Sensitization of GSH synthesis by curcumin curtails acrolein-induced alveolar epithelial apoptosis via Keap1 cysteine conjugation: A randomized controlled trial and experimental animal model of pneumonitis,Journal of Advanced Research

当前位置： X-MOL 学术 › J. Adv. Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Sensitization of GSH synthesis by curcumin curtails acrolein-induced alveolar epithelial apoptosis via Keap1 cysteine conjugation: A randomized controlled trial and experimental animal model of pneumonitis
Journal of Advanced Research ( IF 11.4 ) Pub Date : 2022-06-27 , DOI: 10.1016/j.jare.2022.06.013
Eun Hee Jo ₁ , Ji Eun Moon ₂ , Moon Han Chang ₂ , Ye Jin Lim ₃ , Jung Hyun Park ₄ , Suk Hee Lee ₅ , Young Rae Cho ₆ , Art E Cho ₆ , Seung Pil Pack ₆ , Hyeon-Wee Kim ₇ , Liana Crowley ₈ , Brandy Le ₈ , Aykin-Burns Nukhet ₉ , Yinfeng Chen ₁₀ , Yihang Zhong ₁₁ , Jiangchao Zhao ₁₂ , Ying Li ₁₃ , Hanvit Cha ₂ , Jeong Hoon Pan ₈ , Jae Kyeom Kim ₈ , Jin Hyup Lee ₁₄

Affiliation

Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Republic of Korea; Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea.
Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea; BK21 FOUR Research Group for Omics-based Bio-health in Food Industry, Korea University, Sejong, Republic of Korea; Biological Clock-based Anti-aging Convergence RLRC, Korea University, Sejong, Republic of Korea.
Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea; Health Functional Food Policy Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Republic of Korea.
Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea; Division of Brain Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju, Republic of Korea.
Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea; Biological Clock-based Anti-aging Convergence RLRC, Korea University, Sejong, Republic of Korea.
Biological Clock-based Anti-aging Convergence RLRC, Korea University, Sejong, Republic of Korea; Department of Bioinformatics, Korea University, Sejong, Republic of Korea.
Ottogi Research Center, Anyang, Republic of Korea.
Department of Behavioral Health and Nutrition, University of Delaware, Newark, DE, USA.
Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.
College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.
Department of Animal Science, University of Arkansas, Fayetteville, AR, USA.
Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Foshan University, Foshan, China.
Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea; BK21 FOUR Research Group for Omics-based Bio-health in Food Industry, Korea University, Sejong, Republic of Korea; Biological Clock-based Anti-aging Convergence RLRC, Korea University, Sejong, Republic of Korea; Institutes of Natural Sciences, Korea University, Sejong, Republic of Korea.

Introduction

Epidemiological studies have reported an association between exposures to ambient air pollution and respiratory diseases, including chronic obstructive pulmonary disease (COPD). Pneumonitis is a critical driving factor of COPD and exposure to air pollutants (e.g., acrolein) is associated with increased incidence of pneumonitis.

Objectives

Currently available anti-inflammatory therapies provide little benefit against respiratory diseases. To this end, we investigated the preventive role of curcumin against air pollutant-associated pneumonitis and its underlying mechanism.

Methods

A total of 40 subjects was recruited from Chengdu, China which is among the top three cities in terms of respiratory mortality related to air pollution. The participants were randomly provided either placebo or curcumin supplements for 2 weeks and blood samples were collected at the baseline and at the end of the intervention to monitor systemic markers. In our follow up mechanistic study, C57BL/6 mice (n = 40) were randomly allocated into 4 groups: Control group (saline + no acrolein), Curcumin only group (curcumin + no acrolein), Acrolein only group (saline + acrolein), and Acrolein + Curcumin group (curcumin + acrolein). Curcumin was orally administered at 100 mg/kg body weight once a day for 10 days, and then the mice were subjected to nasal instillation of acrolein (5 mg/kg body weight). Twelve hours after single acrolein exposure, all mice were euthanized.

Results

Curcumin supplementation, with no noticeable adverse responses, reduced circulating pro-inflammatory cytokines in association with clinical pneumonitis as positive predictive while improving those of anti-inflammatory cytokines. In the pre-clinical study, curcumin reduced pneumonitis manifestations by suppression of intrinsic and extrinsic apoptotic signaling, which is attributed to enhanced redox sensing of Nrf2 and thus sensitized synthesis and restoration of GSH, at least in part, through curcumin-Keap1 conjugation.