Dihydromyricetin reverses capecitabine-induced peripheral myelin dysfunction through modulation of oxidative stress.

Previous clinical reports have shown that capecitabine, an oral prodrug of 5-fluorouracil (5-Fu), can induce peripheral neuropathy, resulting in numbness, paresthesia and hypoesthesia. However, the mechanism through which capecitabine causes peripheral nerve injury remains unclear. Here, we demonstrate that systemic administration of capecitabine leads to myelin abnormalities in the peripheral nerves of mice, which are possibly attributed to the death of Schwann cells, the myelinating cells in the peripheral nervous system. Furthermore, our results show that 5-Fu induces significant oxidative stress in Schwann cells by inhibiting the expression of the anti-oxidative protein DJ-1, leading to a decrease in Schwann cell markers. We found that the anti-oxidant dihydromyricetin (DMY) reverses 5-Fu-induced Schwann cell death and oxidative stress and alleviates capecitabine-induced myelin abnormalities. Taken together, our data indicate that capecitabine induces peripheral myelin dysfunction by regulating DJ-1-mediated oxidative stress in Schwann cells and reveal DMY as a potential therapeutic strategy for capecitabine-induced peripheral neuropathy.

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.