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Background & objectives: The purpose of this study was to show the dose response relationship of anti-inflammatory effect of methylsulfonylmethane (MSM) on carrageenan induced rat paw edema as an acute model of inflammation.
Methods: A total of 54 male, Sprague-Dawley rats, weighing 180-190 g, were used. One hundred, 200, 400, 800 and 1200 mg/kg of MSM were administered intraperitoneally to the rats 30 minutes before induction of paw edema with injection of 0.1% carrageenan. Diclofenac was used as a control drug. Rats were divided into three groups: MSM, diclofenac and normal saline, and their paw tissue were collected for the study of inflammatory and oxidative markers (MDA, GSH, TNF-α and IL-1 β). The relationship between the different concentrations of MSM and decrease in rat paw edema was calculated using a simple Emax model.
Results: the ED₅₀ value for effect of MSM on carrageenan induced rat paw edema was 193±9.7 mg/kg. A significant reduction in paw edema following administration of MSM at 200, 400, 800 and 1200 mg/kg was observed, but statistical analysis did not reveal any significant reduction in paw edema after administration of 100 mg/kg. MSM did not show statistically significant difference from control group in tissue level of GSH, but it was able to decrease MDA level significantly. MSM was able to significantly alleviate IL-1 β and TNF-alpha tissue levels.
Conclusion: The recommended anti-inflammatory dosing range of MSM is 200-800 mg/kg for pharmacological studies in rats and the average appropriate dose is 400 mg/kg. Also, it seems that anti-inflammatory effect of MSM is more profound than its anti-oxidant effects.
 

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Background & objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) - induced peptic ulcer disease is a common gastrointestinal disorder affecting many people worldwide. Rosa canina L. is a member of Rosa species that has been widely used as an herbal medicine in many countries. Rosa canina has therapeutic effects against various disorders through its antioxidant, anti-inflammatory and cytoprotective properties. The aim of the present study was to evaluate the potential beneficial effect of Rosa canina on indomethacin-induced ulceration in mice.
Methods: Experiments were performed on male Swiss albino mice. Indomethacin (80 mg/kg, orally) was used to induce gastric ulceration. The extract of Rosa canina fruits (200 and 400 mg/kg/day) was given orally five days before the administration of indomethacin. Normal mice were used as a normal control group.
Results: Macroscopic evaluation of gastric mucosa revealed that indomethacin administration (80 mg/kg) produced apparent gastric mucosal ulcers, while pretreatment with Rosa canina (200 and 400 mg/kg) effectively protected gastric mucosa against indomethacin induced ulcers. Rosa canina significantly increased the level of glutathione (GSH) and decreased the levels of malondialdehyde (MDA) and myeloperoxidase (MPO) in the gastric tissues compared with those in the control group.
Conclusion: Oral treatment with the Rosa canina fruit extract decreased the gastric ulcer induced by indomethacin through antioxidant and anti-inflammatory mechanisms

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Background & objectives: Cancer is the leading cause of death worldwide. In this study, the cytotoxic effect of hydroalcoholic extract of Colutea persica leaf and its synergic effect with doxorubicin were investigated on MCF-7, LNCaP and SKM (as control) cell lines.
Methods: Hydroalcoholic leaf extract of Colutea persica was prepared using maceration method and ethanol 70%. Breast cancer (MCF7), prostate (LNCaP) and fibroblast (SKM) cell lines were cultured in microplates (96 wells) and exposed to various concentrations (10, 7.5, 5, 2.5, 1.25, 0.625, 0.312 and 0.156 mg/ml) of plant extract and doxorubicin (20, 80, 320 and 640 nM) solution. The synergistic effect of 20 nanomol of drug and 0.156 mg / ml of the plant extract was investigated. MTT assay was employed to evaluate the cytotoxic effects of the extract on cell lines at different time intervals (24, 48 and 72 hours). Staining with annexin V and propidium iodide (PI) was used to identify different types of cell death either necrosis or apoptosis.
Results: The plant extracts had cytotoxic effect and cell viability rate was lower than fibroblasts. At different times, the concentration of 10 mg /ml of the extract showed the most growth inhibition of breast and prostate cell lines. The combination effect of plant extract with doxorubicin on cells was not significant (p<0.01). The Annexin V/PI flow cytometry results showed that the percentage of initial apoptosis, delayed apoptosis and necrosis in treated cells increased compared to untreated cell.
Conclusion: Hydroalcoholic extract of Colutea persica leaf inhibits the growth of cancer cells and induce apoptosis in breast and prostate cancer cells.

