Wild Bitter Melon Exerts Anti-Inflammatory Effects by Upregulating Injury-Attenuated CISD2 Expression following Spinal Cord Injury

Abstract EN

Background.

Spinal cord injuries (SCIs) induce secondary neuroinflammation through astrocyte reactivation, which adversely affects neuronal survival and eventually causes long-term disability.

CDGSH iron sulfur domain 2 (CISD2), which has been reported to be involved in mediating the anti-inflammatory responses, can serve as a target in SCI therapy.

Wild bitter melon (WBM; Momordica charantia Linn.

var.

abbreviata Ser.) contains an anti-inflammatory agent called alpha-eleostearic acid (α-ESA), a peroxisome proliferator-activated receptor-β (PPAR-β) ligand.

Activated PPAR-β inhibits the nuclear factor κB (NF-κB) signaling pathway via the inhibition of IκB (inhibitor of NF-κB) degradation.

The role of astrocyte deactivation and CISD2 in anti-inflammatory mechanisms of WBM in acute SCIs is unknown.

Materials and Methods.

A mouse model of SCI was generated via spinal cord hemisection.

The SCI mice were administered WBM intraperitoneally (500 mg/kg bodyweight).

Lipopolysaccharide- (LPS-) stimulated ALT cells (astrocytes) were used as an in vitro model for studying astrocyte-mediated inflammation post-SCI.

The roles of CISD2 and PPAR-β in inflammatory signaling were examined using LPS-stimulated SH-SY5Y cells transfected with si-CISD2 or scramble RNA.

Results.

WBM mitigated the SCI-induced downregulation of CISD2, PPAR-β, and IκB and upregulation of glial fibrillary acidic protein (GFAP; marker of astrocyte reactivation) in the spinal cord of SCI mice.

Additionally, WBM (1 μg/mL) mitigated LPS-induced CISD2 downregulation.

Furthermore, SH-SY5Y neural cells with CISD2 knockdown exhibited decreased PPAR-β expression and augmented NF-κB signaling.

Conclusion.

To the best of our knowledge, this is the first study to report that CISD2 is an upstream modulator of the PPAR-β/NF-κB proinflammatory signaling pathway in neural cells, and that WBM can mitigate the injury-induced downregulation of CISD2 in SCI mice and LPS-stimulated ALT astrocytes.