Iraqi Journal of Pharmaceutical Sciences
Iraqi Journal of Pharmaceutical Sciences (IJPS) is the official journal of the College of Pharmacy, University of Baghdad. The IJPS is a biannual specialized scientific journal which was first founded in 1979. The aim of this journal is to support scientific knowledge and encourage scientific research and publications. The IJPS provides a forum for reporting innovations, production methods, technologies, initiatives and the application of scientific knowledge to all aspects of pharmaceutical sciences, including advanced drug delivery systems, drug targeting, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and pharmacy practice . The journal has issued thirty volumes and fifty three issues from 1979 until December of 2021. Iraqi Journal of Pharmaceutical Sciences (IJPS) is an open access peer-reviewed journal. Open access (OA) refers to a free and unrestricted online access to journal articles. The OA content is open to all with no access fees. For more information on Creative Commons license and the benefits of publishing an open access article
University of Baghdad- College of Pharmacy
Liquiritin Attenuates Diabetic Nephropathy in Type 2 Diabetic Male Rats Irrespective of Antihyperglycemic Effect
Diabetic nephropathy represents one of the common and serious complications of diabetes mellitus and it’s a leading cause of renal failure. Liquiritin is one of the main flavonoids found in Glycyrrhiza glabra that has been shown to have several pharmacological effects, such as the antioxidant, anti-inflammatory, anti-tumor, cardiovascular protection, hepatoprotection, and attenuation of rheumatoid arthritis in experimental animals. The present study investigated the protective effect of liquiritin against diabetic nephropathy in high fat diet and streptozotocin (STZ) induced diabetes mellitus in male rats. In the present study, the type 2 diabetes model was induced by feeding the animals with the high fat diet for four weeks, after that the animals were fasted overnight and injected with a single intraperitoneal dose of STZ 30 mg/kg. Liquiritin was administered daily at a dose of 40 mg/kg for 15 weeks. At the end of the experimental period, blood glucose level, glycated hemoglobin A1 (HbA1c), lipid profile markers, serum renal function parameters, renal index were assed, levels of inflammatory and oxidative markers namely interleukin-1beta (IL-1β), interleukin -6 (IL-6), tumor necrosis factor-alpha (TNF- α), and transforming growth factor-beta (TGF-β1), glutathione (GSH), and malondialdehyde (MDA) were determined in the renal homogenate, and the histopathological examination was performed by the use of hematoxylin and eosin staining, where the histopathological changes in kidney tissues were semi-quantitatively calculated according to a renal pathology scoring system. The diabetic control group showed a significant increase in the glycemic control parameters, and renal function parameters, and showed significant histopathological changes compared with the normal control group. The results revealed that liquiritin significantly improves histopathological changes while doesn’t affect the glycemic control parameters with a reduction in the inflammatory markers and oxidative stress in the renal homogenate. Liquiritin has an ameliorating effect against DN and it can significantly decrease most of the histopathological changes, and oxidative, and inflammatory markers.
diabetes mellitus, diabetic nephropathy, flavonoids, liquiritin, oxidative stress
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Adipsin and Leptin as Therapeutic Targets by Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Mellitus: Review Article
Type 2 diabetes mellitus (T2DM), one of the most common metabolic diseases, is caused by a mix of insulin-sensitive tissues' inadequate response to insulin and pancreatic β-cells' impaired insulin secretion. Adipsin is involved in preserving the homeostasis of adipose tissues and enhancing insulin secretion in response to glucose. Adipose tissue secretes adipokines, which are cell-signaling proteins that have been connected to various pathologies as well as a low-grade state of inflammation. Although the regulation of energy homeostasis is a well-established function of the obesity hormone leptin, there is increasing evidence that leptin is also essential for glycaemic control. The hormone leptin is a 167-residue peptide produced by the Lep gene. Adipose tissue is the main source of its secretion. Leptin levels in the blood are undetectable when the Lep gene is functionally inactivated. To increase the precision of disease prediction, offer fresh perspectives on pathophysiology, and aid in the prevention of type 2 diabetes in the future, a validated novel biomarker is necessary. Targeting endogenous proteins has led to the development of several more advanced diagnostic techniques, with adipsin being one of the most promising targets. Therefore, the aim of this review study is to assess the effects of DPP-4 inhibitors on adipsin and leptin in T2DM. The function of DPP-4 (DPP4) inhibitors has changed in recent years. DPP-4 inhibitors do not result in hypoglycemia or weight gain, have a good safety profile, an anti-inflammatory profile, and do not need dose escalation. It can also be used with older diabetic patients and patients with certain forms of chronic kidney disease. Adipsin has the potential to become an early novel biomarker in patients with T2DM.
