Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793012320220501Effect of turmeric extract on bone healing in an experimental model of femoral bone fracture1972121856110.22038/ajp.2021.18561ENShahab IlkaDepartment of Orthopedics, School of Medicine, Kerman University of Medical Sciences, Kerman, IranAfshin HeshmatiDepartment of Orthopedics, School of Medicine, Kerman University of Medical Sciences, Kerman, IranSeyed Alireza MirabdollahiDepartment of Orthopedics, School of Medicine, Kerman University of Medical Sciences, Kerman, IranAbdollah JafarzadehDepartment of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.Farnaz SedghyDepartment of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran0000-0001-7436-9116Fatemeh BagheriPathology and Stem Cell Research Center, Pathology Department, School of Medicine, Kerman University of Medical Sciences, Kerman, IranOmid AzariDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, IranMohammad Ali MohammadiDepartment of Parasitology, School of Medicine, Kerman University of Medical Sciences, Kerman, IranFatemeh Jafari Dareh DarDepartment of Cardiology, School of Medicine, Kerman University of Medical Sciences, Kerman, IranMoein ArabnadviDepartment of Orthopedics, School of Medicine, Kerman University of Medical Sciences, Kerman, IranJournal Article20210318<strong>Objective</strong>: Following bone trauma, several factors participate in making a balance between the activity of osteoblasts and osteoclasts. The receptor activator of nuclear factor kappa B ligand (RANKL), receptor activator of nuclear factor kappa B (RANK), and osteoprotegerin (OPG) molecules play critical roles in the healing process via regulation of osteoclasts function. Turmeric is suggested to have an anti-osteogenic potential; however, its effect on accelerating bone healing has not been adequately studied. Here, we used a rat model of femur fracture to explore the effect of treatment with turmeric extract on the bone repair and the expression of <em>RANK</em>, <em>RANKL</em>, and <em>OPG</em> molecules.<br /><strong>Materials and methods</strong>: Eight rats were subjected to surgery, randomly divided into two groups, and treated orally with turmeric (200 mg/kg), or olive oil. Four oil-treated rats without bone fracture were used as control group. After six weeks of treatment, the femurs of animals were examined for radiological, histological, and gene expression analysis.<br /><strong>Results</strong>: X-ray radiography showed thicker callus and a more obscure fracture line in the turmeric group. Furthermore, higher osteoblast percentages but no osteoclasts were observed in turmeric-treated animals, representing better repair of bone in the fracture site. Also, real-time analyses showed that treatment with turmeric reduced <em>RANK</em> and <em>RANKL</em> expression (p <0.0001) and lowered <em>RANKL</em>/<em>OPG</em> ratio (p=0.01) in femoral bone tissue.<br /><strong>Conclusion</strong>: Our findings indicated the turmeric ability to facilitate bone hemostasis and optimize the expression of key markers involved in the bone metabolism.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793012320220501Protective effect of Zataria multiflora Boiss against sodium nitrite-induced hepatotoxicity in rats2132231878110.22038/ajp.2021.18781ENFateme AhmadiDepartment of Histology and Bacteriology, Faculty of para veterinary, Ilam University, Ilam, Iran0000-0003-0728-0415Ali Louei MonfaredDepartment of Histology and Bacteriology, Faculty of para veterinary, Ilam University, Ilam, Iran0000-0002-0584-6414Neamatollah ShakaramiDepartment of Histology and Bacteriology, Faculty of para veterinary, Ilam University, Ilam, Iran0000-0002-7645-5306Journal Article20210422<strong>Objective:</strong> Sodium nitrite (NaNO<sub>2</sub>) is used as a color stabilizer and antimicrobial agent in preservation of cured meat and fish. However, extensive use of this agent in the meat industries increased worries about its detrimental effects on human health. <em>Zataria multiflora</em> (<em>Z. multiflora) </em>is a well-known plant with therapeutic properties in the traditional medicine<strong>.</strong> Therefore, the present study was conducted to investigate the protective effect of this plant against sodium nitrite-induced hepatotoxicity.