Screening active components of modified Xiaoyao powder as NRF2 agonists.

Abstract

Nuclear factor (erythroid-derived 2)-like 2 (NRF2) regulates antioxidant enzymes and phase II detoxifying enzymes, such as NAD(P)H: quinone oxidoreductase 1 (NQO1). Modified Xiaoyao powder (MXP) is most frequently used in the prevention and treatment of breast cancer in China. This study aimed to screen active components of MXP for antioxidant stress and chemoprevention, which depend on NRF2-NQO1 signalling pathway. A total of 25 monomeric compounds contained in MXP were screened using an antioxidant response element-luciferase reporter. The most potent antioxidant response element-luciferase inducers were chosen to further examine their effects on NRF2 and NQO1 in MCF-7 cells. These results were then confirmed by determining the oxidative stress levels and chemopreventive effect on inhibiting carcinogenesis transformation in NRF2 knockdown (NRF2KD ) and NRF2 wild-type MCF-10A cells. We found that quercetin, kaempferol, and atractylenolide II in MXP were potent NRF2 inducers, which could up-regulate the expression of NRF2 and its downstream enzymes NQO1. In addition, these components could decrease reduced oxidative stress and inhibit carcinogenesis transformation, which depended on NRF2-NQO1 pathway. In conclusion, NRF2-NQO1 pathway plays an essential role in mediating the activity of MXP and its active components, at least in part; some beneficial effects of MXP may be applicable to breast cancer chemoprevention. Our study firstly found MXP active components including quercetin, kaempferol, and atractylenolide II. Our results firstly demonstrate that NRF2-NQO1 pathway plays an essential role in mediating the activity of MXP and its active components in breast cancer chemoprevention. Our study firstly found that atractylenolide II is a novel NRF2 inducer.

• Authors: Yujie Yang, Yanran Wang, Ting Wang, Xuehua Jiang, Ling Wang
• Journal: Cell biochemistry and function (Cell Biochem Funct) Vol. 35 Issue 8 Pg. 518-526 (Dec 2017) ISSN: 1099-0844 [Electronic] England
• PMID: 29214656 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 John Wiley & Sons, Ltd.

Chemical References

• Antineoplastic Agents, Phytogenic
• Drugs, Chinese Herbal
• Kaempferols
• Lactones
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Plant Extracts
• Sesquiterpenes
• atractylenolide II
• xiaoyao
• kaempferol
• Quercetin
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Breast Neoplasms (prevention & control)
• Cells, Cultured
• Chemoprevention
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (chemistry)
• Female
• Humans
• Kaempferols (chemistry, isolation & purification, pharmacology)
• Lactones (chemistry, isolation & purification, pharmacology)
• Molecular Structure
• NAD(P)H Dehydrogenase (Quinone) (antagonists & inhibitors, genetics, metabolism)
• NF-E2-Related Factor 2 (agonists, metabolism)
• Oxidative Stress (drug effects)
• Plant Extracts (chemistry, isolation & purification, pharmacology)
• Quercetin (chemistry, isolation & purification, pharmacology)
• Sesquiterpenes (chemistry, isolation & purification, pharmacology)
• Structure-Activity Relationship