Effect of CYP3A4 Genetic Polymorphism on Clinical Response of Tamoxifen in Postmenopausal Iraqi Women with Breast Cancer
Breast cancer is the leading cause of death and is the most frequent disease among women. Tamoxifen is an antiestrogen used to treat breast cancer. It may completely halt the disease's progression in high-risk individuals and lower the risk of death and recurrence in premenopausal and postmenopausal women. Variations in tamoxifen responsiveness between individuals may be attributed to polymorphisms in the primary metabolizing enzyme CYP3A4. The wild genotype (GG) of rs35599367 was found to be most common in 100 female breast cancer patients who were hormone receptor positive and taking tamoxifen, according to the study. This genetic variation may have a significant impact, as the GG genotype is strongly linked to significantly lower levels of CA15.3 and estrogen. Therefore, the results of this study imply that CYP3A4 variations may be a useful predictor of a patient's prognosis and response to tamoxifen. Keywords: CA 15.3, CYP3A4 polymorphism, Estradiol, Tamoxifen.
Solubility and Dissolution Rate Enhancement of Simvastatin by Adsorption on Magnesium Aluminum Silicate
Simvastatin (SIM), is an inactive lactone, anti-hyperlipidemic drug. The drug belongs to the class II group according to the biopharmaceutical classification system (BCS) with low bioavailability due to its low solubility. Adsorption technique is an effective technique for improving the solubility and dissolution rate of poorly soluble drugs by using the mesoporous silica. The present study aims to enhance the solubility and dissolution rate of SIM using such technique. Soluplus® and poloxamer 407 were used as surfactants besides magnesium aluminum silicate (MAS) as adsorbent. All the MAS loading SIM formulations were prepared by the solvent evaporation method in different drug: adsorbent: surfactant weight ratios, then evaluated for their percentage yield, drug content, water solubility, dissolution, crystal lattice using X-ray powder diffraction (XRD) and Differential Scanning Calorimetry (DSC) studies and Fourier Transform Infrared Spectroscopy (FTIR) for determination the drug- excipient interaction. All the prepared formula showed improvement of drug solubility. The best result was obtained with formula F8(SIM: MAS: SOLU 1:6:3) that showed, 91.3% yield, 85.5±0.19 % drug content,178.3 -fold increase in solubility compared to solubility of pure drug and 1.6-fold as compared to F6(without soluplus®) and 85.5 % of drug released within 30 minutes with reduced crystallinity of the drug and compatibility between the drug and the additives. Therefore, the adsorption technique can be considered as an efficient method for enhancing the solubility and dissolution rate of SIM.
Pharmaceutical Approach of Nano- Particles as a Targeted Nasal-Brain Delivery System
The first study reported for nasal brain drug delivery was in 1937. The uptake of nasal - brain drug delivery, has received a great deal of attention as a convenient, method for the systemic administration of drugs. Which are low less effective orally, and, only effective if administered by injection. Many well-known different pathways and routes for drug absorption via the nose are affected by various factors. Some of them are factors related to the natural physiology of the nose and mucociliary clearance, enzyme, blood flow in the nasal cavity, and diseases. The bio-fate of drugs instilled in nasal cavity, is mainly affected by the pharmaceutical and pharmacokinetic properties of the drugs Pharmaceutical nanoparticulate carriers, also known as nanomedicines, offer numerous benefits for delivering neurotherapeutics from the nose to the brain. Most types of nanocarriers have been extensively researched for this purpose, including nanoemulsions and solid-lipid nanoparticles (SLNs)., and nanosuspensions. However, there are multiple potential problems associated with the intranasal route of administration of nanocarriers, such as, toxicity and irritation of the nasal mucosa, stability of nanocarriers inside the nasal membranes, and possible degradation of enzymes during passage. In general, the adherence of the traditional formulation to the mucosal membrane of the nasal cavity can be enhanced by including synthetic polymers such as Eudragits, which are derived from acrylic and methacrylic acid. The destiny of nanocarriers is determined by their inherent physicochemical characteristics. For example, the characteristics that can be considered include the composition, particle size, surface charge, as well as surface hydrophobicity or hydrophilicity. Different experimental models were used in the published studies, like in vitro, in vivo and ex-vivo models, besides to cell culture and, cell line models. This quantitative analysis must be revealed as blood- brain drug ratio, besides to absolute, and relative bioavailability of the drug delivered by the brain Moreover, qualitative analysis should be recognized for most of nano particle’s morphology like optical imaging, brain histopathology, fluorescence microscope, and gamma scintigraph. In the following review article, aims are provided a detailed review of literature concerning direct nose-to-brain drug delivery.
