NF-κB inhibitors from Eurycoma longifolia.

Area of Science:

• Phytochemistry
• Pharmacology
• Molecular Biology

Background:

• Eurycoma longifolia roots are traditionally used for various ailments in Southeast Asia.
• Despite known pharmacological activities, the mechanism of E. longifolia's anti-inflammatory effects remains unclear.

Purpose of the Study:

• To isolate and identify compounds from E. longifolia roots that inhibit nuclear factor-kappa B (NF-κB).
• To elucidate the mode of action for the anti-inflammatory activity of E. longifolia.

Main Methods:

• Bioguided isolation using an NF-κB-driven luciferase reporter gene assay.
• Chemical characterization of isolated compounds, including a new quassinoid, eurycomalide C.
• In vitro biological activity evaluation of isolated compounds against NF-κB.

Main Results:

• A new quassinoid, eurycomalide C, and 27 known compounds were identified.
• C19-type and C20-type quassinoids, along with specific alkaloids (β-carboline, canthin-6-one), demonstrated potent NF-κB inhibition (low micromolar IC50).
• Eurycomalactone, 14,15β-dihydroklaieanone, and 13,21-dehydroeurycomanone were identified as highly potent NF-κB inhibitors (IC50 < 1 μM).

Conclusions:

• Specific quassinoids and alkaloids from E. longifolia are effective inhibitors of NF-κB.
• These findings provide molecular insights into the anti-inflammatory properties of E. longifolia, potentially validating its traditional uses.