فهرست مطالب

  • Volume:15 Issue: 1, 2020
  • تاریخ انتشار: 1399/01/30
  • تعداد عناوین: 10
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  • Moloud Kazemi, Farshid Hasanzadeh, Mohsen Minaiyan, Mina Mirian, Afsaneh Lavasanifar, Jaber Emami* Pages 1-13
    Background and purpose

    A simple, rapid, and sensitive reversed-phase high performance liquid chromatography (RP-HPLC) method based on liquid-liquid extraction was developed and validated for
    determination of docetaxel (DTX) in plasma and homogenate tissues of tumor-bearing mice. Experimental approach: Samples were spiked with celecoxib as the internal standard and separation was achieved on a μ-Bondapak C18 HPLC column. The mobile phase consisted of a mixture of acetonitrile/water (40/60 v/v) at flow rate of 1.2 mL/min and the effluent was monitored at 230 nm.

    Results

    Calibration curves were linear over the concentration range of 0.1-10 μg/mL of DTX in plasma and 0.25-50 μg/mL in tissue homogenates with acceptable precision and accuracy. The mean recoveries of the drug from plasma extraction was 94.6 ± 1.44% while those of tissue homogenates ranged from 73.5 ± 3.2 to 85.3 ± 2.8% depending on the type of tissues examined. DTX was stable in biological samples with no evidence of degradation during 3 freeze-thaw cycles and two months of storage at -70 ± 15 °C.
    The developed HPLC method was applied to quantify DTX in the mouse plasma and tissues after intravenous administration of 7.5 mg equivalent DTX/kg dose of DTX-loaded folic acid-polyethylene glycol-heparin-tocopherol (FA-PEG-HEP-CA-TOC) micelle formulation to female Balb/c mice.

    Conclusion

    A simple, sensitive, rapid, accurate, and prudent RP-HPLC method was developed, validated, and applied for DTX determination in plasma and tissues.

    Keywords: Celecoxib, Distribution, Docetaxel, HPLC, Pharmacokinetics, Tissue
  • Sompong Sansenya*, Chankan Winyakul, Kesinee Nanok, Waya S. Phutdhawong Pages 14-25
    Background and purpose

    Carbohydrate hydrolysis enzymes including α-glucosidase and α-amylase are related to type 2 diabetes mellitus. The inhibiting of these enzymes might use for type 2 diabetes
    mellitus treatment. Experimental approach: N-substituted-acetylpyrrolidine linked with -benzyl- (N-(benzyl)-2-acetylpyrrolidine (4a)) and -tosyl- (N-(tosyl)-2-acetylpyrrolidine (4b)) were synthesized and evaluated for their pharmaceutical properties against -glucosidase and -amylase and free radical scavenging activity. The structures of 4a and 4b were determined through spectral studies (1H-NMR).

    Findings /Results

    Both compounds 4a and 4b had highest inhibitory potential on -glucosidase with the IC50 values of 0.52 ± 0.02 and 1.64 ± 0.08 mM, respectively. The kinetic investigation of 4a and 4b against -glucosidase and -amylase were functioned in mixed type inhibition. Moreover, both compounds are more likely to bind with the free enzyme than the enzyme-substrate complex based on the Ki < Ki´ on the -glucosidase and -amylase enzymes. Regarding the free radical scavenging, 4a had a higher capacity than 4b with IC50 values of 1.01 ± 0.010 mM for 4a and 1.82 ± 0.048 mM for 4b.

    Conclusion and implications

     Our results indicated that a derivative of N-substitute-acetylpyrrolidine had high potential to inhibit -glucosidase and -amylase, and their free radical scavenging properties might
    be applied to the therapeutic care of patients with type 2 diabetes mellitus.

    Keywords: -Glucosidase, -amylase inhibitory activity, Diabetes type 2, Type 2 diabetes mellitus, N-acetylpyrrolidine
  • Abbas Abbas, Marziyehi Hajialyan, Leila Hosseinzadeh*, Fereshteh Jalilian, Parichehr Yaghmaei, Sahar Jamshidi Navid, Hajar Motamed Pages 26-35
    Background and purpose

    In the present study, we tried for the first time to examine whether cinnamaldehyde (CA), with herbal nature, can be co-administrated with doxorubicin (DOX, as an anticancer drug) toward U87MG glioblastoma cells to potentiate its cytotoxic effect and overcome or reduce its side effects.
    Experimental approach: The cytotoxic effect of DOX and CA, either individually or in combination,   were evaluated on U87MG cells using the MTT method. The mechanism of action was studied by investigating the mode of cell death using caspase-3 and 9 activations, mitochondrial membrane potential (MMP) as well as sub G1 analysis. The expression of apoptosis- related genes (Bcl-2 and Bax) was also examined.