Enhancing Elderly DiaβCare: Pharmacist-Initiated Counselling and SMS Reminders Impact on Medication Adherence and Clinical Outcomes
Medication non-adherence is a significant challenge in chronic diseases such as type 2 diabetes mellitus (T2DM), particularly among elderly patients, leading to increased healthcare costs and adverse outcomes. This study aimed to assess the impact of pharmacist-led counselling and short message service (SMS) reminders on medication adherence and clinical outcomes in newly diagnosed elderly patients with T2DM. A 12-month prospective, open-label, randomized controlled study was conducted at an outpatient diabetic clinic, with 340 participants randomly assigned to either the Diaβcare or usual care groups. The Diaβcare group received pharmacist counselling sessions and SMS reminders, while the usual care group received standard care. Medication adherence and clinical outcomes, including HbA1C, random blood sugar (RBS), fasting blood sugar (FBS), blood pressure (BP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and body mass index (BMI), were assessed. Statistical analysis used: Sociodemographic characteristics were compared using the Z-test, medication adherence was analysed using the Mann–Whitney test, and clinical outcomes were compared using the t-test (P < 0.05, IBM SPSS v21.0). The Diaβcare group demonstrated significantly improved medication adherence (12.2±7.1%) compared to the control group (0.75±10.2%) (P<0.001). Furthermore, significant reductions in HbA1C, systolic blood pressure (SBP), and LDL cholesterol levels were observed in the Diaβcare group compared to the usual care group (P<0.01). Pharmacist-led Diaβcare effectively enhanced medication adherence and improved clinical outcomes in elderly patients with T2DM. Collaborative efforts among healthcare providers, policymakers, and technologists are essential for scaling up such interventions to enhance global health outcomes.
clinical pharmacist led educational intervention
Molecular Docking,Synthesis and Preliminary Anti-microbial Evaluation of Some New Sulfonohydrazide and 1,3,4-Oxadiaxzole Derivatives of Flurbiprofen
A new series of compounds were derived from 2-(2-fluoro-[1,1'-biphenyl]-4-yl)propanoic acid by reacting flurbiprofen ethyl ester with hydrazine hydrate to get flurbiprofen hydrazid(III) which then reacted with three different sulfonyl chloride compounds (Benzenesulfonyl Chloride, 4-toleunesulfonyl Chloride, 4-chlorosulfonyl Chloride) in the existence of triethylamine. Additionally, compound (III) and carbon disulfide were reacted to yield oxadiazole 2-thione (compound V), which was subsequently reacted with 4-chlorophenacyl bromide and 4-bromophenacyl bromide to yield the final products (Va & Vb). For characterization of the final compounds, FT-IR and 1H-NMR spectroscopy were used . Each final compound(IVa-c,Va-b) was examined for their Anti-Microbial activity against G(+)ve bacteria (Streptococcus pyogenes, Staphylococcus aureus), G(-)ve bacteria (Escherichia coli, Klebsiella pneumoniae) and strain of fungi (Candida albicans). Compound (IVc) showed highest antimicrobial activity against G(-)ve and G(+)ve bacteria and Candida albicans fungi. The ADMET study of the resulting compounds exhibited desirable pharmacokinetic properties along with acceptable estimated drug-like properties. molecular docking revealed good molecular docking results with target protein using ciprofloxacin as the reference.
Evaluation of Antipsoriatic Effect of Ivermectin in Animal model of Psoriasis
Ivermectin (IVR) is widely used for the treatment of onchocerciasis and other nematode infections .Recent studies have reported that IVR has an anti-inflammatory effect and is used in the treatment of allergic asthma, dermatitis, and arthritis. Psoriasis is a chronic immune-mediated inflammatory skin disease in which IL-17 and VEGF play an important role as pro-inflammatory and angiogenic mediators.To evaluate the therapeutic effect of IVR in psoriasis, we used an imiquimod (IMQ)-induced psoriasis model in rats. Twenty-four male wister-albino rats, age 3-4 monthe and weighing 170-200 g were used in this experiment. They were assigned at random into four groups, each group include 6 animals. Rats in each group (except normal control group) are topically administered 62.5 mg of IMQ cream for 10 days, then they were treated for 12 days with one of the following drugs starting from the day four after first application of IMQ cream: the first group treated with subcutaneous (SC) injection of normal saline once daily and consider as positive control group; the second one is Methotrexate (MTX) treated group using conventional dose in autoimmune disease (1.0 mg/kg/week, intraperitoneal injection); and last group is IVR treated group (0.5 mg/kg/day, SC injection). Subcutaneous administration of IVR to the rats, significantly minimize the Psoriasis Area Severity index (PASI) regarding the thickness, scaling and erythema (3.00 ± 2.19) comparing to the positive control group (6.83 ± 1.16) with p value < 0.05. Furthermore, IVR attenuate the histopathological changes of skin lesion with no significant differences comparing to MTX treated group (standard drug for psoriasis treatment). In addition to that, the level of IL-17 and VEGF in psoriatic skin lesion were significantly reduced by IVR and MTX compared to a positive control group (p < 0.05), suggesting the ability of this drug in the alleviation of psoriasis by this mechanism.
