Publications by authors named "Mustafa Ghanadian"

54 Publications

Novel 16,17-epoxy-23-methylergostane derivative from , a soft coral from the Persian Gulf, with apoptotic activities against breast cancer cell lines.

Nat Prod Res 2021 Feb 22:1-10. Epub 2021 Feb 22.

Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

The steroidal and terpenoidal composition of was investigated by chromatography methods. One new (), and four known [gorgasta-5-en-3β-ol (), ergosta-5-en-3β-ol (), ergosta-5, 22()-dien-3β-ol (), 5,8-epidioxy-5α, 8α-ergosta-6, 22E-dien-3β-ol ()] steroids, in addition to one known diterpenoidal alkaloid [sinulasulfone ()] isolated for the first time from . If we named the 23-methylergostane core structure as sinustane, new compound () was elucidated as 16α,17α-epoxysinusta-5-en-3β-ol-20β-yl sulfate based on NMR and HR Mass data. It was submitted for cytotoxic activity evaluation against MCF-7 and MDA-MB-231 cell lines using MTT assay. Apoptosis induction was checked by flow cytometry (annexin V/propidium iodide) staining. To determine the production of reactive oxygen species, and the mitochondrial transmembrane potential (ΔΨm), the DCFDA, and JC-1 probes were used in this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2021.1887178DOI Listing
February 2021

15-Hydroxy-8(17),13(E)-labdadiene-19-carboxylic acid (HLCA) inhibits proliferation and induces cell cycle arrest and apoptosis in ovarian cancer cells.

Life Sci 2021 Feb 29;267:118981. Epub 2020 Dec 29.

Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Aim: 15-Hydroxy-8(17),13(E)-labdadiene-19-carboxylic acid (HLCA) isolated from Juniperus foetidissima, has been recently identified as an antiproliferative agent; however, the molecular basis of antiproliferative effects of HLCA remains unknown. To investigate it, the current study has emphasized the hypothesis that HLCA induced cell death is a consequence of intracellular reactive oxygen species (ROS) production followed by cell cycle arrest and apoptosis.

Main Methods: Human ovarian OVCAR-3 and Caov-4 cells were treated with various concentrations of HLCA (48 h) and the measurement of intracellular ROS was considered. Then, the potential of HLCA in promoting apoptosis was investigated via flow cytometry, western blot, and caspase activity assay. Also, the inhibitory effect of HLCA on the cell cycle was evaluated using flow cytometry and western blot analysis.

Key Findings: We found intracellular (ROS) accumulation in HLCA-treated cells. Subsequent observation of the increment in pro-apoptotic Bax as well as the decrement in antiapoptotic Bcl2 revealed that the HLCA-induced cytotoxicity may be triggered by the intrinsic pathway of apoptosis. Our subsequent experiments suggested that caspase-9 and -3 were activated and led the cells to apoptosis during the process. Cell cycle disruption at the G1 phase via down-regulation of cyclin D1 and Cyclin-dependent kinase 4 (CDK4) was another proved mechanism by which HLCA exerts its antiproliferative effects on the ovarian cell lines, OVCAR-3 and Caov-4, especially at relatively lower concentrations.

Significance: This is the first study that reveals the apoptotic effects of HLCA, suggesting its therapeutic potential as an effective anti-tumor agent. However, further in vivo studies are required to confirm these effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118981DOI Listing
February 2021

New Diterpene Compound from ., 3,7,14,15-Tetraacetyl-5-Propanoyl-13(17)-Epoxy-8,10(18)-Myrsinadiene, Inhibits the Growth of Ovarian Cancer Cells by Promoting Mitochondrial-Mediated Apoptosis.

Nutr Cancer 2020 Sep 16:1-9. Epub 2020 Sep 16.

Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences and Pharmaceutical Sciences Research center, Isfahan University of Medical Sciences, Isfahan, Iran.

Ovarian cancer due to the difficulties in early clinical diagnosis and absence of successfull treatment has poor prognosis and high mortality among all gynecological malignancies. Many evidence has revealed that plants of the Euphorbiaceae family are precious sources of novel bioactive compounds with anti-tumor activities. 3,7,14,15-tetraacetyl-5-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene (TPEM) is a new myrsinane-type diterpene isolated recently by our group from aerial parts of and the present study was aimed to explore its inhibitory effects on growth of two human ovarian cancer cells, OVCAR-3, and Caov-4. The obtained results indicated that growth of OVCAR-3 and Caov-4 cells was significantly inhibited by TPEM in a dose-dependent manner, with the IC50 values of 41.27 ± 1.52 and 36.44 ± 2.41 µM, respectively. Furthermore, using Annexin V-FITC and PI staining it was confirmed that the induced cell death was mainly mediated through apoptotic pathway. Further observations such as decrease in the mitochondrial membrane potential (ΔΨm), increase in the activity of caspase-3 and elevation of the Bax/Bcl-2 ratio suggested the role of mitochondria in the induction of apoptosis by TPEM. ROS level was also remarkably increased in OVCAR-3 and Caov-4 cells in response to TPEM treatment. In conclusion, these findings provide first evidences about potential anticancer properties of TPEM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01635581.2020.1820049DOI Listing
September 2020

Inhibitors of α-Synuclein Fibrillation and Oligomer Toxicity in : The All-Pervading Powers of Flavonoids and Phenolic Glycosides.

ACS Chem Neurosci 2020 10 22;11(19):3161-3173. Epub 2020 Sep 22.

Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, DK- 8000 Aarhus C, Denmark.

There is an intense search for natural compounds that can inhibit the oligomerization and fibrillation of α-synuclein (α-Syn), whose aggregation is key to the development of Parkinson's disease (PD). is a medicinal herb widely used in Middle Eastern food, ceremonies, and perfumes. The herb is known to contain many different polyphenols. Here we investigated the existence of α-Syn fibrillation inhibitors in extract. Different HPLC fractions of the extract were assessed in α-Syn fibrillation and toxicity assays. The most active fractions led to the formation of more α-Syn oligomers but with less toxicity to SH-SY5Y cells, according to MTT and LDH assays. LC-MS analysis identified gallic acid, kaempferol 3-glucoside, kaempferol-3-O-β-rutinoside, and quercetin which were subsequently shown to be strong α-Syn fibrillation inhibitors. Our results highlight the benefits of extract to combat PD at the population level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acschemneuro.0c00528DOI Listing
October 2020

Effects of Extract on Spatial Memory Impairment and Neuronal Differentiation in Rat Model of Alzheimer's Disease.

