Novel Flavan-3,4-diol vernicidin B from Toxicodendron Vernicifluum (Anacardiaceae) as potent antioxidant via IL-6/Nrf2 cross-talks pathways.

Background: Oxidative stress is considered to be a pathological factor of various neurodegenerative diseases. Studies have confirmed the antioxidant activity of T. vernicifluum. However, the main active components responsible for antioxidant activity remain unknown.

Objective: The aim of this study is to explore the activities of vernicidin B on oxidative stress injury induced by HO in SH-SY5Y cells, and the underlying mechanism of vernicidin B in oxidative stress-related neurological diseases is further discussed.

Methods: Various separation methods were used to isolate and identify the compounds in an EtOAc extract of T. vernicifluum. The structures of the isolates were clarified by HR-TOF-MS and 1D/2D NMR data and compared with findings in previous literature. The MTT assay was used to evaluate the potential antioxidant activity of the isolated flavonoids. The apoptosis rate, mitochondrial reactive oxygen species (ROS) level and mitochondrial potential were measured by flow cytometry and fluorescence microscope. The levels of related proteins were detected by Western blotting.

Results: Four new flavan-3,4-diols (1-4, vernicidins A-D) and 11 known flavonoids (5-15) were purified from the EtOAc extract of T. vernicifluum. Among these compounds, vernicidin B showed the most promising potential for protecting SH-SY5Y cells from HO-induced oxidative stress. Moreover, pretreatment with vernicidin B decreased ROS production and mitochondrial membrane potential and significantly attenuated HO-induced apoptosis in a dose-dependent manner. Mechanistically, the antioxidant stress activities of vernicidin B were confirmed to be related to the IL-6/Nrf2 cross-talks pathway and its downstream pathways, including PI3K/Akt/mToR-Gsk3β, JAK2/STAT3 and MAPKs.

Conclusions: Our findings suggested that vernicidin B can improve the oxidative stress injury induced by HO through IL-6/Nrf2 cross-talks pathway, indicating that it may be a potential candidate drug for the treatment of oxidative stress-related neurodegenerative diseases.