<br /><strong>Materials and methods:</strong> Thirty-two male Wistar rats were divided into 4 groups: Control (without any treatment), nitrite (350 mg/kg by gavage for 60 days), NaNO<sub>2</sub> plus <em>Z. multiflora</em> (rats treated with NaNO<sub>2</sub> 350 mg/kg gavage for 60 days and simultaneously received <em>Z. multiflora</em> extract at 200 mg/kg, ip) and <em>Z. multiflora</em> group (rats treated with <em>Z. multiflora</em> extract at 200 mg/kg, ip). At the end of the study, rats were euthanized and liver tissue samples were taken and studied under microscopy. Also, serum levels of liver function enzymes and antioxidant defense systems were measured. The results were analyzed using SPSS software and a p<0.0.5 was considered significant.<br /><strong>Results:</strong> Results showed that NaNO<sub>2 </sub>induces liver injuries and altered hepatic histo-architecture. Also, NaNO<sub>2 </sub>significantly altered the biochemical profiles and antioxidant defense parameters of the liver. However, treatment with <em>Z. multiflora</em> improved tissue integrity as well as antioxidant defense status and biochemical conditions of the liver.<br /><strong>Conclusion: </strong>Administration of <em>Z. multiflora</em> extract has beneficial effects on the NaNO<sub>2</sub>-induced histological and functional toxicity in the liver.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793012320220501Teucrium polium L: An updated review of phytochemicals and biological activities2242401915510.22038/ajp.2021.19155ENSeifollah BahramikiaDepartment of Biology, Faculty of Science, Lorestan University, Khorramabad, Iran0000-0002-9482-6828Parvaneh Hemmati Hassan GavyarDepartment of Biology, Faculty of Science, Lorestan University, Khorramabad, IranRazieh YazdanparastInstitute of Biochemistry and Biophysics, University of Tehran, Tehran, IranJournal Article20210709<strong>Objective:</strong> Medicinal plants and their components are potential novel sources for developing drugs against various diseases. <em>Teucrium polium</em> L. (syn <em>Teucrium capitatum</em> L. or felty germander) from the Lamiaceae family, is widely distributed in the dry and stony places of the hills and deserts of almost all Mediterranean countries, southwestern Asia, Europe, and North Africa. Based on traditional Iranian medicine (TIM), <em>T. polium</em> is used for treating many diseases, including abdominal pain, indigestion, and type 2 diabetes.<br /><strong>Materials and Methods:</strong> In our previous review article published in 2012 and based on 100 articles published from 1970 to 2010, the main compounds purified from <em>T. polium</em> were terpenes, terpenoids, and flavonoids with antioxidant, anticancer, anti-inflammatory, hypoglycemic, hepatoprotective, hypolipidemic, antibacterial, and antifungal activities.<br /><strong>Results:</strong> In this article, the phytochemistry and pharmacological activities of the plant reported from 2011 to 2020 have been evaluated. Therefore, a search was done in the databases PubMed, Science Direct and Google Scholar, Scopus, and Web of Science with the terms "<em>T. polium</em>," "<em>T. capitatum</em>." and felty germander’, which included about 100 articles published since 2011 about <em>T. polium</em> pharmacological activities and isolated compounds. Most studies of this review focused on the antioxidant and antidiabetic effects of the plant<br /><strong>Conclusion:</strong>. Considering the position of <em>T. polium </em>in folk medicine, mainly as an antidiabetic agent, purification, structural and biological characterization of the active components appears essential for effective use of the plant.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793012320220501Nigella sativa oil protects against cadmium-induced intestinal toxicity via promotion of anti-inflammatory mechanisms, mucin expression and microbiota integrity2412561877410.22038/ajp.2021.18774ENAkinleye StephenAkinrindeEnvironmental and Gastrointestinal Toxicology Laboratory, Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Oyo State, Nigeria0000-0001-6883-4595Abimbola OlumideAdekanmbiEnvironmental Microbiology and Biotechnology Laboratory, Department of Microbiology, Faculty of Science, University of Ibadan, Oyo State, Nigeria0000-0002-2871-1002Folake OlayinkaOlojoDepartment of Chemistry, Faculty of Science, The Polytechnic, Ibadan, Oyo State, Nigeria0000-0003-3452-653XJournal Article20210529<strong>Objective:</strong> This study examined the protective effects of <em>Nigella sativa</em> oil (NSO) on cadmium (Cd)-induced alterations affecting gut morphology and microbiota composition, as well as the involvement of mucus glycoprotein (MUC2) and immuno-inflammatory markers (TNFα and IL-2) in the colon of rats.