Adv Biomed Res 2020 22;9:17. Epub 2020 Apr 22.

Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in the older population and characterized by progressive memory and cognitive impairment. , a traditional medicinal herb, has analgesic, sedative, and anti-inflammatory effects and also used to increase memory in Islamic traditional medicine. This study was designed to consider the effects of extract on memory impairment and neurogenesis in the Beta-Amyloid rats' model.

Materials And Methods: Forty-two male Wistar rats were randomly divided into six groups ( = 7) for the evaluation of baseline training performance in the Morris water maze test. Then, amyloid-beta (Aβ1-42) was injected in animal hippocampal CA1 bilaterally in four groups. The first probe trial was performed 21 days after Aβ injection. Then, 250, 500, and 750 mg/kg of extract were administered to three Aβ-injected groups for 1 month; after that, the second probe trial was performed, and rats were sacrificed after 28 days of the second probe trial. The neurogenesis was detected in the hippocampus, by immunohistochemical staining.

Results: This study showed that spatial memory increased in the behavioral test in AD treated group with extract, compared with the AD group ( = 0.02). Immunohistochemical staining revealed that neuronal differentiation has been occurred in the hippocampus in the AD-treated group with extract compared with the AD group ( = 0.01).

Conclusions: This study showed that extract, repaired spatial memory impairment in the Aβ rats, through increased neurogenesis in the hippocampus, which could be related to the flavonoid components in the extract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/abr.abr_173_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282694PMC
April 2020

Cycloarta-23-ene-3beta,25-diol a pentacyclic steroid from Euphorbia spinidens, as COX inhibitor with molecular docking, and in vivo study of its analgesic and anti-inflammatory activities in male swiss mice and wistar rats.

Prostaglandins Other Lipid Mediat 2020 10 4;150:106473. Epub 2020 Jul 4.

Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Background And Aims: Euphorbia is a large genus of flowering plants. In Iran, some plants of this family have been used in the treatment of inflammatory disorders and also to relieve back pain. Euphorbia spinidens is a rich source of Cycloarta-23-ene-3beta,25-diol. Cycloartane structures are the starting material for the synthesis of plant steroids, and the aim of this study is to demonstrate COX inhibitory activity, molecular docking and in vivo approach of anti-inflammatory activity of cycloartane compound isolated from Euphorbia spinidens.

Material And Methods: Plant material was extracted with acetone-chloroform and submitted to column chromatography for fractionation. Based on preliminary H-NMR spectra, cycloartane fraction was selected and purified by repeated recycle HPLC system. The structure and purity of compound were determined by H and C-NMR, HPTLC, and mass spectra. Inhibitory activities of the tested compounds on COX-1 and COX-2 were evaluated by a colorimetric COX (ovine) inhibitor screening method. Vero cells were used to assess the toxicity against the normal cells, and calculate the selectivity index. COX inhibitory activity results were evaluated and confirmed by molecular docking experiments. In the in vivo approach, analgesic activity was assessed by acetic acid-induced abdominal writhing and formalin tests. Croton oil-induced ear edema in mice and carrageenan-induced rat paw edema in rats were used to evaluate anti-inflammatory activity. Pain tests were carried out on male Swiss mice (25-35 g). Male Wistar rats (160-200 g) were used for the carrageenan test.

Results: Cycloart-23-ene-3β,25-diol showedin vitro cyclooxygenase 1 and 2 inhibitory activities with more selectivity for COX-2. Molecular docking by predicting binding energies in COX protein receptors confirmed in vitro COX inhibitory results, and determined the best position for ligand in COX receptors along with its residue interactions in receptor pockets, which must be considered for designing of their inhibitors. In the in vivo studies, cycloartane inhibited significantly acetic acid-induced abdominal contractions and formalin-induced licking behavior at a dose of 200 mg/kg. The same dose reduced croton oil ear edema in mice and carrageenan-induced paw edema in rats.

Conclusion: Therefore, according to these findings, cycloart-23-ene-3beta,25-diol showed promising analgesic and anti-inflammatory effects with low toxicity against normal cells and can be suggested as a template lead for designing anti-inflammatory compounds with good selectivity index, and potency for COX-2 inhibitory activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prostaglandins.2020.106473DOI Listing
October 2020

Melatonin and calcium modulate the production of rosmarinic acid, luteolin, and apigenin in Dracocephalum kotschyi under salinity stress.

Phytochemistry 2020 Sep 25;177:112422. Epub 2020 Jun 25.

Department of Plant Biology, Faculty of Biological Science, Tarbiat Modares University (TMU), POB141115-154, Tehran, Iran. Electronic address:

Melatonin (Mel) and calcium (Ca) have a regulatory role in the induction of specialized metabolites production and defensive responses against stresses. Therefore, in this study, the effects of Mel and Ca and the possible relationship between them in the increase of the production of phenolic compounds in Dracocephalum kotschyi Boiss. under both control and salinity stress conditions were investigated. The results showed that 75 mM NaCl reduced shoot dry biomass but elevated HO content, electrolyte leakage (EL) level, total phenolic and flavonoid contents (TPC and TFC), and DPPH scavenging capacity. Salinity stress also upregulated gene expression of phenylalanine ammonia-lyase (PAL) and rosmarinic acid synthase (RAS), as well as the activities of PAL and tyrosine ammonia-lyase (TAL) enzymes. Pre-treatment of the plants with CaCl and Mel affected these attributes in a dose-dependent manner. Application of 5 mM Ca and 100 μM Mel improved shoot dry biomass and reduced the level of EL and HO content but enhanced TPC and TFC, DPPH scavenging capacity, PAL and TAL activities, PAL and RAS transcripts, and content of rosmarinic acid (RA), luteolin flavone (LF) and apigenin flavone (AF) under salinity stress. Pre-treatment of D. kotschyi with lanthanum chloride (LaCl) as a plasma membrane channel blocker, ethylene glycol tetra-acetic acid (EGTA) as a Ca chelator and trifluoperazine (TFP) as a calmodulin (CaM) antagonist, impaired Mel effects on the above attributes under salinity stress. In contrast, pre-treatment with p-chlorophenylalanine (p-CPA), as an inhibitor of Mel biosynthesis, did not impair the impacts of Ca on the production of phenolic compounds in salt-exposed plants. These results suggested that the effect of Mel on the induction of phenolic compounds production requires the influx of extracellular Ca into the cells and is dependent on Ca/CaM signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phytochem.2020.112422DOI Listing
September 2020

Kopetdaghinanes, pro-apoptotic hemiacetialic cyclomyrsinanes from Euphorbia kopetdaghi.

