Chemical constitutes from Tuber indicum with immunosuppressive activity uncovered by transcriptome analysis

Area of Science:

• Natural Product Chemistry
• Immunology
• Pharmacology

Background:

• Tuber indicum is a source of bioactive natural products.
• Understanding the chemical constituents and biological activities of Tuber indicum is ongoing.
• Novel compounds with potential therapeutic applications are of significant interest.

Purpose of the Study:

• To isolate and characterize new compounds from Tuber indicum.
• To evaluate the immunosuppressive and anti-inflammatory activities of the isolated compounds.
• To elucidate the molecular mechanisms underlying the observed bioactivities.

Main Methods:

• Isolation and structure elucidation of compounds using HRESIMS, NMR, and ECD calculations.
• Transcriptome analysis (RNA-seq) to identify potential bioactivities.
• In vitro assays using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages to assess anti-inflammatory effects.
• Western blotting to investigate signaling pathways (PI3K/Akt).
• In vivo anti-inflammatory assessment in a zebrafish model.

Main Results:

• Three new compounds, a polyketide (1) and two lactams (2 and 3), were isolated and characterized.
• Compound 2 exhibited significant immunosuppressive activity.
• Compound 2 reduced the production of inflammatory mediators (NO, ROS, IL-6, TNF-α, COX-2, iNOS).
• Compound 2 suppressed the PI3K/Akt signaling pathway and modulated PTEN levels.
• Anti-inflammatory effects of compound 2 were confirmed in a zebrafish model.

Conclusions:

• Compound 2, a novel lactam from Tuber indicum, possesses potent anti-inflammatory properties.
• The anti-inflammatory mechanism of compound 2 involves the inhibition of the PI3K/Akt pathway.
• Tuber indicum is a valuable source for discovering new anti-inflammatory agents.