Mume Fructus Total Flavonoids Modulate miR-145-3p Expression to Inhibit Lipopolysaccharide-induced Inflammatory...

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Microglia-mediated inflammation is crucial in neurodegenerative diseases.
• Mume Fructus total flavonoids (MFTF) are bioactive compounds from Mume Fructus.
• Understanding MFTF's anti-inflammatory mechanisms is vital for therapeutic development.

Purpose of the Study:

• To investigate the anti-inflammatory effects of MFTF on lipopolysaccharide (LPS)-induced microglial inflammation.
• To elucidate the underlying molecular mechanisms of MFTF's action.
• To assess MFTF's potential in treating neuroinflammatory disorders.

Main Methods:

• Chemical composition of MFTF analyzed using UPLC-QTOF-MS.
• In vitro microglial inflammation model established using BV2 cells stimulated with LPS.
• Cell viability, proliferation, polarization, and apoptosis-related protein expression assessed.
• Real-time quantitative PCR and Western Blotting used for molecular analysis.
• RNA sequencing explored potential signaling pathways involved.

Main Results:

• MFTF identified 379 compounds and demonstrated anti-inflammatory effects by downregulating M1 markers (iNOS, IL-1β, CD86) and upregulating M2 markers (Arg-1, IL-10, CD206).
• MFTF inhibited pro-apoptotic protein Bad and promoted anti-apoptotic protein Bcl-2.
• MFTF upregulated miR-145-3p expression; inhibition of miR-145-3p partially reversed MFTF's effects.
• RNA sequencing suggested MFTF regulates Toll-like receptor, NOD-like receptor, and NF-κB signaling pathways.

Conclusions:

• MFTF inhibits pro-inflammatory M1 microglia polarization and promotes M2 polarization and proliferation.
• Upregulation of miR-145-3p is a potential mechanism for MFTF's anti-neuroinflammatory effects.
• MFTF shows therapeutic potential for neuroinflammatory disorders.