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

Area of Science:

• Natural Product Chemistry
• Pharmacology
• Medicinal Chemistry

Background:

• Penthorum chinense Pursh is a plant source of bioactive compounds.
• Macrocyclic polyphenols and their derivatives are of interest for therapeutic potential.
• Farnesoid X receptor (FXR) plays a role in bile acid homeostasis and metabolic diseases.

Purpose of the Study:

• To isolate and characterize new HHDP-bridged macrocyclic polyphenols from Penthorum chinense Pursh.
• To evaluate the farnesoid X receptor (FXR) binding activities of the isolated compounds.
• To explore the potential of these compounds as anti-cholestatic agents.

Main Methods:

• Isolation of compounds using chromatographic techniques.
• Structure elucidation using High-Resolution Electrospray Ionization Mass Spectrometry (HR-ESI-MS), Nuclear Magnetic Resonance (NMR) spectroscopy, and Electronic Circular Dichroism (ECD).
• Assessment of FXR activation using luciferase reporter gene assays.

Main Results:

• Three new HHDP-bridged macrocyclic polyphenols (Penthorumside D, E, and F) and three known compounds were isolated.
• Compounds 4 and 6 demonstrated significant FXR activation at 5 µM, with increased luciferase activity.
• Other isolated compounds did not exhibit significant FXR agonistic effects.

Conclusions:

• Compounds 4 and 6 possess promising FXR agonistic effects.
• These compounds may hold potential for the development of novel anti-cholestatic therapies.
• Further investigation into the therapeutic applications of these natural products is warranted.