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Kinetics and molecular docking studies of loganin, morroniside and 7-O-galloyl-D-sedoheptulose derived from Corni fructus as cholinesterase and ß-secretase 1 inhibitors.
Bhakta, Himanshu Kumar; Park, Chan Hum; Yokozawa, Takako; Min, Byung-Sun; Jung, Hyun Ah; Choi, Jae Sue.
Afiliación
  • Bhakta HK; Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea.
  • Park CH; College of Pharmacy, Catholic University of Daegu, Gyeongsan, 712-702, Republic of Korea.
  • Yokozawa T; Graduate School of Science and Engineering for Research, University of Toyama, Toyama, 930-8555, Japan.
  • Min BS; College of Pharmacy, Catholic University of Daegu, Gyeongsan, 712-702, Republic of Korea.
  • Jung HA; Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea. jungha@jbnu.ac.kr.
  • Choi JS; Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea. choijs@pknu.ac.kr.
Arch Pharm Res ; 39(6): 794-805, 2016 Jun.
Article en En | MEDLINE | ID: mdl-27106028
We evaluated the major active components isolated from Corni Fructus: loganin, morroniside, and 7-O-galloyl-D-sedoheptulose as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ß-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) for use in Alzheimer's disease treatment. These compounds exhibited predominant cholinesterase (ChEs) inhibitory effects with IC50 values of 0.33, 3.95, and 10.50 ± 1.16 µM, respectively, for AChE, and 33.02, 37.78, and 87.94 ± 4.66 µM, respectively, for BChE. Kinetics studies revealed that loganin and 7-O-galloyl-D-sedoheptulose inhibited AChE with characteristics typical of mixed inhibitors, while morroniside was found to be a noncompetitive inhibitor against AChE and also exerted mixed BChE inhibitory activities. For BACE1, loganin showed noncompetitive type inhibitory effects, while morroniside and 7-O-galloyl-D-sedoheptulose were found to be mixed inhibitors. Furthermore, these compounds exhibited dose-dependent inhibitory activity with ONOO(-)-mediated protein tyrosine nitration. Molecular docking simulation of these compounds demonstrated negative binding energies for ChEs, and BACE1, indicating high affinity and tighter binding capacity for the active site of the enzyme. Loganin was the most potent inhibitor against both ChEs and BACE1. The data suggest that these compounds together can act as a triple inhibitor of AChE, BChE, and BACE1, providing a preventive and therapeutic strategy for Alzheimer's disease treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de la Colinesterasa / Ácido Aspártico Endopeptidasas / Cornus / Iridoides / Secretasas de la Proteína Precursora del Amiloide / Descubrimiento de Drogas / Glicósidos / Heptosas Idioma: En Revista: Arch Pharm Res Año: 2016 Tipo del documento: Article Pais de publicación: Corea del Sur
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de la Colinesterasa / Ácido Aspártico Endopeptidasas / Cornus / Iridoides / Secretasas de la Proteína Precursora del Amiloide / Descubrimiento de Drogas / Glicósidos / Heptosas Idioma: En Revista: Arch Pharm Res Año: 2016 Tipo del documento: Article Pais de publicación: Corea del Sur