Fitoterapia 2020 Oct 26;146:104636. Epub 2020 May 26.

Department of Clinical Biochemistry, School of Pharmacy & Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

Euphorbia kopetdaghi grows wild in the Northeast parts of Iran. Phytochemical study of its aerial parts led to the isolation of two undescribed cyclomyrsinol macrocyclic diterpenes with a new tetrahydrofuran oxidation pattern containing a hemiacetal group named: kopetdaghinane A and B. The structure of the isolated compounds was elucidated by extensive spectroscopic methods. Cytotoxic activity of kopetdaghinane A was evaluated using standard MTT assay against MCF-7 breast cancer and OVCAR-3 ovary cells. HUVEC cells were used as a normal cell line for calculation of the selectivity index. The MTT showed cyclomyrsinol diterpene has a significant cytotoxic effect with good selectivity indexes against both cell lines but with more selectivity against MCF-7 cells. Apoptosis induction by cyclomyrsinol treatment was confirmed by annexin V-FITC/PI staining, and caspase-6 activation. Western blot analysis showed that the expression of Bcl-2 was noticeably decreased in response to kopetdaghinane A treatment, while the expression of Bax protein was increased. Moreover, the apoptotic effect of cyclomyrsinol was shown to be related to ROS production, and loss of mitochondrial membrane potential (ΔΨm). Taken together, these results showed that kopetdaghinane A inhibits the growth of MCF-7 breast cancer cells through the activation of the mitochondrial apoptotic pathway and may be considered as an investigational compound in breast cancer preclinical study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fitote.2020.104636DOI Listing
October 2020

Jatrophane and rearranged jatrophane-type diterpenes: biogenesis, structure, isolation, biological activity and SARs (1984-2019).

Phytochem Rev 2020 Apr 13:1-72. Epub 2020 Apr 13.

2National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677 USA.

Diterpene compounds specially macrocyclic ones comprising jatrophane, lathyrane, terracinolide, ingenane, pepluane, paraliane, and segetane skeletons occurring in plants of the Euphorbiaceae family are of considerable interest in the context of natural product drug discovery programs. They possess diverse complex skeletons and a broad spectrum of therapeutically relevant biological activities including anti-inflammatory, anti-chikungunya virus, anti-HIV, cytotoxic, and multidrug resistance-reversing activities as well as curative effects on thrombotic diseases. Among macrocyclic diterpenes of , the discovery of jatrophane and modified jatrophane diterpenes with a wide range of structurally unique polyoxygenated polycyclic derivatives and as a new class of powerful inhibitors of P-glycoprotein has opened new frontiers for research studies on this genus. In this review, an attempt has been made to give in-depth coverage of the articles on the naturally occurring jatrophanes and rearranged jatrophane-type diterpenes isolated from species belonging to the Euphorbiaceae family published from 1984 to March 2019, with emphasis on the biogenesis, isolation methods, structure, biological activity, and structure-activity relationship.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11101-020-09667-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152985PMC
April 2020

A new sesquiterpenoid from the shoots of Iranian Daphne mucronata Royle with selective inhibition of STAT3 and Smad3/4 cancer-related signaling pathways.

Daru 2020 Jun 5;28(1):253-262. Epub 2020 Apr 5.

Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

Purpose: Daphne mucronata Royle grown in Iran has shown anticancer activities against different cancer cell lines. Therefore, within this study, we investigate the phytochemical pattern of this plant.

Method: Phytochemical investigation was done using standard column chromatography system: The structures were recognized by the interpretation of one and two-dimensional nuclear magnetic resonance (NMR) spectra and the help of High-Resolution Electrospray Ionization Mass spectroscopy (HR-ESIMS) and Infrared spectroscopy (IR) data. Stereochemistry was determined using 2D and 3D NOESY, and comparison of coupling constant values with literature. The absolute configuration was determined and confirmed using specific rotation and electronic circular dichroism experiments. Cytotoxicity was done against HeLa cells by standard MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Luciferase assay was used to check if the compounds can inhibit the activation of cancer-related signaling pathways. Molecular docking simulation was done for biological activity evaluation and to examine the interaction of the ligand with each of the proteins.

Results: A new sesquiterpenoid, 4,11(12)-guiadiene-1-ol-3-one (4), together with eight specialized metabolites, betulinic acid (1), coniferyl aldehyde (2), oleanolic acid (3), daphnetoxin (5), apigenin (7), syringin (8), and genkwanol A (9) were isolated and reported for the first time from the shoots of the plant. Compound 4 as an undescribed compound was submitted for cytotoxicity assay and showed moderate activity with the IC value of 51.3 ± 4.2 μM against HeLa cancer cells. It showed selective inhibition of Interleukin-6 mediated signal transducer and activator of transcription 3 pathway (STAT-3/ IL-6), and Smad protein / transforming growth factor beta (TGF-β) transcription factors when screened through an array of cancer signaling pathways. Molecular docking confirmed biological tests and showed the interaction with STAT3 and Smad proteins.

Conclusion: An undescribed sesquiterpenoid: 4,11(12)-guiadiene-1-ol-3-one in addition to eight known compounds were isolated. The new sesquiterpene was evaluated for the luciferase assay on 14 main cancer-related signaling pathways and showed selective inhibition of STAT3/IL6, and Smad/ TGF-β transcription factors. Molecular docking simulation showed more interactions with STAT3 than Smad, which confirms better interaction of compound 4 with STAT3 than Smad proteins. Graphical abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40199-020-00336-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214574PMC
June 2020

Design, Formulation, and Physicochemical Evaluation of Vaginal Cream Containing , and extracts for Prevention and Treatment of Trichomoniasis.

Int J Prev Med 2019 9;10:179. Epub 2019 Oct 9.

Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Trichomoniasis is a common sexually transmitted disease that is caused by infection with protozoan parasite called . Metronidazole is the drug of choice for the treatment of this infection. In this study, design, formulation, and physicochemical evaluation of vaginal cream containing , and extracts for the prevention and treatment of trichomoniasis has been investigated.

