DARU Journal of Pharmaceutical Sciences
Year:2014 | Volume:22 | Issue:1|Papers Count:24

Background: Anemia is a common complication among hemodialysis (HD) patients. Although intravenous iron and erythropoiesis-stimulating agents revolutionized anemia treatment, about 10% of HD patients show suboptimal response to these agents. Systemic inflammation and increased serum hepcidin level may contribute to this hyporesponsiveness. Considering the anti-inflammatory properties of omega-3 fatty acids, this study aimed to evaluate potential role of these fatty acids in improving anemia and inflammation of chronic HD patients.Methods: In this randomized, placebo-controlled trial, 54 adult patients with HD duration of at least 3 months were randomized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months.Anemia parameters including blood hemoglobin, serum iron, transferrin saturation (TSAT), erythropoietin resistance index, and required dose of intravenous iron and erythropoietin, and serum concentrations of inflammatory/anti-inflammatory markers including interleukin (IL) -6, tumor necrosis factor (TNF) -a, IL-10, C-reactive protein (CRP), hepcidin, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-a were measured at baseline and after 4 months of the intervention.Results: 45 subjects (25 in the omega-3 and 20 in the placebo group) completed the study. No significant changes were observed in blood hemoglobin, serum iron, TSAT, and required dose of intravenous iron in either within or between group comparisons. Additionally, erythropoietin resistance index as well as required dose of intravenous erythropoietin showed no significant change in the omega-3 group compared to the placebo group.Although a relative alleviation in inflammatory state appeared in the omega-3 group, the mean differences of inflammatory and anti-inflammatory markers between the two groups did not reach statistically significant level except for IL-10-to-IL-6 ratio and serum ferritin level which showed significant changes in favor of omega-3 treatment (P<0.001 and P=0.003, respectively).Conclusion: Omega-3 fatty acids relatively improved systemic inflammation of chronic HD patients without any prominent benefits on anemia. However, future well-designed studies on larger number of patients may determine utility of omega-3 fatty acids in HD patients with respect to inflammation and anemia.

Background: Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells.Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology.Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry.Results: PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility.Conclusion: PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.

Background: Head and neck squamous cell carcinoma (HNSCC) is the 11th leading cancer by incidence worldwide. Surgery and radiotherapy have been the major treatment for patients with HNSCC while chemotherapy has become an important treatment option for locally advanced HNSCC. Understanding of the molecular mechanisms underlying HNSCC impelled the development of targeted therapeutic agents. The development and combinations of targeted therapies in different cellular pathways may be needed to fulfill the unmet needs of current HNSCC chemotherapy.Results: A series of N3-acyl-N5-aryl-3, 5-diaminoindazoles were synthesized and their anti-proliferative activities were evaluated against human cancer cell lines, Caki, A549, AMC-HN1, AMC-HN3, AMC-HN4, AMC-HN6, and SNU449. The cellular selectivity of compound was obtained by the modification of substituent at N5-aryl group of 3, 5-diaminoindazole.Compound 9a and 9b showed more than 7-fold selectivity for AMC-HN4 and AMC-HN3, respectively.Conclusions: N3-acyl-N5-aryl-3, 5-diaminoindazole analogues can be used as hits in the development of anticancer drug for HNSCC.

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Background: Bladder cancer is the second common malignancy of genitourinary tract, and transitional cell carcinomas (TCCs) account for 90% of all bladder cancers. Due to acquired resistance of TCC cells to a wide range of chemotherapeutic agents, there is always a need for search on new compounds for treatment of these cancers.Coumarins represent a group of natural compounds, which some of them have exerted valuable anti-tumor activities. The current study was designed to evaluate anti-tumor properties and mechanism of action of 7-isopentenyloxycoumarin, a prenyloxycoumarin, on 5637 cells (a TCC cell line).Results: MTT results revealed that the cytotoxic effects of 7-isopentenyloxycoumarin on 5637 cancerous cells were more prominent in comparison to HDF-1 normal cells. This coumarin increased the amount of chromatin condensation and DNA damage in 5637 cells by 58 and 33%, respectively. The results also indicated that it can induce apoptosis most probably via activation of caspase-3 in these cells. Moreover, propidium iodide staining revealed that 7-isopentenyloxycoumarin induced cell cycle arrest at G2/M stage, after 24 h of treatment.Conclusion: Our results indicated that 7-isopentenyloxycoumarin had selective toxic effects on this bladder cancer cell line and promoted its effects by apoptosis induction and cell cycle arrest. This coumarin can be considered for further studies to reveal its exact mechanism of action and also its anti-cancer effects in vivo.

