Catecholic Isoquinolines from<i>Portulaca oleracea</i>and Their Anti-inflammatory and β₂-Adrenergic Receptor Agonist Activity

Abstract

Isoquinoline alkaloids possess a wide range of structural features and pharmaceutical activities and are promising drug candidates. Ten water-soluble catecholic isoquinolines were isolated from the medicinal plant Portulaca oleracea, including three new (1-3) and seven known compounds (4-10), along with the known catecholamines 11 and 12 and four other known compounds (13-16). A method of polyamide column chromatography using EtOAc-MeOH as the mobile phase was developed for the isolation of catecholic isoquinolines. Alkaloids 1-12 exhibited anti-inflammatory activities (EC₅₀ = 18.0-497.7 μM) through inhibition of NO production in lipopolysaccharide-induced murine macrophage RAW 264.7 cells. Among these compounds, 11, 2, 5, 4, and 8 were more potent than was the positive control, 3,4-dihydroxybenzohydroxamic acid (EC₅₀ = 82.4 μM), with EC₅₀ values of 18.0, 18.1, 35.4, 36.3, and 58.7 μM, respectively. Additionally, at 100 μM, compounds 1-12 showed different degrees of β₂-adrenergic receptor (β₂-AR) agonist activity in the CHO-K1/GA15 cell line which stably expressed β₂-AR as detected by a calcium assay. The EC₅₀ values of 2 and 10 were 5.1 μM and 87.9 nM, respectively.