Abstract
Carainterol A is a eudesmane sesquiterpenoid extracted from Caragana intermedia. We have reported that carainterol A showed potent glucose consumption activity in C2C12 muscle cells and the db/db mouse model. However, the mechanism of the hypoglycemic effect of carainterol A remains elusive. In this article, we present a network pharmacology approach to predict the target and signaling pathway of carainterol A which was subsequently validated in HepG2 cells. It was demonstrated that carainterol A could increase the protein levels of IRS-1 and the downstream protein kinase AKT phosphorylation at a low micromolar level. These findings suggest that carainterol A can be a valuable lead compound and a promising chemical probe for the insulin signaling pathway.
Highlights
Natural products and their derivatives have been an invaluable source for drug discovery [1].Sesquiterpenoids have aroused considerable interest and attracted continuous attention as they embody impressive architectural diversity, stereochemical intricacies and pronounced biological activities.These properties continue to render sesquiterpenoids as exciting objectives for organic chemists and biologists [2]
We demonstrated that carainterol A could could
The present study indicated that carainterol A possesses multipharmacology attributes through different target groups such as insulin carainterol A possesses multipharmacology attributes through different target groups such as insulin receptor substrate binding, insulin receptor binding and protein tyrosine kinase activity
Summary
Sesquiterpenoids have aroused considerable interest and attracted continuous attention as they embody impressive architectural diversity, stereochemical intricacies and pronounced biological activities. These properties continue to render sesquiterpenoids as exciting objectives for organic chemists and biologists [2]. Carainterol A (1), an architecturally complex and unique eudesmane sesquiterpenoid natural product (Figure 1), was isolated from the aerial part of Caragana intermedia which is a frequently used herb in traditional Chinese medicine. A showed potent activity in increasing glucose consumption in C2 C12 muscle cells. It displayed glucose consumption in a db/db mouse model with a MIC (minimum inhibitory concentration) value that is equivalent to that of metformin [3]. The pharmacological targets associated the mechanism of carainterol A remained elusive
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