IL-17, Imiquimod induce psoriasis, Ivermectine, Psoriasis and VEGF
In-silico Studies, Synthesis and Preliminary Biological Evaluation of New Fluoroquinolones-antioxidants Hybrid Compounds
The present study aims to facilitate the development of new agents with better properties specifically, we focus on modifying the basic structure of quinolones; by introducing new functionality at its C3 position. For this purpose, a series of new conjugation derivatives (IIa-Vb) were designed and synthesized by esterification of quinolones (ciprofloxacin, gatifloxacin, nalidixic acid and norfloxacin) with two types of antioxidants (a: menthol and b: umbelliferone) at their carboxylic group at the C3 position which was replaced by an ester group through a glycol linker. The synthesized compounds were checked and characterized for their purity and chemical structure by spectral techniques (NMR, ATR-FTIR) also they were examined for their Pharmacological activities. In vivo, the anti-inflammatory effect of (IIa-Vb) compounds was estimated using a rat paw edema model and showed good activity for the end compounds IIa and IId, and their anti-inflammatory and antimicrobial effects were subsequently evaluated virtually-molecularly analyzed ; all prepared compounds show-interesting activity compared to the DMSO control group (solvent and control). The new conjugation derivatives were further tested about their antimicrobial activity against both grams positive and gram-negative bacteria , using the well diffusion method; the results showed that all eight synthesized compounds exhibited significant (high) antibacterial activity against gram-negative bacteria (Escherichia coli) compared to the reference drug (ciprofloxacin): (IIa and IIb) in concentration 50 mg, (IIa , IIb and IIIb) in concentration 25 mg (IIa , IIb , IIIb and Va) in concentration 12.5 mg. Higher inhibition and significant activity against gram-positive bacteria (Staphylococcus aureus) were demonstrated with quinoline derivatives: (IIa) in concentrations 50-25 mg, (IIa and Va) in concentration 12.5 mg. The other tested compounds showed good activity against bacterial species, ranging from equal, moderate to acceptable activity. Also the synthesized compounds shown significant antifungal activity against (Candida albicans) when compared with Fluconazole drug :( IIa, IVb, Va and Vb) in concentration 50 mg, (IIa ,Va and Vb) in concentration 25 mg. ADMET analysis of quasi-active molecules was performed and demonstrated an acceptable drug-like profile and desirable pharmacokinetic properties.
Evaluation of the Physicochemical and Antioxidative Properties of Curcumin Metallocomplexes in Self-Microemulsifying Drug Delivery Systems
Curcumin (CUR), an active constituent of turmeric which is capable of forming complexes with metal ions. Even though CUR metallocomplexes displayed better biological activities compared to the free CUR, their application in medicine is limited by their poor aqueous solubility. This research aimed to develop self-microemulsifying drug delivery systems (SMEDDSs) to improve the solubility and the antioxidative activity of CUR metallocomplexes. Mononuclear (1:1) CUR metallocomplexes (CUR-Cu, CUR-Mg and CUR-Fe) were synthesised with Cu2+, Mg2+ and Fe3+ salts. The CUR and CUR metallocomplexes were loaded into the microemulsions (MEs) which contains palm oil, Tween 80 and polyethylene glycol (PEG) 400 at the ratios of 1:7:2 and 1:8:1. All of the MEs formulations appeared to be monophasic and clear, where the pH values were in the range of 6.55-6.78. In both formulations, the solubility of all metallocomplexes were 1.3-3.4-folds higher than the CUR, where CUR-Cu MEs (1:7:2 and 1:8:1) exhibited the highest solubility (965.99 ± 102.59 µg/mL and 986.49 ± 75.31 µg/mL, respectively). In both formulations, CUR-Cu MEs displayed ~2-folds higher %RSA compared to CUR MEs, meanwhile; CUR-Fe displayed the lowest %RSA (~6-7%) which maybe due to the instability of the coordination of ligand-metal complex resulted from the high oxidation state in Fe3+ ion.
Implantation outcome is Associated with Mucin-16, MiR- 1226 and MiR-210 Expression during IVF of Iraqi Females
One of the main obstacles to early pregnancy and assisted reproduction is embryo implantation failure. Endometrial receptivity and the interactions between the embryo and the mother determine implantation. The control of implantation involves several molecules. One such molecule is microRNA (miRNA), which is known to have a role in embryo implantation as a transcriptional regulator of gene expression. The current study evaluates the Expression level of miR-210 and miR-1226 with mucin-16 in infertile females under the IVF program and its influence on embryo implantation by measuring the fold change. This study included 26 successful implantations and 58 failed implantations under an in vitro fertilization program and 44 fertile females as control divided into two subgroups, 21 successful implantations and 23 failed implantations. The first conclusion in the current work is that the infertility cases under the IVF program with fertile failure implantation cases related to significant up-regulation of mucin-16, except successful fertile cases, recorded significant down-regulation. There is a significant positive correlation between mucin16 and miR-210-HG in failure embryo implantation in infertile females and a negative correlation between mucin16 with miR-210-HG and miR-1226 in failure embryo implantation in fertile females. These results recorded that up-regulation of miR-210 and miR-1226 gene expression may affect embryo implantation by regulating mucin-16 gene expression in infertile and fertile females undergoing IVF programs.
