Qinna N, Taha H, Mat, " A novel herbal combination, Etana®, for enhancing erectile function: Efficacy and Safety study in animals. " , "Int J Impot Res.",Vol.21,No.5, , , 10/01/2009
:الملخص
We present herein a new herbal combination called Etana that is composed of five herbal extracts including Panax quinquelotius (Ginseng), Eurycoma longifolia (Tongkat Ali), Epimedium grandiflorum (Horny goat weed), Centella asiatica (Gotu Kola) and flower pollen extracts. Most of the above-mentioned extracts have a long historical and traditional use for erectile dysfunction (ED). On the basis of the mechanism of action of each of the above, a combination is introduced to overcome several physiological or induced factors of ED. This study was conducted to show an enhancement of erectile function in male rats. The animals were observed for 3 h after each administration for penile erection, genital grooming and copulation mounting, and the penile erection index (PEI) was calculated. The maximum response was observed at the concentration of 7.5 mg kg(-1) of Etana. At a 7.5 mg kg(-1) single dose, the percentage of responding rats was 53+/-7 with a PEI of 337+/-72 compared with 17+/-6 with a PEI of 30+/-10 for control animals. This PEI was significantly (P<0.001) higher than each single component and than the sum of any two herbal components of Etana. When compared with sildenafil citrate, Etana induced more pronounced PEI than 0.36 mg kg(-1), but similar to 0.71 mg kg(-1) of sildenafil. Furthermore, full acute and sub-acute toxicity studies showed no toxic effects of Etana. In conclusion, this study describes a new and safe combination of herbal components that enhance erectile function in male rats. Clinical studies are warranted for evaluating Etana's significance in ED.
Download
Elsayed A, Remawi MA, " Formulation and characterization of an oily-based system for oral delivery of insulin. " , "International Journal of Impotence Research",Vol.73,No.2, ELSEVIER, , 11/07/2009
:الملخص
The present work explored the possibility of formulating an oral insulin delivery system by combining the advantages of nanoencapsulation and the use of oily vehicle. The parameters affecting formulation such as association efficiency were characterized. The preparation was evaluated for its chemical, physical and biological stability. The preparation has unimodal particle size distribution with a mean diameter of 108+/-9 nm. Insulin was protected from gastric enzymes by incorporation into lipid-based formulation. The results of RP HPLC and ELISA indicated that insulin was able to withstand the preparation procedure. Insulin in the preparations was stable for a period of one month at storage temperatures of 4 and 25 degrees C. It was also biologically active and stable as demonstrated by the remarkable reduction of blood glucose levels of the STZ-diabetic rats after oral administration of the preparation. Moreover, hypoglycemic effect of nanoparticles administered orally was sustained for a longer period of time compared to the subcutaneous injection. These results clearly evidenced the ability of the nanoparticles to enhance the pharmacological response of insulin when given orally and could be used to deliver other peptides.
Download
Badwan A, Remawi M, , " Enhancement of oral bioavailability of insulin in humans. " , "Neuro Endocrinol Lett.",Vol.30,No.1, , , 03/03/2009
:الملخص
OBJECTIVE: The purpose of this study is to investigate oral absorption of 1, 2 and 3 U/kg oral insulin five test products with different particle sizes in comparison with 0.1 U/kg subcutaneous reference formulation.
METHODS: Twenty five healthy volunteers participated in five studies using a two-phase, two-sequence crossover design with washout period of one day. Mean disposition kinetics was determined by non-compartmental analysis using Kinetica program. Absorption kinetics of insulin products were then determined using SIMCYP simulator utilizing ADAM model.
RESULTS & CONCLUSIONS: Dimensional analysis results showed the superiority of formula 4:2 U/kg oral dose with 57 nm particle size over other oral formulations when compared with subcutaneous route. Optimized intestinal permeability coefficients (x10(-4)) of insulin best test and reference formulations were 0.084 and 0.179 cm/sec respectively. Total fraction of insulin dose absorbed (Fa) for the test and reference products were 3.0% and 19% respectively. Subcutaneous product exhibited higher absorption rate and extent than oral insulin. Yet that was compensated by the increase in other factors such as Fa*, Peff* and oral dose, leading to similar insulin plasma levels and similar effect on glucose infusion rates. Oral insulin bioavailability was shown promising for the development of oral insulin product.
