한빛사 논문
Eun Hee Jo a,b,1, Ji Eun Moon b,c,d,1, Moon Han Chang b,c,d,1, Ye Jin Lim b,e, Jung Hyun Park b,f, Suk Hee Lee b,d, Young Rae Cho d,g, Art E Cho d,g, Seung Pil Pack d,g, Hyeon-Wee Kim h, Liana Crowley i, Brandy Le i, Aykin-Burns Nukhet j, Yinfeng Chen k, Yihang Zhong l, Jiangchao Zhao m,2, Ying Li n,2, Hanvit Cha b,c,d,2, Jeong Hoon Pan i,2, Jae Kyeom Kim i,2,⇑, Jin Hyup Lee b,c,d,o,2,⇑
aToxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Republic of Korea bDepartment of Food and Biotechnology, Korea University, Sejong, Republic of Korea cBK21 FOUR Research Group for Omics-based Bio-health in Food Industry, Korea University, Sejong, Republic of Korea dBiological Clock-based Anti-aging Convergence RLRC, Korea University, Sejong, Republic of Korea eHealth Functional Food Policy Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Republic of Korea fDivision of Brain Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju, Republic of Korea gDepartment of Bioinformatics, Korea University, Sejong, Republic of Korea hOttogi Research Center, Anyang, Republic of Korea iDepartment of Behavioral Health and Nutrition, University of Delaware, Newark, DE, USA jDepartment of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA kFarm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China lCollege of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China mDepartment of Animal Science, University of Arkansas, Fayetteville, AR, USA nGuangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Foshan University, Foshan, China oInstitutes of Natural Sciences, Korea University, Sejong, Republic of Korea
⇑ Corresponding authors.
1 These authors equally contributed to this work.
2 These authors equally contributed to this work as corresponding authors.
Abstract
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.
Conclusions
Our study collectively suggests that curcumin could provide an effective preventive measure against air pollutant-enhanced pneumonitis and thus COPD.
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