Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
230
237
10.29228/jrp.13
885
Antioxidant, anticholinesterase activities and polyphenolic constituents of cones of algerian fir (abies numidica) by lc-esi-ms/ms with chemometric approach
Habiba MOKADDEM-DAROUI
Maya BELHADJ MOSTEFA
Fatma AYDOGMUS-OZTURK
Ebru EROL
Mehmet OZTURK
Abdulselam ERTAŞ
Mehmet EMIN DURU
Ahmed KABOUCHE
Zahia KABOUCHE
The fractions (Fr.1-5) of the hydromethanolic extract of Abies numidica cones were studied for their polyphenol constituents, antioxidant, and anticholinesterase activities. The β-carotene-linoleic acid, cupric reducing power (CUPRAC), DPPH scavenging, and ABTS radical scavenging assays were used to determine antioxidant activity. Fr.3 exhibited the highest antioxidant activity in ABTS test (IC50: 1.29 μg/mL), b-carotene-linoleic acid test (IC50: 18.6 μg/mL) and CUPRAC (A0.5: 33.8 μg/mL) assays. Three fractions (Fr.2-4) promising antioxidant activity were analyzed using LC-MS/MS for their phenolic compositions. Taxifolin (155.9-2816.2 μg analyte/g extract), hyperoside (353.0-2045.5 μg/g), vanillin (1488.9-1529.9 μg/g), tannic acid (1281.6-1416.8 μg/g), rosmarinic acid (1063.1-1149.3 μg/g), coumarin (683.0-772.6 μg/g), quercetin (881.0 μg/g), and catechin (277.7-400.2 μg/g) were identified in the antioxidant fractions. Moreover, the anticholinesterase activity was also performed using the in vitro spectroscopic Ellman method. The antioxidant fractions exhibited moderate butyrylcholinesterase inhibitory activity. The multi-ware analysis was performed to understand the origin of bioactivities. According to principal component analysis, it is detected that the hyperoside, catechin, taxifolin, and tannic acid were responsible for the antioxidant activity. Therefore, the cones of Abies numidica can be considered as potent antioxidant and anticholinesterase sources in food and pharmaceutical industries, commercially.
https://jrespharm.com/abstract.php?id=885
Abies numidicaLC-MS/MSantioxidant activityanticholinesterase activitytaxifolinhyperoside
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
238
248
10.29228/jrp.14
891
Quali-quantitative research on herbal supplements containing black elder (sambucus nigra l.) fruits
Etil GÜZELMERİÇ
Cansel ÇELİK
Nisa Beril ŞEN
Mehmet Ali OÇKUN
Erdem YEŞİLADA
Black elder (Sambucus nigra L.), rich in phenolics, is used as antiviral, especially to treat common cold and flu. The flower of black elder has been approved by German Commission E and ESCOP for its mentioned usage, and in several pharmacopoeias, its qualification parameters were described. However, its fruits with a similar use as the flowers have not been considered by the pharmacopoeias. Even so, the number of black elder fruit supplements marketing with different brands is increasing steadily. This study aimed to evaluate the availability and concentrations of marker components (chlorogenic acid, rutin, and isoquercitrin) in herbal supplements containing black elder fruits comparatively with the reference plant material by high-performance thin-layer chromatography (HPTLC) and a validated high-performance liquid chromatography (HPLC) techniques. Additionally, the total anthocyanin amount was calculated by spectrophotometry in these samples, and the results were expressed as equivalents of cyanidin-3-O-glucoside (C3G). HPTLC fingerprints showed that most of the marketed products did not contain rutin, chlorogenic acid and isoquercitrin. Moreover, their fingerprint comparison with the reference was found to be different. The highest chlorogenic acid, rutin and isoquercitrin amounts were found as 0.742 mg/effervescent tablet (E3), 1.445 mg/capsule (C1), and 0.082 mg/capsule (C1), respectively by HPLC. According to the total anthocyanin content, C1 was determined to have the highest anthocyanin content as 8.705 mg C3G/capsule, whereas E6 was found to have the lowest anthocyanin content as 0.024 mg C3G/effervescent tablet. Consequently, there is an urgent need to establish standardization parameters for black elder fruits.
