Protective effect of zerumbone on sepsis-induced acute lung injury through anti-inflammatory and antioxidative activity via NF-κB pathway inhibition and HO-1 activation

Abstract

Sepsis is a systemic illness for which there are no effective preventive or therapeutic therapies. Zerumbone, a natural molecule, has anti-oxidative and anti-inflammatory properties that may help to prevent sepsis. In the present study, we have assessed the protective effect of zerumbone against sepsis-induced acute lung injury (ALI) and its underlying mechanisms. During the experiment, mice were divided into five groups: a sham group, a sepsis-induced ALI group, and three sepsis groups that are pre-treated with zerumbone at different concentrations. We found that zerumbone greatly decreased the sepsis-induced ALI using histological investigations. Also, zerumbone treatment reduced the sepsis-induced inflammatory cytokine concentrations as well as the number of infiltrating inflammatory cells in BALF compared to non-treated sepsis animals. The zerumbone-pretreated sepsis groups had reduced pulmonary myeloperoxidase (MPO) activity than the sepsis groups. Moreover, the mechanism underlying the protective action of zerumbone on sepsis is accomplished by the activation of antioxidant genes such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), superoxide dismutase (SOD), and heme oxygenase 1 (HO-1). The obtained results revealed that zerumbone inhibited the sepsis-induced ALI through its anti-inflammatory and antioxidative activity via inhibition of the NF-κB pathway and activation of HO-1 pathway. Our findings demonstrate that zerumbone pretreatment suppresses sepsis-induced ALI via antioxidative activities and anti-inflammatory, implying that zerumbone could be a viable preventive agent for sepsis-induced ALI.

Keywords: Sepsis-induced ALI, Anti-inflammatory activity, Antioxidative enzymes, Zerumbone, NF-κB pathway.