    Findings /Results

    Cellular toxicity assay revealed that CA and DOX can potentially reduce the viability of U87MG cells with IC50 at 11.6 and 5 µg/mL, respectively. Exposure with the combination of CA and DOX significantly increased cytotoxic effect of DOX on U87MG cells. The results of SUBG1, MMP, and also caspase-3 and -9 activity assays, in association with the results corresponding to the Bax and Bcl-2 gene expressions, altogether revealed that CA can induce apoptosis on U87MG cells. Moreover, apoptogenic effects of DOX were found to be potentiated by CA.

    Conclusion and implications

    The results of this study revealed the promising cytotoxic and apoptogenic role of CA on U87MG cells. Additionally, our findings demonstrated that CA is able to enhance the apoptosis induced by DOX on human glioblastoma cells. Collectively, these data suggested that  co-exposure of CA and DOX could be effective for treatment of glioblastoma, but further in vivo and clinical studies are still needed to prove these results.

    Keywords: Apoptosis, Cinnamaldehyde, Cytotoxicity, Doxorubicin, U87MG
  • Gholamreza Bahrami, Seyed Shahram Miraghaee*, Bahar Mohammadi, Mohammad Taher Bahrami, Gholamreza Taheripak, Samira Keshavarzi, Atefeh Babaei, Soraya Sajadimajd, Razieh Hatami Pages 36-47
    Background and purpose

    Because of the high prevalence, diabetes is considered a global health threat. Hence, the need for effective, cheap, and comfortable therapies are highly felt. In previous study,  a novel oligosaccharide with strong anti-diabetic activity in the crude extract of Rosa canina fruits,from the rosacea family, was identified. The present study was designed to ensure its efficacy using in vivo and in vitro studies.
    Experimental approach: Crude extract and its purified oligosaccharide were prepared from corresponding herb. Adult male Wistar rats were randomly divided into four groups of 10 each, as follows: group 1, healthy control rats given only sterile normal saline; group 2, diabetic control rats received sterile normal saline; group 3, diabetic rats treated with crude extract of Rosa canina (40% w/v) by oral gavage for 8 weeks; group 4, diabetic rats treated with purified oligosaccharide of Rosa canina (2 mg/kg) by oral gavage for 8 weeks. After treatment, body weight, fasting blood glucose, serum insulin levels and islet beta-cell repair and proliferation were investigated. The possible cytoprotective action of oligosaccharide was evaluated in vitro. The effect of oligosaccharide on apoptosis and insulin secretion in cell culture media were examined. Real-time PCR was used to determine the expression level of some glucose metabolism-related regulator genes.

    Findings / Results

    In the animal model of diabetes, the insulin levels were increased significantly due to the regeneration of beta-cells in the islands of langerhans by the purified oligosaccharide. In vitro cell apoptosis examination showed that high concentration of oligosaccharide increased cell death, while at low concentration protected cells from streptozotocin-induced apoptosis. Molecular study showed that the expression of Ins1 and Pdx1 insulin production genes were increased, leading to increased expression of insulin-dependent genes such as Gck and Ptp1b. On the other hand, the expression of the Slc2a2 gene, which is related to the glucose transporter 2, was significantly reduced due to insulin concentrations.

    Conclusion and implications

    The purified oligosaccharide from Rosa canina was a reliable anti-diabetic agent, which acted by increasing insulin production in beta-cells of the islands of Langerhans.

    Keywords: Apoptosis, Cell viability, Diabetes, Insulin, Rosa canina
  • Negar Dinarvand, Hossein Khanahmad, Sayyed Mohammadreza Hakimian, Abdolkarim Sheikhi, Bahman Rashidi, and Morteza Pourfarzam* Pages 48-56
    Background and purpose

    Breast cancer (BC) is one of the major causes of female cancer-related death. It has recently been demonstrated that metabolic reprogramming including alteration in lipid metabolism is indicated in various types of cancer. The enzymes of the acyl-coenzyme A synthetase long-chain family (ACSLs) are responsible for converting fatty acids to their corresponding fatty acyl-coenzyme A esters which are essential for some lipid metabolism pathways. ACSL4 is one of the isoforms of ACSLs and has            a marked preference for arachidonic and eicosapentaenoic acids. The objective of this study was to evaluate ACSL4 expression, its prognostic significance, and its correlation with p53 tumor suppressor in BC patients.
    Experimental approach: In this study 55 pairs of fresh samples of BC and adjacent non-cancerous tissue were used to analyze ACSL4 expression, using real-time polymerase chain reaction and immunohistochemistry (IHC) staining. The expression of other studied variables was also examined using the IHC technique.

    Findings /Results

    ACSL4 expression was significantly higher in BC tissues compared to the adjacent normal tissue. This upregulation was negatively correlated with Ki-67 and age, and positively correlated  with p53 status. The correlation between ACSL4 and p53 may indicate the role of p53 in the regulation of lipid metabolism in cancer cells, in addition to its role in the regulation of ferroptosis cell death.

