Icariin enhance mild hypothermia-induced neuroprotection via inhibiting the activation of NF-κB in experimental ischemic stroke.

Abstract

Therapeutic hypothermia (TH) is a promising neuroprotective agent for treating stroke. However, its clinical application was limited by the impractical duration. Icariin (ICA) were reported to have therapeutic effect on cerebral ischemia. In this research, our aim was to investigate whether the combination of TH and ICA had better neuroprotective effects on ischemic stroke. An ischemia-reperfusion rat model was established and treated with mild hypothermia, ICA or JSH-23 (inhibitor of NF-κB). Thermistor probe, 2'3'5'-triphenyl tetrazolium chloride (TTC), 5/12-score system, and ELISA were used to detect temperature (rectum, cortex, striatum), infarct volume, neurological deficit, and cerebral cell death of these rats. The expressions of tumor necrosis factor (TNF)-α, Interleukin- 6 (IL-6), nuclear factor-kappa B (NF-κB), nuclear factor erythroid2-related factor (Nrf2), peroxisome proliferator activated receptor gamma (PPARα), PPARγ, Janus kinase 2 (JAK2), p-JAK2, signal transducers and activators of transduction-3 (STAT3), and p-STAT3 were detected by Western blot or q-PCR. Mild hypothermia, ICA, and JSH-23 reduced the cerebral infarct volume, neurological deficit, cerebral cell death of rats, downregulated the expressions of TNF-α, IL-6, C-Caspase 3 and Bax, and the activation of PPARs/Nrf2/NF-κB and JAK2/STAT3 pathways, but elevated the expression of Bcl-2. ICA promoted the effect of mild hypothermia on infarct volume, neurological deficit, and cerebral cell death. Moreover, ICA also enhanced the regulatory effect of mild hypothermia on apoptosis/inflammation factors expressions and activation of PPARs/Nrf2/NF-κB and JAK2/STAT3 pathways. ICA could promote mild hypothermia-induced neuroprotection by inhibiting the activation of NF-κB through the PPARs/Nrf2/NF-κB and JAK2/STAT3/NF-κB pathways in experimental stroke.

• Authors: Mingming Dai, Bin Chen, Xiaozhi Wang, Chang Gao, Hang Yu
• Journal: Metabolic brain disease (Metab Brain Dis) Vol. 36 Issue 7 Pg. 1779-1790 (10 2021) ISSN: 1573-7365 [Electronic] United States
• PMID: 33978900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Flavonoids
• NF-kappa B
• icariin

Topics

• Animals
• Flavonoids
• Hypothermia
• Ischemic Stroke
• NF-kappa B (metabolism)
• Neuroprotection
• Rats
• Reperfusion Injury (metabolism)