Emodin protects lipopolysaccharide-induced myocardial injury and mitochondrial dysfunction via PI3K/AKT signaling pathway based on Network Pharmacology

Abstract

Sepsis combined with myocardial injury is an important cause of septic shock and multiple organ failure. Cardiac dysfunction is a significant manifestation of sepsis and it is associated with the prognosis of the disease. It is assumed that damage to myocardial mitochondrial function is one of the main causes of cardiac dysfunction in septic patients, and the repair of myocardial mitochondrial function may alleviate cardiac dysfunction in septic patients. Emodin has been discovered to serve a variety of pharmacological effects, including anti-tumor, anti-inflammatory, antioxidant, and anti-apoptotic properties. In this study, we investigated the potential protective effect of Emodin on sepsis and revealed the underlying mechanisms using a network pharmacology approach coupled with experimental validation. The model of myocardial injury induced by LPS was established and divided into three groups: the control group, the lipopolysaccharide (LPS) group, and the LPS+Emodin group. The apoptosis rate, reactive oxygen species (ROS), mitochondrial permeability transition pore(MPTP), and mitochondrial membrane potential (MMP) were determined in LPS-induced sepsis Cardiacmyocytes treated with different concentrations of Emodin. In addition, the degree of myocardial mitochondrial damage was evaluated by electron microscopy. Signal pathway-related proteins were determined by Western blotting in vitro. And then, network pharmacology screening revealed TP53, CASP3, ILB, MYC, TNF, PTGS2, and PPARG as the critical overlapping targets in a PPI network, and GO and KEGG analyses revealed the top 10 enriched biological processes and signaling pathways associated with the therapeutic effects of emodin on sepsis. The results show the PI3K-AKT pathway is mainly involved in the emodin-sepsis myocardial injury network. Meanwhile, Emodin has been demonstrated to protect the myocardium from LPS-induced myocardial injury in vitro, and moderate doses of Emodin showed the most prominent effect. Emodin alleviates mitochondrial damage by reducing apoptosis and inhibiting oxidative stress and ameliorates protecting LPS-induced myocardial injury and mitochondrial dysfunction through the PI3K-AKT pathway. This provides a feasible strategy for preventing and treating myocardial injury and mitochondrial dysfunction in sepsis. This study was supported by the Science and Technology Bureau of Zhengjiang (Grant No.SH2022068 and SH2022042). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.