Sesquiterpenoids from Inula britannica and their potential mechanism for immunomodulation

Area of Science:

• Natural Product Chemistry
• Immunology
• Pharmacology

Background:

• The immune system plays a critical role in diseases like Parkinson's and acute lung injury.
• Identifying novel compounds with immunomodulatory activity is crucial for therapeutic development.

Purpose of the Study:

• To isolate and characterize chemical constituents from Inula britannica L.
• To evaluate the immunomodulatory effects of these compounds.
• To elucidate the mechanism of action for active compounds.

Main Methods:

• Immunoregulatory activity-directed separation using phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Ion)-mediated Jurkat T cells.
• Structure elucidation using 1D/2D NMR, HRMS, ECD spectra, and quantum chemical calculations.
• Assay of immunomodulatory effects and mechanistic studies involving kinase phosphorylation and transcription factor translocation.

Main Results:

• Five new aromatic sesquiterpenoid dimers (inulabritanoids J-N) and one new germacrane-type sesquiterpenoid (britanicafanin F) were isolated, along with eight known sesquiterpenoids.
• Compounds 8, 9, and 13 demonstrated significant inhibition of Interleukin-2 (IL-2) and Interferon-gamma (IFN-γ) production.
• Compound 13 inhibited p38, ERK, and JNK phosphorylations, suppressed c-Jun/c-Fos expression, and blocked AP-1 nuclear translocation.

Conclusions:

• Sesquiterpenoids from Inula genus possess significant immunomodulatory properties.
• Compound 13 exhibits a promising mechanism for regulating immune responses by targeting key inflammatory signaling pathways.
• These findings suggest potential therapeutic applications for Inula-derived sesquiterpenoids in immune and inflammatory diseases.