A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1

J Med Chem. 1992 May 29;35(11):1978-86. doi: 10.1021/jm00089a006.


Extracts of Homalanthus nutans, a plant used in Samoan herbal medicine, exhibited potent activity in an in vitro, tetrazolium-based assay which detects the inhibition of the cytopathic effects of human immunodeficiency virus (HIV-1). The active constituent was identified as prostratin, a relatively polar 12-deoxyphorbol ester. Noncytotoxic concentrations of prostratin from greater than or equal to 0.1 to greater than 25 microM protected T-lymphoblastoid CEM-SS and C-8166 cells from the killing effects of HIV-1. Cytoprotective concentrations of prostratin greater than or equal to 1 microM essentially stopped virus reproduction in these cell lines, as well as in the human monocytic cell line U937 and in freshly isolated human monocyte/macrophage cultures. Prostratin bound to and activated protein kinase C in vitro in CEM-SS cells and elicited other biochemical effects typical of phorbol esters in C3H10T1/2 cells; however, the compound does not appear to be a tumor promoter. In skin of CD-1 mice, high doses of prostratin induced ornithine decarboxylase only to 25-30% of the levels induced by typical phorbol esters at doses 1/30 or less than that used for prostratin, produced kinetics of edema formation characteristic of the nonpromoting 12-deoxyphorbol 13-phenylacetate, and failed to induce the acute or chronic hyperplasias typically caused by tumor-promoting phorbols at doses of 1/100 or less than that used for prostratin.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Cytopathogenic Effect, Viral / drug effects
  • Edema / chemically induced
  • HIV-1 / drug effects*
  • Humans
  • Hyperplasia
  • Independent State of Samoa
  • Magnetic Resonance Spectroscopy
  • Mice
  • Monocytes / drug effects
  • Monocytes / microbiology
  • Ornithine Decarboxylase / biosynthesis
  • Phorbol Esters / chemistry
  • Phorbol Esters / isolation & purification*
  • Phorbol Esters / pharmacology
  • Plants, Medicinal / chemistry*
  • Protein Kinase C / metabolism
  • Skin / drug effects
  • Skin / enzymology
  • Skin / pathology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / microbiology
  • Virus Replication / drug effects


  • Phorbol Esters
  • prostratin
  • Protein Kinase C
  • Ornithine Decarboxylase