Download
Eftaiha AF, Qinna N,, " Bioadhesive controlled metronidazole release matrix based on chitosan and xanthan gum. " , "Mar Drugs",Vol.8,No.5, , , 05/25/2010
:الملخص
Metronidazole, a common antibacterial drug, was incorporated into a hydrophilic polymer matrix composed of chitosan xanthan gum mixture. Hydrogel formation of this binary chitosan-xanthan gum combination was tested for its ability to control the release of metronidazole as a drug model. This preparation (MZ-CR) was characterized by in vitro, ex vivo bioadhesion and in vivo bioavailability study. For comparison purposes a commercial extended release formulation of metronidazole (CMZ) was used as a reference. The in vitro drug-release profiles of metronidazole preparation and CMZ were similar in 0.1 M HCl and phosphate buffer pH 6.8. Moreover, metronidazole preparation and CMZ showed a similar detachment force to sheep stomach mucosa, while the bioadhesion of the metronidazole preparation was higher three times than CMZ to sheep duodenum. The results of in vivo study indicated that the absorption of metronidazole from the preparation was faster than that of CMZ. Also, MZ-CR leads to higher metronidazole C(max) and AUC relative to that of the CMZ. This increase in bioavailability might be explained by the bioadhesion of the preparation at the upper part of the small intestine that could result in an increase in the overall intestinal transit time. As a conclusion, formulating chitosan-xanthan gum mixture as a hydrophilic polymer matrix resulted in a superior pharmacokinetic parameters translated by better rate and extent of absorption of metronidazole.
Download
Alshaker HA, Qinna N, " Eriobotrya japonica hydrophilic extract modulates cytokines in normal tissues, in the tumor of Meth-A-fibrosarcoma bearing mice, and enhances their survival time. " , "BMC Complement Altern Med.",Vol.11,No.1, , , 02/04/2011
:الملخص
ABSTRACT: BACKGROUND: Cytokines play a key role in the immune response to developing tumors, and therefore modulating their levels and actions provides innovative strategies for enhancing the activity of antigen presenting cells and polarizing towards T helper 1 type response within tumor microenvironment. One of these approaches could be the employment of plant extracts that have cytokine immunomodulation capabilities. Previously, we have shown that the Eriobotrya japonica hydrophilic extract (EJHE) induces proinflammatory cytokines in vitro and in vivo. Methods: The present study explored the in vivo immunomodulatory effect on interferon-gamma (IFN-gamma), interleukin-17 (IL-17), and transforming growth factor-beta 1 (TGF-beta1) evoked by two water-extracts prepared from EJ leaves in the tissues of normal and Meth-A-fibrosarcoma bearing mice. Results: Intraperitoneal (i.p.) administration of 10 mcg of EJHE and EJHE-water residue (WR), prepared from butanol extraction, increased significantly IFN-gamma production in the spleen (p< 0.01) and lung (p<0.03) tissues at 6-48 hours and suppressed significantly TGF-beta1 production levels (p< 0.001) in the spleen for as long as 48 hours. The latter responses, however, were not seen in Meth-A fibrosarcoma-bearing mice. On the contrary, triple i.p. injections, 24 hours apart; of 10 mcg EJHE increased significantly IFN-gamma production in the spleen (p < 0.02) while only EJHE-WR increased significantly IFN-gamma, TGF-beta1 and IL-17 (p < 0.03 - 0.005) production within the tumor microenvironment of Meth-A fibrosarcoma. In addition, the present work revealed a significant prolongation of survival time (median survival time 72 days vs. 27 days of control, p< 0.007) of mice inoculated i.p. with Meth-A cells followed by three times/week for eight weeks of i.p. administration of EJHE-WR. The latter prolonged survival effect was not seen with EJHE. Conclusions: The therapeutic value of EJHE-WR as an anticancer agent merits further investigation of understanding the effect of immunomodulators' constituents on the cellular components of the tissue microenvironment. This can lead to the development of improved strategies for cancer treatment and thus opening up a new frontier for future studies.
Download
Jinan A. Al-Qaisi, T, " Synthesis and pharmacological evaluation of aminoacetylenic isoindoline-1,3-dione derivatives as anti-inflammatory agents " , "Arabian Journal of Chemistry",Vol.,No., , , 01/05/2011
:الملخص
Aminoacetylenic isoindoline-1,3-dione derivatives were synthesized from the reaction of potassium phthalimide with propargyl bromide to generate 2-(prop-2-yn-1-yl) isoindoline-1,3-dione (ZM1). Treatment of 2-(prop-2-yn-1-yl) isoindoline-1,3-dione with appropriate cyclic amines through Mannich reaction yielded five desired aminoacetylenic isoindoline-1,3-diones called, ZM 2 to ZM6. The IR, NMR and elemental analysis were consistent with the assigned structures. These synthetic compounds, except ZM6, produced significant (p <0.05-0.01) dose-related inhibition of carrageenan-induced edema in rats following 3 and 5 h post oral administration of 5, 10, and 20 mg/kg doses. The percent inhibition of edema varied between the compounds at 10 mg/kg dose being ZM3 >ZM5>ZM4>ZM 2. These percent inhibitions for ZM3 and ZM5 were not significantly different than those of induced by Ibuprofen, Diclofenac and Celecoxib. At 20 mg/kg dose, ZM4 produced a statistically significant reduction of inflammation (p<0.01) 1h following administration and persisted for 5 h. Furthermore, all the compounds showed inhibition of COX-1and COX-2 with maximum inhibition at 5 μM. However, the inhibition values were less than Diclofenac and Celecoxib. The best response was by ZM4 for COX-2 inhibition ranging from 28, 91, and 44%, for 2, 5, and 10 μM, respectively. Other ZM compounds such as ZM2, ZM3, and ZM5 exhibited inhibitory responses for COX-2 more than COX-1 at 5 μM. These results indicate that these ZM compounds have the potential to become anti-inflammatory drugs following further pharmacological and toxicological evaluations.
