Researcher Image
مناف هاشم عبد الرزاق مهدي - Munaf Hashim Abdulrazzaq Zalzala
PhD - professor
College of pharmacy , Department of pharmacology and toxicology
[email protected]
Summary

Dr. Munaf H. Zalzala is a distinguished Professor of Pharmacology and Toxicology at the College of Pharmacy, University of Baghdad. With a career spanning over a decade, Dr. Zalzala has become a leading figure in the fields of pharmacology and toxicology, with particular expertise in liver diseases and lipid metabolism.

Dr. Zalzala obtained his PhD in Pharmacology and Toxicology in 2011 and his MSc in 2005 from the College of Pharmacy, University of Baghdad. Following his PhD, he pursued a prestigious postdoctoral position at MEOMED University in Ohio, USA, from 2013 to 2015. During his postdoctoral research, Dr. Zalzala focused on liver diseases and lipid metabolism, working on groundbreaking studies that have advanced understanding in these critical areas of pharmacology. His research in this field has contributed valuable insights into the treatment and prevention of liver conditions and metabolic disorders.

Upon returning to the University of Baghdad, Dr. Zalzala became an integral part of the Department of Pharmacology and Toxicology. His research now spans across drug safety, toxicity, and metabolic disorders, with a focus on how lipid metabolism affects liver health. His work has been widely published in peer-reviewed journals, and he is a frequent presenter at both national and international scientific conferences.

Dr. Zalzala was promoted to the rank of Professor in recognition of his outstanding contributions to research and education. As a faculty member, he is known for his commitment to mentoring students and junior researchers, inspiring the next generation of scientists and healthcare professionals.

Dr. Zalzala continues to focus on research that improves healthcare outcomes, with a dedication to advancing the understanding of drug interactions and the biological mechanisms underlying liver and metabolic diseases.

Qualifications

PhD in Pharmacology and Toxicology College of Pharmacy, University of Baghdad (2011) Focus: Pharmacology, toxicology, and drug interactions.

Postdoctoral Research Fellowship MEOMED University, Ohio, USA (2013–2015) Specialization: Liver diseases and lipid metabolism.

MSc in Pharmacology and Toxicology College of Pharmacy, University of Baghdad (2005) Focus: Toxicology and pharmaceutical sciences.

Professor of Pharmacology and Toxicology College of Pharmacy, University of Baghdad Department of Pharmacology and Toxicology.

Responsibility

Department of Pharmacology and Toxicology Rapporteur/ College of Pharmacy, University of Baghdad (2006–2009). Responsibilities included overseeing department meetings, facilitating communication between faculty and administration, and ensuring the smooth operation of academic activities within the department.

Director of Graduate Studies/ College of Pharmacy, University of Baghdad (2016–2018). Led the Graduate Studies program, managing admissions, overseeing academic progress, and coordinating research efforts for graduate students. Focused on improving the quality of graduate education and expanding research opportunities.

Head of Department of Pharmacology and Toxicology College of Pharmacy, University of Baghdad (2018–2020). Managed the department, including curriculum development, faculty leadership, and fostering academic research. Guided the department's strategic direction and ensured the integration of cutting-edge research into teaching.

Assistant Dean for Scientific and Student Affairs College of Pharmacy, University of Baghdad (2020–Present). Responsible for overseeing scientific research activities, student academic progress, and extracurricular programs. Provides leadership in student affairs, ensuring a supportive learning environment and promoting academic excellence among students.

Consultant at National Assessment Centre of Medical Competencies, Karbala, Iraq.

Awards and Memberships

Memberships: Iraqi Pharmacists Syndicate

Research Interests

Liver Diseases and Lipid Metabolism: Focus on understanding the molecular mechanisms underlying liver diseases, particularly the role of lipid metabolism in hepatic disorders. Research aims to explore therapeutic strategies for the prevention and treatment of metabolic and liver-related diseases.

Pharmacology of Drug Interactions: Investigating the interactions between various pharmaceutical compounds and their effects on drug efficacy and toxicity, with a goal of optimizing therapeutic outcomes and improving patient safety.

