title: Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B.
abstract: The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca(2+) restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals.
authors: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, and State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Yuhan
authors: Y
authors: Tang
authors: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, and State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Juan
authors: J
authors: Li
authors: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, and State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; National Institute for Nutrition and Food Safety, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors: Chao
authors: C
authors: Gao
authors: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, and State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Yanyan
authors: Y
authors: Xu
authors: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, and State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Yanyan
authors: Y
authors: Li
authors: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, and State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Xiao
authors: X
authors: Yu
authors: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, and State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Jing
authors: J
authors: Wang
authors: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, and State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Liegang
authors: L
authors: Liu
authors: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, and State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Ping
authors: 0000-0002-0192-9546
authors: P
authors: Yao
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D019610:Cytoprotection; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D007249:Inflammation / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D005082:Physical Exertion; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C497112:Atf6 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D019284:Thapsigargin; D011794:Quercetin; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases