Related Experiment Video
Updated: Aug 2, 2025
Exploring the Two Herb Combination Strategy to Treat Injured PC12 Cells
Published on: November 18, 2022
Celastrol Treatment Ameliorated Acute Ischemic Stroke-Induced Brain Injury by Microglial Injury Inhibition and
Fanfan Cao1, Ying Wang1, Yuting Song1,2
1Sino-French Cooperative Central Lab, Gongli Hospital of Shanghai Pudong New Area, No. 207, Juye Rd., Pudong New District, Shanghai 200135, China.
Background:
Stroke is the third main reason of mortality, which is the leading reason for adult disability in the globe. Poststroke inflammation is well known to cause acute ischemic stroke- (AIS-) induced brain injury (BI) exacerbation. Celastrol (CL) has exhibited anti-inflammatory activities in various inflammatory traits though underlying mechanisms remain unknown. So, the present investigation is aimed at studying CL protective mechanism against AIS-induced BI.
Methods:
A mouse model regarding middle cerebral artery occlusion and an oxygen-glucose deprivation (OGD) cell model with or not CL treatment were constructed to study CL protective effects. NF-E2-related factor 2 (Nrf2) was then silenced in BV2 microglia cells (BV2) to study Nrf2 role regarding CL-mediated neuroprotection.
Results:
The results showed that CL treatment suppressed AIS-induced BI by inhibiting NLRP3/caspase-1 pathway activations and induction of apoptosis and pyroptosis in vivo and in vitro. NLRP3/caspase-1 pathway blocking activation suppressed OGD-induced cell pyroptosis and apoptosis. Also, CL treatment reversed OGD-induced microglial injury by promoting Nrf2/heme oxygenase-1 (HO-1) pathway activations. Nrf2 downregulation reversed CL protective effects against OGD-induced microglial injury, pyroptosis, and apoptosis.
Conclusion:
The findings advise that CL treatment ameliorated AIS-induced BI by inhibiting microglial injury and activating the Nrf2/HO-1 pathway.
