The essential oils from Zanthoxylum schinifolium pericarp induce apoptosis of HepG2 human hepatoma cells through increased production of reactive oxygen species

Biol Pharm Bull. 2005 May;28(5):802-7. doi: 10.1248/bpb.28.802.


The volatile extract from dried pericarp of Zanthoxylum schinifolium that was obtained by simultaneous distillation with dichloromethane and water was composed of 29.9% geranyl acetate, 15.8% citronella, 15.4% sabinene and the minor volatile components included beta-myrcene, linalool, (-)-isopulegol, citronellyl acetate, 1,4-dimethyl pyrazole, alpha-terpinene, 3-methyl-6-(1-methylethyl)-2-cyclo-hexene-1-o1 and trans-geraniol. The volatile extract decreased the cell viability and induced apoptotic death in HepG2 human hepatoma cells in a concentration- and time-related manner. In addition, the volatile extract increased the production of reactive oxygen species in a dose-dependent manner. Pretreatment of the cells with Trolox, a well-known antioxidant, significantly suppressed the generation of reactive oxygen species and cell death induced by the extract. However, caspase-3 activity was not changed in the extract-treated cells, suggesting that the extract-induced apoptosis of HepG2 cells is caspase-3 independent. Furthermore, in nude mice inoculated with Huh-7 human hepatoma cells, the extract significantly inhibited tumor development. These results suggest that the volatile extract from Zanthoxylum schinifolium pericarpium is a good candidate for hepatocellular carcinoma (HCC) therapy and that reactive oxygen species are the key signaling molecules in the volatile extract-induced cell death in HepG2 cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oils, Volatile / isolation & purification
  • Oils, Volatile / pharmacology*
  • Oils, Volatile / therapeutic use
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Reactive Oxygen Species / metabolism*
  • Xenograft Model Antitumor Assays
  • Zanthoxylum*


  • Oils, Volatile
  • Plant Extracts
  • Reactive Oxygen Species