Background: Coumarins are an important class of widely distributed heterocyclic natural products exhibiting a broad pharmacological profile. In this work, a new series of coumarins bearing substituted 3, 4-dihydro-2Hbenzothiazines were described as potential analgesic agents. The clinical use of NSAIDs as traditional analgesics is associated with side effects such as gastrointestinal lesions and nephrotoxicity. Therefore, the discovery of new safer drugs represents a challenging goal for such a research area.Results: The target compounds 3- (3-methyl-3, 4-dihydro-2H-benzo [b] [1, 4] thiazin-3-yl) -2H-chromen-2-ones 2a-u were synthesized and characterized by spectral data. The antinociceptive properties of target compounds were determined by formalin-induced test and acetic acid-induced writhing test in mice. Among the tested compounds, compound 2u bearing 2- (4- (methylsulfonyl) benzoyl) - moiety on benzothiazine ring and 4- (methylsulfonyl) phenacyloxy- group on the 7 position of coumarin nucleus showed better profile of antinocecieption in both models. It was more effective than mefenamic acid during the late phase of formalin-induced test as well as in the acetic acid-induced writhing test.Conclusion: Considering the significant antinoceciptive action of phenacyloxycoumarin derivatives, compound 2u prototype might be further used as model to obtain new more potent analgesic drugs.

Background and purpose of the study: Acenaphtho derivatives have been reported as antitumor agents. Due to this fact and also with the aim of developing the chemistry of potentially bioactive heterocyclic compounds via efficient reactions, a facile procedure for the synthesis of 9- (alkylthio) -acenaphtho [1, 2-e] -1, 2, 4-triazines via two step condensation of thiosemicarbazide and acenaphtylene-9, 10-quinone to form acenaphtho [1, 2-e] -1, 2, 4-triazine-9 (8H) -thiones and subsequent reaction with benzyl chloride derivatives is reported.Methods: 9- (alkylthio) acenaphtho [1, 2-e] -1, 2, 4-triazines were synthesized via the reaction of acenaphtho-9, 10-quinone with thiosemicarbazide, and then with the benzyl chloride derivatives. Cytotoxicity of some prepared compounds was assessed through MTT assay on three different human cancerous cell lines (HL-60, MCF7, and MOLT-4 cells). Molecular docking studies were performed via AutoDock4.2 software in order to confirm an apoptosis-inducing activity of acenaphtho scaffolds via the Bcl-2 protein.Results: Excellent yields of the products, short reaction times and simple work-up are attractive features of this synthetic protocol. The evaluated compounds exhibited moderate to good cytotoxic activities. Docking results on the active site of B-cell lymphoma 2 (Bcl-2) supported the experimental biological data and agreed well with previous in silico data for commonly used anti-cancer drugs. Moreover; results were analyzed considering binding efficiency indices.Conclusions: The outcomes of the present study may be helpful in future targeting of Bcl-2 with the aim of developing apoptosis-inducing agents.

Purpose of the study: Comparative in vitro studies were carried out to determine the adsorption characteristics of 3 drugs on activated charcoal (AC) and sodium polystyrene sulfonate (SPS). Activated charcoal (AC) has been long used as gastric decontamination agent for tricyclic antidepressants (TCA).Methods: Solutions containing drugs (amitriptyline, clomipramine, or doxepin) and variable amount of AC or SPS were incubated for 30 minutes.Results: At pH 1.2 the adsorbent: drug mass ratio varied from 2: 1 to 40: 1 for AC, and from 0.4: 1 to 8: 1 for SPS.UV–VIS spectrophotometer was used for the determination of free drug concentrations. The qmax of amitriptyline was 0.055 mg/mg AC and 0.574 mg/mg SPS, qmax of clomipramine was 0.053 mg/mg AC and 0.572 mg/mg SPS, and qmax of doxepin was 0.045 mg/mg AC and 0.556 mg/mg SPS. The results of adsorption experiments with SPS revealed higher values for the qmax parameters in comparison with AC.Conclusion: In vitro gastric decontamination experiments for antidepressant amitriptyline, clomipramine, and doxepin showed that SPS has higher qmax values than the corresponding experiments with AC. Therefore, we suggest SPS is a better gastric decontaminating agent for the management of acute TCA intoxication.

