Schisandrin B attenuates lipopolysaccharide-induced activation of hepatic stellate cells through Nrf-2-activating anti-oxidative activity.

Activated hepatic stellate cells (HSCs) are known to have a potential role in increasing the deposition of ECM and elevating proliferation in liver fibrosis, which can be driven by lipopolysaccharide (LPS). Schisandrin B (SB) is a dibenzocyclooctadiene derivative of Schisandra chinensis with anti-oxidative stress activity, but its effective target is unknown. Here, we have evaluated whether SB is protective against the LPS-induced activation of HSCs and have explored the underlying anti-oxidative stress mechanisms of SB. HSCs were treated with SB 1 h prior to LPS, and then incubated for indicated time. Nrf-2 in HSCs was inhibited genetically. The simultaneous effects on Nrf-2 activity, oxidative stress, cell proliferation, and ECM deposition were examined. SB decreased LPS-induced cell proliferation, fibrosis, and oxidative stress in HSCs. We further demonstrated that the protective effects of SB in LPS-induced HSCs activation involve the modulation of Nrf-2. SB, specifically targeting Nrf-2, attenuates the oxidative stress in HSCs. SB also reduces LPS-induced fibrosis and cell viability in HSCs. In addition, Nrf-2 may serve as a therapeutic target for infections or periods of chronic oxidative stress and may help with future drug discovery.