Cytotoxicity and anti-hepatitis B virus activities of saikosaponins from Bupleurum species.
Saikosaponins, the main active constituents of Bupleurum spp., have been shown to possess immunomodulatory, hepatoprotective, anti-tumor and anti-viral activities. In this study, saikosaponins a, c and d were evaluated for cytotoxicity and anti-hepatitis B virus ( HBV) activities. Results showed that, with the exception of saikosaponins a and d, HBV-transfected human hepatoma cells (2.2.15 cells) cultured with saikosaponin c showed a significantly lower level of HBeAg in culture medium. Saikosaponin c also possessed activity in inhibiting HBV DNA replication; this inhibitory effect was not due to the cytotoxicity of saikosaponin c or its effect on 2.2.15 cell proliferation. Although saikosaponin d exhibited cytotoxicity on 2.2.15 cells, it failed to inhibit HBV multiplication. The cytotoxicity of saikosaponin d against HepG2 human hepatocellular carcinoma cells was due to the induction of apoptosis through the activation of caspases 3 and 7, which subsequently resulted in poly-ADP-ribose-polymerase (PARP) cleavage. DNA fragmentation was clearly noted at more than 6 h after HepG2 cells exposure to saikosaponin d. The present study concludes that saikosaponin c exhibits anti-HBV activity and saikosaponin d possesses potent cytotoxicity against human hepatocellular carcinoma cells.
Chiang
Lien-Chai
LC
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Ng
Lean Teik
LT
Liu
Li-Teh
LT
Shieh
Den-En
DE
Lin
Chun-Ching
CC
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D029972:Bupleurum; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor / Q000187:drug effects; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D000998:Antiviral Agents; D017931:DNA Primers; D004279:DNA, Viral; D010936:Plant Extracts; D012503:Saponins; D009828:Oleanolic Acid; C025759:saikosaponin D