Gene expression, implantation, Mucin-16 gene, IVF, microRNA-210, microRNA-1226
Design, Development, and Optimization of Spanlastics for Delivery of Rizatriptan Benzoate
Spanlastics are nanovascular drug delivery systems that use surfactants, including hydrophilic and hydrophobic medicines . Spanlastics enhance the ability of medicines to enter the body and provide a continuous release over extended periods . These vesicles possess a high degree of elasticity and flexibility , enabling to improve the transportation of medications through different methods of administrations . Box-behnken design was utilized to establish a relationship between the formulation parameters, specifically the amount of Span 60 , cremophor EL 40 and sonication time and important quality attributes , namely particle size , polydispersity index (PDI) and entrapment efficiency (EE%) . The spanlastic formulations were developed using response surface central composite design and formulated using an ethanol injection . The developed using response surface central composite design and formulated using an ethanol injection . The formulations were analyzed to identify the optimal formula with a tiny particle size , lower PDI and a high EE%. The optimized formula underwent additional analysis using zeta potential measurement in-vitro release profile , Fourier Transform Infrared (FTIR) Analysis , Field Emission Scanning Electron Microscopy (FESEM) ,Differential Scanning Calorimetry Analysis (DSC) and X-ray Diffraction Analysis (XRD) .The improved formulation exhibited a particle size of (84,98)nm, a PDI of 0.1993 and an EE% of (53.69)% . There is a little discrepancy between the observed and predicated values . The zeta potential was - 22. 37 . The optimum formula showed an appropriate release of 88.5% over 8 hr . The compatibility analysis demonstrated that RNB is compatible with the other excipients .Analysis of the vesicle shape revealed that it was nearly spherical . Furthermore , the drug molecule was seen to exist in an amorphous condition within spanlastic formula . In summary , the result demonstrated that spanlastic have the capacity to serve as a carrier for medicine delivery systems .
Box-Behnken design was utilized for formulation of Rizatriptan Benzoate spanlatics nanovesicular system
Cremophore and span60 used to formulate the RNB spanlastics
TEM, FESM ,XRD, DSC ,Cumlative Drug Release
Evaluate the Effect of Ethanol Fraction of Iraqi Hibiscus tiliaceus L. Leaves Extract on Mitotic Index and Micronucleus Frequency in Comparison with Metformin in Male Rats
Hibiscus tiliaceus L. is a member of the Malvaceae family. It has been documented to exhibit antibacterial, antioxidant, anti-inflammatory, expectorant, anthelmintic, and anticancer properties. The objective of this study was to assess the impact of ethanol leaf extract from Hibiscus tiliaceus L. on methotrexate-induced chromosomal aberrations, specifically the Mitotic Index and Micronucleus Frequency, in spleen and bone marrow cells. The comparison was made with metformin. The study involves the categorization of the animals into five groups, with each group consisting of six rats. The rats are then subjected to the following treatments: Group I (negative control) consisted of six rats that were administered a daily oral dose of 1ml/kg/day of distilled water for seven consecutive days. Group II (positive control): Six rats were administered a solitary dose of 20mg/kg of methotrexate on the initial day. Group III consisted of six rats who were administered a daily oral dose of 100 mg/kg of metformin for a period of seven consecutive days. Group IV consisted of six rats who were administered a daily oral dose of 250 mg/kg of the ethanol fraction for seven consecutive days. In Group V, six rats were administered a daily oral dose of 500 mg/kg of the ethanol fraction for seven consecutive days. The results indicate that the ethanol extract of Hibiscus tiliaceus leaves, at both doses, significantly reduced the mitotic index in bone marrow cells and spleen cells compared to the negative control group. Additionally, it significantly increased the appearance of micronuclei in bone marrow cells. In conclusion, the ethanol extract of Hibiscus tiliaceus leaves exhibited a strong effect on the mitotic index and micronucleus appearance in bone marrow and spleen cells of rats.