Download
Mallah EM, Hamad MF,, " Plasma concentrations of 25-hydroxyvitamin D among Jordanians: Effect of biological and habitual factors on vitamin D status " , "BMC Clin Pathol",Vol.11,No., , , 04/08/2011
:الملخص
BACKGROUND: Vitamin D is cutaneously synthesized following sun exposure (vitamin D3) as well as it is derived from dietary intake (vitamin D3 and D2). Vitamin D2 and D3 are metabolized in the liver to 25-hydroxyvitamin D (25(OH)D). This metabolite is considered the functional indicator of vitamin D stores in humans. Since Jordan latitude is 31oN, cutaneous synthesis of vitamin D3 should be sufficient all year round. However, many indications reveal that it is not the case. Thus, this study was conducted to determine the 25(OH)D status among Jordanians. METHODS: Three hundred healthy volunteers were enrolled in a cross sectional study; 201 females and 99 males. 25(OH)D and calcium concentrations were measured by enzyme linked immunosorbent assay and spectroscopy techniques, respectively. All participants filled a study questionnaire that covered age, sex, height, weight, diet, and dress style for females. Females were divided according to their dress style: Western style, Hijab (all body parts are covered except the face and hands), and Niqab (all body parts are covered including face and hands). RESULTS: The average plasma 25(OH)D levels in males and females were 44.5 +/-10.0 nmol/l and 31.1 +/- 12.0 nmol/l, respectively. However, when female 25(OH)D levels were categorized according to dress styles, the averages became 40.3, 31.3 and 28.5 nmol/l for the Western style, Hijab and Niqab groups, respectively. These 25(OH)D levels were significantly less than those of males (p<0.05, 0.001, 0.001, respectively). In addition, the plasma 25(OH)D levels of the Western style group was significantly higher than those of Hijab and Niqab groups (p<0.001). Furthermore, dairy consumption in males was a positive significant factor in vitamin D status. Even though calcium concentrations were within the reference range, the Hijab and Niqab-dressed females have significantly less plasma calcium levels than males (p< 0.01). CONCLUSIONS: Very low plasma 25(OH)D levels in females wearing Hijab or Niqab are highly attributed to low sunlight or UVB exposure. In addition, most of males (76%) and Western style dressed females (90%) have 25(OH)D concentrations below the international recommended values (50 nmol/l), suggesting that although sun exposure should be enough, other factors do play a role in these low concentrations. These findings emphasize the importance of vitamin D supplementation especially among conservatively dressed females, and determining if single nucleotide polymorphisms of the genes involved in vitamin D metabolism do exist among Jordanians.
Download
Assaf S, Al-Jbour N,, " Factors Involved in Formulation of Oily Delivery System for Proteins Based on PEG-8 Caprylic/Capric Glycerides and Polyglyceryl-6 Dioleate in a Mixture of Oleic Acid with Chitosan " , "Journal of Dispersion Science and Technology",Vol.32,No., , , 08/15/2011
:الملخص
Systematic experimental work is required to improve knowledge related to the use of oily delivery systems. This work aimed to examine the influence of different molecular weights chitosan on formation and solubilization ability of w/o system of Labrasol, Plurol Oleique, water and oleic acid. Phase diagrams were constructed. Size measurements were performed for each surfactant in oleic acid. Interfacial tension of chitosan was measured between oleic acid and water at pH 1.5 and 6.25. Effect of chitosan on microemulsion size was studied. When used to deliver rh-insulin to diabetic rats, the mixture showed reduction in blood glucose compared to control.
Elsayed A, Al-Remawi, " Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin " , "AAPS PharmSciTech",Vol.12,No., AAPS, USA, 09/15/2011
:الملخص
The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.
Matalka KZ, Attallah, " Dopamine selectively modulates lipopolysaccharide-induced TNF-alpha, IFN-gamma and IL-10 within mice tissues " , "Neuro Endocrinol Lett",Vol.12,No., , , 08/01/2011
:الملخص
OBJECTIVES: Dopamine (DA) administration in sepsis is used to modulate the hypotensive condition and to normalize the blood vessels perfusion. However, whether this administration of DA has an effect on the release of cytokines in vivo deserves investigation.
