Schizandrin protects H9c2 cells against lipopolysaccharide-induced injury by downregulating Smad3.

Abstract

Schizandrin is a major bioactive constituent of Schisandra chinensis (Turcz.) Baill with antioxidant and anti-inflammatory properties. The objective of this study was to explore the potential effects of schizandrin on a cell model of myocarditis. The H9c2 cells were treated withschizandrin alone or in combination with lipopolysaccharide (LPS),after which, cell survival, migration, and the release of inflammatory cytokines were assessed. Moreover, downstream effectors and signaling pathways were studied to reveal the possible underlying mechanism. As a result, LPS stimulation induced significant cell damageas cell viability was repressed and the apoptosis was induced. Inthe meantime, LPS promoted the release of proinflammatory cytokinesincluding interleukin 1β (IL-1β), IL-8, IL-6, and tumor necrosis factor (TNF-α) while repressingthe release of the anti-inflammatory cytokine IL-10. Schizandrin could promote H9c2 cellmigrationand long-term treatment (7 days) enhanced cell viability. More interestingly, pretreatment with schizandrin attenuated LPS-induced cell lossand inflammatory response. Besides this, Smad3 was a downstream effector of schizandrin. The beneficial effects of schizandrin on the H9c2 cells were attenuated when Smad3 was overexpressed. Moreover, the silencingof Smad3 deactivated c-Jun N-terminal kinase (JNK) and nuclear factor κB (NF-κB) pathways. This study preliminarily demonstrated that schizandrin prevented LPS-induced injury in the H9c2 cells and promoted the recovery of myocardialtissues by enhancing cell viability and migration. Schizandrin conferred its beneficial effects possibly by downregulating Smad3 and inhibiting the activation of JNK and NF-κB pathways.