Background: The deposition of amyloid peptides is associated with Alzheimer’s disease (AD). These amyloid peptides are derived from the amyloid protein precursor (APP). Silymarin, a standardized extract of milk thistle, which is currently used in liver diseases, may be effective in the inhibition of amyloid formation. However, its effect has not been assessed on APP expression.Results: In this study, first, the effect of silymarin was examined on the passive avoidance learning in a rat model of AD. This model was induced by the intracerebroventricular injection of Ab peptide (Ab1-42) in Wistar rats. Rats were treated with 70 and 140 mg/kgof the extract, once a day, for 4 weeks. Memory function that was evaluated in a shuttle-cage test, showed improvement upon administration of this extract. Brain amyloid plaques had also decreased upon administration of the extract. Furthermore, APP gene expression was compared in treated and untreated groups. The result showed that silymarin was able to suppress APP expression.Conclusion: Our results are in accordance with the in vitro tests concerning the positive antiamyloidogenic property of the main component of silymarin, namely silibinin. We suggest that the beneficial effect of sylimarin in the AD model is related to its capacity to disaggregate amyloid plaques and to suppress APP expression.Considering the limited side effects of silymarin, this compound could be of use in AD therapy.

Background: Juglans regia L. (J. regia) is one of the medicinal plants traditionally used for treatment of diabetes in Iranian medicine. The effect of this plant has already been investigated on animal models; however, this is the first study conducted on human subjects. The aim of this study is to investigate the hypoglycemic effect of J. regia leaves aqueous extract in type 2 diabetes patients. Fifty eight Iranian male and female patients with type 2 diabetes were enrolled. The patients were randomly allocated into two groups. One group (n=30) received J. regia leaves extract while the other group (n=28) received placebo. Fasting blood samples were collected at the beginning of the study and after two months for determination of HbA1c and blood glucose level as a main outcome and insulin, SGOT, SGPT, and ALP level as secondary outcome.Results: Our analysis showed that serum fasting HbA1C and blood glucose levels were significantly decreased and the insulin level was increased in patients in the J. regia arm.Conclusions: The results indicate that J. regia aqueous extract favorably affects blood levels of glucose, insulin and HbA1C in type 2 diabetic patients.

Background: Alopecia is a dermatological disorder with psychosocial implications on patients with hair loss. Hair loss is one of the most feared side effects of chemotherapy. Plants have been widely used for hair growth promotion since ancient times in Ayurveda, Chinese and Unani systems of medicine. The effect of extracts of Cuscuta reflexa Roxb.in testosterone induced alopecia was reported.Objective: In the present study, the efficacies of the extracts of Cuscuta reflexa in promoting hair growth in cyclophosphamide-induced hair loss have been determined.Materials and methods: The study was performed by treated with petroleum ether and ethanolic extract of Cuscuta reflexa at the dose 250 mg/kg in male swiss albino rats. Cyclophosphamide (125 mg/kg) was used to induce alopecia.Results: Groups treated with extracts of plant showed hair regrowth. Histopathology and gross morphologic observations for hair regrowth at shaved sites revealed active follicular proliferation.Conclusions: It concluded that extracts of Cuscuta reflexa shown to be capable of promoting follicular proliferation or preventing hair loss in cyclophosphamide-induced hair fall.

