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Research Article

Protective effect and mechanism of styrax on ischemic stroke rats: metabonomic insights by UPLC-Q/TOF-MS analysis

, , , , , , , , , , & show all
Pages 1318-1331 | Received 22 Sep 2022, Accepted 04 Aug 2023, Published online: 24 Aug 2023
 

Abstract

Context

Styrax is used for prevention and treatment of cerebrovascular diseases. However, the underlying mechanism remains unclear.

Objective

To elucidate styrax’s anti-ischemic stroke protective effects and underlying mechanisms.

Materials and methods

An ischemic-stroke rat model was established based on middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were randomly assigned to the following groups (n = 10) and administered intragastrically once a day for 7 consecutive days: sham, model, nimodipine (24 mg/kg), styrax-L (0.1 g/kg), styrax-M (0.2 g/kg) and styrax-H (0.4 g/kg). Neurological function, biochemical assessment, and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based serum metabonomics were used to elucidate styrax’s cerebral protective effects and mechanisms. Pearson correlation and western blot analyses were performed to verify.

Results

The addition of 0.4 g/kg styrax significantly reduced cerebral infarct volume and neurobehavioral abnormality score. Different doses of styrax also decrease MDA, TNF-α, IL-6, and IL-1β, and increase SOD and GSH-Px in ischemic-stroke rats (p < 0.05; MDA, p < 0.05 only at 0.4 g/kg dose). Biochemical indicators and metabolic-profile analyses (PCA, PLS-DA, and OPLS-DA) also supported styrax’s protective effects. Endogenous metabolites (22) were identified in ischemic-stroke rats, and these perturbations were reversible via styrax intervention, which is predominantly involved in energy metabolism, glutathione and glutamine metabolism, and other metabolic processes. Additionally, styrax significantly upregulated phosphorylated AMP-activated protein kinase and glutaminase brain-tissue expression.

Conclusion

Styrax treatment could ameliorate ischemic-stroke rats by intervening with energy metabolism and glutamine metabolism. This can help us understand the mechanism of styrax, inspiring more clinical application and promotion.

Author contributions

FM, RL, XL, and MZ equally contributed to this work. HT, JW, and FM conceived the idea and revised the manuscript. FM, XL, RL, and SH designed the research, conducted most of the experiments, and wrote the paper. JZ, MZ, CG, YG, and MX assisted experiments. FM, HZ, and RL collated and analyzed data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 81903837, 72074218). The disciplinary promotion program of Xijing Hospital in basic research project (XJZT18MJ16, XJZT19Z08), and the Natural Science Basic Research Project of Shaanxi Province (No.2021SF-345).