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Differential modulation of bradykinin-induced relaxation of endothelin-1 and phenylephrine contractions of rat aorta by antioxidants

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Acta Pharmacologica Sinica 2007年第10期28卷 1566-1572页

作者： Ogechukwu ANOZIE Richonda ROSS Adebayo O OYEKAN Momoh A YAKUBU Vascular Biology UnitCenter for Cardiovascular Diseases college of pharmacy and health sciences texas southern university Houston texas 77004 USA

Aim:We tested the hypothesis that bradykinin （BK）-induced relaxation of phe-nylephrine （PE） and endothelin-1 （ET-1） contractions can be differentially modu-lated by reactive oxygen species （ROS）.Methods:Aortic rings isolated fromSprague-Dawley rats were used for the *** contribution of ROS to PE(1×10-9-1×10-5mol/L)-and ET-1 (1×10-10-1×10-8mol/L)-induced contractions andthe influence of ROS in BK (1×10-9-1×10-5mol/L) relaxation of PE (1×10-7mol/L) orET-1 (1×10-9mol/L)-induced tension was evaluated in the aorta in the presence orabsence of the following antioxidants:catalase （CAT,300 U/mL）,superoxidedismutase （SOD,300 U/mL）,and vitamin C (1×10-4mol/L).Results:Tension gen-erated by ET-1 (1×10-9mol/L) or PE (1×10-7mol/L) was differentially relaxed by BK(1×10-5mol/L),producing a maximal relaxation of 75%±5% and 35±4%,*** BK (1×10-5mol/L)-induced relaxation of PE (1×10-7mol/L) tension was signifi-cantly enhanced from 35%±4% （control） to 56%±9%,60%±5%,and 49%±6% bySOD,CAT,and vitamin C,respectively （P<0.05,n=8）.However,the relaxation ofET-1 (1×10-9mol/L) tension was significantly attenuated from 75%±5% （control）to 37%±9%,63%±4%,and 39%±7% by SOD,CAT,and vitamin C,respectively（P<0.05,n=8）.On the other hand,CAT had no effect on PE-induced tension,whileSOD enhanced PE-induced tension （36%,P<0.05,n=10） and vitamin C attenuated（66%,P<0.05,n=8） the tension induced by *** contrast,SOD or vitamin C hadno effect,but CAT attenuated （44%,P<0.05,n=9） the tension induced by ***:We have demonstrated that O2-and H2O2differentially modulate BKrelaxation in an agonist-specific manner.O2-attenuates BK-induced relaxation ofPE contraction,but contributes to the relaxation of ET-1 contraction.O2-seems toinhibit PE contraction,while H2O2contributes to ET-1-induced ***,ROS differentially modulate vascular tone depending on the vasoactive agentthat is used to generate the tone.

关键词： bradykinin endothelin-1 phenylephrine reactive oxygen species superoxide hydrogen peroxide relaxation contraction antioxidants

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Quantification and pharmacokinetic study of tumor-targeting agent MHI148-clorgyline amide in mouse plasma using liquid chromatography-electrospray ionization tandem mass spectrometry

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Journal of Pharmaceutical Analysis 2018年第3期8卷 153-159页

作者： Zhijun Wang Bogdan Z.Olenyuk Jean Chen Shih Jeffrey Wang Center for Advancement of Drug Research and Evaluation College of Pharmacy Western University of Health Sciences Department of Pharmaceutical sciences College of Pharmacy Marshall B.Ketchum University Department of Pharmacology and Pharmaceutical sciences School of Pharmacy Department of Cell and Neurobiology Keck School of Medicine USC-Taiwan Center for Translational Research University of Southern California Department of Pharmaceutical sciences College of Pharmacy Western University of Health Sciences

A high-performance liquid chromatography-electrospray ionization tandem mass spectrometric （HPLC- ESI-MS/MS） method was developed for the quantification of MHl148-clorgyline amide （NMl-amide）, a novel tumor-targeting monoamine oxidase A inhibitor, in mouse plasma. The method was validated in terms of sensitivity, precision, accuracy, recovery and stability and then applied to a pharmacokinetic study of NMl-amide in mice following intravenous administration. NMl-amide together with the internal standard （IS）, MHI-148, was extracted by protein precipitation using acetonitrile. Multiple reaction monitoring was used for quantification of NMl-amide by detecting m/z transition of 491.2-361.9, and 685.3-258.2 for NMl-amide and the IS, respectively. The lower limit of quantification （LLOQ） of the HPLC- MS/MS method for NMl-amide was 0.005 μg/mL and the linear calibration curve was acquired with R2〉 0.99 in the concentration range of 0.005-2μg/mL. The intra- and inter-day precisions of the assay were assessed by percentage of the coefficient of variations, which was within 9.8% at LLOQ and 14.0% for other quality control samples, whereas the mean accuracy ranged from 86.8% to 113.2%. The samples were stable under storage and experimental conditions. This method was successfully applied to a pharmacokinetic study in mice following intravenous administration of 5 mg/kg NMl-amide.