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Objective: A case with reversible symmetrical sensorineural hearing loss following hydroxychloroquine therapy is described.Case summary: A 57-year-old, human immunodeficiency virus (HIV) positive man was referred to the HIV clinic of Imam Khomeini Hospital, Tehran with chief complaint of bilateral slowly progressive hearing loss starting from two months ago. The man had history of rheumatoid arthritis diagnosed from 3 months ago and was administered hydroxychloroquine 200 mg and prednisolone 5 mg twice daily. Audiometry test showed moderate to severe neuronal hearing loss and reduced speech recognition in both ears of the patient. With suspicion of hydroxychloroquine-induced hearing loss, this drug was discontinued. After 2 months of hydroxychloroquine discontinuation, his audiometry findings were improved.Discussion: A few cases of hydroxychloroquine-induced hearing loss have been reported. All of the cases were non-HIV positive individuals. Irreversible hearing loss was developed following long-term therapy with hydroxychloroquine. The present case was a HIV-positive man who developed hearing loss following short course (one month) hydroxychloroquine therapy and his problem was resolved following discontinuation of hydroxychloroquine and continuation of prednisolone.Conclusions: Hydroxychloroquine-induced hearing loss may reversibly occur following short term therapy in HIV patients.

Background: Drug release in a patient’s body is of particular interest to the pharmaceutical industry. One of the most essential types of drug release is the gradual release based on a behavior, which is called a profile or modified release. The investigation of the time-oriented quality characteristic is one of the newest topics in the area of product design. There are already several approaches addressing this issue. In this paper, a mathematical model is proposed to find the suitable values of the controllable factors in a drug to achieve the profile of the drug release in the patient’s body.Results: The proposed method has several advantages over the existing methods.Conclusion: The authors feel that by adjusting the control factors during the production process the drug release profile become closer to the reference profile.

Background: Traditional drug discovery approaches are mainly relied on the observed phenotypic changes following administration of a plant extract, drug candidate or natural product. Recently, target-based approaches are becoming more popular. The present study aimed to identify the cellular targets of crocin, the bioactive dietary carotenoid present in saffron, using an affinity-based method.Methods: Heart, kidney and brain tissues of BALB/c mice were homogenized and extracted for the experiments.Target deconvolution was carried out by first passing cell lysate through an affinity column prepared by covalently attaching crocin to agarose beads. Isolated proteins were separated on a 2D gel, trypsinized in situ and identified by MALDI-TOF/TOF mass spectrometry. MASCOT search engine was used to analyze Mass Data.Results: Part of proteome that physically interacts with crocin was found to consist of beta-actin-like protein 2, cytochrome b-c1 complex subunit 1, ATP synthase subunit beta, tubulin beta-3 chain, tubulin beta-6 chain, 14-3-3 protein beta/alpha, V-type proton ATPase catalytic subunitA, 60 kDa heat shock protein, creatine kinase b-type, peroxiredoxin-2, cytochrome b-c1 complex subunit 2, acetyl-coA acetyltransferase, cytochrome c1, proteasome subunit alpha type-6 and proteasome subunit alpha type-4.Conclusion: The present findings revealed that crocin physically binds to a wide range of cellular proteins such as structural proteins, membrane transporters, and enzymes involved in ATP and redox homeostasis and signal transduction.

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Some studies showed that piperine (the alkaloid of piper nigrum) can change the activities of microsomal enzymes.Midazolam concentration is applied as a probe to determine the CYP3A enzyme activity. This study was done to determine piperine pretreatment role on midazolam plasma concentration.Twenty healthy volunteers (14 men and 6 women) received oral dose of piperine (15 mg) or placebo for three days as pretreatment and midazolam (10 mg) on fourth day of study and the blood samples were taken at 0.5, 2.5 and 5 h after midazolam administration. The midazolam plasma levels were assayed using HPLC method (C18 analytical column, 75: 25 methanol: water as mobile phase, UV detector at 242 nm wavelength and diazepam as internal standard).Data were fit in a “one-compartment PK model” using P-Pharm 1.5 software and analyzed under statistical tests.The mean ±SD of the age and body mass index were 24.3±1.83 years (range: 21–28 years) and 23.46 ± 2.85, respectively. The duration of sedation in piperine receiving group was greater that the placebo group (188±59 vs.102±43 min, p<0.0001). Half-life and clearance of midazolam were higher in piperine pretreatment group compared to placebo [1.88±0.03 vs.1.71±0.04 h (p<0.0001) and 33.62±0.4 vs.37.09±1.07 ml/min (p<0.0001), respectively].According to the results, piperine can significantly increases half-life and decreases clearance of midazolam compared to placebo. It is suggested that piperine can demonstrate those effects by inhibition CYP3A4 enzyme activity in liver microsomal system.