Toxicology of Environmental and Chemical Agents: Studying the toxic effects of environmental chemicals and pharmaceuticals on biological systems, aiming to develop models that predict toxicity and safeguard against harmful exposures.

Drug Safety and Efficacy: Exploring the balance between drug safety and therapeutic effectiveness, with a particular focus on the long-term impact of pharmaceuticals on human health, especially in the context of chronic diseases.

Mechanisms of Toxicity: Examining the cellular and molecular mechanisms that lead to toxicity, identifying biomarkers for early detection, and developing strategies to mitigate toxic responses in clinical settings.

Academic Area

Teaching and researching the principles of drug action. Also, focusing on the molecular and cellular mechanisms by which chemicals and drugs induce toxicity.

Teaching materials
Material
College
Department
Stage
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pharmacology I
كلية الصيدلة
الادوية والسموم
Stage 3
pharmacology I
كلية الصيدلة
الادوية والسموم
Stage 3
Teaching

pharmacology I, Advanced Physiology, Advanced Pharmacology, pharmaceutical Biotechnology, Mechanistic Toxiciology.

Supervision

2 PhD student 1 MSc student

Publication Date
Mon Jan 01 2024
Journal Name
Current Research In Pharmacology And Drug Discovery
Papaverine attenuates the progression of alpha naphthylisothiocyanate induce cholestasis in rats
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Publication Date
Mon Apr 15 2024
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Evaluation of the Wound-Healing Activity and Apoptotic Induction of New Quinazolinone Derivatives
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Background: Chemotherapeutic medication treatment for cancer is typically used in conjunction with other techniques as part of a routine regimen. It is well established that the capacity of different chemotherapeutic drugs to induce apoptosis is correlated with their anticancer efficacy. Quinazolinone-based drugs have demonstrated excellent responses from several cancer cell types. These substances have a lot of potential for use as building blocks in the creation of apoptosis inducers. Objective: To assess the new quinazolinone derivatives (M1 and M2) that were recently synthesized for their potential to halt wound healing and to use the acridine orange/propidium iodide (AO/PI) double stain to assess their capacity to induce apopto

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Publication Date
Wed May 31 2023
Journal Name
Research Journal Of Pharmacy And Technology
Renoprotective effects of Guggulsterone against Cisplatin-Induced Kidney Damage in White Female Albino Rats
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Background: Gugglusterone has been reported to provide protection against inflammatory and oxidative reactions of different pathological conditions. Objectives: The main object of this research work is to evaluate the renoprotective effects of guggulsterone in the prevention of cisplatin-induced nephrotoxicity in rats via assessment of renal function and histological study. Materials and methods: Rats in this study were split into four groups which comprise a control group, an induction group, a third group receiving low-dose guggulsterone, and a fourth group receiving high-dose guggulsterone. Results: a single dose of cisplatin drug has jeopardisedrenal physiology that has been demonstrated in histopathology sections and elevation

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Publication Date
Sat Sep 30 2023
Journal Name
Romanian Journal Of Rheumatology
Association between genetic polymorphism in tumor necrosis factor-alpha gene and adverse effects of etanercept in rheumatoid arthritis patients
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Background. Gene polymorphisms affect etanercept’s pharmacokinetics, pharmacodynamics, and side effects. This effect is evidenced by the extensive genetic variation in the drug’s targets. Objectives. This study aims to find the association between different genotypes of the promoter region of the TNF-α gene at -308G/A(rs1800629), -857C/T(rs1799724), -863 C/A(rs1800630), -1031 T/C (rs1799964), -806 C/T (rs4248158) and -376 G/A (rs1800750) and the side effects of ETN that occurred to Iraqi RA patients. Method. The trial included patients with rheumatoid arthritis who had been using ETN for at least six months. The participants were from the Baghdad Teaching Hospital Rheumatology Unit. The PCR was sequenced to determine the polymo

