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

Ting Zhong; Meichen Li; Hongshan Wu; Daoping Wang; Jianyu Liu; Yongnan Xu; Yanhua Fan

doi:10.1016/j.phymed.2022.154041

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

Phytomedicine. 2022 Jun:100:154041. doi: 10.1016/j.phymed.2022.154041. Epub 2022 Mar 11.

Authors

Ting Zhong¹, Meichen Li², Hongshan Wu¹, Daoping Wang³, Jianyu Liu⁴, Yongnan Xu⁵, Yanhua Fan⁶

Affiliations

¹ State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, PR China.
² Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
³ State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China.
⁴ Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: burningice@126.com.
⁵ Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: ynxu@syphu.edu.cn.
⁶ State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, PR China. Electronic address: fanyhkyem@163.com.

PMID: 35306369
DOI: 10.1016/j.phymed.2022.154041

Abstract

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 H₂O₂ 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 H₂O₂-induced oxidative stress. Moreover, pretreatment with vernicidin B decreased ROS production and mitochondrial membrane potential and significantly attenuated H₂O₂-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 H₂O₂ 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.

Keywords: IL-6/Nrf2 cross-talks; JAK2/STAT3; MAPKs; Oxidative stress; PI3K/Akt/mToR-Gsk3β; Vernicidin B.

MeSH terms

Antioxidants* / pharmacology
Apoptosis
Flavonoids* / pharmacology
Humans
Hydrogen Peroxide
Interleukin-6 / metabolism
NF-E2-Related Factor 2 / metabolism
Neurodegenerative Diseases*
Oxidative Stress
Phosphatidylinositol 3-Kinases / metabolism
Plant Extracts / pharmacology
Proto-Oncogene Proteins c-akt / metabolism
Reactive Oxygen Species / metabolism
Toxicodendron* / chemistry

Substances

Antioxidants
Flavonoids
Interleukin-6
NF-E2-Related Factor 2
Plant Extracts
Reactive Oxygen Species
Hydrogen Peroxide
Proto-Oncogene Proteins c-akt