METHODS AND RESULTS: Pre-exposure of DA (1 μg/ml) to whole blood enhanced IL-10 (30%) production level following LPS stimulation. This IL-10 enhancement became statistically significant (p<0.001) upon the addition of D2-DA receptor (DAR) antagonists, Clozapine or Haloperidol. Furthermore, systemic administration of DA (0.5–50 mg/kg) in mice suppressed significantly LPS-induced TNF-α levels in blood, liver, spleen, brain, and lungs; IL-10 levels in blood, brain and liver; and IFN-γ levels in blood, liver, brain, and lungs. On the other hand, DA enhanced significantly LPS-induced IL-10 production in the lungs and spleen, and IFN-γ levels in the spleen. Administration of Clozapine (54 mg/kg) or Haloperidol (62 mg/kg) with LPS (1 μg) and DA (5 mg/kg) reversed DA suppressive effects on LPS-induced cytokines in blood, IFN-γ in brain and lungs, and enhanced significantly LPS-induced IL-10 production in blood, spleen, liver, and lungs.
CONCLUSIONS: These results indicate that DA modulatory effect on LPS-induced blood cytokines-producing cells is mediated mainly by D2-DAR (D2/ D3/D4) through enhancing immune cells migration and extravasation into tissues. Furthermore, DA selectivity on cytokines modulation is tissue specific, mediated by the type of DAR expressed and on the immune cells lodged in each tissue.
Download
Qinna NA, Kamona B, , " Effects of Prickly Pear dried leaves, Artichoke leaves, Turmeric and Garlic extracts and their combinations on preventing dyslipidemia in rats " , "ISRN Pharmacology",Vol.2012,No., , , 08/15/2012
:الملخص
The successful use of herbal combinations in managing diseases or conditions over a single herb has lead us to evaluate the antidyslipidemic properties of the combination of the artichoke leaves extract, turmeric extract, prickly pear dried leaves (PPL) and garlic extract versus each one alone in two different hyperlipidemic animal models. A two-week treatment of each of the natural extracts, combination 1 (artichoke, turmeric and PPL) or combination 2 (artichoke, turmeric, PPL and garlic) prior to a single intraperitoneal injection of Pluronic F-127 resulted in decreasing significantly serum LDL levels by garlic and PPL extracts and serum LDL/HDL ratios by turmeric, PPL, combination 1 and 2. In a 10-day high fat diet model, only the combination 1 and 2 lowered serum cholesterol, LDL by 8–12%, decreased significantly triglycerides, LDL/HDL ratio; and increased significantly HDL (P < 0.0001). However, a long term treatment of each natural product for 7 weeks resulted in decreasing significantly serum LDL levels and LDL/HDL ratio (P < 0.05–0.0001). Furthermore, only artichoke and PPL inhibited significantly HMG-CoA reductase activity (P < 0.05). In conclusion, short term, as well as long term, treatment using the combination of artichoke, turmeric, PPL and garlic extract prevents dyslipidemia; partially through inhibiting HMG-CoA reductase.
Qinna NA, Mallah EM,, " Effect of licorice and grapefruit juice on paracetamol pharmacokinetics in human saliva " , "Int J Pharm Pharm Sci",Vol.4,No.4, , , 10/15/2012
:الملخص
The effect of grapefruit juice and liqorice juice on salivary pharmacokinetics of paracetamol (acetaminophen, APAP) in 8 healthy subjects (4 males and 4 females) was investigated. Paracetamol tablet (500 mg) was administered to the volunteers with either 240 mL grapefruit juice, licorice juice or water followed by saliva samples collection at different time intervals in a sequential study design with washout period of 3 days. Results have shown unexpected significant decrease in salivary Cmax and AUC of paracetamol due to grapefruit consumption with delay in Tmax (p < 0.05), while licorice consumption did not produce any significant changes in all tested parameters. However, a notable increase in the Cmax and AUC in females receiving licorice juice, but not in males, was revealed when compared to female control group. Therefore, in order to remove the confounding results of gender effect, the pharmacokinetic parameters of paracetamol following ingestion of grapefruit and licorice juice were analyzed for each sex separately and showed no differences within each gender when compared to the water control group. In addition, smoking had shown essentially no effect on paracetamol pharmacokinetics except a shift in Tmax when licorice juice was consumed. In conclusion, consuming grapefruit juice and licorice juice along with paracetamol could cause differences in the salivary pharmacokinetics of paracetamol and should be avoided until further clinical studies establish the safety of such interactions in both males and females.
