Prostratin
Prostratin is a phorbol ester that is isolated from the bark of the mamala tree (Homalanthus nutans), which is native to Samoa. It is a non-tumor promoting phorbol ester that has potential use in the treatment of HIV due to its ability to flush the virus out of latent reservoirs in the body.
History
The use of prostratin in traditional Samoan medicine was first documented by ethnobotanist Paul Alan Cox in the 1980s. The compound was later isolated and identified by researchers at the National Cancer Institute in the United States.
Mechanism of Action
Prostratin acts by binding to and activating Protein Kinase C (PKC), an enzyme that plays a key role in cellular signaling pathways. This activation of PKC leads to the activation of the NF-κB pathway, which in turn leads to the transcription of latent HIV proviruses. This "flushing out" of the virus allows antiretroviral drugs to target and eliminate the virus.
Potential Use in HIV Treatment
Prostratin is currently being investigated for its potential use in the "shock and kill" strategy for curing HIV. This strategy involves using a drug to reactivate latent HIV reservoirs (the "shock"), followed by the use of antiretroviral drugs to kill the reactivated virus. Prostratin's ability to reactivate latent HIV makes it a promising candidate for this strategy.
Research and Development
Research into the potential use of prostratin in HIV treatment is ongoing. In 2001, the AIDS Research Alliance (ARA) obtained a license from the Samoan government to develop prostratin as a drug. The ARA has since conducted preclinical studies and is currently seeking funding for clinical trials.
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Contributors: Prab R. Tumpati, MD