Pregabalin versus Montelukast in the management of uremic pruritus in hemodialysis patients
Many patients with chronic kidney (CKD) disease experience uremic pruritus (UP), which lowers quality of life. The intensity of UP varies and can cause anything from occasional pain to total restlessness during the day or night. this trial aimed to compare the efficacy of pregabalin and montelukast in uremic pruritus among CKD undergoing hemodialysis. For four weeks, this was a randomize prospective- intervention trial. patients with end-stage renal disease, between the ages of 30 and 75, been on hemodialysis at least one year and persistently severe pruritus had been included. Patients were split into Group P (n=25) receiving 50 mg of pregabalin and Group M (n=25) receiving 10 mg of montelukast. Every week, the effectiveness of the medications was evaluated using a numeric rating scale (NRS) and a 5D itch score. Compared to baseline, montelukast and pregabalin reduce 5-D scale (p<0.05). Between the two medications, no noticeable distinctions were seen (p>0.05). the study concluded that montelukast and pregabalin medication, have a positive effect on reducing UP while there were no significant differences observed between the two drugs.
Exploring the Chemical Composition and Cytotoxic Effect of Hexane Extract of Aerial Portions of Iraqi Amaranthus viridis on A549 Cell-Line
Amaranthus viridis (green amaranth), is naturally grown in Iraq belongs to the Amaranthaceae family, and is considered pseudocereal. This herb displays various classes of secondary metabolites including polyphenols, and phytosterols, in addition to other types of terpenes and fatty derivatives. Anti-inflammatory, antioxidant, antidiabetic, cardioprotective, and hepatoprotective are among the evaluated and proven clinical activities. Recently herbal remedies have emerged as a noteworthy new therapeutic option for several cancers. The most common cause of cancer mortality in Iraq is lung cancer. Few previous studies stated the invitro anticancer effect of this herb on the MCF-7 breast cancer cell and against HepG2, B16F10 melanoma, and HT-29 cancer cells. In Iraq, there is no previous study regarding the phytochemistry and the cytotoxic effect of this herb despite its wide distribution. n.hexane extract of A. viridis whole aerial parts was prepared by maceration and Soxhlet extraction methods, and subjected to GC/MS and HPLC analysis to characterize and quantify its constituents mainly phytosterols.. In GC/MS, the total number of identified compounds was thirteen and seventeen, and the extraction yield was 0.66 %, and 1.017% for cold and hot hexane extract respectively. bis(2-ethylhexyl) phthalate was the major constituent in cold hexane extract. Omega-3 (9,12,15-Octadecatrienoic acid, (Z,Z,Z)-) was only detected in the cold extract. 2(4H)-Benzofuranone, 5,6,7,7a-tetrahydro-4,4,7a-trimethyl-, (R)- and squalene were identified in both extracts and at a higher proportion in hot extract. 9,12-Octadecadienoic acid (Z,Z), homosalate were only detected in hot hexane extract and for the first time in an Iraqi plant. HPLC analysis revealed the presence of campesterol, stigmasterol, spinasterol, and beta-sitosterol in greater amounts in the hot than cold extract. Campasterol is the least concentrated, while spinasterol is the most concentrated. Based on the result, hot hexane extract was evaluated for its invitro anticancer effect against the A549 cell line using MTT assay. Results from the MTT assay showed no cytotoxic effect for hot hexane extract and an IC50 value of 1393 μg/ml, which may be due to its antioxidant effect
Comparative Study of Montelukast with Dexamethasone for Possible Protection against Endotoxic Effect of Lipopolysaccharide in Male Mice
Endotoxic septic shock (ESS) is a serious clinical syndrome caused by gram-negative bacterial infections. ESS refers to infected patients with high bloodstream endotoxin levels and activity and a high rate of cardiovascular, pulmonary, hepatic, and renal failure. The endotoxin in the bacterial cell wall can evoke neutrophil monocytes and secrete inflammatory mediators like cytokines, nitric oxide, histamine, and bradykinin, causing local and systemic inflammation, severe vasodilation, endothelial dysfunction, increased capillary permeability, vascular fluid extravasation, and disseminated intravascular coagulation. Mice were utilized as experimental animals for research by inducing endotoxemia or a septic-like condition that closely simulates septic shock in humans via administering lipopolysaccharide (LPS) isolated from a particular bacterial strain at an appropriate dose. This study examined whether montelukast and dexamethasone protect male mice from LPS-induced endotoxicity. Twenty-eight Albino mice were randomly assigned to four groups (seven per group): Group I (control) mice were given 0.25–0.5 ml of distilled water by oral gavage once daily for a week and euthanized on the 8th day. Group II mice received 10 mg/kg intraperitoneal LPS and were euthanized on the second day. Group III mice received oral gavage dexamethasone 2.5 mg/kg once daily for a week. Two hours following the final dosage, LPS was given and euthanized on the 8th day. Group IV mice received oral gavage montelukast (20 mg/kg) once daily for a week. Two hours after the last dose, LPS was given and euthanized on the 8th day. Results show that pretreatment with both drugs lowers serum TNF-α, IL-6, RANK, and OPG levels, as well as cathepsin-G and neutrophil elastase gene expression. In conclusion, montelukast may have a promising protective effect from LPS-induced endotoxicity and may be an option as a protective drug from inflammatory consequences in humans.