关键词： MH1148-clorgyline HPLC Mass spectrometry Pharmacokinetics

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Phytochemical Analysis of Medicinal Plants with Kidney Protective Activities

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Chinese Journal of Integrative Medicine 2012年第10期18卷 790-800页

作者： Eric Jung-chi Lien Linda Lin-min Lien Rubin Wang Jeffrey Wang Department of Pharmacology and Pharmaceutical sciences School of PharmacyUniversity of Southern California Department of Chemistry & Biochemistry University of California Department of Pharmaceutical sciences College of PharmacyWestern University of Health Sciences

In view of the increasing number of patients undergoing kidney dialysis or transplant every year, a survey of the literature on renal protective medicinal plants was undertaken. Most of them are from traditional Chinese medicine （TCM）. Although many of the medicinal herbs reported have not been investigated in terms of active chemical ingredients, some do have compounds well characterized. They fall into a wide range of structures. Several groups of compounds with well established activities are discussed. These include： antioxidant phenolic compounds like tannins, flavonoids, isoflavonoids, unsaturated organic acids and lignans; circulation enhancing compounds like saponins, and basic alkaloids with multiple targets （G-protein coupled receptors）. Also presented are proinflammatory and antiinflammatory fatty acids like linoleic （n-6） and α-Iinolenic （n-3） acids, respectively. Attention is also drawn to the plants containing nephrotoxic aristolochic acid. Different directions of future research are also presented. We hope that this review may provide some leads for new drug discovery and development, and more rational application of TCM.

关键词： kidney protective herbs kidney protection natural products antioxidants free radical scavengers immunomodulating agents antiinflammatory agents structure-activity relationship physicochemical parameters

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The safety,efficacy and pharmaceutical quality of male enhancement nutraceuticals bought online:Truth versus claim

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Journal of Integrative Medicine 2021年第3期19卷 232-242页

作者： Mohamed Ismail Nounou Heba AEassa Nada AHelal Khaled Aboul Fotouh Ihab Mansoor Isabel KLatz Cindy Zheng Hadeer AEassa Dina Mohamed Diana MHuynh Abigail RWiss Jessica Sweeney Monica TOakes Mark MMikhail Nadine Amine Harshvir Kaur Natalia Echeverry Kamila Orzechowski Doreen Szollosi Department of Pharmaceutical sciences School of Pharmacy&Physician Assistant Studies(SOPPAS)University of Saint Joseph(USJ)HartfordConnecticut 06103USA Department of Pharmaceutics and Industrial pharmacy Faculty of PharmacyAL-Azhar UniversityCairo 11651Egypt Pharmaceutical sciences Department Irma Lerma Rangel College of PharmacyTexas A&M Health Science CenterTexas A&M UniversityCollege StationTexas 77843USA Division of Molecular Pharmaceutics and Drug Delivery College of PharmacyThe University of Texas at AustinTexas 78712USA Department of Pharmaceutics Faculty of PharmacyAssiut UniversityAssiut 71526Egypt Department of Pharmaceutics Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt Department of Public health sciences College of Health SciencesThe University of Texas at El PasoTX 79968USA Genetic Engineering and Biotechnology Research Institute University of Sadat CitySadat 32897Egypt Department of Industrial pharmacy Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt

