Hamamelitannin from Hamamelis virginiana inhibits the tumour necrosis factor-alpha (TNF)-induced endothelial cell death in vitro.

Abstract

The tumour necrosis factor-alpha (TNF) inhibitory activity of hamamelitannin from Hamamelis virginiana was investigated by assessing the TNF-mediated EAhy926 endothelial cell death and adhesiveness to monocytes. Treatment of the cells by TNF (25 ng/ml) and actinomycin D (0.1ng/ml) resulted in significant DNA fragmentation (34+/-0.6, n=4) and cytotoxicity (97+/-4.5%, n=6) following treatment for 8 and 24h, respectively. One to 100 microM concentrations of hamamelitannin inhibited the TNF-mediated endothelial cell death and DNA fragmentation in a dose-dependent manner. One hundred % protection against TNF-induced DNA fragmentation and cytotoxicity was obtained for hamamelitannin concentrations higher than 10 microM. The protective effect of hamamelitannin was comparable with that of a related compound epigallocatechin gallate while gallic acid was a weak protective agent (<40% protection). EAhy926 endothelial cells upregulated (by 4- to 7-fold) the surface expression of intercellular adhesion molecule-1 (ICAM-1) and adhesiveness to monocytic U937 cells after treatment with TNF (0.5ng/ml) for 6 or 24h. Concentrations (1-100 microM) of hamamelitannin that inhibited the TNF-mediated cell death and DNA fragmentation, however, failed to inhibit the TNF-induced ICAM-1 expression and EAhy926 cell adhesiveness to U937 cells. Thus, hamamelitannin inhibits the TNF-mediated endothelial cell death without altering the TNF-induced upregulation of endothelial adhesiveness. The observed anti-TNF activity of hamamelitannin may explain the antihamorrhaegic use of H. virginiana in traditional medicine and its claimed use as a protective agent for UV radiation.

• Authors: Solomon Habtemariam
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 40 Issue 1 Pg. 83-8 (Jan 2002) ISSN: 0041-0101 [Print] England
• PMID: 11602283 (Publication Type: Journal Article)

Chemical References

• Free Radical Scavengers
• Hexoses
• Plant Extracts
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Dactinomycin
• Gallic Acid
• hamamelitannin

Topics

• Apoptosis (drug effects)
• Cell Adhesion (drug effects)
• Cell Line
• Cell Survival (drug effects)
• DNA Fragmentation (drug effects)
• Dactinomycin (toxicity)
• Dose-Response Relationship, Drug
• Drug Interactions
• Endothelium (drug effects, metabolism, pathology)
• Enzyme-Linked Immunosorbent Assay
• Free Radical Scavengers (pharmacology)
• Gallic Acid (analogs & derivatives, isolation & purification, pharmacology)
• Hamamelis (chemistry)
• Hexoses (isolation & purification, pharmacology)
• Humans
• Intercellular Adhesion Molecule-1 (biosynthesis)
• Plant Extracts (isolation & purification, pharmacology)
• Tumor Necrosis Factor-alpha (toxicity)
• Up-Regulation