<br /><strong>Materials and Methods</strong>: Male Wistar rats, randomized into four groups, were treated either with distilled water (control), CdCl<sub>2 </sub>(100 mg/kg), CdCl<sub>2</sub>+NSO (1 ml/kg) or NSO alone. After the experiments, faecal samples were processed for microbial culture on various selective media, while intestinal segments were prepared for histopathological examination and immunohistochemistry. The composition of NSO was analyzed using Gas Chromatography-Mass Spectrometry (GC-MS).<br /><strong>Results:</strong> Oral Cd administration provoked dramatic increases in faecal counts of potentially pathogenic bacteria (Staphylococci, Enterococci, <em>Pseudomonas</em> and <em>Escherichia coli</em>)<em>, </em>while decreasing probiotic lactobacilli counts. Cadmium treatment caused down-regulation of colonic MUC2 (p=0.003) and IL-2 (p=0.03), but increased TNFα (p=0.034), along with reduced goblet cell counts and mucus production. Conversely, treatment with NSO significantly improved Lactobacilli counts (p=0.042), while reducing the levels of potentially pathogenic species. In addition, NSO significantly restored colonic expressions of MUC2 (p=0.001), TNFα (p=0.007) and IL-2 (p=0.025) to control levels. GC-MS analysis of NSO revealed the presence of the active ingredient, thymoquinone and a high content of unsaturated fatty acids, including trans-13-octadecenoic acid and oleic acid.<br /><strong>Conclusion:</strong> This study highlights the intestinal mucus, microbiota and immuno-inflammatory system as important protective targets of NSO against Cd-induced intestinal toxicity.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793012320220501Crocus sativus (saffron) in the treatment of female sexual dysfunction: a three-center, double-blind, randomized, and placebo-controlled clinical trial2572681971410.22038/ajp.2022.19714ENLadan KashaniInfertility Ward, Arash Hospital, Tehran University of Medical Sciences, Tehran, IranSahar AslzadehPsychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, IranKamyar ShokraeePsychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran0000-0003-2828-2989Ahmad ShamabadiPsychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran0000-0002-5211-2827Borna Tadayon NajafabadiDepartment of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, CanadaMorteza JafariniaPsychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, IranSophia EsalatmaneshInfertility Ward, Arash Hospital, Tehran University of Medical Sciences, Tehran, IranShahin AkhondzadehPsychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran0000-0002-2277-5101Journal Article20211105<strong>Objective:</strong> One of the traditional aphrodisiacs used in various cultures is <em>Crocus sativus</em>, commonly called saffron. Previous studies have pointed to the possible applicability of saffron for sexual dysfunction in both men and women. This study investigates the effects of saffron capsules on female sexual dysfunction.<br /><strong>Materials and Methods:</strong> This study was a parallel-group, double-blind, randomized, placebo-controlled clinical trial. Participants, who were married women between 18 and 55 years of age suffering from severe sexual dysfunction, were randomized to receive either 15 mg <em>Crocus sativus</em> capsules twice daily or placebo. The treatment continued for 6 weeks, and patients were evaluated every 2 weeks. The primary outcome was the change in the female sexual function index score. Other outcomes included the female sexual function index sub-domains.