https://jrespharm.com/abstract.php?id=891
Sambucus nigra L.black elderhigh-performance thin-layer chromatography (HPTLC)high-performance liquid chromatography (HPLC)spectrophotometryquality control
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
249
257
10.29228/jrp.15
892
Chemical composition and cytotoxic potency of essential oil from seseli petraeum m. bieb. (apiaceae)
Alev ÖNDER
Ahsen Sevde ÇINAR
Filiz BAKAR-ATEŞ
Luis NOGUERA-ARTIAGA
Ángel Antonio CARBONELL-BARRACHINA
The present study aimed to investigate the chemical composition and in vitro cytotoxic activity of the fruit essential oil of Seseli petraeum M. Bieb. growing in the Northern side of Anatolia. The Seseli petraeum essential oil was obtained by hydrodistillation from the fruits and analyzed by GC/MS to determine its chemical composition. The major components have been determined as carotol (17.25%), γ-terpinene (10.73%), β-farnesene (8.50%), p-cymene (7.93%), germacrene-D (7.65%), and sabinene (7.31%). The cytotoxic activity of the essential oil was evaluated by MTT assay in vitro on cell proliferation with MCF-7 (Human breast adenocarcinoma) and A549 (Human lung carcinoma) cells. The results showed that the essential oil has potent cytotoxicity against treated cancer cells, whereas it was more cytotoxic in MCF-7 cells (IC50=390.38 μg/mL). The results demonstrated that S. petraeum essential oil has a marked cytotoxic effect against treated cancer cells. Although this effect is likely to be caused by carotol owing to a major component of the oil, further designed studies are necessary due to the possibility of activity, and maybe it occurred due to the synergistic effects of the oil components. The findings of this study may promote the use of the species for pharmaceutical purposes.
https://jrespharm.com/abstract.php?id=892
Apiaceaeanticancercytotoxicityessential oilSeseli
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
258
270
10.29228/jrp.16
896
Evaluation of in vitro antioxidants activities, hepatoprotective and haematological effects of ethanol extract of anthocleista vogelii stem bark (avsb) on carbon tetrachloride (ccl<sub>4</sub>) induced rats
Robert UROKO
Chinedu NWUKE
Amarachi AGBAFOR
Josephat OKWOR
Anthocleista vogelii stem bark extract (AVSB) is used as a hepatoprotective protective and blood-boosting agent locally without any scientific evidence. This study evaluated the in vitro antioxidants activity, hepatoprotective and haematological effects of ethanol extract of AVSB on carbon tetrachloride (CCl4) induced rats. Thirty rats distributed into 5 groups (n = 6) were used. Group 1 was the normal control rats without CCl4 induction, group 2 was the CCl<sub>4</sub> control (CCl<sub>4</sub> induced untreated rats) while groups 3 – 6 were CCl<sub>4</sub> induced rats treated with 100 mg/kg/day of silymarin, 100, 200 and 500 mg/kg/day of AVSB respectively for 14 days. The results indicated high levels of total phenols, flavonoid, vitamin E, vitamin C, Β-carotene and lycopene in the AVSB. The AVSB exhibited a dose-dependent increase in ferric reducing antioxidant power, DPPH and nitric oxide radicals scavenging activities similar to vitamin C, rutin and curcumin respectively. The CCl<sub>4</sub> induction significantly (P<0.05) elevated total bilirubin concentrations, serum ALT, AST and ALP activities and significantly (P<0.05) decreased PCV, RBC, WBC, platelet counts, and Hb, total protein and albumin concentrations and caused liver necrosis in the untreated rats relative to the normal control. Treatment with AVSB significantly reversed the altered serum ALT, AST and ALP activities, total bilirubin, total protein, albumin and Hb concentrations including haematological indices and liver histomorphology to normal compared with the CCl<sub>4</sub> control. The findings of this study indicated that the AVSB is rich in antioxidant components, in vitro antioxidant activity, and possesses hepatoprotective and improves haematological indices
