Author/Authors :
Kung, Woon-Man Department of Exercise and Health Promotion - College of Kinesiology and Health - Chinese Culture University, Taipei, Taiwan , Lin, Chai-Ching Department of Biotechnology and Animal Science - College of Bioresources - National Ilan University, Yilan, Taiwan , Kuo, Chan-Yen Graduate Institute of Systems Biology and Bioinformatics - National Central University, Chungli, Taiwan , Juin, Yu-Ching Department of Biotechnology and Animal Science - College of Bioresources - National Ilan University, Yilan, Taiwan , Wu ,po-Ching Department of Biomechatronic Engineering - College of Bioresources - National Ilan University, Yilan, Taiwan , Lin, Muh-Shi Department of Biotechnology and Animal Science - College of Bioresources - National Ilan University, Yilan, Taiwan
Abstract :
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.
Keywords :
Wild Bitter Melon , Exerts Anti-Inflammatory , Upregulating Injury-Attenuated , CISD2 Expression following , Spinal Cord Injury