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Background & objectives: Paraquat is a toxic herbicide that is widely used in many countries. Paraquat selectively accumulates in the lung tissue and leads to severe pulmonary injury through the oxidative and inflammatory processes. The plant Rosa canina L. has been used for long years as an herbal medicine throughout the world. Rosa canina L. is a member of Rosacea family and shows therapeutic effects against numerous disorders by its antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the antioxidant effect of Rosa canina fruits on the paraquat induced lung injury in a mouse model.
Methods: Animal experiments were performed on male NMRI mice. Paraquat was injected at a single dose (20 mg/kg, ip) to induce pulmonary damage in mice. The extract of Rosa canina fruits (200 and 400 mg/kg/day, orally) administered by gavage for four days after the injection of paraquat. The treated mice were compared to normal mice as a control group. At the end of the experiment, lung tissue samples were collected for biochemical analysis.
Results: The results showed that administration of paraquat caused an oxidant-antioxidant imbalance in the lung tissue. However, treatment with Rosa canina increased the levels of glutathione (GSH) and catalase (CAT) antioxidants and decreased the levels of malondialdehyde (MDA) and myeloperoxidase (MPO) in the lung tissues compared with those in the paraquat group.
Conclusion: Treatment of paraquat-exposed mice with the extract of Rosa canina fruits improved oxidant-antioxidant balance in the lung tissue of mice. In other words, the present study demonstrated that Rosa canina has remarkable antioxidant effects against paraquat induced oxidative damage.
 

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Background & objectives: Drug-repurposing is the study on application of existing drugs for treatment or control of other diseases. Major advantage of the technique relies on a nominated drug molecule that is applied for pharmacodynamics optimization due to lack of serious pharmacokinetics challenges. According to the importance of the subject, a present contribution has been dedicated to the in-silico analysis of a few drug classes with the aim of achieving potential anti-leishmanial pharmacophores.   
Methods: 3D structure of protein targets within leishmania parasite were retrieved from Brookhaven Protein Data Bank (PDB) on the basis of literature reports to evaluate the related complexes with drugs via molecular docking. Qualitative and quantitative analysis of drug-target interaction patterns in docked complexes offered drugs with higher binding affinities toward targets and finally structural patterns or hypothetical anti-leishmanial pharmacophores were proposed with regard to the top-ranked pharmaceutical compounds.
Results: Highest free binding energy could be estimated for Nateglinide in binding to farnesyl diphosphate synthase (ΔG_b -13.30 kcal/mol). Among steroids, Norgestrel synthase (ΔG_b -9.48 kcal/mol) and Testosterone synthase (ΔG_b -8.05 kcal/mol) exhibited higher enzyme binding affinities and Arg82 was a key residue in making hydrogen bonds. Within fused tricyclic structural patterns, mirtazapine exhibited highest binding affinity to deoxy uridine triphosphate (ΔG_b -8.64 kcal/mol). In Carbamazepine, amide substituent of the central ring facilitated the formation of two effective hydrogen bonds with Gln21 and Asn25 in deoxy uridine triphosphate. 
Conclusion: On the basis of obtained results for steroids and fused tricyclic scaffolds, it will be possible to design molecules that can inhibit several pathogenic targets simultaneously.

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Background & objectives: Due to the existence of various issues and limitations associated with traditional buccal drug delivery systems such as the disability to consume food whilst using topical drugs in the mouth cavity, unpredictable drug release profile, undesirable taste, low patient adherence to therapy, and accelerated drug removal with saliva, these conventional methods are now rapidly becoming replaced with oral thin films as more precise and novel oral drug delivery platforms. The current study aims to discuss the design and characterization of betamethasone-loaded oral thin films with the aim of improved drug delivery in mouth cavity diseases.
Methods: In this study, oral thin films with and without betamethasone were fabricated through the solvent casting method as a common, fast, and affordable technique prior to being evaluated for different physiochemical characteristics including weight, width, surface pH, disintegration period in vitro conditions, and swelling rates as well as drug release profiles at different intervals.
Results: Obtained oral films were demonstrated to possess adequate homogeneity, flexibility, and mechanical resistance. Accordingly, the average surface pH for films without and with betamethasone was equal to 6.75 and 6.66, respectively, which are in notable compatibility with the neutral pH of the oral cavity. Betamethasone-loaded films’ disintegration duration appeared to be superior to that of films without betamethasone and was in close correlation with their higher swelling rates. Further experiments revealed 25-30% drug release in the initial 20 minutes, followed by more than 90% betamethasone release in 360 minutes in a sustained manner.
Conclusion: These results are indicative of betamethasone oral films’ satisfactory physiochemical properties and potential applicability as a sufficient oral drug delivery platform in mouth cavity diseases such as oral lichen planus or recurrent mouth sores. By sticking to the mouth mucosa, these films can significantly reduce drug removal with saliva and thus ameliorate sufficient delivery of therapeutic agents to specific mouth lesions. Moreover, they can alleviate some of the issues and limitations of traditional topical oral drug delivery and improve treatment or control of disease symptoms.
 

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