Phellodendrine Exerts Protective Effects on Intra-abdominal Sepsis by Inactivating AKT/NF-kB Signaling.

Abstract

Acute kidney injury (AKI) and acute lung injury (ALI) are major complications of intra-abdominal sepsis, leading to increased mortality. Phellodendrine (PHE) is a characteristic and important active ingredient of Phellodendri Cortex, possessing multiple pharmacological properties. This study intends to explore the effect of PHE on intra-abdominal sepsis-induced AKI and ALI. An intra-abdominal infection-induced rat model of sepsis was established by fecal intraperitoneal injection, followed by the administration of PHE. ELISA was used to determine plasma levels of inflammatory cytokines. Hematoxylin-eosin, Periodic acid Schiff, and Masson trichrome staining were employed for histopathological analysis of rat kidney and lung tissues. Western blotting was used to estimate the AKT/NF-κB signaling-related protein levels. The results showed that PHE improved the survival rate of septic rats and reduced plasma levels of proinflammatory cytokines. PHE administration attenuated pathological lesions in the kidneys and lungs of septic rats. Mechanistically, PHE treatment blocked AKT/NF-κB signaling in septic rats' kidneys and lungs. In conclusion, PHE ameliorates intra-abdominal sepsis-induced kidney and lung injury possibly by inactivating AKT/NF-kB signaling.