Andrographolide Attenuates LPS-Induced Cardiac Malfunctions Through Inhibition of IκB Phosphorylation and Apoptosis in Mice.

Background/aims: Cardiac malfunction is a common complication in sepsis and significantly increases the mortality of patients in septic shock. However, no studies have examined whether andrographolide (And) reduces LPS-induced myocardial malfunction.

Methods: Left ventricular systolic and diastolic functions were examined using echocardiography. TNF-α and IL-1β protein levels were detected by an enzyme-linked immunosorbent assay (ELISA). NO oxidation products were determined using Griess reagent. Protein expression levels of inhibitors of NF-κBα (IκB) and phospho-IκB were determined via Western blot. Oxidative injury was determined by measuring myocardial lipid peroxidation and superoxide dismutase activity. Cardiac apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nickend-labeling (TUNEL) and cardiac caspase 3/7 activity.

Results: And blunted LPS-induced myocardial malfunctions in mice. LPS induced TNF-α, IL-1β, and NO production as well as I-κB phosphorylation. Cardiac apoptosis was attenuated via incubation with And, but the extent of oxidative injury remained unaffected.

Conclusion: And prevents LPS-induced cardiac malfunctions in mice by inhibiting TNF-α, IL-1β, and NO production, IκB phosphorylation, and cardiac apoptosis, indicating that And may be a potential agent for preventing myocardial malfunction during sepsis.