Download
Matalka KZ, Alfarhou, " Anti-inflammatory aminoacetylenic isoindoline-1,3-dione derivatives modulate cytokines production from different spleen cell populations " , "Int Immunopharmacol",Vol.In Press,No., , , 07/25/2012
Athamneh NA, Tashtou, " A new controlled-release liquid delivery system based on diclofenac potassium and low molecular weight chitosan complex solubilized in polysorbates " , "Drug Dev Ind Pharm",Vol.39,No.8, , , 08/16/2013
:الملخص
A complex of low molecular weight chitosan (LMWC) with oleic acid and diclofenac potassium (DP) was prepared and dispersed in high concentrations of polysorbate 20, 60 and 80 in water to form a solution which releases its components slowly. The formed complex was characterized using different analytical methods. The size of the resulted nanoparticles and the effect of tweens on size were followed using dynamic light scattering (DLS). The release of DP from this delivery system was monitored by altering the molecular weight of chitosan and the type and concentration of the polysorbates used. The most suitable preparation consisted of DP, LMWC 13 kDa, and oleic acid. This was dispersed in 5% Tween 80 and the release was followed by the adaptation of USP II apparatus using a cellophane bag. This preparation offers a release of up to 24 h.
Qinna NA, Muhi-Eldee, " Non-Selective Inhibition of Cyclooxygenase Enzymes by Aminoacetylenic Isoindoline 1,3-Diones " , "Inflamm Allergy Drug Targets",Vol.11,No., Bentham Science Publishers, , 09/01/2012
:الملخص
The reported pharmacological activities of acetylenic and phthalimide groups promoted our interest to synthesize a novel series of N-[4-(t-amino-yl)-but-2-yn-1-yl] isoindoline-1,3-diones as anti-inflammatory compounds. The aim of this research is to investigate the selectivity of two compounds, ZM4 and ZM5, on inhibiting cyclooxygenase (COX) in vitro and in silico as well as reducing carrageenan-induced edema in rats. Oral administration of 5-20 mg/kg ZM4 and ZM5 reduced significantly carrageenan-induced edema in dose-and time dependent manner. Furthermore, the IC50 values induced by ZM4 and ZM5 were in the range of 3.0-3.6 M for COX1 and COX 2 but were higher than those induced by Diclofenac and Celecoxib, respectively. Docking of ZM4 and ZM5 in both COX enzymes, on the other hand, exhibited the conventional binding modes that are usually adopted by different non-steroidal anti-inflammatory drugs (NSAIDs). Furthermore, ZM4 and ZM5 bind to COX enzymes as strongly as Flurbiprofen and Celecoxib. In conclusion, aminoacetylenic isoindoline 1, 3-dione compounds have shown anti-inflammatory activity by inhibiting COX-1 and COX-2 enzymes. Interestingly, the best hits showed inhibition at low micromolar levels although they are not selective at this stage. Further research will be conducted to improve both selectivity and potency.
Shakir R, Muhi-Eldee, " Analgesic and Toxicity Studies of Aminoacetylenic Isoindoline-1,3-dione Derivatives. " , "ISRN Pharmacol",Vol.2012,No.2012: 657472, , , 12/20/2012
:الملخص
We have developed a series of minoacetylenic isoindoline-1,3-dione compounds and showed their anti-inflammatory activities by reducing carrageenan-induced rat paw edema and modulating proinflammatory and anti-inflammatory cytokines. In the present study and due to efficacy reasons, we are exploring only two of these compounds, namely, ZM4 and ZM5, to reveal their analgesic activity and toxicity. Following oral administration, both compounds were effective in reducing significantly (P < 0.05-0.001) acetic acid-induced writhing behavior, hot plate latency test, and formalin-induced paw licking time as antinociceptive indicators in mice and rats, respectively. Regarding the toxicity, the acute (20, 50, and 150 mg/kg) and repeated oral administration (10, 20, and 50 mg/kg) of these compounds for ten days did not produce any mortality and the compounds were considered well tolerated. However, repeated oral administration of 50 mg/kg of both compounds induced erythropoiesis by means of increasing significantly red blood cells, hemoglobin, and packed cell volume. Moreover, these compounds did not induce gastric lesions in the stomach of experimental animals at the doses that exhibited analgesic and anti-inflammatory activity compared to indomethacin as a positive control. The results indicate that ZM4 and ZM5 possess potential analgesic activity while being preliminarily safe and have minimal ulcerogenic activity.
Download
Matalka KZ, Alsaadi , " Enhancing Doxorubicin-induced MCA-fibrosarcoma cytotoxicity by an Eriobotrya japonica hydrophilic butanol-treated extract through natural killer cells activation. " , "",Vol.S18-003,No., , , 12/31/2012
:الملخص
The combination of cytotoxic drugs with immunotherapy should be more effective than monotherapy alone since
both therapeutic modalities may target different mechanisms. In addition, combination therapy may reduce adverse
events associated with cytotoxic drugs. Eriobotrya japonica hydrophilic butanol-treated extract (EJWR) was found
to modulate cytokines by enhancing IL-12, IFN-γ and TNF-α in vitro and in vivo and within tumor microenvironment.