https://jrespharm.com/abstract.php?id=896
Anthocleista vogeliiantioxidant activitycarbon tetrachloridehepatoprotectivehaematological indices
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
271
276
10.29228/jrp.17
894
Effect of food supplement of humic origin on the hematological and biochemical parameters in the cr (vi) exposed rats
Oksana BUCHKO
Viktoriia HAVRYLIAK
Andriy PYLYPETS
Taras BUCHKO
The study aimed to investigate the effect of Humilid, a biologically active food supplement, on
biochemical and hematologic parameters in the blood of rats exposed to hexavalent Chromium. Wistar male rats were
used in experiments. All animals were divided into 4 groups. Animals of experimental groups D<sub>2</sub> and D<sub>3</sub> received a
1% solution of food supplement Humilid in a dose of 2 ml/kg of body weight during 28 days. Rats of groups D<sub>1</sub> and
D<sub>2</sub> were injected with potassium bichromate (K<sub>2</sub>Cr<sub>2</sub>O<sub>7</sub>) in the dose of 2 mg Cr (VI)/kg of body weight from 14 days of
the experiment. Animals of the C group were administered a 0.9% NaCl solution for 14 days. Data were analyzed
using the ANOVA test. It has been found that administration of potassium bichromate caused the cytotoxic effect on
rat’s organism, inhibition of the synthetic function of the liver, hypoglycemic effect, toxic anemia and leukocytosis.
The treatment with humic substances provided a marked normalization of the biochemical and hematological
parameters in the blood of chromium-exposed animals. Biologic active supplement Humilid reduces the toxic effect of
chromium on the rat body, normalizes metabolism, and exhibits hepatoprotective and adaptogenic effects. Our
findings show that Humilid supplementation may be helpful in the abrogation of heavy metal toxicity.
https://jrespharm.com/abstract.php?id=894
HumilidChromiumratshematologybiochemical parameters
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
277
286
10.29228/jrp.18
889
Mechanism of antinociceptive action of syringic acid
Mehmet Evren OKUR
Ayşe Arzu ŞAKUL
Syringic acid presents various biological properties such as antioxidant, anti-inflammatory, anticancer, and other activities. The present experiment aimed to investigate the effect of the oral administration of syringic acid (10, 50, and 100 mg/kg) on its possible nociceptive response using hot-plate and tail-flick assay in the Balb-C mice model. The mice were pre-treated with 5 mg/kg atropine 15 min before, 1mg/kg mecamylamine 20 min before, 1mg/kg ketanserin 30 min before, 1 mg/kg ondansetron 30 min before, 1mg/kg yohimbine 30 min before, 1 mg/kg prazosin 30 min before and 5 mg/kg naloxone 15min before the administration of the Syringic acid. Dose-dependent antinociceptive activity of syringic acid was reported for 50 and 100 mg/kg doses in tail-flick and hot-plate assays, respectively. In further, mecamylamine, yohimbine, and naloxone significantly reversed syringic acid-induced response to thermal stimuli in tail-flick and hot-plate assays, respectively. From the data, it was confirmed that syringic acid presents central antinociceptive effects which may be coordinated by supraspinal/spinal mediated cholinergic, opioidergic, and adrenergic, inflection.
