, Karnataka, India0000-0002-0598-4630Prasanna Raja ChandrasekaranResearch and Development centre, Natural Remedies Pvt Ltd, Plot No. 5B, Veerasandra Indl. Area, 19th K.M. Stone, Hosur Road, Bangalore 560100, Karnataka, IndiaChandrasekaran Chinampudur VelusamiResearch and Development centre, Natural Remedies Pvt Ltd, Plot No. 5B, Veerasandra Indl. Area, 19th K.M. Stone, Hosur Road, Bangalore 560100, Karnataka, IndiaPrashanth D’SouzaResearch and Development centre, Natural Remedies Pvt Ltd, Plot No. 5B, Veerasandra Indl. Area, 19th K.M. Stone, Hosur Road, Bangalore 560100, Karnataka, IndiaDeepak MundkinajedduResearch and Development centre, Natural Remedies Pvt Ltd, Plot No. 5B, Veerasandra Indl. Area, 19th K.M. Stone, Hosur Road, Bangalore 560100, Karnataka, IndiaJournal Article20190218<strong>Objective:</strong> The present study was aimed to study anti-diarrhoeal activity of a polyherbal formulation (PHF) in rats and elucidate its mechanism of action.<br /> <strong>Materials and Methods:</strong> Anti-diarrhoeal activity of PHF was investigated using castor oil-induced diarrhoea, small intestinal transit and enteropooling models in rats. PHF was tested at 75, 150 and 300 mg/kg rat body weight. Loperamide was used as a reference control for <em>in vivo</em> studies. Anti-secretory action was evaluated against heat labile enterotoxin (from <em>Escherichia coli</em>)induced secretion in rat ileal loop model. The effect of PHF (12.5-100 µg/ml) on cAMP-dependent secretory activity was investigated against forskolin-induced cAMP release in HT-29 cells.<br /> <strong>Results:</strong> PHF demonstrated significant (p≤0.05) anti-diarrhoeal activity by increasing the time for first faecal drop and inhibited diarrhoeal episodes by 43, 58 and 60% at 75, 150 and 300 mg/kg body weight, respectively in a dose-dependent manner. Also, the intestinal transit was inhibited upto 33% and the weight of secretory contents induced by castor oil was significantly reduced by PHF, approximately 29% in enteropooling assay. On the other hand, the intestinal loop instilled with PHF and enterotoxin from <em>E. coli </em>demonstrated 61% inhibition of fluid accumulation as compared to loop instilled with enterotoxin only. <em>In vitro </em>studies indicated that PHF inhibits cAMP release in HT-29 cells corroborating the anti-secretory effects observed in aforesaid studies.<br /> <strong>Conclusion:</strong> The results suggest that the PHF possesses anti-diarrhoeal activity, evident through reduced faecal output, decreased intestinal transit and anti-secretory activities.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793010420200701Anti-oxidant and anti-inflammatory potential of aqueous extracts of leaves, barks and roots of Bixa orellana L. (Bixaceae) on acetaminophen-induced liver damage in mice4284391438010.22038/ajp.2019.14380ENDavid DjibersouLaboratory of Applied Biochemistry, Department of Biological Sciences, Faculty of Science, University of Ngaoundere, PO Box 454 Ngaoundere, Adamawa, CameroonBorris Rosnay Galani TietcheuLaboratory of Applied Biochemistry, Department of Biological Sciences, Faculty of Science, University of Ngaoundere, PO Box 454 Ngaoundere, Adamawa, Cameroon0000-0002-4324-5951Pascal Dieudonne ChuisseuBasic Science Department, Faculty of Health Sciences, Université des Montagnes, PO Box 208 Bangangté, West, CameroonNicolas NjintangLaboratory of Applied Biochemistry, Department of Biological Sciences, Faculty of Science, University of Ngaoundere, PO Box 454 Ngaoundere, Adamawa, CameroonJournal Article20190921<strong>Objective:</strong> <em>Bixa orellana </em>is a plant from the Bixaceae family, for which, limited information is available on hepatoprotective properties. This study aimed at evaluating the protective effects of this plant on sub-acute acetaminophen (APAP)-induced liver injury in mice.<br /> <strong>Materials and Methods:</strong> Various aqueous extracts were prepared from roots, leaves, and barks. Albino mice were divided into six groups: a control group, an APAP group; a silymarin group (positive control) and three test groups. Mice were treated orally with APAP (250 mg/kg) followed 3 hr later by plant extracts, silymarin (50 mg/kg) or distilled water (10 ml/kg) administration once daily, for seven days. After treatment, animals were sacrificed, the liver was collected and different biochemical parameters were measured. Histological analyses were performed using hematoxylin/eosin staining and the qualitative phytochemical content of plant extracts was evaluated using conventional methods.<br /> <strong>Results:</strong> Administration of <em>B. orellana</em> barks decoction (250 mg/kg) significantly reduced alanine aminotransferase levels (p<0.001), unlike leaves and roots extracts. Moreover, the bark infusion had the highest activity compared to macerate and decoction. It significantly reduced malondialdehyde levels (p<0.001) and increased the levels of glutathione, superoxide dismutase and catalase, at doses of 250 and 500 mg/kg compared to the APAP group. A significant (p<0.001) decrease of tumor necrosis factor-α levels and leukocyte infiltration was found following treatment with bark infusion. The infusion content evaluation revealed the presence of polyphenols, saponins, tannins, sterols, anthraquinones, and coumarins and the absence of alkaloids.<br /> <strong>Conclusion:</strong> These results show that infusion from <em>B. orellana</em> barks is hepatoprotective against APAP-induced toxicity via antioxidant and anti-inflammatory mechanisms.