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Publication Date
Fri Nov 03 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synergistic Effects of 2-Deoxy-D-Glucose and Cinnamic Acid with Erlotinib on NSCLC Cell Line
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Background: In spite of all efforts, Non-small cell lung cancer (NSCLC) is a fatal solid tumor with a poor prognosis as of its high metastasis and resistance to present treatments. Tyrosine kinase inhibitors (TKI) such as erlotinib are efficient in treating NSCLC but the emergence of chemoresistance and adverse effects substantially limits their single use. Objective: in this study, the combination treatments of either 2-deoxy-D-glucose (2DG) or cinnamic acid (CINN) with erlotinib (ERL) were tested for their possible synergistic effect on the proliferation and migration capacity of NSCLC cells. Methods: In this study, NSCLC model cell line A549 was used to investigate the effects of single compounds and their combination on cell gro

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Publication Date
Mon May 01 2023
Journal Name
Journal Of Medicine And Life
Mucoprotective effect of ellagic acid in 5 fluorouracil-induced intestinal mucositis model
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Publication Date
Fri Nov 03 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Possible Protective Effect of Low Dose of Papaverine on ANIT Induce Cholestasis in Rat
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Abstract Intrahepatic cholestasis is clinical syndrome which cause either by defect in synthesis or bile acid flow, the pathophysiology of cholestasis is complicated by a number of  variables, including oxidative stress, inflammatory response, and  dysregulation of bile acid transporter . Rats, mice, and guinea pigs were utilized as experimental animals, and ANIT was administered to them in order to create a model that closely resembled intrahepatic cholestasis in human. This study examined the protective effects of papaverine, a non-narcotic opium alkaloid derived from papaver somniferum and discovered as an FXR agonist, on cholestasis in rats induced by alpha-naphthylisothiocyanate (ANIT). Rats utilized in this study divid

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Publication Date
Wed Nov 01 2023
Assessment of ellagic acid action in 5-fluorouracil induced intestinal mucositis: Assessment of ellagic acid action in 5-fluorouracil induced intestinal mucositis
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The intestinal mucositis define as inflammation and ulceration in the gastrointestinal tract wall and in some case in the oral cavity these cause by treatment with antineoplastic drug like 5-fluorouracil and Irinotecan and other types of chemotherapeutics drugs , 5-Fluorouracil-induced intestinal mucositis (IM) is consider as one of the more common tumor issue .it cause series of undesirables symptoms like severe diarrhea ,abdominal pain , stomach uncomfortable and other. The aim of this current study to see how ellagic acid act to  Attenuates 5-FU-Induced Intestinal Mucositis and  Diarrhea in Mice . we induced the intestinal mucositis by injected the mice intraperitoneally in 5-fluorouracil about 50mg per kg daily for

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Publication Date
Mon Feb 27 2023
Journal Name
Drug Development & Registration
Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 Cells
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Introduction. Chemotherapy with Cabazitaxel (CBZ) is a typical first-line treatment option for naïive castration-resistant prostate cancer resistant to docetaxel. On the other hand, Cabazitaxel's therapeutic success is constrained by chemoresistance and side effects.

Aim. To assess whether 6 alpha-ethylchenodeoxycholic acid (6-ECDCA), a selective agonist for bile acid receptors will enhance the efficacy of CBZ in androgen-independent prostate cancer cells.

Materials and methods. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay was used to assess the cytotoxicity of 6-ECDCA and CBZ medicines or t

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Publication Date
Tue Jul 26 2022
Journal Name
Frontiers In Veterinary Science
Berbamine and thymoquinone exert protective effects against immune-mediated liver injury via NF-κB dependent pathway
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Background

Immune-mediated hepatitis is a severe impendence to human health, and no effective treatment is currently available. Therefore, new, safe, low-cost therapies are desperately required. Berbamine (BE), a natural substance obtained primarily from Berberis vulgaris L, is a traditional herbal medicine with several bioactivities, such as antimicrobial and anticancer activities. Thymoquinone (TQ), a phytochemical molecule derived from the Nigella sativa plant's black cumin seeds, has attracted interest owing to itsanti-inflammatory, antioxidant, and anticancer properties.