Objective:Nutraceutical products are widely used for their claimed therapeutic ***,falsified or adulterated nutraceuticals present a major health threat to *** study investigates the pharmaceutical quality,safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100%***:Three batches of six male enhancement products were tested to detect the presence and levels of adulterants via high-performance liquid chromatography(HPLC).The pharmaceutical quality of the selected nutraceuticals was tested with near infrared spectroscopy(NIR)and Se De *** cytotoxic effects of these products on HepG2 cells were determined through cell proliferation(XTT)and lactate dehydrogenase(LDH)cytotoxicity ***,the in vitro inflammatory effects of these products were investigated using murine J774 macrophages through cytokine release ***:HPLC analysis detected the presence of sildenafil citrate,a vasodilator,and the active ingredient in Viagra and Revatio,in all batches of the products we *** of sildenafil citrate ranged from 0.45 mg to 51.85 mg among different *** assessment showed inter-and intra-batch heterogeneity in product *** of the XTT and LDH assays showed significant cytotoxic effects of the analyzed *** analysis revealed that the viability of HepG2 treated with tested products varied from 27.57%to 41.43%.Interestingly,the male enhancement products also showed anti-inflammatory ***:Despite their labeling as 100%natural,all products tested in this study contained levels of sildenafil citrate,which was not reported on the *** was a lack of pharmaceutical uniformity among products of the same batch and across different ***,the products we tested had cytotoxic *** study findings highlight the adulteration,poor quality and hazard of these ***,strict regulation of these product

关键词： Nutraceuticals Adulteration Erectile dysfunction Sildenafil citrate Online market

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Folic acid-induced animal model of kidney disease

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Animal Models and Experimental Medicine 2021年第4期4卷 329-342页

作者： Liang-Jun Yan Department of Pharmaceutical sciences College of PharmacyUniversity of North Texas Health Science CenterFort WorthTexasUSA

The kidneys are a vital organ that is vulnerable to both acute kidney injury(AKI)and chronic kidney disease(CKD)which can be caused by numerous risk factors such as ischemia,sepsis,drug toxicity and drug overdose,exposure to heavy metals,and *** spite of the advances in our understanding of the pathogenesis of AKI and CKD as well AKI transition to CKD,there is still no available therapeutics that can be used to combat kidney disease effectively,highlighting an urgent need to further study the pathological mechanisms underlying AKI,CKD,and AKI progression to *** this regard,animal models of kidney disease are *** article reviews a widely used animal model of kidney disease,which is induced by folic acid(FA).While a low dose of FA is nutritionally beneficial,a high dose of FA is very toxic to the *** a brief description of the procedure for disease induction by FA,major mechanisms of FA-induced kidney injury are then reviewed,including oxidative stress,mitochondrial abnormalities such as impaired bioenergetics and mitophagy,ferroptosis,pyroptosis,and increased expression of fibroblast growth factor 23(FGF23).Finally,application of this FA-induced kidney disease model as a platform for testing the efficacy of a variety of therapeutic approaches is also *** that this animal model is simple to create and is reproducible,it should remain useful for both studying the pathological mechanisms of kidney disease and identifying therapeutic targets to fight kidney disease.

关键词： acute kidney injury chronic kidney disease ferroptosis fibroblast growth factor 23 folic acid mitochondria mitophagy oxidative stress pyroptosis

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Glaucomatous optic neuropathy treatment options:the promise of novel therapeutics,techniques and tools to help preserve vision

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Neural Regeneration Research 2018年第7期13卷 1145-1150页

作者： Najam A.Sharif Department of Global Alliances & External Research Global Ophthalmology Research & DevelopmentSanten Incorporated Department of Pharmaceutical sciences Texas Southern University Department of Pharmacology and Neuroscience University of North Texas Health Sciences Center Department of pharmacy sciences Creighton University Department of Surgery & Cancer Imperial College of Science and TechnologySt.Mary's Campus

Peripheral vision loss followed by ＂tunnel vision＂ and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma（POAG） and normotensive glaucoma（NTG）.These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells（RGCs） accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic *** patients suffering from this glaucomatous optic neuropathy（GON） first notice visual impairment when they have lost 〉 40% of their RGCs,early diagnosis is the key to retard the progression of *** intraocular pressure（IOP）,low cerebrospinal and/or low intracranial fluid pressure,advancing age,and ethnicity are major risk factors associated with ***,retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic,inflammatory,oxidative and mechanical insults also contribute to vision loss in POAG/*** treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs,combination drug products,and surgical *** recently approved multi-pharmacophoric drugs（e.g.,rho kinase inhibitor,Netarsudil;a drug conjugate,Latanoprostene Bunod） and novel aqueous humor drainage devices（i Stent and Cy Pass） are also gaining acceptance for treating POAG/*** and regenerative agents,coupled with electroceutical,mechanical support systems,stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat *** latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures,thereby providing a gain of function of the visual system for the glaucoma patients.