This was associated with enhancing survival time of mice bearing intra-peritoneal MCA fibrosarcoma (MCA FS).
In the present work, we evaluated the combination of EJWR with doxorubicin (Dox) on MCA FS cytotoxicity using
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay in the absence and presence of
spleen cells or Natural Killer (NK) lymphocytes from tumor bearing mice. The results showed that Dox exhibited
mild cytotoxicity to healthy spleen cells and EJWR reversed such cytotoxicity. In addition, increasing concentrations
of Dox induced 40% (p<0.01) MCA FS cytotoxicity. This percent increased significantly to 60% at Dox 5 μM when
co-cultured with NK cells from tumor bearing mice and increased further to 80% (p<0.01) when Dox was combined
with EJWR. The latter increase in cytotoxicity was significantly (p<0.01) higher than each agent alone. This
enhancement was associated with significant production of TNF-α and retaining IFN-γ levels from NK cells lysates.
This concluded that the immunomodulator, EJWR, mediates NK activation and enhances Dox- induced MCA FS
cytotoxicity.
Qinna NA, Akayleh FT, " Evaluation of a functional food preparation based on chitosan as a meal replacement diet " , "J Funct Foods",Vol.5,No.2, Elsevier, , 04/01/2013
:الملخص
The ability of chitosan to entrap large amounts of water when dispersed in an oily phase was utilized to formulate a novel meal replacement functional food. Furthermore, the proposed preparation can be fortified with nutrients. The purpose of this formulation was to produce an edible low calorie pseudo-fatty rich meal that can enhance the feeling of satiety when ingested. Different concentrations of chitosan and pectin were tested to find out a stable preparation with acceptable physical characteristics. It was found that a preparation containing 1% chitosan and 6% pectin is suitable to be consumed as a meal replacement diet. The safety of such preparation was assessed by repeated dose administration to rats. A set of other in vivo experiments was performed to assess the ability of this preparation to enhance satiety. The ingestion of chitosan preparation resulted in reduced body weight, food and water intake, and reduced faecal excretion in the emulsion administered rats (p < 0.05). Furthermore, serum lipids of tested rats were not essentially changed. Accordingly, the investigated chitosan emulsion could be introduced as a low calorie, relatively stable and a safe functional food preparation for enhancing satiety when ingested as a meal replacement diet.
Al- Akkam EJ, Abdul , " Development and validation of a sensitive and accurate method for determination of atorvastatin and rosuvastatin in rat plasma by reversed-phase high performance liquid chromatography with UV detection " , "Int J Pharm Pharm Sci.",Vol.5,No.Suppl 2, , , 05/01/2013
:الملخص
Objective: To develop a new, accurate, precise and rapid isocratic reversed-phase high performance liquid chromatographic/ultraviolet (RP-HPLC/UV) method for the determination of atorvastatin (ATV) and rosuvastatin (RST) in rat plasma using diclofenac sodium and naproxen sodium, as an internal standard (IS), respectively.
Methods: ATV and RST were analyzed on a BDS hypersil C18 column (250 mm× 4.6 mm, 5μm), applying methanol: water (68:32, v/v) and (63:37 v/v), respectively, in isocratic mode as a mobile phase. Its pH was adjusted to 3.0 with trifluroacetic acid at a flow rate of 1 ml/min. The peak response was monitored at 241nm after injecting a 100μl sample into HPLC system. The direct liquid–liquid extraction procedure was applied to rat plasma samples using methyl-tert-butyl ether as an extraction solvent after protein precipitation with ammonium acetate buffer. The different HPLC experimental parameters were optimized and the method was validated according to standard guidelines.
Results: A peak area was obtained for ATV and RST with 11.35 and 6.65min retention time, respectively, while their respective IS appeared at 15.73 and 10.463min. The calibration curves were linear over concentration ranges of 20-200ng/ml of ATV and RST. The lower limit of detection (LLOD) values were found to be 1.35 and 7.2ng/ml, for ATV and RST, respectively, while their respective lower limit of quantification (LLOQ) values were 10.3 and 8.5ng/ml. The average recoveries of the suggested method in rat plasma were 96.48% and 91.43%, for ATV and RST, respectively. The percent of relative standard deviation (%RSD) of ATV in plasma was in the range of 0.124–0.536 % and 0.194–1.071%, for intra-day and inter-day studies, respectively, while for RST was in the range of 0.218-1.909% and 0.217-1.971%.
Conclusion: The method was found sensitive, accurate, and precise in rat plasma and could be applied for the quantification of these compounds in plasma and other biological fluids such as liver homogenate samples, for pharmacokinetics and drug-drug interaction studies, using animal models.
