Advances in health-promoting effects of natural polysaccharides: Regulation on Nrf2 antioxidant pathway

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Abstract

Natural polysaccharides (NPs) possess numerous health-promoting effects, such as liver protection, kidney protection, lung protection, neuroprotection, cardioprotection, gastrointestinal protection, anti-oxidation, anti-diabetic, and anti-aging. Nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway is an important endogenous antioxidant pathway, which plays crucial roles in maintaining human health as its protection against oxidative stress. Accumulating evidence suggested that Nrf2 antioxidant pathway might be one of key regulatory targets for the health-promoting effects of NPs. However, the information concerning regulation of NPs on Nrf2 antioxidant pathway is scattered, and NPs show different regulatory behaviors in their different health-promoting processes. Therefore, in this article, structural features of NPs having regulation on Nrf2 antioxidant pathway are overviewed. Moreover, regulatory effects of NPs on this pathway for health-promoting effects are summarized. Furthermore, structure-activity relationship of NPs for health-promoting effects by regulating the pathway is preliminarily discussed. Otherwise, the prospects on future work for regulation of NPs on this pathway are proposed. This review is beneficial to well-understanding of underlying mechanisms for health-promoting effects of NPs from the view angle of Nrf2 antioxidant pathway, and provides a theoretical basis for the development and utilization of NPs in promoting human health.

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Transcriptional Regulation by Nrf2

Claudia Tonelli, Iok In Christine Chio, David Tuveson (2018)

Abstract Significance: Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that coordinates the basal and stress-inducible activation of a vast array of cytoprotective genes. Understanding the regulation of Nrf2 activity and downstream pathways has major implications for human health. Recent Advances: Nrf2 regulates the transcription of components of the glutathione and thioredoxin antioxidant systems, as well as enzymes involved in phase I and phase II detoxification of exogenous and endogenous products, NADPH regeneration, and heme metabolism. It therefore represents a crucial regulator of the cellular defense mechanisms against xenobiotic and oxidative stress. In addition to antioxidant responses, Nrf2 is involved in other cellular processes, such as autophagy, intermediary metabolism, stem cell quiescence, and unfolded protein response. Given the wide range of processes that Nrf2 controls, its activity is tightly regulated at multiple levels. Here, we review the different modes of regulation of Nrf2 activity and the current knowledge of Nrf2-mediated transcriptional control. Critical Issues: It is now clear that Nrf2 lies at the center of a complex regulatory network. A full comprehension of the Nrf2 program will require an integrated consideration of all the different factors determining Nrf2 activity. Future Directions: Additional computational and experimental studies are needed to obtain a more dynamic global view of Nrf2-mediated gene regulation. In particular, studies comparing how the Nrf2-dependent network changes from a physiological to a pathological condition can provide insight into mechanisms of disease and instruct new treatment strategies.

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Targeting oxidative stress in disease: promise and limitations of antioxidant therapy

Henry Forman, Hongqiao Zhang (2021)

Oxidative stress is a component of many diseases, including atherosclerosis, chronic obstructive pulmonary disease, Alzheimer disease and cancer. Although numerous small molecules evaluated as antioxidants have exhibited therapeutic potential in preclinical studies, clinical trial results have been disappointing. A greater understanding of the mechanisms through which antioxidants act and where and when they are effective may provide a rational approach that leads to greater pharmacological success. Here, we review the relationships between oxidative stress, redox signalling and disease, the mechanisms through which oxidative stress can contribute to pathology, how antioxidant defences work, what limits their effectiveness and how antioxidant defences can be increased through physiological signalling, dietary components and potential pharmaceutical intervention. Although oxidative stress is associated with a broad range of diseases, therapeutic antioxidant approaches have so far been disappointing. Here, Forman and Zhang review the roles of oxidative stress and redox signalling in disease, assess antioxidant therapeutic strategies and highlight key limitations that have challenged their clinical application.