Design, Molecular Docking and QSAR Study for New Propionic Acid Derivatives
A series of conformationally constrained new Propionic acid derivatives were subjected to a synergistic integration of docking and quantitative structure-activity relationship (QSAR) techniques to optimize non-steroidal anti-inflammatory agents (NSAIDs). Examining the particular conditions for COX-2 inhibition selectivity among these congeners as selective cyclooxygenase-2 (COX-2) inhibitors was the aim of the study. The combination of these methodologies accelerates the identification and optimization of lead compounds, facilitating efficient prediction and screening of compound libraries. This integrated approach not only expedites drug discovery but also provides a rational foundation for the design of novel molecules with desired pharmacological activities, particularly in the context of NSAIDs and similar therapeutic agents
Keywords: Conformationally constrained Propionic acid derivatives, Docking, Quantitative structure-activity relationship (QSAR), Non-steroidal anti-inflammatory agents (NSAIDs), COX-2 inhibition selectivity, Selective cyclooxygenase-2 (COX-2) inhibitors, Drug discovery, Rational drug design, Pharmacological activities.
Formulation, Statistical Optimization and In Vitro ‎Evaluation of Transdermal Anastrozole Nanospanlastic
<a title="Formulation and Evaluation of Nanospanlastic Anastrozole for Transdermal Delivery: Statistical Optimization and In Vitro ‎Characterization" href="https://bijps.uobaghdad.edu.iq/index.php/bijps/In postmenopausal women, anastrozole reduces estrogen levels, which may inhibit the development of certain breast cancers that need estrogen to increase in the body. The limitations of anastrozole are the first-pass action, limited aqueous solubility, and gastrointestinal issues. Additionally, improving skin permeability, controlling drug release, and shielding sensitive molecules from deterioration are just a few of the uses for nanoparticles that are gaining popularity. Spanlastics are elastic, malleable nanovesicles based on surfactants. They comprise an edge activator (EA) and a nonionic surfactant. In this study, anastrozole nanospanlastic (Ana-SPLs) was created to improve patient compliance and control anastrozole transdermal distribution as an alternative to the oral route. Therefore, the study aimed to develop a formulation that could get around these problems by using the advantages of the transdermal administration route and nanotechnology concepts. Minimized sizes with higher absolute zeta potential Ana-SPLs were formulated using a response-surface randomized User-Defind method. In addition to one category component that addresses the kind of EA, two numerical variables were examined: Span 60 to EA ratio (w/w) and sonication duration (min). Zeta potential (mV) and particle size (nm) were investigated as responses. A mathematical optimization technique was used to forecast the optimal variable values. With a sonication period of 5 minutes, the optimized formulation with a Span 60: SDC ratio of 9:1 w/w revealed particle dimensions of 128 nm with a zeta potential of -32 mV. Formula (F2) was seen using transmission electron microscopy to have a homogeneous, spherical shape. Because of its tiny particle size, high entrapment efficiency percentage (80.2 ± 4.3%), and 12-hour release pattern, formula (F2) was selected for further analysis. The compatibility study did not consider the interaction of Ana with other components. The previously described findings suggest spanlastics may be potentially effective drug carriers for transdermal medication administration.">In postmenopausal women, anastrozole reduces estrogen levels, which may inhibit the development of certain breast cancers that need estrogen to increase in the body. The limitations of anastrozole are the first-pass action, limited aqueous solubility, and gastrointestinal issues. Additionally, improving skin permeability, controlling drug release, and shielding sensitive molecules from deterioration are just a few of the uses for nanoparticles that are gaining popularity. Spanlastics are elastic, malleable nanovesicles based on surfactants. They comprise an edge activator (EA) and a nonionic surfactant. In this study, anastrozole nanospanlastic (Ana-SPLs) was created to improve patient compliance and control anastrozole transdermal distribution as an alternative to the oral route. Therefore, the study aimed to develop a formulation that could get around these problems by using the advantages of the transdermal administration route and nanotechnology concepts. Minimized sizes with higher absolute zeta potential Ana-SPLs were formulated using a response-surface randomized User-Defind method. In addition to one category component that addresses the kind of EA, two numerical variables were examined: Span 60 to EA ratio (w/w) and sonication duration (min). Zeta potential (mV) and particle size (nm) were investigated as responses. A mathematical optimization technique was used to forecast the optimal variable values. With a sonication period of 5 minutes, the optimized formulation with a Span 60: SDC ratio of 9:1 w/w revealed particle dimensions of 128 nm with a zeta potential of -32 mV. Formula (F2) was seen using transmission electron microscopy to have a homogeneous, spherical shape. Because of its tiny particle size, high entrapment efficiency percentage (80.2 ± 4.3%), and 12-hour release pattern, formula (F2) was selected for further analysis. The compatibility study did not consider the interaction of Ana with other components. The previously described findings suggest spanlastics may be potentially effective drug carriers for transdermal medication administration.
