Nimbolide Targets Multiple Signalling Pathways to Reduce Neuroinflammation in BV-2 Microglia

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• Neuroinflammation plays a critical role in various neurological disorders.
• Microglia are key immune cells in the brain, and their activation contributes to neuroinflammation.
• Limonoids, like nimbolide from the neem plant, possess potential therapeutic properties.

Purpose of the Study:

• To investigate the anti-neuroinflammatory effects of nimbolide in lipopolysaccharide (LPS)-activated BV-2 microglia.
• To elucidate the molecular mechanisms underlying nimbolide's action on inflammatory pathways.
• To explore the role of antioxidant pathways and specific proteins in nimbolide's anti-inflammatory effects.

Main Methods:

• BV-2 microglia cells were treated with varying concentrations of nimbolide followed by LPS stimulation.
• Analysis of inflammatory mediators (TNFα, IL-6, IFNγ, NO, PGE2) and related proteins (p-p65, p-IκBα, p38, JNK).
• Assays for reactive oxygen species (ROS) generation, antioxidant protein expression (HO-1, NQO-1), Nrf2 nuclear translocation, and SIRT-1 activity.

Main Results:

• Nimbolide significantly reduced pro-inflammatory cytokines, NO, and PGE2 in LPS-activated microglia.
• It inhibited LPS-induced activation of NF-κB and MAPK signaling pathways.
• Nimbolide demonstrated antioxidant effects by reducing ROS and enhancing HO-1/NQO-1 expression, linked to Nrf2 activation and SIRT-1 nuclear accumulation.

Conclusions:

• Nimbolide exhibits potent anti-neuroinflammatory effects in microglia.
• Its mechanism involves the dual inhibition of NF-κB and MAPK pathways.
• Activation of Nrf2-mediated antioxidant responses and SIRT-1 activity contributes to nimbolide's therapeutic potential.