Aim

This c

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Publication Date
Thu Mar 03 2022
Journal Name
Archives Of Rheumatology
Association of tumor necrosis factor-alpha promoter region gene polymorphism at positions -308G/A, -857C/T, and -863C/A with etanercept response in Iraqi rheumatoid arthritis patients
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Objectives: This study aims to evaluate the association between polymorphisms in the promoter region of the tumor necrosis factor-alpha (TNF-α) gene at locations -308G/A, -857C/T, and -863C/A with the tendency of being non-responder to etanercept.

Patients and methods: Between October 2020 and August 2021, a total of 80 patients (10 males, 70 females; mean age: 50 years; range, 30 to 72 years) with rheumatoid arthritis (RA) receiving etanercept for at least six months were included. The patients were divided into two groups responders and non-responders, based on their response after six months of continuous treatment. Following polymerase chain reac

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Publication Date
Fri Feb 25 2022
Journal Name
Egyptian Journal Of Chemistry
Design, molecular docking, synthesis, and in vitro pharmacological evaluation of biomolecules-histone deacetylase inhibitors conjugates with carbohydrazide as a novel zinc-binding group
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Publication Date
Wed Mar 15 2023
Journal Name
Bionatura
Immune-protective effect of topical paquinimod administration against imiquimod-induced psoriasis-like inflammation in mice
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Psoriasis is a chronic, inflammatory condition that primarily affects the skin, hair, and joints and is associated with significant humanistic and economic consequences. This work induced psoriasis in mice using an imiquimod 5% cream, an immune response modifier that can cause psoriasis-like skin inflammation when given orally. Paquinimod is prepared as an ointment and has been topically given to mice before imiquimod application. In this study, albino mice were allocated into five groups and treated as follows: the control group received only a daily application of cream based on shaved back (62.5mg/2cm) with a daily topical dose of ointment for 14 consecutive days with the oral vehicle. The Imiquimod group received a daily topical

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Publication Date
Fri Jun 16 2023
The Possible Protective Effect of Cinnamic Acid on Ovalbumin-Induced Asthma in Mice
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Asthma is a chronic respiratory disorder in which immunological and structural cells play a role. The limits of conventional medicines necessitate the development of innovative therapeutic techniques for asthma. In the present study, we investigated the possible protective effect of cinnamic acid (CA) on ovalbumin-induced asthma in a mouse model. Sixty albino male mice BALB/c type weighing (20-30) grams were chosen at random and divided into five groups each one contains 12 animal: Group I: PBS/liquid paraffin control. Group II: asthma model group. Group III: cinnamic acid control group; mice received cinnamic acid (50 mg/kg) in liquid paraffin orally by gavage. Group IV: asthma model / group of (25 mg / kg) cinnamic acid; mice received

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Publication Date
Fri Jun 16 2023
The Ameliorating Effect of Oral Paquinimod Administration against Imiquimod Induced Psoriasis-like Inflammation in Mice
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               Psoriasis is a chronic, inflammatory condition that primarily affects the skin, hair, and joints and is associated with significant humanistic and economic consequences. Psoriasis was induced in mice in this work using an imiquimod 5% cream, an immune response modifier that can cause psoriasis-like skin inflammation when given orally. Paquinimod is prepared as a suspension and has been orally given to mice before imiquimod application. The current study found that paquinimod suspension reduced psoriasis area and severity index, spleen index, skin thickness ,TNF-α,IL-23,IL17 level and gene expression of TN

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Publication Date
Thu Jan 07 2021
Journal Name
Indian Journal Of Forensic Medicine & Toxicology
Guggulsterone Suppresses Ovalbumin- Induced Inflammation in Rat Asthmatic Model
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Publication Date
Sun Dec 25 2022
Synthesis, Molecular Docking Study and Cytotoxicity Evaluation of some Quinazolinone Derivatives as Nonclassical Antifolates and Potential Cytotoxic Agents
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Abstract

A series of new 4(3H)-quinazolinone derivatives (S1-S4) were synthesized and characterized   by FTIR,1HNMR and 13CNMR .Their cytotoxic activity against a set of human cancer cell lines MCF-7 (breast) and A549 (lung) was evaluated using MTT assay. To detect their selectivity toward cancer cells, the compounds were also tested against epithelial cells derived from normal human fibroblast (NHF). Methotrexate (MTX) was used as a reference for comparison . All the tested compounds exhibited toxicity against the normal cells lower than cancer cells. All the tested compounds displayed higher cytotoxicity against lung cancer cell line (A549) than MTX with the most