Anastrozole, Edge activator, Nanospanlastic, Surface randomized design, Transdermal.
Association of Carnosinase-2 Single Nucleotide Polymorphism (rs 6566810) with Serum Carnosine and Carnosinase-2 Levels in Type 2 Diabetics with Cardiovascular Diseases in Iraq
Carnosine have several important biological activities, as implicated by its effects on several diseases such cardiovascular disease, diabetes mellitus, cancer and can play important role in improving the functional capability during ischemic circumstances. Carnosine levels in diabetes patients may be affected by genetic variants in the carnosinase-2 gene, which may also be linked to development of cardiovascular problems. The purpose of this study was to examine the impact of the Carnosinase-2 gene polymorphism SNP (rs 6566810) on serum levels of carnosine and carnosinase-2 and their relationship to CVD in type 2 diabetes (T2DM) patients with and without CVD compared to healthy controls
Polymorphisms of (rs6566810) in carnosinase-2 gene contributes indirectly to the development of CVD in T2DM patients carrying AC
Cilnidipine Alleviates Alpha‑naphthyl isothiocyanate -Induced Cholestasis in Rats
Cholestasis is defined as a reduction or stagnation in bile secretion and flow. Inflammation results from blocked bile that leaks into the bloodstream and accumulates in the organs. It was postulated that cilnidipine would mitigate the liver damage linked to cholestasis by its confirmed farnesoid x receptor (FXR) activation. Hence, this study aimed to examine the impact and potential anticholestatic capabilities of cilnidipine in the rat’s model of cholestasis produced by α‑naphthyl isothiocyanate (ANIT), which is a widely used model that resembles human cholestasis. The white albino rats used in this investigation were separated into three distinct groups, with eight in each group. Negative control (Group I), in this group, rats get corn oil orally (1ml/kg) 48 hours before euthanized; Positive control (Group II), in this group, rats get a single dosage of Alpha-naphthyl isothiocyanate (ANIT) (100mg/kg) orally 48 hours before euthanized; Treatment group (Group III), in this group, rats get orally (cilnidipine 10 mg/kg) for seven successive days, on the fifth day, rats received a single oral dose of ANIT (100mg/kg) 48 hours before euthanized. The results demonstrated that cilnidipine pretreatment decreased the levels of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bile acids (TBA), direct bilirubin (DBIL), and total bilirubin (TBIL). Additionally, cilnidipine therapy also resulted in a decrease in oxidative stress and inflammatory mediators. In conclusion, cilnidipine alleviates cholestasis in rats, which ANIT induces, according to the findings.
Formulation and characterization of Flurbiprofen loaded terpesomes
Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) primarily indicated for the relief of pain and inflammation associated with rheumatoid arthritis and osteoarthritis. However, like all other NSAIDs, it is associated with gastrointestinal discomfort. Also, multiple dosing is required due to its short half-life which results in decreasing patient compliance and adherence when the drug is given orally. Delivering flurbiprofen systemically through other routes is quite an appealing approach to overcome its distressing adverse effects and reduce its dosing frequency. Flurbiprofen was formulated to be carried in a terpene-enriched ultra-deformable liposomal system called “terpesome” utilizing the thin film hydration technique. Limonene, alpha pinene, and cineole are three types of terpenes of different degrees of lipophilicity that were used in the construction of the terpesome along with soybean lecithin and sodium deoxycholate as an edge activator. A 23. 31 full factorial design was used in designing 23 formulas, and the optimized formula was chosen based on the desirability index of minimum vesicle size and PDI, and maximum entrapment efficiency. The optimized formula (comprised of 50 mg of flurbiprofen, 263 mg of soybean lecithin, 100 microliter of cineole, and 0% SDC) was shown to have a vesicular size of 195 nm, PDI of 0.3, and entrapment efficiency of 62%. Entrapment efficiency was higher in cineole containing terpesomes compared to limonene and alpha pinene counterparts most probably due to the hydrophilic nature (log P = 2.8) of cineole, which has low affinity to the phospholipid content in the vesicle causing repulsion between the vesicle content creating an ample space to efficiently house the flurbiprofen within. The in vitro release study of the optimized formula using cellulose dialysis membrane showed that an 88% of the drug was released after eight hours in comparison to the flurbiprofen suspension which released more than 90% after 4 hours confirming the role of the terpesomal vesicles in delaying drug release. In conclusion, terpesomes were prepared successfully with optimum properties to be ready for incorporation into an advanced and suitable drug delivery systems for a desirable enhancement of patient compliance and adherence.