Methods: Ethyl acetate extract of leaves, water fraction of root, and hydroalcoholic extract of leaves was prepared and used for anti-trichomonas experiments. Then, based on results, different formulations of vaginal cream containing mixed extracts were prepared and physicochemical evaluation was conducted. In the next step, anti-trichomonas effect of selective formulation was tested .

Results: The mixed concentrates containing 2.5 mg/ml , 0.06 mg/ml , and 1 mg/ml showed 100% growth inhibition (GI) during 24 h. Furthermore, the mixture containing 1.25 mg/ml , 0.03 mg/ml , and 0.5 mg/ml showed 92% GI in the first 24 h. The selective formulation passed all of physicochemical test and also showed 100% GI for anti-trichomonas experiments in the first 24 h.

Conclusions: The mixed concentrates containing 2.5 mg/ml , 0.06 mg/ml of , and 1 mg/ml of are the mixture which showed the highest percentage of GI (100%) after 24 h. The selective formulation of vaginal cream containing this mixture of extracts was detected 100% GI in the first 24 h.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijpvm.IJPVM_525_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826777PMC
October 2019

Therapeutic effects of Cyperus rotundus rhizome extract on memory impairment, neurogenesis and mitochondria in beta-amyloid rat model of Alzheimer's disease.

Metab Brain Dis 2020 03 16;35(3):451-461. Epub 2019 Nov 16.

Departments of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

Alzheimer's disease (AD) is a progressive neurodegenerative disturbance leading to memory deficit, cognitive decline, and behavioral disturbance. Deposition of Amyloid beta plaques, neurofibrillary tangle and mitochondrial impairment are common neuropathological signs in AD. In this study, the effect of standardized Cyperus rotundus(C. rotundus) extract in three different doses of 250, 500, and 750 mg/kg on memory, neurogenesis and mitochondrial mass in the beta amyloid rat model was assessed. For this purpose, 42 male Wistar rats were randomly divided into six groups (n = 7) to evaluate baseline training performance in Morris water maze test. Amyloid beta (Aβ) was injected in animal hippocampal CA1 bilaterally in four groups. After 21 days, a decrease was observed in spending time in target quadrant in the first probe trial in Aβ injected groups. Following that, 250, 500, and 750 mg/kg of C. rotundus extracts were administered to three out of four groups for a period of one month. BrdU (Bromodeoxyuridine) was intraperitoneally injected in all groups on the last 7 days of treatment. Then, 28 days after the last BrdU injection, the second probe trial was run, and rats were sacrificed. The neurogenesis and mitochondrial distribution were detected in hippocampus, by immunohistochemical staining. At last, it was observed that C. rotundus, almost recovered memory impairment, in addition to increasing in mitochondrial mass in CA1 and neurogenesis in dentate gyruse in the beta-amyloid rat model of Alzheimer's disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11011-019-00493-2DOI Listing
March 2020

Sesquiterpene lactones from shoot culture of with cytotoxicity against prostate and breast cancer cells.

Res Pharm Sci 2019 Aug;14(4):329-334

Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

Plant tissue culture is used to grow plant cells, tissues, or organs under sterile and determined conditions on culture media. It is alternative to traditional vegetative propagation, and is applied as an effective technology for the production of valuable secondary metabolites. The () was obtained from shoot culture grown on MS (Murashige and Skoog 1962) medium. Shade-dried aerial parts of grown (50 g) were extracted with dichloromethane-acetone (90:10). The extract was submitted for isolation to sephadex gel chromatography and preparative thin layer chromatography, which resulted in identification of one known eudesmanolide named artemin or 2,5-dihydroxy-12, 6-eudesmanolide-4(15)-en for the first time in this plant. In cell cytotoxicity test, artemin showed cytotoxic activity against DU-145,LNCaP prostate cancer, and MCF-7 breast cancer cells with IC values of 82.2 ± 5.6, 89.1 ± 6.3 and 111.5 ± 6.7 μM , respectively. Artemin was more active against prostate cancer cells with approximately same cytotoxicity against LNCaP androstane dependent cells and DU 145 which is androstane independent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1735-5362.263557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714112PMC
August 2019

Centaurea cyanus extracted 13-O-acetylsolstitialin A decrease Bax/Bcl-2 ratio and expression of cyclin D1/Cdk-4 to induce apoptosis and cell cycle arrest in MCF-7 and MDA-MB-231 breast cancer cell lines.

J Cell Biochem 2019 10 3;120(10):18309-18319. Epub 2019 Jun 3.

Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, I.R. Iran.

Natural products are considered recently as one of the source for production of efficient therapeutical agents for breast cancer treatment. In this study, a sesquiterpene lactone, 13-O-acetylsolstitialin A (13ASA), isolated from Centaurea cyanus, showed cytotoxic activities against MCF-7 and MDA-MB-231 breast cancer cell lines using standard 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To find the mechanism of action of cytotoxicity, annexin V/propidium iodide (PI) staining was performed for evaluation of apoptosis. This process was further confirmed by immunoblotting of anti- and proapoptotic, Bcl-2 and Bax, proteins. Cell cycle arrest was evaluated by measurement of fluorescence intensity of PI dye and further confirmed by immunoblotting of Cdk-4 and cyclin D1. Mitochondrial transmembrane potential (ΔΨm) and generation of reactive oxygen species (ROS) were measured using the JC-1 and DCFDA fluorescence probes, respectively. These experiments showed that 13ASA is a potent cytotoxic agent, which activates apoptosis-mediated cell death. In response to this compound, Bax/Bcl-2 ratio was noticeably increased in MCF-7 and MDA-MB-231 cells. Moreover, 13ASA induced cell cycle arrest at subG1 and G1 phases by decreasing protein levels of cyclin D1 and Cdk-4. It was done possibly through the decrease of ΔΨm and increase of ROS levels which induce apoptosis. In conclusion, this study mentioned that 13ASA inhibit the growth of MCF-7 and MDA-MB-231 breast cancer cell lines through the induction of cell cycle arrest, which triggers apoptotic pathways. 13ASA can be considered as a susceptible compound for further investigation in breast cancer study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.29141DOI Listing
October 2019

Quercetin promotes learning and memory performance concomitantly with neural stem/progenitor cell proliferation and neurogenesis in the adult rat dentate gyrus.

Int J Dev Neurosci 2019 May 26;74:18-26. Epub 2019 Feb 26.

Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

The decline in neurogenesis is a very critical problem in Alzheimer disease. Different biological activities have been reported for medicinal application of quercetin. Herein, we investigated the neurogenesis potential of quercetin in a rat model of Alzheimer's disease induced by amyloid-beta injection. Rats were randomly divided into Control, Alzheimer + Saline and Alzheimer + Quercetin groups. Following the administration of Amyloid-beta, rats in the Alzheimer + Quercetin group received 40 mg/kg/day quercetin orally for one month. Our data demonstrated amyloid-β injection could impair learning and memory processing in rats indicated by passive avoidance test evaluation. We noted that one-month quercetin treatment alleviated the detrimental effects of amyloid-β on spatial learning and memory parameters using Morris water maze analysis. Quercetin was found to increase the number of proliferating neural stem/progenitor cells. Notably, quercetin increased the number of DCX-expressing cells, indicating the active dynamic growth of neural progenitor cells in the dentate gyrus of the hippocampus. We further observed that the quercetin improved the number of BrdU/NeuN positive cells contributed to enhanced adult neurogenesis. Based on our results, quercetin had the potential to promote the expression of BDNF, NGF, CREB, and EGR-1 genes involved in regulating neurogenesis. These data suggest that quercetin can play a valuable role in alleviating Alzheimer's disease symptoms by enhancing adult neurogenesis mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijdevneu.2019.02.005DOI Listing
May 2019

The effect of frankincense (Boswellia serrata, oleoresin) and ginger (Zingiber officinale, rhizoma) on heavy menstrual bleeding: A randomized, placebo-controlled, clinical trial.

Complement Ther Med 2019 Feb 27;42:42-47. Epub 2018 Sep 27.

Department of Persian Medicine, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Objectives: To evaluate the effect of frankincense (Boswellia serrata, oleoresin) and ginger (Zingiber officinale, rhizoma) as complementary treatments for heavy menstrual bleeding (HMB) among women of reproductive age.

Design: Randomized, placebo-controlled, clinical trial.

Setting: Gynecology outpatient clinics.

Interventions: Patients with HMB (n = 102) were randomly assigned to three groups. All patients received ibuprofen (200 mg) and either frankincense (300 mg), ginger (300 mg), or a placebo, which contains 200 mg anhydrous lactose as the filling agent and was similar in appearance to the two other drugs. Patients received the medications three times a day for seven days of the menstrual cycle, starting from the first bleeding day and this was repeated for two consecutive menstrual cycles.

Main Outcome Measures: Amount and duration of menstrual bleeding and quality of life (QOL).

Results: Duration of menstrual bleeding was decreased in the frankincense (-1.77 ± 2.47 days, P = 0.003) and ginger (-1.8 ± 1.79 days, P = 0.001) groups, but not in the placebo group (-0.52 ± 1.86 days, P = 0.42). Amount of menstrual bleeding was decreased in all (P < 0.05), with no difference among the study groups (P > 0.05). More improvement in QOL was observed in the frankincense (-25.7 ± 3.1; P < 0.001) and ginger (-29.2 ± 3.7: P < 0.001) groups compared to the placebo group (-15.07 ± 3.52; P < 0.001) and between the groups, differences were statistically significant (P = 0.02).

Conclusions: Ginger and frankincense seem to be effective complementary treatments for HMB. Further studies with a larger sample size and longer follow-up are warranted in this regard.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctim.2018.09.022DOI Listing
February 2019

Molecular aspects of pancreatic β-cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA.

J Cell Physiol 2019 06 22;234(6):8411-8425. Epub 2018 Nov 22.

School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Metabolic syndrome is known as a frequent precursor of type 2 diabetes mellitus (T2D). This disease could affect 8% of the people worldwide. Given that pancreatic β-cell dysfunction and loss have central roles in the initiation and progression of the disease, the understanding of cellular and molecular pathways associated with pancreatic β-cell dysfunction can provide more information about the underlying pathways involved in T2D. Multiple lines evidence indicated that oxidative stress, microRNA, and long noncoding RNA play significant roles in various steps of diseases. Oxidative stress is one of the important factors involved in T2D pathogenesis. This could affect the function and survival of the β cell via activation or inhibition of several processes and targets, such as receptor-signal transduction, enzyme activity, gene expression, ion channel transport, and apoptosis. Besides oxidative stress, microRNAs and noncoding RNAs have emerged as epigenetic regulators that could affect pancreatic β-cell dysfunction. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in T2D pathogenesis. Here, we summarized the molecular aspects of pancreatic β-cell dysfunction. Moreover, we highlighted the roles of oxidative stress, microRNAs, and noncoding RNAs in pancreatic β-cell dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.27755DOI Listing
June 2019

Two new dammarane triterpenes isolated from Bunge & Bien with cytotoxicity against DU-145 and LNCaP prostate cancer cell lines.

J Asian Nat Prod Res 2020 Jan 17;22(1):38-46. Epub 2018 Nov 17.

Department of Pharmacognosy, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

From the aerial parts of Bunge & Bien, a new 3-oxo-4-oxa-A-homo-25,26,27-trinordammarano-24,20-lactone triterpene (, a new natural product 20,25-dihydroxy-3-oxodammarane triterpene ), together with known 5-hydroxy-3,6,7,8,3',4',5'-heptamethoxyflavone (), have been isolated and characterized. The chemical structure of the new compounds was determined by 1D and 2D NMR and HR tandem MS measurements. All three compounds were subjected to biological tests for evaluation of their cytotoxicity against prostate (DU-145 and LNCaP) cancer cells. Compounds , , and showed cell growth inhibition in a dose dependent manner against DU-145 and LNCaP cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10286020.2018.1538211DOI Listing
January 2020

The Effects of . in Preventing Memory Loss, Anxiety, and Oxidative Stress on Lipopolysaccharide-induced Neuroinflammation Rat Models.

Int J Prev Med 2018 12;9:85. Epub 2018 Oct 12.

Drug Applied Research Center, Tabriz Medical University, Tabriz, Iran.

Objective: Several factors lead to memory loss, the most important of which is brain aging that is caused mostly by neuroinflammation and oxidative stress. The need of finding preventive treatments of memory impairment in elderly encouraged authors to assess the effect of on memory loss, anxiety, and antioxidant indices on neuroinflammation rat models.