    Conclusion and implications

     Our results indicated that the expression of ACSL4 may be considered as a prognostic indicator and potential therapeutic target in BC. However, further studies are needed to confirm the significance of these findings

    Keywords: ACSL4, Breast cancer, p53, Tumor suppressor
  • Asie Poorassar, Mohammad Reza Shams Ardekani, Valiollah Hajhashemi*, Roja Rahimi, Mehran Mirabzadeh Ardakani, Mohammadreza Aghayeghazvini Pages 57-65
    Background and purpose

    Obesity is a global health problem and also a well-known risk for many diseases. Although some synthetic drugs have been marketed for the treatment of obesity, natural remedies may be considered as safe and cost-effective alternatives. Lac (Kerria lacca Kerr) is a product from  animal origin and is sold as seedlac or shellac. This drug is very famous among Unani practitioners for  its antiobesity effects. The aim of the present study was to evaluate the antiobesity potential of lac in rats.
    Experimental approach: The effect of lac on rats fed with a high-fat diet (HFD) was investigated  through determination of the changes in body weight, and serum levels of leptin. In addition, the effect of lac on total cholesterol, triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) was studied. Male Wistar rats (170-220 g) were divided into eight groups;  a control group with normal diet, the HFD group received a HFD, and the experimental groups received the HFD containing 0.1, 0.2, and 0.4% (w/w) of seedlac or 0.1, 0.2, and 0.4% (w/w) of shellac for 12 weeks. The body weight of each rat was measured once a week. At the end of the experiment, animals were sacrificed and serum concentrations of cholesterol, TG, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and leptin were determined.

    Results

    The study showed that seedlac and shellac significantly prevented increasing body weight and the levels of serum leptin were decreased in treated groups compared with HFD group. Also, shellac decreased TG level and both shellac and seedlac exerted a significant increase in HDL-C concentration.

    Conclusion and implications

    Lac had weight-reducing properties and could be a promising alternative for controlling obesity

    Keywords: Leptin, Obesity, Seedlac, Shellac
  • Tahereh Eteraf Oskouei*, Ayda Shafiee Khamneh, Fariba Heshmati Afshar, Abbas Delazar Pages 66-75
    Background and purpose

    Research on new drugs with a natural source and low side effects is a priority in pharmacology studies. The present study was conducted to investigate the anti-inflammatory  and anti-angiogenesis effects of bee pollen extract in the air pouch model of inflammation.
    Experimental approach: To achieve this goal, male rats were moderately anesthetized and then 20 and 10 mL of sterile air were subcutaneously injected into the intrascapular area of the back of the rat on first and third days, respectively. On day 6, inflammation was induced by intrapouch injection of carrageenan. Normal saline in the control group and bee pollen methanolic extract (50, 100, and 200 mg/pouch)   were administered at day 6, simultaneously with carrageenan, and then for 2 consecutive days only normal saline and the extracts were injected. Following sacrificing the rats the pouch was opened and the exudate volume, leukocyte accumulation, granulation tissue weight, vascular endothelial growth factor (VEGF), interleukin 1beta, and tumor necrosis factor alpha (TNF-α) concentrations were determined 3 days  after induction of inflammation. In order to investigate the angiogenesis, the granulation tissue was removed, homogenized in the Drabkin's reagent, and then centrifuged. The supernatant was filtered and the hemoglobin concentration was determined using a spectrophotometer.

    Results

    Bee pollen extract significantly decreased the exudate volume, leukocyte accumulation, granulation tissue weight, angiogenesis, VEGF, and TNF-α concentration.

    Conclusion and implications

     The findings of the current study revealed that bee pollen methanolic extract has an anti-inflammatory and anti-angiogenesis effect, which could be attributed to the inhibition of VEGF and TNF-α production in the inflammatory exudates.

    Keywords: Air pouch, Angiogenesis, Bee pollen, Inflammation, TNF-α, VEGF
  • Ehsan Malekara, Mona Pazhouhi, Iraj Rashidi, Cyrus Jalili* Pages 76-86
    Background and purpose

    Breast cancer is the most commonly occurring cancer in women around the world. Despite new advances in cancer therapy, breast cancer remains a disease with high morbidity   and mortality. Snake venom is a poisonous mixture of different molecules, such as carbohydrates, nucleosides, amino acids, lipids, proteins, and peptides. Previous studies demonstrated that some snake venoms showed in vitro anti-cancer effects. In this study, the effects of the Iranian snake  (Vipera raddei kurdistanica) venom on breast cancer cells were investigated.
    Experimental approach: The effect of increasing concentrations of snake venom on breast cell viability was assessed by trypan blue, MTT, and lactate dehydrogenase measurements. Apoptosis was detected  and quantified by fluorescent staining and DNA fragmentation assay. The expression level of some apoptotic-related genes was investigated using real-time polymerase chain reaction (RT-PCR).The Western blotting method was also used to detect the protein expression profiles in the cells.