Nidal A. Qinna
:الملخص
The increased use of herbal remedies combined with their increasing availability in pharmacies, beauty and nutrition shops and supermarkets necessitates the evaluation of their efficacies and safety. The objective of the present study is to evaluate the safety of the rectal administration of the dry leaf extract of witch hazel (Hamamelis virginiana L. Family: Hamamelidaceae), one of the traditionally used herbs for treating hemorrhoids. H. virginiana dry leaf extract was formulated in suppositories. An acute single dose study on rabbits and a 28 day repeated dose rectal administration of hamamelis extract on rats were preformed. No deaths occurred in either the placebo or the hamamelis treated rabbits. The general condition of all the rabbits was normal without any significant changes in their body weights. The changes in clinical and hematological parameters were non significant (p > 0.05). In the 28 day repeated dose study, no deaths occurred and normal body weight gains were recorded in all groups. Before sacrifice, the rats behaved normally with no detected signs of sickness or discomfort. After sacrifice, the inspected organs were normal in morphology and histopathology without any detected weight differences. All treated rats showed normal biochemical and hematological profiles compared to placebo treated animals (p > 0.05). The results obtained from the present study indicate that the rectal administration of H. virginiana dry leaf extract (up to 300 mg/kg) formulated as suppositories was devoid of systemic toxicity.
Download
HTA Tbeekh, WAA Dayy, " Pomegranate Juice affects on Pharmacokinetic Parameters of Metronidazole by using HPLC-MS " , "World Journal of Pharmacy and Pharmaceutical Sciences",Vol.3,No.7, , , 07/01/2014
:الملخص
Objective: To quantify Metronidazole in rat serum by using HPLC/MS and to study the effect of pomegranate fresh juice on the Metronidazole pharmacokinetics Methods: The serum samples were prepared by using protein precipitation method with Clindamycin in methanol solution. A gradient mobile phase system and ACE 5 C18 column were used for the analysis. Rats (n=4) were treated with a single ordinary dose (5ml/kg) of freshly squeezed pomegranate juice 30 min before orally administered-Metronidazole while other groups of rats (n=4) were treated with a multiple dose of the juice twice daily for two days versus DW pretreated rats (n=2). The study protocol was approved by the ethical committee of Graduate Studies at Faculty of Pharmacy and Medical Sciences of University of Petra/Amman-Jordan (March, 2012). Key findings: The analytical method was linear with acceptable recovery, precision and accuracy. The results show that there was a significant increase in the Metronidazole pharmacokinetic parameters (Cmax and AUC, P<0.05) after pretreatment with multiple dose of pomegranate juice. Conclusions: Pomegranate juice with a multiple dose pre-treatment could be a good intestinal but not hepatic enzymes inhibitor for Metronidazole metabolism.
Download
Mujtaba M Badr, Nida, " Dichloroacetate modulates cytokines toward T helper 1 function via induction of the interleukin-12–interferon-γ pathway " , "OncoTargets and therapy",Vol.7,No., , , 04/01/2014
:الملخص
Background
Dichloroacetate (DCA) is one of the new, promising anticancer drugs. DCA restores normal mitochondrial function and enables cancer cells to undergo apoptosis. In addition, DCA was found to modulate certain signaling pathways involving some transcription factors. The latter encouraged us to study DCA immunomodulatory activity on cytokines and their association with increasing DCA cancer cell cytotoxicity.
Methods and results
Cell viability assay was used to determine the effect of different concentrations of DCA on the survival of 3-methylcholanthrene (MCA) fibrosarcoma cell line. DCA decreased the percent survival of MCA fibrosarcoma in a dose-dependent manner (P<0.01). Furthermore, this percent survival was further reduced when MCA fibrosarcoma cells were cocultured with mouse splenocytes. The latter was observed at 10 mM DCA (P<0.01), and the inhibitory concentration at 50% dropped from 23 mM to 15.6 mM DCA (P<0.05). In addition, DCA significantly enhanced interferon (IFN)-γ but not interleukin (IL)-17 production levels in unstimulated and stimulated mouse spleen cells. To investigate the mechanism of DCA on IFN-γ production, DCA cytokine modulatory effect was tested on unstimulated macrophages, T-cells, and natural killer cells. DCA significantly increased IL-12 production from macrophages but did not modulate the production of IFN-γ from either T-cells or natural killer cells. Moreover, the DCA-enhancing effect on IFN-γ production was reversed by anti-IL-12 antibody. Also, the DCA cytokine modulatory effect was tested in vivo after inducing mouse skin inflammation using phorbol 12-myristate 13-acetate (PMA). DCA restored PMA-lowered IFN-γ and IL-12 levels and normalized PMA-increased transforming growth factor-β level, but it inhibited IL-10 levels even further (P<0.05).
Conclusion
DCA has immunomodulatory activity, mainly via activation of the IL-12–IFN-γ pathway and is able to modulate cytokines toward T helper 1 lymphocyte function. These DCA immunomodulatory effects are promising and further investigations are required to develop protocols for its use in cancer treatment.