关键词： glaucoma ocular hypertension glaucomatous optic neuropathy drainage device optic nerve degeneration retinal ganglion cells nerve regeneration neuroprotection

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Neuroaxonal and cellular damage/protection by prostanoid receptor ligands,fatty acid derivatives and associated enzyme inhibitors

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Neural Regeneration Research 2023年第1期18卷 5-17页

作者： Najam A.Sharif Department of Pharmaceutical sciences College of Pharmacy and Health SciencesTexas Southern UniversityHoustonTXUSA Department of Pharmacology and Neuroscience University of North Texas Health Sciences CenterFort WorthTXUSA Department of pharmacy sciences School of Pharmacy and Health ProfessionsCreighton UniversityOmahaNEUSA Singapore Eye Research Institute(SERI) SingaporeSingapore Duke-NUS Medical School SingaporeSingapore Department of Surgery&Cancer Imperial College of Science and TechnologySt.Mary’s CampusLondonUK Global Alliances and External Research Ophthalmology Innovation CenterSanten Inc USAEmeryvilleCAUSA

Cellular and mitochondrial membrane phospholipids provide the substrate for synthesis and release of prostaglandins in response to certain chemical,mechanical,noxious and other *** D_(2),prostaglandin E_(2),prostaglandin F_(2)α,prostaglandin I_(2)and thromboxane-A_(2)interact with five major receptors(and their sub-types)to elicit specific downstream cellular and tissue *** general,prostaglandins have been associated with pain,inflammation,and edema when they are present at high local concentrations and involved on a chronic ***,in acute settings,certain endogenous and exogenous prostaglandins have beneficial effects ranging from mediating muscle contraction/relaxation,providing cellular protection,regulating sleep,and enhancing blood flow,to lowering intraocular pressure to prevent the development of glaucoma,a blinding *** classes of prostaglandins are implicated(or are considered beneficial)in certain central nervous system dysfunctions(e.g.,Alzheimer’s,Parkinson’s,and Huntington’s diseases;amyotrophic lateral sclerosis and multiple sclerosis;stroke,traumatic brain injuries and pain)and in ocular disorders(e.g.,ocular hypertension and glaucoma;allergy and inflammation;edematous retinal disorders).This review endeavors to address the physiological/pathological roles of prostaglandins in the central nervous system and ocular function in health and disease,and provides insights towards the therapeutic utility of some prostaglandin agonists and antagonists,polyunsaturated fatty acids,and cyclooxygenase inhibitors.

关键词： AL-8810 axon brain central nervous system cyclooxygenase inhibitors neuron neuroprotection ocular polyunsaturated fatty acids prostaglandins

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Redox imbalance stress in diabetes mellitus: Role of the polyol pathway

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Animal Models and Experimental Medicine 2018年第1期1卷 7-13页

作者： Liang-jun Yan Department of Pharmaceutical sciences UNT System College of PharmacyUniversity of North Texas Health Science Center

In diabetes mellitus, the polyol pathway is highly active and consumes approximately 30% glucose in the body. This pathway contains 2 reactions catalyzed by aldose reductase(AR) and sorbitol dehydrogenase, respectively. AR reduces glucose to sorbitol at the expense of NADPH, while sorbitol dehydrogenase converts sorbitol to fructose at the expense of NAD+, leading to NADH production. Consumption of NADPH, accumulation of sorbitol, and generation of fructose and NADH have all been implicated in the pathogenesis of diabetes and its complications. In this review, the roles of this pathway in NADH/NAD+redox imbalance stress and oxidative stress in diabetes are highlighted. A potential intervention using nicotinamide riboside to restore redox balance as an approach to fighting diabetes is also discussed.

关键词： diabetes mellitus fructose NADH/NAD^+ oxidative stress polyol pathway redox imbalance stress

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Delayed atomoxetine or fluoxetine treatment coupled with limited voluntary running promotes motor recovery in mice after ischemic stroke

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Neural Regeneration Research 2021年第7期16卷 1244-1251页

作者： Faisal F.Alamri Abdullah Al Shoyaib Nausheen Syeara Anisha Paul Srinidhi Jayaraman Serob T.Karamyan Thiruma V.Arumugam Vardan T.Karamyan Department of Pharmaceutical sciences School of PharmacyTexas Tech University Health Sciences CenterAmarilloTXUSA Department of Pharmacology Faculty of PharmacyYerevan State Medical UniversityYerevanArmenia Department of Physiology Anatomy and MicrobiologySchool of Life SciencesLa Trobe UniversityMelbourneAustralia Center for Blood Brain Barrier Research School of PharmacyTexas Tech University Health Sciences CenterAmarilloTXUSA college of sciences and health Profession King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research CenterJeddahSaudi Arabia

