Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway

Abstract

Cardiac depression in sepsis is associated with the increased morbidity and mortality. Although myofilaments damage, autonomic dysfunction, and apoptosis play roles in sepsis-induced myocardial dysfunction, the underlying mechanism is not clear. All of these possible factors are related to NFκB signaling, which plays the main role in sepsis signaling. Thaliporphine was determined to possess anti-inflammatory and cardioprotective activity by suppressing NFκB signaling in rodents. The purpose of this study is to further prove this protective effect in larger septic animals, and try to find the underlying mechanisms. The systolic and diastolic functions were evaluated in vivo by pressure-volume analysis at different preloads. Both preload-dependent and -independent hemodynamic parameters were performed. Inflammatory factors of whole blood and serum samples were analyzed. Several sepsis-related signaling pathways were also determined at protein level. Changes detected by conductance catheter showed Thaliporphine could recover impaired left ventricular systolic function after 4 hours LPS injection. It could also reverse the LPS induced steeper EDPVR and gentler ESPVR, thus improve Ees, Ea, and PRSW. Thaliporphine may exert this protective effect by decreasing TNFα and caspase3 dependent cell apoptosis, which was consistent with the decreased serum cTnI and LDH concentration. Thaliporphine could protect sepsis-associated myocardial dysfunction in both preload-dependent and -independent ways. It may exert these protective effects by both increase of “good”-PI3K/Akt/mTOR and decrease of “bad”-p38/NFκB pathways, which followed by diminishing TNFα and caspase3 dependent cell apoptosis.

Evaluation of cardiac troponin I in serum and myocardium of rabbits with experimentally induced polymicrobial sepsis

“…An increased serum cTnI concentration was reported in dogs with systemic inflammatory response syndrome [16]. In a study on rabbit endotoxemia, serum cTnI concentrations increased after LPS infusion [21]. Serum cTnI concentrations in the present study also increased.…”

A rat study model of depression‐driven chronic prostatitis by modulating thePI3K/Akt/mTORnetwork

“…Since mTOR is known to be the main regulator of protein translation, changes in the mTOR activity in the brain region exerts a significant impact on pain symptoms, possibly in relation to pelvic pain of CP (Cho et al, 2018). A previous study reported that mTOR could negatively regulate NF‐κB activation and the MMP9 expression in the cells to reduce inflammatory responses (Lee et al, 2012).…”

“…A previous study reported that mTOR could negatively regulate NF-κB activation and the MMP9 expression in the cells to reduce inflammatory responses (Lee et al, 2012).…”

Natural Aporphine Alkaloids with Potential to Impact Metabolic Syndrome

“…Thaliporphine can recover the impairment of left ventricular systolic function after lipopolysaccharide injection, which is consistent with the reduction in LDH concentration, as well as TNF-α and caspase3 dependent cell apoptosis. Further study shows that thaliporphine protects against myocardial dysfunction both preload-dependently and –independently in lipopolysaccharide-induced endotoxemic rabbits, possibly by up-regulating the PI3K/Akt/mTOR pathway and down-regulating the p38 MAPK/NF-κB pathway [ 90 ]. These observations indicate that thaliporphine may be a novel agent for attenuating endotoxin-induced metabolic disorders with organ injury.…”