Catecholic Isoquinolines from Portulaca oleracea and Their Anti-inflammatory and β2-Adrenergic Receptor Agonist Activity

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 mu M) 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 mu M), with EC50 values of 18.0, 18.1, 35.4, 36.3, and 58.7 mu M, respectively. Additionally, at 100 mu M, compounds 1-12 showed different degrees of beta(2)-adrenergic receptor (beta(2)-AR) agonist activity in the CHO-K1/GA15 cell line which stably expressed beta(2)-AR as detected by a calcium assay. The EC50 values of 2 and 10 were 5.1 mu M and 87.9 nM, respectively.