Shiraz University of Medical SciencesTrends in Pharmaceutical Sciences2423-37225320190901The anti- proliferative effects of Ferulago angulata on human promyelocytic leukemia cell line (HL-60)1231304584010.30476/tips.2019.82917.1017ENZahraRezaei DezakiCellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran0000-0001-7229-6056ParinazKarimiCellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranBatoulPourgheysariMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranAminSoltaniaMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranFatemehZeilabibCellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranJournal Article20190510Aim: Ferulago angulata is a medicinal plant with bioactive compounds having antioxidant activities. F.angulata extract can be a good candidate as chemo- preventive agent against cancer cells. In this study, the pro-apoptotic activities of F.angulata were investigated on human promyelocytic leukemia cell line (HL-60).<br /> <br />Material and Methods: HL-60 cell line was cultured in RPMI 1640 medium and then treated with different concentrations of F.angulata extracts. The effect of extract on cell viability was measured by MTS assay. The apoptosis was evaluated using flowcytometry. IC50 was calculated by probit analysis and the groups were compared using Kruscal wallis test.<br /><br />Result: Our results show that F.angulata decreased cell viability in a concentration of more than 500 µg/ml with an IC5 of about 1000 µg/ml. Apoptosis was observed in all concentrations, but only was remarkable in more than 500 µg/ml. <br /><br />Conclusion: F.angulata can induce anti-proliferative activities against HL-60 cells. A complete understanding of molecular events and pharmacokinetics of the elements and clinical trials in animal models are required for dose determination and its interaction with other components of combination chemotherapy.https://tips.sums.ac.ir/article_45840_f03d2b6fa8f01fcd1211c655ff8b08ce.pdfShiraz University of Medical SciencesTrends in Pharmaceutical Sciences2423-37225320190901Periplasmic production of the recombinant eugenol synthase from Ocimum basilicum1311364579410.30476/tips.2019.83489.1027ENNedaMazareiDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.AnahitaMoradiDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.Seyyed SoheilRahmatabadiDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.ShivaHemmatiDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences,
Shiraz, Iran.Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.0000-0001-9071-9569Journal Article20190929Eugenol, the main bioactive compound of clove oil, is a simple molecule with considerable pharmacological properties, including analgesic, antimicrobial, and anti-inflammatory effects. Eugenol is synthesized in several plant species such as Ocimum basilicum (basil) through the activity of eugenol synthase enzyme. Regarding the valuable applications of eugenol as well as notable advantages of the secretory production of recombinant proteins, the excretory production of eugenol synthase has been targeted in this study. Eugenol synthase coding sequence was inserted after pelB peptide in the pET22b vector and expressed in E. coli to investigate if the secretory production of the recombinant protein is possible. Additionally, enzyme purification by Ni-NTA affinity chromatography, extraction of the enzyme from periplasmic fraction, and salting out of the enzyme secreted into the medium by ammonium sulfate precipitation were carried out. Our results showed the presence of eugenol synthase in the cytosol, periplasm, and culture medium with concentrations of about 208.8 µgml-1, 212.5 µgml-1, and 332.0 µgml-1, respectively. The results of this study are useful for further studies to produce large-scale eugenol synthase as an unlimited source of the eugenol compound.https://tips.sums.ac.ir/article_45794_4a71dd4cca90fab0c98010dddd41159b.pdfShiraz University of Medical SciencesTrends in Pharmaceutical Sciences2423-37225320190901Discovery of Potential Natural Dipeptidyl Peptidase-4 Inhibitors for Type-2 Diabetes Treatment via Structure-Based Virtual Screening1371444580410.30476/tips.2019.83480.1026ENSaraRanjbarPharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, IranMehraneMohammadabadi KamareiDepartment of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranAmirhosseinSakhtemanDepartment of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranMehdiKhoshneviszadehDepartment of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranJournal Article20190601Dipeptidyl peptidase IV (DPP-4) is a serine protease that plays a crucial role in glucose metabolism; hence, it is a significant target for type II diabetes mellitus treatment. DPP-4 inhibitors decrease glucose concentrations in such patients by preventing the rapid degradation and thereby lengthening the physiological actions of hypoglycemic incretin hormones. In this study, a structure-based virtual screening strategy was applied to search for novel natural DPP4 inhibitors. From the Supernatural database, 1856 natural structures were picked up and were subjected to molecular docking analysis. Thirteen of them were identified to form more stable complexes than the co-crystallized ligand with the DPP-4 protein. The drug-likeness and pharmacokinetic properties of the top five compounds were also predicted. It was proved that the compounds were compliant with the drug-likeness rules and possess favorable pharmacokinetic properties. The proposed natural compounds can be introduced as potential DPP-4 inhibitors that might be promising leads for further drug development.https://tips.sums.ac.ir/article_45804_5a22e0bdf4923e970d9bed512059a7e3.pdfShiraz University of Medical SciencesTrends in Pharmaceutical Sciences2423-37225320190901Expression of miR-221/222 is affected by Triclosan in MCF-7 cells1451524582510.30476/tips.2019.84087.1031ENKeivanMobiniDepartment of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranFatemehEskandariDepartment of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranGholamhossinTamaddonDiagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.AfshinMohammadi-BardboriDepartment of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.0000-0003-2203-6322Journal Article20190401Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS) is a broad-spectrum antibacterial commonly used in cosmetics, dentifrices, soap, and other consumer products. There is growing concern that estrogenic environmental compounds that act as endocrine disrupting chemicals might potentially have adverse effects on hormone-sensitive organs such as the breast. Overexpression of miR-221/222 has been observed in a number of advanced malignancies indicating that miR-221/222 could be potential therapeutic targets for epithelial cancer. In present study we investigated TCS effects on miR-221/222 expression level in breast cancer cell line MCF-7.