Huanglian Jiedu decoction alleviates ischemia‐induced cerebral injury in rats by mitigating NET formation and activiting GABAergic synapses

• DOI: 10.1111/jcmm.18528
• Publication Date: 2024-08-05T04:41:40Z
• Authors: Youxiang Cui; Mingyue Cui; Leilei Wang; Ning Wang; Yao Chen; Shuquan Lv; Limin Zhang; Congai Chen; Yanwen Yang; Feng Wang; Lichun Wang; Huantian Cui
• Keywords: Nissl body; Penumbra

Abstract Huanglian Jiedu decoction (HLJD) has been used to treat ischemic stroke in clinic. However, the detailed protective mechanisms of HLJD on have yet be elucidated. The aim this study is elucidate underlying pharmacological based inhibition neuroinflammation and amelioration nerve cell damage. A middle cerebral artery occlusion reperfusion (MCAO/R) model was established rats received treatment. Effects neurological function assessed Bederson's score, postural reflex test asymmetry score. 2, 3, 5‐Triphenyltetrazolium chloride (TTC) staining, Hematein eosin (HE) Nissl staining were observe pathological changes brain. Then, transcriptomics screen differential genes brain tissue MCAO/R following intervention. Subsequently, effects neutrophil extracellular trap (NET) formation‐related neuroinflammation, gamma‐aminobutyric acid (GABA)ergic synapse activation, damage proliferation validated using immunofluorescence, western blot enzyme‐linked immunosorbent assay (ELISA). Our results showed that intervention reduced score rats. Pathological indicated treatment decreased infarction area, mitigated neuronal increased numbers bodies. Transcriptomics suggested affected 435 Among them, several involving NET formation GABAergic synapses pathways dysregulated. Subsequent experimental validation MPO + CitH3 positive expression protein PAD4, p‐P38/P38, p‐ERK/ERK levels IL‐1β, IL‐6 TNF‐α, reversed increase Iba1 TLR4 , p65 NLRP3 area Moreover, GABA levels, elevated GABRG1 GAT3, TUNEL Ki67 exerts a multifaceted impact ischemia‐induced injury This effectively inhibits by mitigating formation, concurrently improves fosters through activating synapses.