Antiviral effect of Curcuma longa Linn extract against hepatitis B virus replication.
BACKGROUND
A medicinal herb Curcuma longa Linn has been used for treating various liver diseases caused by hepatitis B virus (HBV) in Asia.


OBJECTIVE
The study was performed in order to investigate the antiviral activity of Curcuma longa Linn against HBV replication in liver cells.


METHODS
Aqueous extract of Curcuma longa Linn (CLL) was prepared and used to analyze its antiviral activity against HBV replication in HepG 2.2.15 cells, which contain HBV genomes. The inhibitory effect of CLL on HBV replication was examined by testing the levels of secreted HBV surface antigens (HBsAg), HBV DNAs, and HBV RNAs in HepG 2.2.15 cells using ELISA, Southern blot, and Northern blot analyses. Cytotoxic activities of CLL extract on various liver cells were analyzed by MTT assay. To dissect the inhibitory mechanism of CLL extract on HBV replication, the levels of p53 protein and p53 mRNAs were analyzed by Western blot and RT-PCR in HepG 2.2.15 cells. The repression of CLL extract on HBV transcription was analyzed by RT-PCR and CAT assay.


RESULTS
CLL extract repressed the secretion of HBsAg from HepG 2.2.15 cells. CLL extract also suppressed the production of HBV particles and the level of intracellular HBV RNAs in HepG 2.2.15 cells, suggesting that CLL extract inhibits HBV replication. We found that the anti-HBV activity of CLL extract is mediated through enhancing the cellular accumulation of p53 protein by transactivating the transcription of p53 gene as well as increasing the stability of p53 protein. It turned out that CLL extract repressed the transcription of HBx gene by suppressing HBV enhancer I and X promoter through p53 protein. In addition, CLL extract did not have any cytotoxic effects on liver cells.


CONCLUSIONS
These data showed that CLL extract represses HBV replication through enhancing the level of p53 protein. CLL extract can be used as a safe and specific drug for patients with liver diseases caused by HBV infection.
Kim
Hye Jin
HJ
Department of Microbiology, Chungnam National University, Daejeon 305-764, South Korea.
Yoo
Hwa Seung
HS
Kim
Jin Chul
JC
Park
Chan Su
CS
Choi
Mi Sun
MS
Kim
Mijee
M
Choi
Hyangsoon
H
Min
Jung Sun
JS
Kim
Yong Soo
YS
Yoon
Seong Woo
SW
Ahn
Jeong Keun
JK
D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D030024:Curcuma; D004279:DNA, Viral / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D016679:Genome, Viral; D006509:Hepatitis B / Q000188:drug therapy* / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008099:Liver / Q000821:virology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D010936:Plant Extracts; D012333:RNA, Messenger; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53