Five new clerodane diterpenoids from Callicarpa integerrima and their anti-inflammatory activity

Area of Science:

• Natural Products Chemistry
• Pharmacology
• Immunology

Background:

• Callicarpa integerrima is a plant source of bioactive compounds.
• Inflammasomes, particularly NLRP3, are key regulators of inflammation and pyroptosis.
• Pyroptosis is a pro-inflammatory form of programmed cell death.

Purpose of the Study:

• To isolate and characterize new clerodane diterpenoids from Callicarpa integerrima.
• To evaluate the anti-inflammatory potential of isolated compounds, focusing on pyroptosis and inflammasome activation.

Main Methods:

• Isolation of compounds using chromatographic techniques.
• Structure elucidation via NMR, HR-ESI-MS, IR, UV, specific rotations, ECD, and computational analysis.
• In vitro assays to measure LDH release, IL-1β suppression, and ASC speck formation.

Main Results:

• Five new clerodane diterpenoids, calintegerinoids A-E, were identified.
• Compound 3 exhibited potent inhibition of LDH release (IC50 = 1.27 μM) compared to Andrographolide (IC50 = 8.01 μM).
• Compound 3 suppressed IL-1β release, blocked NLRP3 inflammasome activation, and reduced pyroptosis and ASC speck formation.

Conclusions:

• Calintegerinoids A-E are novel clerodane diterpenoids from Callicarpa integerrima.
• Compound 3 displays significant anti-inflammatory properties by inhibiting NLRP3 inflammasome assembly and pyroptosis.
• This study highlights the therapeutic potential of compound 3 for inflammatory diseases.