Materials And Methods: Different fractions of were prepared. The subject rats were grouped in 11 groups of 10 each. In the nine treated groups, the extract gavage began 1 week before intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) and continued for 2 weeks after the last injection of LPS. Behavioral tests, including passive avoidance and elevated plus-maze (EPM) tests, were run on days 24, 25, and 26 and the subjects were sacrificed on the day after the last behavioral test, and their hippocampus was isolated to measure the oxidative stress markers.

Results: Assessment of oxidative stress markers in hippocampus samples revealed that the amounts of endogenous antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and total antioxidant activity) in the groups that received different fractions were less than their equivalent figures in LPS-control group, and levels of malondialdehyde (MDA) in treatment groups were less than MDA level in LPS-control group. Moreover, the treatment groups with different fractions of revealed better performance compared to LPS-control group in shuttle-box test. In EPM test, the groups with different fractions revealed lower stress level in comparison with LPS-control group. The best performance in memory test and the lowest level of stress in EPM was observed in the group with aqueous fraction at 600 mg/kg dose, and the least figures of oxidative stress markers were of the group with aqueous fraction at 600 mg/kg dose.

Conclusion: The oral administration of different fractions of , especially aqueous fraction, prevented from memory deficits and stress through controlling oxidative stress and inflammation processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijpvm.IJPVM_75_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202774PMC
October 2018

Alterations in lipid peroxidation, lipid profile, insulin sensitivity, and hepatic histopathological changes in diabetic rats following the treatment with Salvadora persica.

J Cell Biochem 2019 03 30;120(3):3696-3708. Epub 2018 Sep 30.

School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

We examined the effects of various partitions of Salvadora persica extract on lipid profile (LP), lipid peroxidation, and insulin sensitivity (IS) of diabetic rats. The rats were divided into normal control, diabetic control (DC), standard, sham, and test groups. The test groups were treated with an oral dose of 200, 400, and 600 mg/kg of crude, aqueous, and ethyl acetate partition of S. persica extract. After 21 days of experiment, the fasting blood glucose (FBS), LPs, lipid peroxidation, IS, liver enzymes levels, liver histopathology, and body weight alteration were evaluated. A significant decrease in FBS and lipid profile (except HDL) were observed in rats treated with various dose of extract compared with the DC rats ( P < 0.05). Treating diabetic rats with various extracts of S. persica meaningfully decreased the level of malondialdehyde ( P < 0.05). Animals treated with various dose of aqueous extract showed better results ( P < 0.01). On the basis of used indirect indexes to determine IS, all partitions of extracts showed anti-insulin resistance effects in diabetic rats. On the basis of our statistical analyzing, treating diabetic rats with all of the three extracts of S. persica decreased the elevated levels of alanine phosphatase, aspartate aminotransferase, and alanine transferase. Also, pathological changes in the liver tissue were reduced following treatment with the S. persica. In conclusion, our results give evidence that the S. persica extract, especially aqueous partition, has a healing effect on diabetes and can be considered as an alternative therapy for this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.27649DOI Listing
March 2019

Novel Effects of Extract on Patients with Neurocognitive Disorder and Depression: A Clinical Trial Study.

Int J Prev Med 2018 29;9:57. Epub 2018 Jun 29.

Department of Pathology, School of Medicine, Kerman University of Medical Sciences, Islamic Republic of Iran.

Background: Dementia as a major cognitive neurological disorder is defined as impairment in one or more cognitive territories compared with the former level of performance. This disorder disrupts patient's independence, and the patient would need others aid in order of doing daily and complex activities. The aim of this study was to evaluate the efficacy of Rosa damascena extract in the improvement of cognitive function in patients with dementia.

Methods: This study is a randomized double-blind, placebo-controlled clinical trial on 40 patients older than 55 years with dementia referred to Specialized Elderly Patients Clinic in 2015-2016. Patients were divided randomly into two groups (control and intervention). The intervention group used donepezil and capsules, and in control group, placebo capsule instead of added on donepezil. Four test was filled three times at the study initiation, after month one and also after month three: Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination Revised (ACE-R) were used for cognition evaluation, for depression assessment, Geriatric Depression Scale was administered, and checklist of memory and behavioral disorders were filled.

Results: The results showed add-on donepezil and versus placebo improved cognitive impairment based on MMSE with = 0.002, ACE-R with total = 0.001, depression ( = 0.012), behavioral disorders ( < 0.001), and daily activity ( < 0.001).

Conclusions: The extract affected cognitive impairment of dementia patients significantly and also have significant effects on improving depression and behavioral problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijpvm.IJPVM_199_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036771PMC
June 2018

Pimpinelol, a novel atypical Sesquiterpene lactone from Pimpinella haussknechtii fruits with evaluation of endoplasmic reticulum stress in breast cancer cells.

Fitoterapia 2018 Sep 27;129:198-202. Epub 2018 Jun 27.

Department of Biochemistry, Isfahan University of Medical Sciences, Isfahan, Iran.

Pimpinella haussknechtii is an annual native plant grows in west of Iran. Phytochemical study of the fruits of P. haussknechtii led to the isolation of a novel irregular sesquiterpene lactone with a new skeletone and oxidation pattern named: pimpinelol. The structure of the isolated compound was elucidated by extensive spectroscopic methods. Cytotoxic activity of Pimpinelol was evaluated using standard MTT assay against breast cancer cells. Induced endoplasmic reticulum stress and related gene expressions were evaluated with fluorescence microscopy analysis and real time PCR, respectively. These findings confirmed that Pimpinelol concentrations dependently increased protein aggregation and the mRNA expression of ATF-4, CHOP, GADD34 and TRIB3 in MCF-7 breast cancer cell line. According to the obtain results, we demonstrated for the first time that Pimpinelol decreased breast cancer cell viability by inducing ER stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fitote.2018.06.024DOI Listing
September 2018

Synthesis and Leishmanicidal Activities of Six Quercetin Derivatives.

Adv Biomed Res 2018 24;7:64. Epub 2018 Apr 24.

Department of Medicinal Chemistry, Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Today, leishmaniasis is a widespread, infectious parasitic disease caused by spp. Natural-derived compounds are likely to provide a valuable source of new pharmaceuticals, and among them, quercetin derivatives may have antileishmanial effects. The antileishmanial activity of 3,5,7,3',4'-pentahydroxyflavonol (quercetin) derivatives is partly attributed to the position and pKa of phenolic or catechol hydroxyl groups. Therefore, to optimize their leishmanicidal effect, the structural features of quercetin and its derivatives were improved by acylation or alkylation of hydroxyl groups and changing their pKa and consequently their activities.