<br /><strong>Results:</strong> Seventy-four patients were equally randomized to each group, and 34 in each group completed the trial. Participants in both groups experienced improved total scores at each visit. However, a repeated-measures ANOVA revealed that time ´ treatment differed between groups in favor of the saffron group (p=0.050). During the 6<sup>th </sup>week follow-up, the saffron group had a 62% score improvement from baseline. Desire, lubrication, and satisfaction were female sexual function index domains in which saffron demonstrated superiority over placebo. The adverse event profile was similar for the groups, and no participant discontinued treatment.<br /><strong>Conclusion:</strong> Findings of this study suggest that saffron might be a safe and effective option to ameliorate female sexual dysfunction. Further robust research is warranted.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793012320220501Effect of hydro-alcoholic extract of Cinnamomum zeylanicum on nitric oxide metabolites in brain tissues following seizures induced by pentylenetetrazole in mice2692801957810.22038/ajp.2022.19578ENAmir HosseinAssaranApplied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, IranFarimah BeheshtiNeuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran. Department of Physiology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, IranNarges MarefatiDepartment of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.Roghayeh RashidiPharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, IranMahmoud HosseiniPsychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-6425-5123Bahram BibakNatural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran. Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran0000-0001-6675-0806Farzaneh ShakeriNatural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran. Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, IranJournal Article20210524<strong>Objective:</strong> The effects of <em>Cinnamomum zeylanicum</em> on oxidative stress imposed by pentylenetetrazole (PTZ) was examined in mice brain tissues.<br /><strong>Materials and Methods:</strong> Animals were divided into five groups as follows: 1- control group which received saline; 2- PTZ group (100 mg/kg, ip); and groups 3 to 5 which received (100, 200, and 400 mg/kg) of <em>C. zeylanicum</em> for seven days prior to PTZ injection. The latencies of the first minimal clonic seizure (MCS) and the first generalized tonic-clonic seizure (GTCS) and levels of oxidant and antioxidant biomarkers were measured.<br /><strong>Results:</strong> Treatment with the two higher doses of the extract significantly increased the MCS and GTCS latencies (p<0.05 to p<0.001). Malondialdehyde (MDA) and nitric oxide (NO) levels were increased, but superoxide dismutase (SOD), catalase (CAT), and thiol were decreased in both cortical and hippocampal tissues of the PTZ group compared to the controls (p<0.001). Pretreatment with the two higher doses of <em>C. zeylanicum</em> significantly led to a significant correction in NO, MDA, SOD and CAT levels in the hippocampus and cortex compared to the PTZ group (p<0.05 to p<0.001).<br /><strong>Conclusion: </strong>Antioxidant and anticonvulsant effects of <em>C. zeylanicum</em> in PTZ-injected animals may suggest its potential therapeutic effect on nervous diseases such as seizures.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793012320220501Protective effect of aqueous and ethanolic extracts of Lippia citriodora Kunth. on acrylamide-induced neurotoxicity2812941917310.22038/ajp.2021.19173ENZahra TandisepanahSchool of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranAmir ForoutanfarSchool of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranAli AziminiaSchool of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranMahboobeh Ghasemzadeh RahbardarSchool of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-5491-572XBibi Marjan RazaviTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-7450-9286Hossein HosseinzadehDepartment of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-3483-851XJournal Article20210515<strong>Objective</strong>: Acrylamide (ACR) neurotoxicity is induced by different mechanisms such as oxidative stress and apoptosis. Scientific researchs have indicated the antioxidative properties of <em>Lippia citriodora</em>. The protective effect of <em>L. citriodora</em> aqueous and ethanolic extracts on ACR-induced neurotoxicity was investigated.