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Publication Date
Sat Dec 11 2021
The Safranal Effect against Cyclophosphamide-Induced Liver Injury
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The liver is the primary organ for drug metabolism, elimination, Cyclophosphamid is the classical alkylating agent nitrogen mustard, its metabolism into two cytotoxic metabolites, and increase reactive oxygen species that is make liver toxicity. Safranal as the most abundant chemical in saffron essential oil, it have anti-oxidant, anti-inflammatory, antiapoptic and free radical scavenger activity. The aim of study is to assess the protective effects of safranal on the cyclophosphamide-induce liver toxicity in rat model. This occur by using five different groups of rats; control group, treatment group, cyclophosamide group (intraperitoneal i.p), cyclophosamide and (50mg and 100mg) oral safranal treatment groups. This study showed this pro

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Publication Date
Sat Dec 24 2022
The Effect of TNF-Alpha Gene Polymorphisms At -376 G/A, -806 C/T, and -1031 T/C on The Likelihood of Becoming a Non-Responder to Etanercept in A Sample of Iraqi Rheumatoid Arthritis Patients
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Tumor necrosis factor-alpha (TNF-α) antagonists’ therapy are expensive and has a non-responsive rate between 30% to 40% in rheumatoid arthritis patients. Genetic variation plays a vital role in the responsiveness to this type of therapy.The aim of this study is to investigate if the presence of genetic polymorphism in the TNF-α gene promoter region at locations -376 G/A (rs1800750), -806 C/T (rs4248158), and -1031 T/C (rs1799964) affects rheumatoid arthritis patient's tendency to be a non-responder to etanercept.

Eighty RA patients on etanercept (ETN) for at least six months were recruited from the Rheumatology Unit at Baghdad Teaching Hospital. Based on The European League Against Rheumatism response (EULAR) criteria, patient

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Publication Date
Sat Jun 19 2021
Protective Effects of Safranal Against Selenite-Induced Cataract in Rats
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         Cataract, which is the opacity inside clear ocular lens of eye, result in the scattering of visible light as it passes via the lens and consequently deterioration in optical image. The aim of the present study was to investigate whether safranal, an active constituent of Crocus sativus L. stigmas, has a protective effect on the cataract in the rat's pups. The animals were randomly divided into five groups, each of which consisted of 7 rat pups. Group I served as normal control (vehicle administration). For testing cataract induction, animals of Groups II, III, and IV were administered a single subcutaneous injection of sodium selenite on postpartum day 12. After sodium selenite intoxicatio

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Publication Date
Mon Dec 23 2019
Inhibition of NF-kB Pathway by Gggulsterone in the Protective Effects of Cyclophosphamide-Induced Renal Toxicity
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Cyclophosphamide which acts as cytotoxic alkylating agent can induce a renal damage through the toxic metabolites which result from metabolic activation of Cyclophosphamide by cytochrome P-450 inside hepatocyte and develop renal toxicity by direct binding with cellular organelles in the urinary tract cells. Guggulsterone is a sterol derived from plant has ability to bind to farsenoid X receptor, mineral corticosteroid receptor, androgen receptor, glucocorticoid receptor and estrogen receptor.

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Publication Date
Thu Dec 09 2021
Study The Anti-Asthmatic Activity of Guggulsterone In Ovalbumin-Induced Asthma In Rat
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Asthma is a chronic in?ammatory respiratory disease associated with the changes of asthmatic airway structural that result from interact remodeling and in?ammatory processes lead to obstruction of airway. Guggulsterone (GS) is a bioactive compound and plant steroid present in  guggul gum of Commiphora wightii, which has anti-inflammatory and antioxidant activities. This study designed to investigate of anti-inflammatory activity of gugglsterone in improvement of asthma. Forty eight healthy albino male rats divided to six groups, Group I: Control group (distal water), Group II: Positive control group (distal water) with sensitization, Group III: Guggulsterone (25 mg/kg/day) with sens