Download
1. Ghanim, B.Y. and Qinna, N.A., " Nrf2/ARE Axis Signalling in Hepatocyte Cellular Death " , "Molecular Biology Reports",Vol.-,No., -, -, 01/01/2022
:الملخص
-
Ghanim, B.Y., Ahmad, M.I., Abdallah, Q.M., Qatouseh, L.A. and Qinna, N.A, " Modulation of NRF2/ARE pathway-and cell death-related genes during drug-induced liver injury " , "Human & Experimental Toxicology",Vol.-,No., -, -, 12/01/2021
:الملخص
-
Abdelmalek, S., AlEjielat, R., Rayyan, W.A., Qinna, N. and Darwish, D., " Changes in public knowledge and perceptions about antibiotic use and resistance in Jordan: a cross-sectional eight-year comparative study " , "BMC public health",Vol.-,No., -, -, 11/04/2021
:الملخص
-
4. Khaleel, A., Meqbel, A., Alejielat, R., Batarseh, Y.S., Elbakkoush, A.A., Ghanim, B.Y., Batarseh, C.I. and Qinna, N.A., " Identifying gene clusters as signature biomarkers for predicting methotrexate effectiveness and potential side effects during Rheumatoid Arthritis therapy " , "International Journal of Pharmaceutical Research",Vol.-,No., -, -, 09/30/2021
:الملخص
-
-
Nawzat D. Al-Jbour, , " Influence of Glucosamine and the low molecular weight chitosan on Ibuprofen plasma concentration following oral administration in rats " , "11th Eurasia Conference on Chemical Sciences",Vol.,No., , Dead Sea, Jordan, 10/09/2010
:الملخص
The effect of complexing ibuprofen with glucosamine or the low molecular weight chitosan (LMWC) on increasing the bioavailability of ibuprofen was studied. LMWC was prepared from high molecular weight chitosan using the acid hydrolysis method. The complexes were characterized using the DSC, FT-IR, and liquid H-NMR. The used weight ratios of ibuprofen to glucosamine were (1:1), (1:2), (1:3), and (1:4). The plasma concentration–time profiles using (HPLC method) of ibuprofen complexes showed that the bioavailability of ibuprofen in the blood increases as the amount of glucosamine increases compared with ibuprofen reference, and the ratio of (1:4) showed the maximum bioavailability. Also chitosan with average molecular weights of 1 kDa, 1.3 kDa, 6 kDa, and 13 kDa were complexed with ibuprofen in a ratio of (4:1). The plasma concentration-time profile showed that the bioavailability of ibuprofen increases when chitosan molecular weight ≤ 1.3kDa, while the molecular weights of 6 and 13kDa did not affect its bioavailability. This could be due to conformational changes that may occur from extended chain into coiled sphere as the molecular weight of chitosan increases. So this study showed the potential of complexing ibuprofen with glucosamine and the LMWC in decreasing drug metabolism, increasing its bioavailability and then decreasing the doses given to patients.
Maryam H. Shubbar, N, " Impact of Glucosamine on the bioavailability of Paracetamol after oral administration in rats " , "11th Eurasia Conference on Chemisrty Sciences",Vol.,No., , Dead Sea, Jordan, 10/08/2010
:الملخص
In previous work, glucosamine increased the plasma serum level of ibuprofen administered to rats. It is proposed that this increase is due mainly to the inhibition of ibuprofen metabolism. Metabolic enzyme inhibition is the primary mechanism for drug-drug pharmacokinetic interactions. In this study, paracetamol has been chosen as a second drug model. Both paracetamol and glucosamine have effects in treatment of osteoarthritis. While paracetamol is a common analgesic and antipyretic drug, glucosamine plays a key role in building the cartilage.
The effect of administration of different ratios of glucosamine on paracetamol bioavailability was studied on rats. Paracetamol doses tested were 30 mg/kg and 10 mg\kg formulated with glucosamine in ratios of (1:1), (1:3), (1:4). The blood serum were prepared from blood samples collected from the rat tales at different time intervals and analyzed using a validated HPLC method.
The plasma concentration–time profiles of the combinations showed that the bioavailability of paracetamol in the blood increases as the amount of glucosamine in the preparation increase compared with paracetamol reference. Furthermore, the (1:4) ratio enhanced the maximum bioavailability where the cmax increased by 46% and the AUC increased by 96% compared to paracetamol reference. In contrast, the combination with paracetamol at a higher dose (30 mg\kg) gave less escalation in the cmax and did not increase the AUC significantly.
In conclusion, glucosamine may increase the bioavailability of paracetamol by altering its metabolism in the liver. It is expected that the increase in paracetamol bioavailability at low dose is due to the competition between glucosamine and paracetamol on the binding site of CYP 450 enzyme in liver.
