The Investigation on the Effect of β-caryophyllene on Ferroptosis and Neuroprotection Mechanisms in Rats with Vascular Dementia

ZHAO Wei; WU Jie

doi:10.3969/j.issn.2096-305X.2025.04.006

Abstract：Objective To verify the effect of β-stilbene on ferroptosis in brain tissues of rats with vascular dementia(VaD)and explore its neuroprotective mechanism.Methods During the experimental operation,the muscles,fascia and other tissues of the rats were carefully dissected to fully expose the bilateral common carotid arteries.Subsequently,only suturing was performed on them,which was used as the sham operation group.In another group of rats,the bilateral common carotid arteries were also exposed,but ligation was used,and thus the VaD model of SD rats was successfully established.After the model preparation was completed,the rats with successfully prepared models were selected and randomly divided into the model group and the β-caryophyllene administration group.Seven days after the successful establishment of the model,rats in the β-caryophyllene administration group were injected withβ-caryophyllene(408 mg/kg)through the tail vein.After continuous administration for two weeks,rats in each group were taken for the Morris water maze test.The next day,some rats were randomly selected from each group,and their brain tissues were taken for hematoxylin-eosin(HE)staining.Strictly follow the operation steps in the kit manual to complete the determination of Fe2+,malondialdehyde(MDA),glutataione(GSH),and superoxide dismutase(SOD)contents in brain tissue.Using the Western Blot method,the protein contents of glutathioneperoxidase 4(GPX4)and acyl-coA synthetase long-chain family member 4(ACSIA)in each group were detected.Results The results of the Morris water maze experiment indicated that during the period from the 2nd to the 5th day after β-caryophyllene administration treatment,the escape latency of rats was shortened,the stay time in the target area was prolonged,and the number of times they crossed the platform increased.Compared with the sham operation group,the levels of Fe2+and MDA in the brain tissue of rats in the model group were significantly increased,the content of GSH decreased,the activity of SOD decreased,the number of hippocampal cells decreased and nuclear contraction occurred.Compared with the model group,the levels of Fe2+and MDA in the brain tissue of rats in the β-caryophyllene administration group decreased,the content of GSH increased,the activity of SOD enhanced,the number of hippocampal cells increased,and the tissue morphology tended to be normal.The Western Blot results showed that the content of GPX4 protein in the hippocampal tissue of the model group was significantly lower than that of the sham operation group,while the content of ACSL4 protein was higher.Compared with the model group,the expression of GPX4 was upregulated and the expression of ACSL4 was downregulated in the hippocampal tissue of the β-caryophyllene group.Conclusion β-caryophyllene may protect cerebral neurons by inhibiting ferroptosis of cerebral neurons in VaD rats,thereby improving learning and spatial memory abilities of VaD rats.