    Findings / Results

    After treatment for 24, 48, 72, and 96 h, the cell viability was significantly reduced in a time- and dose-dependent manner (P < 0.05). The venom effect on normal breast cells was significantly smaller than cancer cells (P > 0.05). Apoptosis was significantly increased (P < 0.05). The RT-PCR and western blot data confirmed the increase of apoptosis in cells treated with venom.

    Conclusion and implications

    These data suggested that the vipera raddei kurdistanica venom had a cytotoxic property via activation of apoptosis in breast cancer cells

    Keywords: Apoptosis, Breast cancer, Cell culture, Vipera raddei kurdistanica, Snake venom
  • Bahar Baniahmad, Leila Safaeian*, Golnaz Vaseghi, Mohammad Rabbani, Behnoosh Mohammadi Pages 87-96
    Background and purpose

    Doxorubicin (DOX) is an effective agent for the treatment of many neoplastic diseases. Cardiotoxicity is the major side effect of this drug and limits its use. Vanillic acid (VA) is a pharmaceutical compound from the phenolic acids family. The present study is an attempt to investigate the possible helpful effects of VA against DOX-induced cardiotoxicity in rats.
    Experimental approach: For induction of cardiotoxicity, male Wistar rats received total of six doses of DOX (2.5 mg/kg i.p.) three times per week from days 14 to 28. Treatment groups received daily oral doses of VA (10, 20, and 40 mg/kg) two weeks before DOX injection and then plus DOX for 2 weeks. At the end of experiment, systolic blood pressure (SBP) and heart rate (HR) were detected using tail-cuff method. Lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB), serum glutamic oxaloacetic transaminase (SGOT), malondialdehyde (MDA), and ferric reducing antioxidant power (FRAP) were measured in serum samples. Troponin-I and toll-like receptor 4 (TLR4) were measured in cardiac tissue. All the measurements processed spectrophotometrically using commercial ELISA kits. Cardiac tissue was also processed for histopathological examination.
    Findings /

    Results

    Treatment with VA significantly increased SBP compared to the DOX group and restored HR near to the normal level. Administration of VA at all of doses, decreased serum levels of LDH, SGOT, CK-MB, MDA, cardiac troponin-I, cardiac TLR4 and increased FRAP value.

    Conclusion and implications

     These results suggest that VA may exert cardioprotective effects against DOX-induced cardiotoxicity by decreasing oxidative stress and biomarkers of cardiotoxicity, suppression of TLR4 signaling and consequently inflammation pathway.

    Keywords: Antioxidant, Cardiotoxicity, Doxorubicin, TLR4, Vanillic acid
  • Vajihe Akbari, Mahboubeh Rezazadeh*, Zahra Ebrahimi Pages 97-106
    Background and purpose

    Bone regeneration can be accelerated by localized delivery of statins. Here, we aimed to evaluate the effect of two thermosensitive hydrogels containing rosuvastatin (RSV) on proliferation and differentiation of human osteoblast-like MG-63 cells.
    Experimental approach: Firstly, chitosan (CTS)/glycerophosphate (GP)/gelatin (G) thermosensitive hydrogel was prepared and characterized based on rheological properties, in vitro erosion, and release pattern of RSV and then the optimized mixture was loaded with nanoparticles containing RSV(NRSV).  Secondly, the effect of NRSV-embedded in CTS/GP/G on cell viability, alkaline phosphate activity,  and cell calcification was evaluated using MG-63 cells and compared with RSV-embedded into hyaluronic acid (HA)/Pluronic® F127 (PF127) hydrogel. 

    Findings / Results

    CTS/GP mixtures with 1 and 1.5 % gelatin existing in solution with low viscosity at  4 °C were solidified at 32-34 °C while the mixture containing 2% gelatin was jellified at room temperature. The gelation times of CTS/GP/G with 1 and 1.5% gelatin were 72 and 44 s, respectively. The hydrogel containing 3% w/v NRSV was also converted to a semisolid upon increasing the temperature to 33-36 °C. Due to the higher gel strength of CTS/GP/G compared to HA/PF127 hydrogel, the release rate of RSV from the NRSV-embedded CTS/GP/G hydrogel was significantly slower than that of HA/PF127 system. As revealed by alkaline phosphatase and mineralization assays, NRSV-embedded in CTS/GP/G hydrogel had the most promotive effect on differentiation of osteoblasts among other mixtures.

    Conclusion and implication

    NRSV-embedded in CTS/GP/G hydrogel could be efficiently used in the future for bone defects such as osteoporosis and bone fractures.

    Keywords: Rosuvastatin, Thermosensitive hydrogel, Tissue engineering