Planta Med 2012; 78 - PI425
DOI: 10.1055/s-0032-1321112

Investigation onto the mechanism behind the hepatoprotective effect of cucurbitacin compounds

H Arjaibi 1, F Halaweish 1
  • 1Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD 57007

Cucurbitacins are natural triterpenoids known for their potent anticancer and anti-inflammatory activities. Recent studies showed that cucurbitacins protect HepG2 cell line against CCl4 induced toxicity. The mechanism behind this cytoprotection is unknown. The hepatoprotective effect of cucurbitacin compounds might be due to the inhibition of tumor necrosis factor-alpha (TNF-α), an important inflammatory factor that connects inflammation and cancer. Previous reports demonstrated the role of TNF-α in tumor proliferation, migration, invasion and angiogenesis. TNF-α is produced due to the activation of IKK/NF-kB pathway in liver cells. Identification of a cucurbitacin molecular target was achieved using in Silico drug design approaches. Molecular docking of 300 natural and virtual cucurbitacin analogs over IKKβ and IKKαβ crystal structures was conducted. Docking data revealed approximately 100 potential cucurbitacin analogs with higher binding affinity to the hydrophobic pocket of IKKβ and IKKαβ compared to standard IKK inhibitor (BMS-345541). Cucurbitacin B, D, and iso-D were isolated from Cucurbita texana and characterized using spectroscopic techniques. In vitro cytotoxicity assay was conducted to measure the cytoprotective concentration of cucurbitacins on BRL-3A rat liver cell line. The result of the ELISA assays of TNF-α and IL-6 from pretreated liver cell line with natural cucurbitacins compounds will be presented.