https://jrespharm.com/abstract.php?id=889
Antinociceptionmuscarinic receptorsopioidergic receptorsα2-adrenoceptorssyringic acid
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
287
291
10.29228/jrp.19
901
Bortezomib synergizes with nocodazole in p53 mediated dna damage response signalling in a549 lung cancer cells
Gülşah ALBAYRAK
The adoption of new treatment modalities is required to improve outcomes in lung cancer treatment as lung cancer has lowest survival rates, along with liver and pancreatic cancer. Bortezomib is a proteasome inhibitor that has higher anticancer effect in combination therapies. The aim of this study was to investigate whether bortezomib could have additional anticancer effect with antineoplastic tubulin binding agent -nocodazole in A549 lung cancer cells. Apoptosis related gene expression levels of Noxa, Bcl-xL, Casp3 and Casp7 were measured by real-time PCR after treatment with 30 nM bortezomib, 0.3 μg/ml nocodazole and with their combination for 24 hours. Synergistic effect on DNA damage response was investigated at protein levels by checking p53 and cleaved PARP expressions. Induction of apoptotis was determined at protein expression level by western blotting of XIAP, Bcl-X and Bim. It was found that nocodazole combined bortezomib treatment induced apoptosis via p53 mediated DNA damage response signalling. P53 and cleaved PARP protein expressions were increased significantly after combination treatment. Apoptosis related genes Noxa, Casp3 and Casp7 mRNA expressions were elevated significantly after combination treatment. This study concludes that bortezomib potentiates the effect of nocodazole via DNA damage induced apoptosis in A549 lung cancer cells.
https://jrespharm.com/abstract.php?id=901
BortezomibNocodazoleDNA damagelung cancer
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
292
304
10.29228/jrp.20
893
Naphthoquinone–thiazole hybrids bearing adamantane: synthesis, antimicrobial, dna cleavage, antioxidant activity, acid dissociation constant, and drug-likeness
Ayşegül DOĞAN
Sadin ÖZDEMİR
Mustafa Serkan YALÇIN
Hayati SARI
Yahya NURAL
In this study, four novel naphthoquinone–thiazole hybrids bearing adamantane were synthesized by reaction of naphthoquinone–aroylthiourea derivatives with 1-adamantyl bromomethyl ketone in 75-85% yield and were characterized using 1H/13C NMR, FT-IR, and HRMS techniques. Various biological activities of the synthesized compounds, such as antibacterial, antifungal, DNA cleavage, and antioxidant activities, were screened. The compounds showed antibacterial activity against Escherichia coli, Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus hirae, and Legionella pneumophila subsp. pneumophila strains with MIC values in the range of 4–64 μg/mL and antifungal activity against Candida albicans strains with MIC values in the range of 16–64 μg/mL. The compounds had DNA cleavage activity at 250 and 500 μg/mL. Additionally, the antioxidant activity of the compounds was assessed based on the radical scavenging effect of the stable DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and the compounds exhibited acceptable antioxidant activity. The acid dissociation constants (pKa) of the compounds were determined potentiometrically in 30% (v/v) dimethyl sulfoxide–water at an ionic background of 0.1 mol L<sup>-1</sup> NaCl, at 25 ± 0.1 °C, and the HYPERQUAD computer program was used to calculate the pKa values from the data obtained from potentiometric titrations. Prediction of the drug-likeness properties of the compounds was performed with the use of the MolSoft website, and the compounds had promising drug-likeness model scores within a range of 1.09–1.56.
https://jrespharm.com/abstract.php?id=893
NaphthoquinonethiazoleadamantaneantimicrobialantioxidantDNA cleavageacid dissociation constantdrug-likeness
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
305
317
10.29228/jrp.21
890
Benzilic acid based new 2-aryl-1,3-thiazolidin-4-one derivatives: synthesis and anticancer activity
Özlen GÜZEL-AKDEMİR
Kübra DEMİR-YAZICI
Some new derivatives of 2-aryl-1,3-thiazolidin-4-one derivatives were produced (3a-p and 4a-p) in the search of potentially active new molecules with antitumor features. Compounds were obtained by cyclocondensation of 2-hydroxy-2,2-diphenyl-N-[(substituted phenyl)methylene]acetohydrazides (2) and mercaptoacetic acid or 2-mercaptopropionic acid. Identification and characterization of 32 new 2-aryl substituted thiazolidin-4-ones were performed with spectral and elemental analyzes. Compound 3c, 3g, 3j, 4g, 4n, and 4p were chosen as prototypes and assayed for their anticancer activity against diverse several cancer cell lines with in vitro primary anticancer test in the National Cancer Institute. Compound 4g exhibited significant anticancer activity with the inhibition value 84.19% against a leukemia cell line MOLT-4 while compound 4p had a remarkable inhibition ratio (72.11%) against the growth of a CNS (central nervous system) cancer cell line SF-295 in the primary screen. These preliminary and important results indicated that the compounds carried 2-aryl-1,3-thiazolidin-4-one scaffold can be evaluated as potentially promising anticancer agents.
