Three New HHDP-Bridged Macrocyclic Polyphenols With FXR Agonistic Activity From Penthorum chinense Pursh.

Three new HHDP-bridged macrocyclic polyphenols, designated as Uvangoletin-7-O-4'',6''- (S)-HHDP-β-D-glucopyranoside (Penthorumside D, 1), Uvangoletin-7-O-3''-O-galloyl-4'',6''-(S)-HHDP-β-D-glucopyranoside (Penthorumside E, 2), and, Pinocembrin-7-O-{4'',6''-[7''',7''''-(3''',3'''',4''',4''''-tetrahydroxydibenzofurandicarboxyl)]}-β-D-glucopyranoside (Penthorumside F, 3), along with three known compounds (4-6), were isolated from the aerial parts of Penthorum chinense Pursh. Among them, 1 and 2 are chalcone glycosides, while 3 is a flavanone glycoside. Their structures were elucidated by HR-ESI-MS, NMR spectrum and electronic circular dichroism (ECD), in combination with data from known analogues. The farnesoid X receptor (FXR) binding activities of the isolated compounds were evaluated, using luciferase activities examination. Compounds 4 and 6 exhibited significant FXR activation at 5 µM (p = 0.003 and 0.014), with luciferase activities increasing by 1.28- and 1.18-fold compared to the vehicle control, taking GW4064 as positive control. In contrast, other compounds did not show significant agonistic effects (p > 0.05). These findings suggested 4 and 6 exerted promising FXR agonistic effects with potential for development as anti-cholestatic agents.