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NRF2, a Transcription Factor for Stress Response and Beyond

Feng He, Xiaoli Ru, Tao Wen (2020)

Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the cellular defense against toxic and oxidative insults through the expression of genes involved in oxidative stress response and drug detoxification. NRF2 activation renders cells resistant to chemical carcinogens and inflammatory challenges. In addition to antioxidant responses, NRF2 is involved in many other cellular processes, including metabolism and inflammation, and its functions are beyond the originally envisioned. NRF2 activity is tightly regulated through a complex transcriptional and post-translational network that enables it to orchestrate the cell’s response and adaptation to various pathological stressors for the homeostasis maintenance. Elevated or decreased NRF2 activity by pharmacological and genetic manipulations of NRF2 activation is associated with many metabolism- or inflammation-related diseases. Emerging evidence shows that NRF2 lies at the center of a complex regulatory network and establishes NRF2 as a truly pleiotropic transcription factor. Here we summarize the complex regulatory network of NRF2 activity and its roles in metabolic reprogramming, unfolded protein response, proteostasis, autophagy, mitochondrial biogenesis, inflammation, and immunity.

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Author and article information

Contributors

Jiang-Hong Luo: URI : http://loop.frontiersin.org/people/1752609/overview

Jing Li: URI : http://loop.frontiersin.org/people/2202102/overview

Zi-Chun Shen: URI : http://loop.frontiersin.org/people/2201917/overview

Xiao-Fan Lin: URI : http://loop.frontiersin.org/people/2202115/overview

Ao-Qiu Chen: URI : http://loop.frontiersin.org/people/2201905/overview

Yi-Fei Wang: URI : http://loop.frontiersin.org/people/2202127/overview

Er-Sheng Gong: URI : http://loop.frontiersin.org/people/1816484/overview

Dan Liu: URI : http://loop.frontiersin.org/people/1828917/overview

Qi Zou: URI : http://loop.frontiersin.org/people/1966252/overview

Xiao-Yin Wang: URI : http://loop.frontiersin.org/people/1913302/overview

Journal

Journal ID (nlm-ta): Front Nutr

Journal ID (iso-abbrev): Front Nutr

Journal ID (publisher-id): Front. Nutr.

Title: Frontiers in Nutrition

Publisher: Frontiers Media S.A.

ISSN (Electronic): 2296-861X

Publication date (Electronic): 16 February 2023

Publication date Collection: 2023

Volume: 10

Electronic Location Identifier: 1102146

Affiliations

[1] ¹School of Public Health and Health Management, Gannan Medical University , Ganzhou, China

[2] ²Key Laboratory of Environment and Health of Ganzhou, Gannan Medical University , Ganzhou, China

[3] ³Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang, College of Biology and Environmental Engineering, Zhejiang Shuren University , Hangzhou, China

[4] ⁴State Key Laboratory of Food Science and Technology, Nanchang University , Nanchang, China

Author notes

Edited by: Vignesh Muthusamy, Indian Agricultural Research Institute (ICAR), India

Reviewed by: Veda Krishnan, Indian Agricultural Research Institute (ICAR), India; Amirtham Dhamodarasamy, Tamil Nadu Agricultural University, India

*Correspondence: Dan Liu, danliu@ 123456zjsru.edu.cn

Xiao-Yin Wang, xywang@ 123456gmu.edu.cn

^†These authors share first authorship

This article was submitted to Nutrition and Food Science Technology, a section of the journal Frontiers in Nutrition

Article

DOI: 10.3389/fnut.2023.1102146

PMC ID: 9978827

PubMed ID: 36875839

SO-VID: a1c682e8-f680-4046-b6bd-450087cb05ae

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 18 November 2022

Date accepted : 30 January 2023

Page count

Figures: 3, Tables: 5, Equations: 0, References: 212, Pages: 27, Words: 20480

Funding

This work was financially supported by Jiangxi Provincial Natural Science Foundation (20202BABL216081); the Open Project Program of State Key Laboratory of Food Science and Technology, Nanchang University (SKLF-KF-202212); the Open Project of Key Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases, Ministry of Education (XN202001); and University-Level Scientific Research Projects of Gannan Medical University (QD201913, 201107, and QD202128).

Advances in health-promoting effects of natural polysaccharides: Regulation on Nrf2 antioxidant pathway

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Sushruta Journal of Health Policy & Opinion

Most cited references 212

Transcriptional Regulation by Nrf2

Targeting oxidative stress in disease: promise and limitations of antioxidant therapy

NRF2, a Transcription Factor for Stress Response and Beyond

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