Xuebijing Injection Alleviate Sepsis-induced Myocardial Damage by Inhibiting Apoptosis via PI3K/AKT/Foxo3a and MAPK Signaling Pathways

Abstract

Background Xuebijing injections (XBJ) originate from the traditional Chinese medicine (TCM) prescription XuefuZhuyu Decoction. It is composed of five Chinese herbal extracts; Carthami flos, Paeoniae radix rubra, Chuanxiong rhizoma, Salviae miltiorrhizae, and Angelicae Sinensis radix. The China Food and Drug Administration approved XBJ as a TCM preparation for the adjuvant treatment of sepsis. However, the mechanisms underlying the effects of XBJ on sepsis-induced myocardial damage (SIMD) have yet to be fully elucidated. This study explores the potential therapeutic mechanism of XBJ on SIMD. Methods In this study, rats were randomly assigned to three groups: Sham group, cecal ligation and puncture (CLP) group, and XBJ group. Echocardiography, myocardial enzymes and hematoxylin-eosin (H&E) were used to detect cardiac function. IL-1β, IL-6 IL-10, TNF-α, SOD and MDA in serum were measured using ELISA kits. The AutoDockTools Vina was utilized for molecular docking to analyze the mechanism of binding of XBJ with PI3K, AKT, Foxo3a, ERK1/2, P38 and JNK protein. Western blotting was conducted to analyze the levels of p-PI3K, PI3K, p-AKT, AKT, p-Foxo3a, Foxo3a, p-ERK1/2, ERK1/2, p-P38, P38, p-JNK, JNK, Bax, Bcl-2, Cleaved-Caspase 3, and Survivin proteins in myocardial tissue. Immunofluorescence staining was utilized to examine the activity levels of PI3K, AKT, Foxo3a, ERK1/2, P38 and JNK in cardiac tissue. Immunohistochemical detection of Bax, Bcl-2 and Cleaved-Caspase 3 expression. Results The results of echocardiography, myocardial enzyme and H&E test showed that XBJ could effectively improve the myocardial injury caused by CLP with the increase of treatment time. XBJ decreased IL-1β, IL-6, TNF-α and MDA levels, but increased SOD and IL-10 level in CLP-induced SIMD in ELISA. Molecular docking analysis indicated that there was a strong and stable affinity of XBJ for PI3K/AKT/Foxo3a and MAPK signaling pathways. XBJ treatment led to the downregulation of p-PI3K, p-AKT, p-Foxo3a, Bax, Cleaved-Caspase 3, p-ERK1/2, p-P38 and p-JNK levels, while upregulating Bcl-2, and Survivin protein levels (p < 0.05). Conclusion XBJ may alleviate SIMD by suppressing cell apoptosis and inflammation possibly via the PI3K/AKT/Foxo3a and MAPK signaling pathways.