<br />In this experimental study, we detect the expression of miR-221 and miR-222 in MCF-7 through the quantificational real time polymerase chain reaction (QRT PCR) assay. <br />Our results showed that the expression level of miR-221 was induced by TCS and expression level of miR-222 inhibited by TCS.<br />Overall, phytoestrogens and TCS may act as an estrogen receptor agonist at lower concentrations via estrogen pathway (ER) while inhibiting the growth of MCF-7 cells at higher concentrations via non-ER pathwayshttps://tips.sums.ac.ir/article_45825_a08ff91ac6b2c60fa182002f182a86e2.pdfShiraz University of Medical SciencesTrends in Pharmaceutical Sciences2423-37225320190901Citrus aurantium (bitter orange) seeds oil: pharmacognostic, anti-inflammatory and anti-nociceptive properties1531644560410.30476/tips.2019.82996.1020ENAzadehHamediMohammad M.ZarshenasDepartment of phytopharmaceuticals (Traditional Pharmacy), School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Essence of Parsiyan Wisdom Institute, Traditional Medicine and Medicinal Plant Incubator, Shiraz University of Medical
Sc0000-0002-8185-4993AkramJamshidzadehDepartment of Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-4461-7291SaeedAhmadiDepartment of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranRezaHeidariDepartment of Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-7038-9838ArdalanPasdaranMedicinal Plants Processing Research Center, Department of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranJournal Article20190801The present investigation was carried out to evaluate the pharmacognostic properties of Citrus aurantium seeds as well as its anti-inflammatory activities. The n-hexane fraction of seed oil extracted via a Soxhlet extractor and subjected to pharmacognostic assays, HPTLC and GC-MS analysis for determination of fatty acids and sterols. The possible anti-inflammatory and antinociceptive activities in rats were evaluated using formalin-induced paw licking, oedema and myeloperoxidase activity assessment. Total ash, acid insoluble and water soluble ash values were determined as 35.83 ± 4.92, 6.67 ± 2.89 and 28.33 ± 5.77 mg/g, respectively. HPTLC assessment revealed the presence of different fatty acids and steroidal triterpenes. The principal fatty acids of the seed oil were linoleic acid (C18:2, 50.10 ± 2.58 %) and Oleic acid (C18:1, 30.14 ± 0.39). Esterified (2.40 mg/g) and free β-sitosterol (32.90 mg/g), free campesterol (3.9 mg/g) and free stigmasterol (10.165 mg/g) were detected in the oil. Seed oil exhibited anti-inflammatory properties in the first and the second phases of formalin test. Also, it had anti-edematogenic effects but exerted no effects on myeloperoxidase activity.https://tips.sums.ac.ir/article_45604_a8d6e088946aab7c8de51f36ac164110.pdfShiraz University of Medical SciencesTrends in Pharmaceutical Sciences2423-37225320190901Influence of quercetin and chrysin on the intestinal permeability of paclitaxel, a substrate of P-glycoprotein and CYP3A4 using in vitro rat gut sacs1651724586610.30476/tips.2019.82814.1015ENRavindra BabuPingiliDepartment of Pharmacology, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada-520010, Andhra Pradesh, India0000-0002-6265-139XManasa AparnaKambhampatiDepartment of Pharmacology, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada-520010, Andhra Pradesh, IndiaSowjanyaVakaDepartment of Pharmacology, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada-520010, Andhra Pradesh, IndiaNaveen BabuKilaruDepartment of Pharmaceutics and Pharmaceutical Biotechnology, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada-520010, Andhra Pradesh, IndiaJournal Article20190802P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) play a significant role in the disposition and elimination of drugs. The objective of this study was to investigate the mechanism underlying the interaction between paclitaxel (substrate of P-gp and CYP3A4) and quercetin and chrysin (known modulator of P-gp and CYP3A4) using everted gut sacs in vitro models. Rat everted and non-everted gut sacs (NEGS) are simple and useful in vitro models to investigate the role of P-gp and CYP3A4 in drug disposition. NEGS were used to evaluate the transport of paclitaxel from mucosal to serosal (M-to-S) side of the intestine. NEGS were loaded with 1mL of modified Krebs-Ringer bicarbonate (KRB) buffer containing paclitaxel (50μg/mL) in the presence or absence of known P-gp and CYP3A4 inhibitors (quercetin and chrysin).The paclitaxel levels in incubated samples were dteremined by UV-spectrophotometer at 227 nm. The same experiment was repeated with everted gut sacs (EGS) to study the transport of paclitaxel from serosal to mucosal (S-to-M) side of the intestine. The apparent permeability coefficient (Papp), efflux ratio and net efflux were determined. In vitro study results showed that the Papp, net efflux and efflux ratio of paclitaxel were significantly increased by quercetin and chrysin. The present study results revealed that quercetin and chrysin enhanced the intestinal absorption of paclitaxel by inhibiting its absorption via P-gp and/or the CYP3A4-mediated biotransformation in intestine.https://tips.sums.ac.ir/article_45866_215fee165913b7ece381bb66225fc1de.pdf