<br /><strong>Materials and methods</strong>: Male Wistar rats were randomly divided into 13 groups: (1) control, (2) ACR (50 mg/kg, i.p.), (3-6) ACR+aqueous extract (12.5, 25, 50, and 100 mg/kg, i.p.), (7-10) ACR+ethanolic extract (12.5, 25, 50, and 100 mg/kg, i.p.), (11) aqueous extract (100 mg/kg), (12) ethanolic extract (100 mg/kg), and (13) ACR+Vitamin E (200 mg/kg, every other day, i.p.). After 11 days, gait score, MDA, and GSH levels in brain cortical tissue were measured. In the <em>in vitro</em> test, the viability of PC12 cells (using MTT test), the amount of reactive oxygen species (ROS; using DCFH-DA method), and the protein levels of Bax, Bcl2 and caspase 3 (by western blotting) were measured.<br /><strong>Results</strong>: In the <em>in vitro</em> study, the IC<sub>50</sub> for the treatment of PC 12 cells with ACR after 24 hr was 6 mM. ACR decreased cell viability, but increased ROS level, Bax/Bcl-2 ratio, and caspase-3 protein level. Pre-treatment by <em>L. citriodora</em> extracts (15-120 µg/ml) ameliorated the toxic effects of ACR on PC12 cells. In the <em>in vivo</em> experiment, ACR-induced movement disorders increased MDA but decreased GSH content. The extracts of <em>L. citriodora</em> improved ACR toxic effects.<br /><strong>Conclusion</strong>: Aqueous and ethanolic extracts of <em>L. citriodora</em> were found to reduce ACR-induced neurotoxicity via inhibiting oxidative stress and apoptosis.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793012320220501Targeted delivery of galbanic acid to colon cancer cells by PLGA nanoparticles incorporated into human mesenchymal stem cells2953082002210.22038/ajp.2022.20022ENMahboubeh EbrahimianNanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranSanaz ShahgordiDepartment of Immunology, School of Medicine, Golestan University of Medical Sciences, Gorgan, IranRezvan Yazdian-RobatiMolecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, IranLeila EtemadPharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranMaryam HashemiDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranZahra SalmasiDepartment of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-8725-8252Journal Article20220111<strong>Objective:</strong> The aim of this study was to investigate the efficacy of mesenchyme stem cells (MSCs) derived from human adipose tissue (hMSCs) as carriers for delivery of galbanic acid (GBA), a potential anticancer agent, loaded into poly (lactic-co-glycolic acid) (PLGA) nanoparticles (nano-engineered hMSCs) against tumor cells.<strong> </strong><br /><strong>Materials and Methods:</strong> GBA-loaded PLGA nanoparticles (PLGA/GBA) were prepared by single emulsion method and their physicochemical properties were evaluated. Then, PLGA/GBA nanoparticles were incorporated into hMSCs (hMSC/PLGA-GBA) and their migration ability and cytotoxicity against colon cancer cells were investigated. <br /><strong>Results:</strong> The loading efficiency of PLGA/GBA nanoparticles with average size of 214±30.5 nm into hMSCs, was about 85 and 92% at GBA concentration of 20 and 40 μM, respectively. Nano-engineered hMSCs showed significant higher migration to cancer cells (C26) compared to normal cells (NIH/3T3). Furthermore, nano-engineered hMSCs could effectively induce cell death in C26 cells in comparison with non-engineered hMSCs. <br /><strong>Conclusion: </strong>hMSCs could be implemented for efficient loading of PLGA/GBA nanoparticles to produce a targeted cellular carrier against cancer cells. Thus, according to minimal toxicity on normal cells, it deserves to be considered as a valuable platform for drug delivery in cancer therapy.Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793012320220501Some natural hypomethylating agents in food, water and environment are against distribution and risks of COVID-19 pandemic: Results of a big-data research3093241952010.22038/ajp.2022.19520ENMohammad Reza BesharatiDepartment of Computer Engineering, Sharif University of Technology, Tehran, Iran. Quran Miracle Research Institute, Shahid Beheshti University, Tehran, IranMohammad IzadiDepartment of Computer Engineering, Sharif University of Technology, Tehran, IranAlireza TalebpourDepartment of Computer Science and Engineering, Shahid Beheshti University, Tehran, Iran. Quran Miracle Research Institute, Shahid Beheshti University, Tehran, IranJournal Article20210210<strong>Objective:</strong> This study analyzes the effects of lifestyle, nutrition, and diets on the status and risks of apparent (symptomatic) COVID-19 infection in Iranian families.