AUTHOR=Pan San-Po , Pirker Teresa , Kunert Olaf , Kretschmer Nadine , Hummelbrunner Scarlet , Latkolik Simone L. , Rappai Julia , Dirsch Verena M. , Bochkov Valery , Bauer Rudolf 

TITLE=C13 Megastigmane Derivatives From Epipremnum pinnatum: β-Damascenone Inhibits the Expression of Pro-Inflammatory Cytokines and Leukocyte Adhesion Molecules as Well as NF-κB Signaling

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01351

DOI=10.3389/fphar.2019.01351

ISSN=1663-9812

ABSTRACT=<p>In order to identify active constituents and to gain some information regarding their mode of action, extracts from leaves of <italic>Epipremnum pinnatum</italic> were tested for their ability to inhibit inflammatory gene expression in endothelial- and monocyte-like cells (HUVECtert and THP-1, respectively). Bioactivity-guided fractionation using expression of <italic>PTGS2</italic> (COX-2) mRNA as a readout resulted in the isolation of two C13 megastigmane glycosides, gusanlungionoside C (<bold>1</bold>) and citroside A (<bold>3</bold>), and the phenylalcohol glycoside phenylmethyl-2-<italic>O</italic>-(6-<italic>O</italic>-rhamnosyl)-ß-D-galactopyranoside (<bold>2</bold>). Further analysis identified six additional megastigmane glycosides and the aglycones β-damascenone (<bold>10</bold>), megastigmatrienone (<bold>11</bold>), 3-hydroxy-β-damascenone (<bold>12</bold>), and 3-oxo-7,8-dihydro-α-ionol (<bold>13</bold>). Pharmacological analysis demonstrated that <bold>10</bold> inhibits LPS-stimulated induction of mRNAs encoding for proinflammatory cytokines and leukocyte adhesion molecules, such as TNF-α, IL-1β, IL-8, COX-2, E-selectin, ICAM-1, and VCAM-1 in HUVECtert and THP-1 cells. <bold>10</bold> inhibited induction of inflammatory genes in HUVECtert and THP-1 cells treated with different agonists, such as TNF-α, IL-1β, and LPS. In addition to mRNA, also the upregulation of inflammatory proteins was inhibited by <bold>10</bold> as demonstrated by immune assays for cell surface E-selectin and secreted TNF-α. Finally, using a luciferase reporter construct, it was shown, that <bold>10</bold> inhibits NF-κB-dependent transcription. Therefore, we hypothesize that inhibition of NF-κB by β-damascenone (<bold>10</bold>) may represent one of the mechanisms underlying the <italic>in vitro</italic> anti-inflammatory activity of <italic>Epipremnum pinnatum</italic> extracts.</p>