Dietary Flavonoid Hyperoside Induces Apoptosis of Activated Human LX-2 Hepatic Stellate Cell by Suppressing Canonical NF-κB Signaling.
Hyperoside, an active compound found in plants of the genera Hypericum and Crataegus, is reported to exhibit antioxidant, anticancer, and anti-inflammatory activities. Induction of hepatic stellate cell (HSC) apoptosis is recognized as a promising strategy for attenuation of hepatic fibrosis. In this study, we investigated whether hyperoside treatment can exert antifibrotic effects in human LX-2 hepatic stellate cells. We found that hyperoside induced apoptosis in LX-2 cells and decreased levels of α-smooth muscle actin (α-SMA), type I collagen, and intracellular reactive oxygen species (ROS). Remarkably, hyperoside also inhibited the DNA-binding activity of the transcription factor NF-κB and altered expression levels of NF-κB-regulated genes related to apoptosis, including proapoptotic genes Bcl-Xs, DR4, Fas, and FasL and anti-apoptotic genes A20, c-IAP1, Bcl-X L , and RIP1. Our results suggest that hyperoside may have potential as a therapeutic agent for the treatment of liver fibrosis.
Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.
Liwen
0000-0001-7135-3418
L
Wang
Department of Hematology and Tangshan Key Laboratory, Translational Medical Center, North China University of Science and Technology, Tangshan, Hebei 063000, China.
Zhiwei
0000-0002-7579-148X
Z
Yue
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.
Mengzheng
0000-0002-4788-8073
M
Guo
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.
Lianying
0000-0002-9423-1621
L
Fang
Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
Liang
L
Bai
Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
Xinyu
0000-0002-0871-7992
X
Li
Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
Yongqing
Y
Tao
Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
Suying
S
Wang
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.
Qiang
0000-0002-7668-6868
Q
Liu
Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
Dexian
D
Zhi
Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
Hui
0000-0002-3710-3607
H
Zhao
D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D019587:Dietary Supplements; D005419:Flavonoids / Q000008:administration & dosage*; D030342:Genetic Diseases, Inborn / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D005419:Flavonoids; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C021304:hyperoside; D011794:Quercetin