Sudden sensorineural hearing loss (SSNHL) is a debilitating condition with an incidence of nearly 20 per 100, 000 in populations. Metronidazole-induced ototoxicity is an extremely rare etiology of SSNHL. In this report, we describe a young female with bilateral SSNHL due to oral use of metronidazole. A 23 years old female presented to the emergency department with acute bilateral hearing loss. We found out that her hearing loss had started 4 days after initiation of metronidazole which was administered for treatment of diarrhea. This case report shows that physicians should be aware of the uncommon side effects while prescribing metronidazole to patients in order to manage the possible adverse events on time.

Background: Mirtazapine (MRZ) is a human antidepressant drug metabolized to 8-OH mirtazapine (8-OH) and dimethylmirtazapine (DMR) metabolites. Recently, this drug has been proposed as a potential analgesic for use in a multidrug analgesic regime in the context of veterinary medicine. The aim of this study was to assess the pharmacokinetics of MRZ and its metabolites DMR and 8-OH in rats.Findings: Eighteen fasted, healthy male rats were randomly divided into 3 groups (n=6). Animals in these groups were respectively administered MRZ at 2 and 10 mg/kg orally and 2 mg/kg intravenously. Plasma MRZ and metabolite concentrations were evaluated by HPLC-FL detection method. After intravenous administration, MRZ was detected in all subjects, while DMR was only detected in three.8-OH was not detected. After oral administration, MRZ was detected in 3 out of 6 rats treated with 2 mg/kg, it was detected in 6 out of 6 animals in the 10 mg/kg group.DMR was only detectable in the latter group, while 8-OH was not detected in either group. The oral bioavailability was about 7% in both groups.Conclusions: The plasma concentration of the MRZ metabolite 8-OH was undetectable, and the oral bioavailability of the parental drug was very low.

Background: In cancer cells, apoptosis is an important mechanism that influences the outcome of chemotherapy and the development of chemoresistance. To find the genes involved in chemoresistance and the development of gastric cancer, we used the suppression subtractive hybridization method to identify the genes that are overexpressed in gastric cancer tissues compared to normal gastric tissues.Results: In the suppression subtractive hybridization library we constructed, the most highly overexpressed genes were humanin isoforms. Humanin is a recently identified endogenous peptide that has anti-apoptotic activity and has been selected for further study due to its potential role in the chemoresistance of gastric cancer. Upregulation of humanin isoforms was also observed in clinical samples by using quantitative real-time PCR. Among the studied isoforms, humanin isoform 3, with an expression level of 4.166±1.44 fold, was the most overexpressed isoform in GC.Conclusions: The overexpression of humanin in gastric cancer suggests a role for chemoresistance and provides new insight into the biology of gastric cancer. We propose that humanin isoforms are novel targets for combating chemoresistance in gastric cancer.

Graphene, the new allotrope of carbon is a single layer of monocrystalline graphite with sp2 hybridized carbon atoms. This compound has received worldwide attention due to its extraordinary physical and chemical properties.Duo to the widespread application of geraphenes, concerns are raising about its environmental safety or the safety protocols for handling and waste of graphene-based materials. The generation of reactive free radicals, adsorption of important biomolecules, and physical toxicity of graphene also matter. Hereby we criticize the concerns on the toxicity of graphenes to provide some perspective on the potential hazards of future development in graphene-based biomaterials.