https://jrespharm.com/abstract.php?id=890
1,3-Thiazolidin-4-onebenzilic acidmercaptoacetic acid2-mercaptopropionic acidanticancer agents
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
318
330
10.29228/jrp.22
888
Structure-based virtual screening and molecular dynamics simulations for detecting novel candidates as fgfr1 inhibitors
Güneş ÇOBAN
Structure-based virtual screening (SBVS) was performed to predict lead compounds for fibroblast growth factor receptor 1 (FGFR1) inhibition screening the kinase inhibitor database taken from ChEMBL. The prepared kinase inhibitor database consisted of 48017 ligands were screened in ATP binding site of FGFR1 by CCDC Gold software using virtual screening parameters to filter out. After then, 720 ligands were docked inside FGFR1 using default docking parameters of CCDC Gold software. The GOLD fitness score values of 70 and 80 was used a threshold value for screening and docking process, respectively. The ligands as reduced numbers to twenty-two in terms of docking results were utilized to calculate MMGBSA free binding energy from 10 ns molecular dynamics simulations (MDS). For refinement of results, six of twenty-two ligands which have better calculated MMGBSA free binding energy were exposed to 100 ns MDS. Then, 100 ns MDS trajectories of six compounds were used to calculate MMGBSA free binding energy, and MDS were expended to 250 ns for three ligands which have highest free binding energies. By free binding energies calculated from expanded MDS, were used to predict the most promising candidates (compounds G9 and G10) for FGFR1 inhibition. Structure stability, binding modes and energy decomposition analysis were performed to insight into dynamic behaviors of compounds G9 and G10 inside FGFR-1.
https://jrespharm.com/abstract.php?id=888
FGFR1virtual screeningmolecular dynamics simulationsfree binding energy
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
331
340
10.29228/jrp.23
895
Effects of particle size and tapped density on the content uniformity of repaglinide - metformin fixed dose tablet combination
Onur PINARBAŞLI
Gülistan Pelin GURBETOĞLU
Bahar KÖKSEL ÖZGEN
Nagehan SARRAÇOĞLU
Asuman AYBEY DOĞANAY
The study proposes a solution to content uniformity problem of repaglinide-metformin HCl fixed dose tablet combination with optimization of particle size distribution and tapped density of repaglinide and metformin granules. The developed dosage forms contain less than 0.5% w/w repaglinide and more than 75% w/w metformin hydrochloride in the composition, resulting in content uniformity problems. A route for, minimizing susceptibility to segregation during the tablet press operation, thereby improving content uniformity, was studied through adjusting the particle size distribution and tapped density of the granules. In this study, a new specification in manufacturing method was developed for obtaining repaglinide and metformin granules with particle size distribution and tapped density properties optimized for tablet homogeneity. Specific particle size distribution and tapped density specifications between metformin HCl and repaglinide granules were described as (i) particle size distribution (D90, D50 and D10) of metformin HCl granule should be less than or equal to three times of particle size distribution (D90, D50 and D10) of repaglinide granule; and (ii) tapped density of metformin HCl granule should be less than or equal to two times of tapped density of repaglinide granule. Assay and in vitro dissolution rate analysis were performed by validated HPLC methods.
