Epimedium Aqueous Extract Ameliorates Cerebral Ischemia/Reperfusion Injury through Inhibiting ROS/NLRP3-Mediated Pyroptosis

Abstract

Cerebral ischemia/reperfusion causes exacerbated neuronal damage involving excessive neuroinflammation and oxidative stress. ROS is considered a signal molecule to activate NLRP3; thus, the ROS/NLRP3/pyroptosis axis plays a vital role in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI). Therefore, targeting the inhibition of the ROS/NLRP3/pyroptosis axis may be a promising therapeutic tactic for CIRI. Epimedium (EP) contains many active ingredients (ICA, ICS II, and ICT), which have a wide range of pharmacological activities. However, whether EP can protect against CIRI remains unknown. Thus, in this study, we designed to investigate the effect and possible underlying mechanism of EP on CIRI. The results showed that treatment with EP dramatically mitigated brain damage in rats following CIRI, which was achieved by suppressing mitochondrial oxidative stress and neuroinflammation. Furthermore, we identified the ROS/NLRP3/pyroptosis axis as a vital process and NLRP3 as a vital target in EP-mediated protection. Most interestingly, the main compounds of EP directly bonded with NLRP3, as reflected by molecular docking, which indicated that NLRP3 might be a promising therapeutic target for EP-elicited cerebral protection. In conclusion, our findings illustrate that ICS II protects against neuron loss and neuroinflammation after CIRI by inhibiting ROS/NLRP3-mediated pyroptosis.

Targeting the PANoptosis signaling pathway for myocardial protection: therapeutic potential of Xian Ling Gu Bao capsule

“…Prior studies have demonstrated the efficacy of Epimedium brevicornu Maxim. along with its primary active metabolites ICS II and ICA, in combating a range of diseases owing to their potent antiinflammatory and antioxidant attributes (Liu et al, 2020;Wu et al, 2023). Consequently, the pharmacological profile of XLGB has motivated further investigation into its therapeutic potential for MI and its associated molecular targets.…”

“…Tissue assessment was carried out using the BCA protein assay as described in our previous study (Wu et al, 2023). Subsequently, the lysates were normalized to equal amounts per group, and 10 μg of protein from the tissue lysates were separated using 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis.…”