Linked Life Data

20100662

Source:http://linkedlifedata.com/resource/pubmed/id/20100662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-2-17
pubmed:abstractText
The inhibition of 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1), which catalyzes the conversion of inactive 11-ketoglucocorticoids to active 11beta-hydroxyglucocorticoids, emerged as promising strategy to treat symptoms of the metabolic syndrome, including obesity and type 2 diabetes. In this study the leaves of the anti-diabetic medicinal plant loquat (Eriobotrya japonica) were phytochemically investigated following hints from a pharmacophore-based virtual screening and a bioactivity-guided approach. Determination of the 11beta-HSD1 and 11beta-HSD2 inhibitory activities in cell lysates revealed triterpenes from the ursane type as selective, low micro-molar inhibitors of 11beta-HSD1, that is, corosolic acid (1), 3-epicorosolic acid methyl ester (4), 2-alpha hydroxy-3-oxo urs-12-en-28-oic acid (6), tormentic acid methyl ester (8), and ursolic acid (9). Importantly, a mixture of loquat constituents with moderate activities displayed a pronounced additive effect. By means of molecular modeling studies and the identification of the 11beta-HSD1-inhibiting 11-keto-ursolic acid (17) and 3-acetyl-11-keto-ursolic acid (18) a structure-activity relationship was deduced for this group of pentacyclic triterpenes. The mechanism of action elucidated in the present work together with the previously determined pharmacological activities provides these natural products with an astonishing multi-targeted anti-diabetic profile.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1464-3391
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1507-15
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches.
pubmed:affiliation
Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria. Judith.rollinger@uibk.ac.at
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't