Materials And Methods: In this study, during a regioselective method, quercetin derivatives were synthesized. The structures of synthesized compounds were confirmed by mass, IR, H-, and C-NMR spectral data. The antileishmanial activities of compounds 1-6 were compared with glucantime as the standard drug against promastigotes of using standard cell-based leishmanicidal assay.

Results: In this study, during a regioselective method, two 7-O-quercetin derivatives (5 and 6), and three quercetin acetate derivatives (2, 3, and 4) were synthesized. In detail, the IC values found against were (1) 2.5 ± 0.92; (2) 2.85 ± 0.99; (3) 15.5 ± 1.95; (4) 13.5 ± 3.5; (5) 2.6 ± 0.57; and (6) 1.3 ± 0.35 μM while IC value of glucantime as the standard drug was 88.5 ± 9.47 μM.

Conclusions: The present study showed an effective antileishmanial activity of quercetin semisynthetic compounds (1-6) against promastigotes of . Among them, quercetin analogs with more lipophilic and iron-chelating activity showed more antiparasite activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/abr.abr_76_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952540PMC
April 2018

A New Taraxastane Triterpene from with Cytotoxic Activity Against Prostate Cancer Cells.

Iran J Pharm Res 2018 ;17(1):336-342

Biochemistry Department, Isfahan Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

In this research, aerial parts of Lam were collected from Sanandaj city in Kurdistan province at the West of Iran. It was extracted by maceration using acetone as solvent. The isolation of compounds were carried out with repeated column chromatography using silica gel and normal preparative HPLC using YMC-Pack-Sil column and hexane: ethyl acetate as mobile phase. The structures of isolated compounds were elucidated by extensive 1 and 2D-NMR as well as HRESI-MS spectra and the cytotoxicity was done against DU-145 human prostate cancer cell line using standard MTT assay. It afforded a new 12-taraxastane derivative and two known cycloartane triterpenes including: taraxast-12-ene-3β,20,21(α)-triol (1), cycloartane-3β,25-diol (2), and cycloartane-3β,24,25-triol (3). They exhibited cytotoxic effects, with IC values of 12.2 ± 2.9, 27.5 ± 4.9, and 18.3 ± 1.4 µM, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937103PMC
January 2018

Antihyperlipidemic Effect of Different Fractions Obtained from Hydroalcoholic Extract in Rats.

Int J Prev Med 2018 9;9:30. Epub 2018 Mar 9.

Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: This study was aimed to screen the antihyperlipidemic effect of different fractions of to obtain the most efficient herbal fraction for isolation of bioactive constituents responsible for hypolipidemic activity.

Methods: Chloroform, butanol, and aqueous fractions were obtained from hydroalcoholic extract of aerial parts using partitioning process. To induce hyperlipidemia, dexamethasone (Dex) was injected 10 mg/kg/day (s.c.) for 8 days. In the test groups, animals received 50, 100 and 150 mg/kg of hydroalcoholic extract and different fractions orally simultaneously with Dex. Serum lipid profile and hepatic marker enzymes were evaluated using biochemical kits.

Results: All treatments, especially chloroform and aqueous fractions, reversed serum lipid markers in hyperlipidemic rats. Maximum reduction in triglyceride (60.2%, < 0.001) and maximum elevation in high-density lipoprotein (HDL) (35.0%, < 0.01) was observed for chloroform fraction. Maximum cholesterol-lowering effect (29.0%, < 0.001) and maximum reduction in low-density lipoprotein were found for hydroalcoholic extract (72.9%, < 0.001). Aqueous fraction improved all lipid markers at the highest dose. Butanol fraction decreased triglyceride at the lowest dose (43.9%, < 0.001) and increased HDL (33%, < 0.05) at the highest dose. There was a significant increase in alanine aminotransferase and aspartate aminotransferase levels in all tested groups compared to normal group ( < 0.001).

Conclusions: This study showed strong antihyperlipidemic effect of various fractions derived from hydroalcoholic extract of . Chloroform and aqueous fractions may be worthy candidates for isolation of bioactive hypolipidemic constituents. However, possible hepatotoxicity should be considered for clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijpvm.IJPVM_100_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869962PMC
March 2018

Bioassay-directed isolation of quaternary benzylisoquinolines from with bactericidal activity against .

Res Pharm Sci 2018 Apr;13(2):149-158

Brucellosis Department, Razi Vaccine and Serum Research Institute, Karaj, I.R. Iran.

Bonge. (Syn: Boiss. & Buhse) is a shrub widely distributed in Middle East and central part of Asia. An ethnobotanical study revealed that indigenous and tribal people in Iran use root decoction for treatment of brucellosis. Therefore, the aim of this study was bioassay directed isolation of antibacterial compounds from this plant based on their bactericidal activity against . Briefly, the ethanol extract of was fractioned and subjected to preliminary antibacterial screening tests against Brucella. The more active fraction (Fr.3) was subjected to purification by repeated chromatography systems. Quaternary benzylisoquinoline alkaloids including columbamine, palmatine, berberine, and jatrorhizine were four main components identified in the selected active fraction. Except for berberine which is reported before, palmatine, columbamine and jatrorhizine are isolated for the first time from this plant. Anti-brucellosis properties of isolated compounds were studied against under different test conditions. In minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) results, jatrorhizine () showed more antibacterial activity with MIC and MBC of 0.78 and 1.56 μg/mL, respectively. In both agar well diffusion and disk diffusion ANOVA results showed that there were statistically significant differences between compounds versus placebo in all of the tested concentration ( <0.001). In conclusion, all of four alkaloids showed potent antibacterial activity against but jatrorhizine and columbamine with free hydroxyl group on C-3 or C-2 showed more activity than palmatine and berberine without any free hydroxyl group on their structures. The antibacterial effects of columbamine (15 μg/mL) and jatrorhizine (15 μg/mL) were comparative to streptomycin (10 μg/mL) as standard drug which candidate them for more pharmacological researches to find new antibacterial agents against brucellosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1735-5362.223797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842486PMC
April 2018

Biotic elicitation for scopolamine production by hairy root cultures of .

