UNASSIGNED: Cardiac dysfunction is a complication commonly encountered by patients with endotoxemia. Fangchinoline (Fan) is a natural bisbenzylisoquinoline alkaloid. This study aimed to investigate the cardioprotective effect of Fan against lipopolysaccharide (LPS)-induced acute cardiac dysfunction.
UNASSIGNED: Rats were administered with Baicalin (100 mg/kg) and Fan (30 or 60 mg/kg) via intraperitoneal injection (i.p.) for 3 days, followed by LPS treatment (10 mg/kg, i.p.). The rats were randomly grouped (n=10): the control group, the LPS group, the LPS + Baicalin group, the LPS + Fan groups. Echocardiography and hematoxylin and eosin (HE) staining were performed to detect cardiac dysfunction. Cardiac function were also determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), ELISA, and western blot, respectively. The protective mechanisms of Fan were analyzed by western blot and qRT-PCR.
UNASSIGNED: LPS induced the depression of cardiac function, myocardial inflammation, and apoptosis. These changes were associated with decreased GRP78 and GADD34, increased C/EBP-homologous protein (CHOP) and cleaved caspase-12. Fan significantly reduced the release of inflammatory cytokines such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-18, and IL-6. Furthermore, Fan treatment increased superoxide dismutase (SOD) and decreased malondialdehyde (MDA. Notably, Fan inhibited myocardial apoptosis following ER stress in the LPS-induced rat model and stimulated phosphorylation activation of ERK1/2 and NF-κB p65 proteins.
UNASSIGNED: Fan deficiency alleviated LPS-induced endotoxemia in rats. Therefore, Fan may be a new therapeutic approach for the treatment of cardiac dysfunction.