https://jrespharm.com/abstract.php?id=895
Repaglinidemetformin HClfixed dose combinationcontent uniformityparticle size distributiontapped density
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
341
351
10.29228/jrp.24
897
Quality by design-based evaluation and optimization of ceftibuten flexible dispersible tablet design with high drug loading using design-expert software
Saravana Perumal GOVINDAN
Senthamarai RAJAGOPALAN
Anbarasu KUMAR
There are challenges in developing dispersible tablets with a high drug loading of a water-insoluble drug having flexibility, either as dispersible in water or as dispersible in the oral cavity before swallowing with overall acceptability. Overall acceptability is determined by the characteristics of the drug product and user acceptance. This study aimed to design and optimise the flexible dispersible tablets design using a model drug, namely ceftibuten with the drug loading of about 72%w/w of targeted tablet weight, in a statistically significant manner using design-expert software. The significant effects of screened input parameters on target responses were characterised based on the half-normal plot for the magnitude of effects, pareto chart for standardised effects, and variance analysis for the statistically significant model. The characterised design was optimised using the response surface method (RSM). The optimised target response was statistically confirmed based on the extent of statistical significance (very significant <0.01, significant <0.05 but >0.01). Among the input factors studied, crospovidone concentration shows a statistically very significant effect (<0.0001) on target response namely in vitro disintegration time, in vivo disintegration time, and overall acceptability of intended flexible dispersible tablet design. The outcome of designed and evaluated flexible dispersible tablets (FDT) using design-expert software demonstrated its ability to predict the design space with a statistical significance, which maximises the robust product characteristics and overall user acceptance.
https://jrespharm.com/abstract.php?id=897
Quality by designdesign of experimentsceftibutenflexible dispersible tablethigh drug loadinguser acceptance testingdesign-expert software
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2021
25
3
352
358
10.29228/jrp.25
907
Higher alpha-synuclein aggregate density does not lead to more severe dopaminergic cell loss in the aav-mediated overexpression model of parkinson’s disease: a time-course study
Banu Cahide TEL
İnci KAZKAYASI
Gökçen TELLİ
Elif ÇINAR
Sevgi Uğur MUTLUAY
Gül YALÇIN-ÇAKMAKLI
Esen SAKA
Bülent ELİBOL
Pathological intracellular aggregation of alpha-synuclein (a-syn) is the hallmark of Parkinson’s disease (PD). Our aim is to explore the outcomes of long-term a-syn pathology with its functional correlates in the PD model by AAV (adeno-associated virus)-mediated a-syn overexpression in substantia nigra (SN). Female Wistar rats (220-260 g) received a unilateral injection of AAV-human-a-syn or green fluorescent protein (GFP) gene into the SN. The animals were tested for motor functions with cylinder test at 8, 12 weeks or 9 months post-injection. The intensity of a-syn accumulation or GFP in striatum and dopaminergic neuronal loss in SN, dopaminergic terminal loss in striatum and synaptic integrity were analyzed by a-syn, GFP, tyrosine hydroxylase (TH) and synaptophsin immunohistochemistry, respectively. At all time-points, AAV-human-a-syn injected animals displayed more motor dysfunction and TH-positive cell loss compared to AAV-GFP injected group. A-syn immunoreactivity was present in the nigral neurons as well as the striatal terminals in all animals that received AAV-a-syn. Striatal TH density analysis showed a decrease in both 12-weeks and 9 months a-syn groups compared to controls. However, TH-positive neuron count was lower in 9-months group compared to 12-weeks group. Hence, the motor performance of 9-month group showed an improvement which may be a sign of a compensatory mechanisms against a-syn-induced neurodegeneration. The findings of this study implicate that higher a-syn density in SN does not always lead to worse motor function or more severe dopaminergic cell loss. This may support the hypothesis that a-syn aggregates are the end-product of a cellular defense mechanism rather than being causative pathology.
https://jrespharm.com/abstract.php?id=907
Alpha-synucleinParkinson’s diseaseadeno associated viral vectorsanimal model