Effect and Mechanism of Xijiajing Formula on Cyclophosphamide Induced-Cardiotoxicity in Mice

PENG Mengqi; WEI Xiaohong; LIN Hongyuan; ZHANG Xiaowei; SHANG Hongcai

Abstract：Objective To evaluate the protective effect of Xijiajing formula on cyclophosphamide-induced cardiotoxicity in mice and to explore its mechanism of action.Methods Sixty ICR male mice were randomly divided into Control group,Model group,Xijiajing formula low,medium,high doses(5.525,11.05,22.10 g/kg)groups.Three dose groups of Xijiajing were given prophylactic medication orally for 7 days,once a day.On the 7th day,mice in the Model group and Xijiajing intervention groups were intraperitoneally injected with cyclophosphamide 200 mg/kg.The cardiac function in each group of mice was monitored by ultrasound after the last administration of drugs.ELISA was performed to determine the levels of myocardial injury markers CK-MB,LDH,and cTnT,as well as the indicators of oxidative stress and ferroptosis markers CAT,SOD,MDA,and GSH in serum and cardiac tissues of mice.Western blot was used to detect the protein expression levels of tyrosine protein kinase(Fyn)and cyclooxygenase-2(COX2),signaling molecules that regulate iron death,in mouse heart tissues.Results Compared with the Control group,the Model group had reduced ventricular wall amplitude,significantly lower LVEF and LVFS(P<0.05).Serum levels of CK-MB,LDH,cTnT,CAT,and MDA were significantly higher(P<0.05),while SOD and GSH levels were significantly lower(P<0.05)in Model group.Cardiac tissues levels of MDA was significantly higher(P<0.05),and GSH was significantly lower(P<0.05)in Model group.Protein expression levels of Fyn and COX2 were significantly higher(P<0.05)in Model group.Compared with the Model group,the LVEF and LVFS of mice in the Xijiajing formula high doses group were significantly higher(P<0.05).The serum levels of CK-MB,LDH,cTnT,CAT,and MDA were significantly decreased(P<0.05),while the levels of SOD and GSH were significantly increased(P<0.05)in mice of Xijiajing low,medium,and high dose groups.MDA levels were significantly reduced(P<0.05)and GSH levels were significantly increased(P<0.05),while Fyn and COX2 protein levels decreased(P<0.05)in the heart tissues of mice in the Xijiajing formula high dose group.Conclusion Xijiajing formula significantly attenuated cyclophosphamide-induced myocardial injury in mice,and its effects may be related to the modulation of Fyn-COX2,inhibition of oxidative stress and ferroptosis pathway.