The bioactive alkaloids identified from Cortex Phellodendri ameliorate benign prostatic hyperplasia via LOX-5/COX-2...

Area of Science:

• Pharmacology
• Natural Products Chemistry
• Medicinal Chemistry

Background:

• Benign prostatic hyperplasia (BPH) involves inflammation, with lipoxygenase-5 (LOX-5) and cyclooxygenase-2 (COX-2) identified as key targets.
• Bioactive alkaloids from Cortex Phellodendri (CP) show efficacy in treating BPH in rat models.
• The interaction of CP alkaloids with LOX-5 and COX-2 in BPH remains uncharacterized.

Purpose of the Study:

• To identify bioactive alkaloids targeting the LOX/COX pathways for BPH treatment.
• To elucidate the molecular mechanisms of alkaloid action on LOX-5 and COX-2.

Main Methods:

• An affinity-ultrafiltration mass spectrometry approach screened for dual LOX-5/COX-2 ligands from CP alkaloid extract.
• High-resolution mass spectrometry characterized alkaloid structures.
• Protein and mRNA expression levels of LOX-5 and COX-2 were analyzed in BPH model rats.
• Enzyme activity assays and molecular docking evaluated alkaloid-protein interactions.

Main Results:

• Bioactive alkaloids from CP suppressed both LOX-5 and COX-2 expression, reducing inflammation in BPH.
• Demethyleneberberine demonstrated potent inhibition of LOX-5 and COX-2, while palmatine and berberine showed moderate activity.
• Molecular docking confirmed demethyleneberberine's favorable interaction with LOX-5/COX-2.

Conclusions:

• This study is the first to demonstrate the dual inhibitory effects of CP alkaloids on LOX-5 and COX-2 in BPH.
• CP alkaloids ameliorate BPH by targeting both LOX-5 and COX-2 pathways.
• This research provides a foundation for discovering novel, natural product-derived drug leads for BPH with potentially fewer side effects.