Background: Long-term clinical employment of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant side effects including gastrointestinal (GI) lesions and kidney toxicity. In this paper we designed and synthesized new imidazolyl-1, 3, 4-oxadiazoles and 1, 2, 4-triazoles by molecular hybridization of previously described anti-inflammatory compounds in the hope of obtaining new safer analgesic and anti-inflammatory agents.Methods: The target structures were synthesized by preparation of 5-methyl-1H-imidazole-4-carboxylic acid ethyl ester 5.The reaction of hydrazine hydrate with this ester afforded the 5-methyl-1H-imidazole-4-carboxylic acid hydrazide 6 which was converted to target compounds 7-15 according to the known procedures. In silico toxicity risk assessment and drug likeness predictions were done, in order to consider the privileges of the synthesized structures as drug candidates.Results and discussion: The analgesic and anti-inflammatory profile of the synthesized compounds were evaluated by writhing and carrageenan induced rat paw edema tests respectively. Compounds 8, 9 and 11-13 and 15 were active analgesic agents and compounds 8, 9 and 11-13 showed significant anti-inflammatory response in comparison with control. Compounds 11 and 13 were screened for their ulcerogenic activities and none of them showed significant ulcerogenic activity. The active Compounds 11 and 12 showed the highest drug likeness and drug score.Conclusions: The analgesic and anti-inflammatory activities of title compounds were comparable to that of standard drug indomethacin with a safer profile of activity. The results revealed that both of oxadiazole and triazole scaffolds can be determined as pharmacophores. The in silico predictions and pharmacological evaluations showed that compounds 11 and 12 can be chosen as lead for further investigations.

Background: Neurosurgical procedures such as craniotomy and brain tumor resection could potentially lead to unavoidable cerebral injuries. Matrix metalloproteinase-9 (MMP-9) is up-regulated in neurological injuries. Statins have been suggested to reduce MMP- 9 level and lead to neuroprotection. Atorvastatin preoperatively administered to evaluate its neuroprotective effects and outcome assessment in neurosurgical-induced brain injuries after glial tumor resection. In this prospective, randomized, double-blind, placebo-controlled trial, 42 patients undergoing glial tumor surgery randomly received 40 mg atorvastatin or placebo twice daily from seven days prior to operation and continued for a 3 weeks period. Plasma MMP-9 concentration measured 4 times, immediately before starting atorvastatin or placebo, immediately before surgery, 24 hours and two weeks after the surgery. Karnofsky performance score was assessed before first dose of atorvastatin as a baseline and 2 months after the surgery.Results: Karnofsky performance scale after surgery raised significantly more in Atorvastatin group (11.43+/-10.62 vs.4.00+/-8.21) (p=0.03). Atorvastatin did not significantly reduce MMP-9 plasma concentration 24 hours after surgery in comparison to placebo. No statistical significance detected regarding length of hospital stay among the groups. Significant reduction in MMP-9 plasma concentration was recorded in atorvastatin group two weeks after surgery (p=0.048).Conclusions: Significant statistical differences detected with atorvastatin group regarding MMP-9 plasma concentration, clinical outcome and Karnofsky performance score. Consequently, atorvastatin use may lead to better outcome after neurosurgical procedures.

Background: Antidepressants have been shown to affect levels of brain-derived neurotrophic factor (BDNF) and VGF (non-acronymic) whose transcriptions are dependent on cAMP response element binding protein (CREB) in long term treatment. The aim of this study was to verify the subacute antidepressant effects of crocin, an active constituent of saffron (Crocus sativus L.), and its effects on CREB, BDNF, and VGF proteins, transcript levels and amount of active, phosphorylated CREB (P-CREB) protein in rat hippocampus.Methods: Crocin (12.5, 25, and 50 mg/kg), imipramine (10 mg/kg; positive control) and saline (1 mL/kg; neutral control) were administered intraperitoneally (IP) to male Wistar rats for 21 days. The antidepressant effects were studied using the forced swimming test (FST) on day 21 after injection. Protein expression and transcript levels of genes in the rat hippocampus were evaluated using western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively.Results: Crocin significantly reduced the immobility time in the FST. Western blot analysis showed that 25 and 50 mg/kg of crocin increased the levels of CREB and BDNF significantly and dose dependently. All doses of crocin increased the VGF levels in a dose-dependent manner. Levels of p-CREB increased significantly by 50 mg/kg dose of crocin. Only 12.5 mg/kg crocin could significantly increase the transcript levels of BDNF. No changes in CREB and VGF transcript levels were observed in all groups.Conclusions: These results suggest that crocin has antidepressant-like action by increasing CREB, BDNF and VGF levels in hippocampus.