<br /><strong>Materials and Methods:</strong> A relatively extensive questionnaire survey was conducted on more than 20,000 Iranian families (residing in more than 1000 different urban and rural areas in the Islamic Republic of Iran) to collect the big data of COVID-19 and develop a lifestyle dataset. The collected big data included the records of lifestyle effects (<em>e.g.</em> nutrition, water consumption resources, physical exercise, smoking, age, gender, health and disease factors, etc.) on the status of COVID-19 infection in families (<em>i.e.</em> residents of homes). Therefore, an online self-reported questionnaire was used in this retrospective observational study to analyze the effects of lifestyle factors on the COVID-19 risks. The data collection process spanned from May 10, 2020 to March 19, 2021 by selecting 132 samples from more than 40 different social network communities.<br /><strong>Results:</strong> The research results revealed that food and water sources, which contain some natural hypomethylating agents, mitigated the risks of apparent (symptomatic) COVID-19 infection. Furthermore, the computations on billions of permutations of nutrition conditions and dietary regime items, based on the data collected from people’s diets and infection status, showed that there were many dietary conditions alleviating the risks of apparent (symptomatic) COVID-19 infection by 90%. However, some other diets tripled the infection risk.<br /><strong>Conclusion:</strong> Some natural hypomethylating agents in food, water, and environmental resources are against the spread and risks of COVID-19.<br /> Mashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-793012320220501Enhancing the efficacy of Hypericum perforatum in the treatment of an experimental model of multiple sclerosis using gold nanoparticles: an in vivo study3253361957410.22038/ajp.2022.19574ENMahmoud MahmoudiImmunology Research Center, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranMaryam RastinImmunology Research Center, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranMohammad Kazemi ArababadiDepartment of Laboratory Sciences, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, IranAkbar AnaeigoudariDepartment of Physiology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran0000-0002-1422-393xReza NosratabadiDepartment of Medical Immunology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran0000-0002-9829-8997Journal Article20210811<strong>Objective: </strong><em>Hypericum perforatum</em> is a herbal medicine used in traditional medicine for the treatment of depression due to its antidepressant and anti-inflammatory activities. Therefore, we evaluated the therapeutic efficacy of <em>H. perforatum</em> extract (HPE) in combination with gold nanoparticles (HPE-GNP) against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis.<strong> </strong><br /><strong>Materials and Methods: </strong>EAE was induced in C57BL/6 mice with subcutaneous injection of MOG35-55 emulsified in complete Freund's adjuvant, and intraperitoneal pertussis toxin. Mice were treated with drugs in free (HPE) and nano-form (HPE-GNP) preparations. Splenocytes were isolated from all mice and the level of inflammatory and anti-inflammatory cytokines were evaluated by ELISA. The expression of T cells' transcription factors was also assessed using Real-Time PCR.<br /><strong>Results: </strong>Clinical score was reduced after HPE-GNP treatment. This change was associated with a decrease in the incidence and infiltration of inflammatory cells into the central nervous system. Additionally, treatment with HPE-GNP decreased the level of pro-inflammatory cytokines (IFN-γ, IL-17A and IL-6) and increased anti-inflammatory cytokines (TGF-β, IL-10 and IL-4). The real-time analysis revealed a decrease in the level of <em>T-bet</em> and <em>ROR-γt</em> but an increase in <em>FoxP3</em> and <em>GATA3</em> expression.<br /><strong>Conclusion: </strong>The current study demonstrated that HPE-GNP could potentially reduce clinical and pathological complications of EAE, but laboratory data showed that HPE-GNP was significantly more effective than HPE in the treatment of EAE.