Mol Biol Res Commun 2017 Dec;6(4):169-179

Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

The (-)-hyoscyamine, atropine and scopolamine (hyoscine) are three valuable tropane alkaloids while scopolamine is the most important member of this group for the pharmaceutical industry due to its higher demand compared to hyoscyamine and atropine. Scopolamine is an anticholinergic reagent with several therapeutic applications. In the current study, the hairy roots culture of was used as an advantageous method for production of scopolamine. The hairy roots are formed by and have genetic stability, high growth rate and lateral branching. In this study, the effect of and as biotic elicitors on the production of scopolamine in hairy roots was investigated. The amount of scopolamine in the hairy roots was detected by HPLC analysis and compared with control samples after 0, 12 and 24 hours. Results showed that, and enhanced scopolamine production in the culture while the atropine content was decreased. Although in the control samples with no bacterial elicitation no scopolamine was detected, elicitation by caused production of scopolamine and about 0.03 gram and 0.017 gram of it was detected in 100 gram dried hairy roots after 12 and 24 hours respectively. In elicited hairy roots, scopolamine was not produced after 12 hours. However, about 0.025 gram of this tropane alkaloid was detected in 100 gram dried hairy roots after 24 hours. In conclusion, and induced the scopolamine production in hairy roots.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22099/mbrc.2017.25776.1275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762989PMC
December 2017

Mitochondrial and caspase pathways are involved in the induction of apoptosis by nardosinen in MCF-7 breast cancer cell line.

Res Pharm Sci 2018 Feb;13(1):12-21

Department of Clinical Biochemistry and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

Natural products isolated from plants provide a valuable source for expansion of new anticancer drugs. Nardosinen (4,9-dihydroxy-nardosin-6-en) is a natural sesquiterpene extracted from . Recently, we have reported the cytotoxic effects of nardosinen in various cancer cells. The aim of the current study was to investigate the anticancer features of nardosinen as well as its possible molecular mechanisms of the nardosinen cytotoxic effect on breast tumor cells. MTT assay showed that nardosinen notably inhibited cell proliferation in a dose-dependent manner in MCF-7 breast cancer cells. The growth inhibitory effect of nardosinen was associated with the induction of cell apoptosis, activation of caspase-6, increase of reactive oxygen species (ROS), and loss of mitochondrial membrane potentials (ΔΨm). Western blot assay following treatment with nardosinen showed that the expression levels of the Bax were significantly up-regulated and the expression levels of the Bcl-2 were significantly down-regulated. Our results finally exhibited that nardosinen induces apoptosis in breast cancer cells via the mitochondrial and caspase pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/1735-5362.220963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772077PMC
February 2018

Jatropha-6(17),11E-diene class derivatives induce apoptosis effects in OVCAR-3 and Caov-4 ovarian cancer cell lines via a mitochondrial pathway.

Biochem Cell Biol 2017 12 27;95(6):616-627. Epub 2017 Jun 27.

a Department of Clinical Biochemistry, School of Pharmacy & Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

We investigated the molecular mechanism of apoptosis induced by novel jatropha-6(17),11E-diene class derivatives, compounds A, B, and C that were extracted from Euphorbia osyridea Boiss, in the ovarian cancer cell lines Caov-4 and OVCAR-3. The OVCAR-3 and Caov-4 cell lines were treated with different concentrations of these compounds. Cytotoxicity was evaluated using MTT, clonogenic survival assay, and flow cytometry assays. The production of reactive oxygen species (ROS), mitochondrial membrane potential (Δ), and the activity of caspase 3 and 9 were evaluated. Compounds A, B, and C reduced cell viability in a dose-dependent manner (P < 0.05). The IC values were calculated as 46.27 ± 3.86, and 38.81 ± 3.30 μmol/L for compound A, 36.48 ± 3.18 and 42.59 ± 4.50 μmol/L for compound B, and 85.86 ± 6.75 and 75.65 ± 2.56 μmol/L for compound C against the Caov-4 and OVCAR-3 cell lines, respectively. Apoptosis evaluation showed that jatrophane derivatives increase both early and late apoptosis (P < 0.01). These compounds also increased ROS generation, Δ, and the activity of caspase 3 and 9 in the treated cells. These results showed that compounds A and B have significant inhibitory effects on OVCAR-3 and Caov-4 proliferation and induction of apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1139/bcb-2017-0034DOI Listing
December 2017

New 6(17)-epoxylathyrane diterpene: aellinane from Euphorbia aellenii induces apoptosis via mitochondrial pathway in ovarian cancer cell line.

Toxicol Mech Methods 2017 Oct 28;27(8):622-630. Epub 2017 Jul 28.

c Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences , Isfahan , Iran.

Euphorbia species have been used in traditional medicine in many countries for the treatment of cancer. This article aims to evaluate the capability of a new lathyrane diterpene isolated from Euphorbia aellenii to induce apoptosis in the Caov-4 cell line to determine the underlying mechanism of its anticancer effects. A new 6(17)-epoxylathyrane diterpenes: aellinane from Euphorbia aellenii was evaluated for viability of Caov-4 cells by MTT method. Apoptosis induction by lathyrane diterpene was confirmed by annexin V-FITC/PI staining, and caspase-6 activation. The Bcl2 and Bax protein content were detected by Western blot analysis. Finally, we employed the fluorescent ROS detection kit and fluorochrome JC-1 to determine ROS levels and loss of mitochondria membrane potential (ΔΨm) in Caov-4 cells, respectively. The results show that lathyrane diterpene has significant cytotoxic effect against Caov-4 cells. The IC50 value was 45 μM. Annexin V/propidium iodide (PI) staining and caspase-6 activity assay confirmed that lathyrane diterpene is able to induce apoptosis in Caov-4 cells. The results also demonstrate that lathyrane diterpene up-regulated Bax and down-regulated Bcl-2 proteins. Moreover, apoptotic effect of lathyrane diterpene was also related to ROS production and loss of mitochondrial membrane potential (ΔΨm). This study demonstrated that lathyrane diterpene has profound activity against Caov-4 cells. Analysis of apoptosis-related proteins revealed that lathyrane diterpene triggered the mitochondrion-mediated apoptosis pathway, which led to the loss of mitochondrial membrane potential (ΔΨm) and activation of caspase-6. Therefore, we believe that lathyrane diterpene might be a promising natural compound in ovarian cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15376516.2017.1347735DOI Listing
October 2017