Protective effects of curcumin against liver fibrosis through modulating DNA methylation.
Recent research has demonstrated that advanced liver fibrosis in patients could be reversed, but no approved agents are available for the treatment and prevention of liver fibrosis in humans. Curcumin (CUR) is the principal curcuminoid of turmeric. Inhibitory effects of CUR and its underlying mechanisms in liver fibrogenesis have been explored. In the present study, we hypothesized that epigenetic mechanisms contribute to the protective effects of CUR against liver fibrosis. We used CCl4-induced liver injury in BALB/c mice and the rat hepatic stellate cell line HSC-T6 as experimental models. Genomic DNA methylation was analyzed by MeDIP-chip and verified by real-time PCR on MeDIP-enriched DNA. The mRNA and protein expressions of DNMT1, α-SMA, and Col1α1 were determined by real-time PCR and Western blotting, respectively. The methylation statuses of FGFR3, FZD10, Gpx4, and Hoxd3 were further confirmed by quantitative methylation-specific PCR (qMSP). Our results showed that CUR treatment reversed liver injury in vivo and in vitro, possibly through down regulation of DNMT1, α-SMA, and Col1α1 and by demethylation of the key genes. In conclusion, aberrant methylation is closely associated with liver fibrosis and CUR treatment may reverse liver fibrosis by epigenetic mechanisms.
The First Clinical Medical School, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China; Department of Medical Nursing, Jiangsu Jiankang Vocational College, Nanjing 210029, China.
Peng
P
Wu
The First Clinical Medical School, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China.
Rui
R
Huang
The First Clinical Medical School, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China.
Ya-Li
YL
Xiong
Drum Tower Clinical School of Integrated Chinese and Western Medicines, Nanjing University of Traditional Chinese Medicine, Nanjing 210008, China. Electronic address: dr.wu@nju.edu.cn.
Chao
C
Wu
D000818:Animals; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage*; D019175:DNA Methylation / Q000187:drug effects*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020011:Protective Agents / Q000008:administration & dosage*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats
D020011:Protective Agents; D011506:Proteins; D003474:Curcumin
Curcumin; DNA methylation; Liver fibrosis; Therapy