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Publication Date
Wed Jan 30 2019
Journal Name
International Journal Of Applied Pharmaceutics
THE IMPACT OF NEW TARGETING METHODS IN THE CANCER THERAPY
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Rapid development has achieved in treating tumor to stop malignant cell growth and metastasis in the past decade. Numerous researches have emerged to increase potency and efficacy with novel methods for drug delivery. The main objective of this literature review was to illustrate the impact of current new targeting methods to other previous delivering systems to select the most appropriate method in cancer therapy. This review first gave a brief summary of cancer structure and highlighted the main roles of targeting systems. Different types of delivering systems have been addressed in this literature review with focusing on the latest carrier derived from malarial protein. The remarkable advantages and main limitations of the later

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Publication Date
Tue Mar 15 2016
Journal Name
Hepatology
Carboxylesterase 2 prevents liver steatosis by modulating lipolysis, endoplasmic reticulum stress, and lipogenesis and is regulated by hepatocyte nuclear factor 4 alpha in mice
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Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). So far, the underlying mechanism remains poorly understood. Here, we show that hepatic carboxylesterase 2 (CES2) is markedly reduced in NASH patients, diabetic db/db mice, and high‐fat diet (HFD)‐fed mice. Restoration of hepatic CES2 expression in db/db or HFD‐fed mice markedly ameliorates liver steatosis and insulin resistance. In contrast, knockdown of hepatic CES2 causes liver steatosis and damage in chow‐ or Western diet‐fe

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Publication Date
Thu Feb 01 2018
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European Journal Of Drug Metabolism And Pharmacokinetics
Effects of Human Sulfotransferase 2A1 Genetic Polymorphisms 3 on the Sulfation of Tibolone
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Publication Date
Tue Jun 23 2015
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Nature Communications
A metabolic stress-inducible miR-34a-HNF4α pathway regulates lipid and lipoprotein metabolism
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Publication Date
Sat Jul 30 2016
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Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice
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Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption. OCA markedly inhibits hepatic cholesterol 7α‐hydroxylase (Cyp7a1) and sterol 12α‐hydroxylase (Cyp8b1) partly through inducing small heterodimer partner, leading to reduced bile acid pool size and al

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Publication Date
Sun Jun 09 2019
Possible Amelioration of the Severity of Nutritional Steatohepatitis by Guggulsterone in Mice: guggulsterone and steatohepatitis in mice
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Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, which characterized by steatosis, inflammation, and fibrosis. The aim of this designed study is to evaluate the ability of guggulsterone to prevent high fat diet induced steatohepatitis in mice. Five groups of male mice were selected and treated as the following: group I, mice had free access to standard commercial diet and considered as control group, group II, mice were fed a specially formulated high-fat diet for 12 weeks to induce non-alcoholic liver disease, while groups III, IV and V the mice were administered high fat diet containing guggulsterone at 500, 1000 and 2000 ppm concentration respectively for 12 weeks. Maintaini

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Publication Date
Thu Dec 06 2018
Ameliorating Effect of Oral Guggulsterone Administration in Imiquimod-Induced Psoriasis in Mice
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Psoriasis is a common chronic skin condition characterized by infiltration of inflammatory cells into the epidermis and altered keratinocyte differentiation.

In this work, psoriasis was induced by an imiquimod 5% cream, an immune response modifier that can induce psoriasis-like skin inflammation when applied topically in mice. Guggulsterone prepared as a suspension and has been orally given to mice before imiquimod application. The results of the current study showed that guggulsterone suspension can significantly reduce psoriasis area and severity index in (guggul suspension+imiquimod group as compared with both control group and (vehicle suspension+imiquimod ) group.

 

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Publication Date
Fri Jul 01 2011
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Saudi Pharmaceutical Journal
Free radical scavenging activity of silibinin in nitrite-induced hemoglobin oxidation and membrane fragility models
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Mon Oct 06 2014
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Hepatic Carboxylesterase 1 Is Induced by Glucose and Regulates Postprandial Glucose Levels
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