title: The effects of pollen, propolis, and caffeic acid phenethyl ester on tyrosine hydroxylase activity and total RNA levels in hypertensive rats caused by nitric oxide synthase inhibition: experimental, docking and molecular dynamic studies.
abstract: The objective of the present study was to evaluate the effects of propolis, pollen, and caffeic acid phenethyl ester (CAPE) on tyrosine hydroxylase (TH) activity and total RNA levels of Nω-nitro-L-arginine methyl ester (L-NAME) inhibition of nitric oxide synthase in the heart, adrenal medulla, and hypothalamus of hypertensive male Sprague dawley rats. The TH activity in the adrenal medulla, heart, and hypothalamus of the rats was significantly increased in the L-NAME group vs. control (p < 0.05). Treatment with L-NAME led to a significant increase in blood pressure (BP) in the L-NAME group compared to control (p < 0.05). These data suggest that propolis, pollen, and CAPE may mediate diminished TH activity in the heart, adrenal medulla, and hypothalamus in hypertensive rats. The decreased TH activity may be due to the modulation and synthesis of catecholamines and BP effects. In addition, the binding mechanism of CAPE within the catalytic domain of TH was investigated by means of molecular modeling approaches. These data suggest that the amino acid residues, Glu429 and Ser354 of TH may play a pivotal role in the stabilization of CAPE within the active site as evaluated by molecular dynamics (MD) simulations. Gibbs binding free energy (ΔGbinding) of CAPE in complex with TH was also determined by post-processing MD analysis approaches (i.e. Poisson-Boltzmann Surface Area (MM-PBSA) method).
authors.affiliation: a Computational Biology and Molecular Simulations Laboratory, Department of Biophysics , School of Medicine, Bahcesehir University , Istanbul , Turkey.
authors.forename: Ramin
authors.initials: R
authors.lastname: Ekhteiari Salmas
authors.affiliation: a Computational Biology and Molecular Simulations Laboratory, Department of Biophysics , School of Medicine, Bahcesehir University , Istanbul , Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.affiliation: b Department of Medicinal and Aromatic Plants , Vocational School of Technical Sciences , Aksaray , Turkey.
authors.forename: Mehmet Fuat
authors.initials: MF
authors.lastname: Gulhan
authors.affiliation: c Faculty of Arts and Science, Department of Biotechnology , Omer Halisdemir University , Nigde 51240 , Turkey.
authors.forename: Merve
authors.initials: M
authors.lastname: Duruyurek
authors.affiliation: d Department of Pharmacology , New York Medical College , Valhalla 10595 , NY , USA.
authors.forename: Huda I
authors.initials: HI
authors.lastname: Abdullah
authors.affiliation: c Faculty of Arts and Science, Department of Biotechnology , Omer Halisdemir University , Nigde 51240 , Turkey.
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Selamoglu
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002109:Caffeic Acids / Q000008:administration & dosage; D020134:Catalytic Domain; D002395:Catecholamines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives; D011058:Pollen / Q000009:adverse effects; D011429:Propolis / Q000008:administration & dosage; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry / Q000235:genetics*
chemical_list: D002109:Caffeic Acids; D002395:Catecholamines; D011429:Propolis; D019001:Nitric Oxide Synthase; D014446:Tyrosine 3-Monooxygenase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D019331:NG-Nitroarginine Methyl Ester
keywords: CAPE; L-NAME; MM-PBSA; hypertension; molecular dynamics (MD) simulations; pollen; propolis; tyrosine hydroxylase