Catecholic Isoquinolines from Portulaca oleracea 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 (EC = 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 (EC = 82.4 μM), with EC 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 β-adrenergic receptor (β-AR) agonist activity in the CHO-K1/GA15 cell line which stably expressed β-AR as detected by a calcium assay. The EC values of 2 and 10 were 5.1 μM and 87.9 nM, respectively.

Biologically active isoquinoline alkaloids covering 2014–2018

“…The EC 50 value of (R)-(+)-1-benzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline was 87.9 nM. 31 Corynoline (314) from C. bungeana inhibited inflammatory mediators in LPS-stimulated RAW264.7 cells and attenuated LPS-induced acute lung injury in mice by activating Nrf2. 96,292,293 The unique alkaloid dactyllactone A (126) inhibited the expression of IL-1β and PGE2 in a dose-dependent manner in LPS-induced RAW264.7 cells.…”

“…[28][29][30] 6,7-Dihydroxy-1-methyl-3,4-dihydroisoquinolone (14), (S)-(−)-salsolinol (15), 6,7-dihydroxy-3,4-dihydroisoquinolone (16), and (R)-(+)-1-isobutyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (17), were isolated from the medicinal plant Portulaca oleracea. 31 These four simple isoquinoline alkaloids contained 6,7-dihydroxy substitution but different saturation or substituents at C-1. Four "naphthalene-devoid" tetra-and dihydroisoquinolines, named ealaines A−D (18−21), were isolated from the Congolese plant Ancistrocladus ealaensis.…”

“…Four "naphthalene-devoid" tetra-and dihydroisoquinolines, named ealaines A−D (18−21), were isolated from the Congolese plant Ancistrocladus ealaensis. 32 Akihisa et al 33 isolated noroxyhydrastinine Corydalis tomentella [28] 402 Oleracein E Portulaca oleracea [31] 403 Pipermullesine B Piper mullesua [108] 404 Pipermullesine C Piper mullesua [108] 405 Delavatine A Incarvillea delavayi [109] 406 Neotatarine Acorus calamus [110] Cryptocarya griffithiana, and Dehaasia longipedicellata, over the past 5 years. [34][35][36][37][38][39] (+)-N-Methylisococlaurine (24) also was found in Cryptocarya species and (−)-N-methylcoclaurine (25) was identified in the rhizomes of Sinomenium acutum in 2014.…”

“…40 Berbithine (26) and 6-( [1,3]dioxolo[4,5-g]isoquinoline-5-carbonyl)-2,3-dimethoxybenzoic acid methyl ester (27) were isolated from the rhizome of Coptis chinensis. 41 In 2018, several benzylisoquinoline alkaloids, including 24, 25, norcolaurine-4′-O-glucoside (28), N-methylhigenamine (29), norcoclaurine-6-O-glucoside (30), norcoclaurine (31), argemexirine (32), lotusine (33), isococlaurine (34), armepavine (35), 6-demethy-4′-methyl-N-methylcoclaurine (36), coclaurine (37), N-nor-O-methylarmepavine (38), isococlaurine-5′-Opentoside (39), and coclaurine-5′-O-pentoside (40) were identified from P. nelumbinis through UPLC-ESI-QTOF-MS. 30 Subsequently, juzirine (41) was identified from the aerial parts of Leonurus japonicus. 42 (R)-(+)-1-Benzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (42) from P. oleracea showed anti-inflammatory and β2-adrenergic receptor agonist activities.…”

“…28 Oleracein E (402) was isolated from the medicinal plant P. oleracea. 31 In the search to find potential antitumor agents from isoquinoline alkaloids, the most commonly studied bioactivity is the cytotoxicity of new isolated and known compounds from plants. In this review, we list in Table 2 we found that most compounds exhibited moderate cytotoxicity with IC 50 values ranging from 10 to 50 μM.…”