Polycyclic Polyprenylated Acylphloroglucinols from Hypericum himalaicum

Area of Science:

• Natural Product Chemistry
• Pharmacology
• Medicinal Chemistry

Background:

• The plant *Hypericum himalaicum* is a source of bioactive natural products.
• Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of compounds with diverse biological activities.
• Understanding the chemical constituents and pharmacological properties of *H. himalaicum* is important for potential therapeutic applications.

Purpose of the Study:

• To isolate and characterize new PPAPs from *Hypericum himalaicum*.
• To elucidate the structures and absolute configurations of the isolated compounds.
• To evaluate the anti-inflammatory potential of the isolated compounds in vitro.

Main Methods:

• Isolation and purification of compounds using chromatographic techniques.
• Structure elucidation utilizing High-Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR) spectroscopy (1D and 2D).
• Determination of absolute configurations via Molybdenum(IV) acetate-induced circular dichroism (ICD), Electronic Circular Dichroism (ECD), and NMR calculations.
• In vitro anti-inflammatory assays using lipopolysaccharide (LPS)-induced RAW264.7 macrophages.

Main Results:

• Six new vicinal diol-containing PPAPs were isolated and characterized.
• Compound 1 demonstrated significant anti-inflammatory activity by attenuating nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) secretion.
• Compound 1 downregulated the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and inhibited reactive oxygen species (ROS) release.
• The anti-inflammatory effects of compound 1 were linked to the inhibition of Nuclear Factor-kappa B (NF-κB) and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) signaling pathways.

Conclusions:

• The study successfully identified novel PPAPs from *Hypericum himalaicum*, expanding the known chemical diversity of this compound class.
• Compound 1 exhibits potent anti-inflammatory properties, suggesting its potential as a lead compound for drug development.
• The findings provide mechanistic insights into the anti-inflammatory action of compound 1, highlighting its modulation of key inflammatory signaling cascades.