Zhongguo Zhong Yao Za Zhi. 2026 May;51(9):2461-2470. doi: 10.19540/j.cnki.cjcmm.20251113.710.
ABSTRACT
This study aimed to investigate the neuroprotective effects and potential mechanism of Xiaoxuming Decoction(XXM) against cerebral ischemia-reperfusion injury in mice. The middle cerebral artery occlusion/reperfusion model was established in male KM mice using the suture method. The experimental animals were randomly divided into the following groups: sham, model, nimodipine, XXM, Mahuang-Guizhi(MG), and Xiaoxuming Decoction without Mahuang-Guizhi(DXXM). Neurological function deficit scores were assessed using the Zea Longa scoring system. Cerebral infarction rate was measured by 2,3,5-triphenyltetrazolium chloride(TTC) staining. Pathological changes in brain tissue were observed via hematoxylin and eosin(HE) staining and Nissl staining. Non-targeted metabolomics analysis was performed using the ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) to explore the potential mechanism. Serum interleukin-1β(IL-1β) and matrix metalloproteinase-2(MMP-2) levels were detected by the enzyme-linked immunosorbent assay(ELISA). Additionally, the expression of tight junction proteins in the blood-brain barrier was detected by Western blot. According to the results, compared with the model group, both XXM and DXXM interventions significantly improved neurological function scores while reducing cerebral infarction rate, neuronal damage, and pathological changes in brain tissue. XXM exhibited a superior protective effect than DXXM did. MG intervention also improved neurological function scores and alleviated pathological damage. Metabolomics analysis revealed 82, 23, and 187 differential metabolites screened from the XXM, MG, and DXXM groups, respectively. The metabolic pathways commonly affected by both XXM and DXXM were purine, alanine, aspartate, and glutamate metabolism, while MG primarily affected the arachidonic acid metabolism pathway. ELISA results showed that XXM and MG significantly reduced IL-1β and MMP-2 levels, while DXXM significantly reduced IL-1β levels. Western blot results indicated that both XXM and DXXM up-regulated the expression of tight junction proteins in the brains of model mice. In conclusion, XXM and DXXM may exert anti-cerebral ischemia-reperfusion injury effects by inhibiting inflammatory factor release, reducing excitatory amino acid toxicity, and enhancing the expression of tight junction proteins in the blood-brain barrier via purine, alanine, aspartate, and glutamate metabolism pathway regulation. XXM exhibited superior effects compared to DXXM. MG may exert neuroprotective effects, to some extent, by regulating arachidonic acid metabolism and reducing pro-inflammatory factor levels.
PMID:42392799 | DOI:10.19540/j.cnki.cjcmm.20251113.710