Currently, there is an unmet need for treatments promoting post-stroke functional *** aim of this study was to evaluate and compare the dose-dependent effect of delayed atomoxetine or fluoxetine therapy(starting on post-stroke day 5), coupled with limited physical exercise(2 hours daily voluntary wheel running;post-stroke days 9 to 42), on motor recovery of adult male mice after photothrombotic *** drugs are selective norepinephrine or serotonin reuptake inhibitors indicated for disorders unrelated to *** predetermined primary end-point for this study was motor function measured in two tasks of spontaneous motor behaviors in grid-walking and cylinder ***, we quantified the running distance and speed throughout the study, the number of parvalbumin-positive neurons in the medial agranular cortex and infarct *** sensorimotor tests revealed that neither limited physical exercise nor a drug treatment alone significantly facilitated motor recovery in mice after ***, combination of physical exercise with either of the drugs promoted restoration of motor function by day 42 post-stroke, with atomoxetine being a more potent *** was accompanied by a significant decrease in parvalbumin-positive inhibitory interneurons in the ipsilateral medial agranular cortex of mice with recovering motor function, while infarct volumes were comparable among experimental *** further validated in larger studies, our observations suggest that add-on atomoxetine or fluoxetine therapy coupled with limited, structured physical rehabilitation could offer therapeutic modality for stroke survivors who have difficulty to engage in early, high-intensity ***, in light of the recently completed Assessment o F Fluoxet INe In s Troke recover Y(AFFINITY) and Efficacy o F Fluoxetine-a randomis Ed Controlled Trial in Stroke(EFFECTS) trials, our observations call for newly designed studies where fluoxetine or atomoxeti

关键词： drug repurposing neural repair physical exercise physiotherapy post-stroke recovery pre-clinical trial FLAME trial selective norepinephrine reuptake inhibitor selective serotonin reuptake inhibitor stroke pharmacotherapy

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Proteomic Analysis of Salt-Induced Changes in Protein Expression in PPAR<i>α</i>Null Mice

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Pharmacology & pharmacy 2014年第11期5卷 996-1005页

作者： Patience O. Obih Adebayo Oyekan college of pharmacy Xavier University of Louisiana New Orleans USA college of pharmacy and health sciences Texas Southern University Houston USA

PPARs are ligand-activated nuclear transcription factors that regulate β-oxidation of fatty acids in the cardiovascular system and PPARα isoform is a putative target for regulation of cardiovascular function. High salt diet is an injurious stimulus to cardiovascular function but its effect on PPARα and PPARα–associated profile of proteins is unknown. Quantitative proteomics involving a two-dimensional electrophoresis (2D-DIGE) followed by LC-MS/MS technology was used to characterize the changes in protein expression profile in the kidney, heart, and blood vessels from PPARα null (KO) and wild type (WT) mice placed on normal (0.3%, NS) or high salt (4% NaCl, HS) diet. Initial biological variation analysis using DeCyder software (v. 6.0) revealed the presence of 20 upregulated proteins and 9 proteins that are downregulated in the kidney, aorta, and heart tissues from KO and WT mice. A multimodality comparison of the differentially expressed proteins showing ≥ 1.5-fold change, ≥20% appearance at P ≤ 0.05 between strains (WT vs KO) and treatment (NS vs HS) revealed that HS diet affected 20 proteins in WT mice and 17 proteins in KO mice. However, 9 proteins were altered between WT and KO placed on NS and 7 proteins were altered by HS between WT and KO mice. The identified proteins include but not limited to those involved in fatty acid oxidation (FAO), mitochondrial electron transport chain, amino acid metabolism, stress response, DNA synthesis, and programmed cell death. HS diet led to upregulation of FAO enzymes viz: acyl-coenzyme A dehydrogenase, transketolase, and electron-transferring-flavoprotein dehydrogenase to different extents in WT and KO mice. These data showed differential and protein-specific responses to HS diet in PPARα WT and KO mice that probably reflect the functional capacities of PPARα as a means to limiting any salt-induced injury to the heart, kidney, and blood vessels.

关键词： PPARα β-Oxidation Salt Diet Proteome

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