Prostratin is a

protein kinase C In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and ...

activator found in the bark of the mamala tree of

Samoa Samoa, officially the Independent State of Samoa; sm, Sāmoa, and until 1997 known as Western Samoa, is a Polynesian island country consisting of two main islands (Savai'i and Upolu); two smaller, inhabited islands (Manono Island, Manono an ...

, ''

Homalanthus nutans ''Homalanthus nutans'', known locally as the mamala tree, is a species of plant in the family Euphorbiaceae. In Australia it is known as the bleeding heart and the Queensland poplar. Samoan healers use the tree's bark in a concoction made to t ...

'' (

Euphorbiaceae Euphorbiaceae, the spurge family, is a large family of flowering plants. In English, they are also commonly called euphorbias, which is also the name of a genus in the family. Most spurges, such as '' Euphorbia paralias'', are herbs, but some, ...

). While prostratin was originally isolated and identified as a new

phorbol ester Phorbol esters are a class of chemical compounds found in a variety of plants, particularly in the families Euphorbiaceae and Thymelaeaceae. Chemically, they are ester derivatives of the tetracyclic diterpenoid phorbol. Biological activity Protein ...

from species of the genus ''Pimelea'' (

Thymelaceae The Thymelaeaceae are a cosmopolitan family of flowering plants composed of 50 genera (listed below) and 898 species.Zachary S. Rogers (2009 onwards)A World Checklist of Thymelaeaceae (version 1) Missouri Botanical Garden Website, St. Louis. ...

) in Australia, the antiviral activity of prostratin was discovered during research on the

traditional knowledge Traditional knowledge (TK), indigenous knowledge (IK) and local knowledge generally refer to knowledge systems embedded in the cultural traditions of regional, indigenous, or local communities. According to the World Intellectual Property Org ...

of Samoan healers in

Falealupo Falealupo is a village in Samoa situated at the west end of Savai'i island from the International Date Line used until 29 December 2011. The village has two main settlements, Falealupo-Uta, situated inland by the main island highway and Falealu ...

village by ethnobotanist

Paul Alan Cox Paul Alan Cox is an American ethnobotanist whose scientific research focuses on discovering new medicines by studying patterns of wellness and illness among indigenous peoples. Cox was born in Salt Lake City in 1953. Education After receiving h ...

and a team at the U.S. National Cancer Institute. Samoan healers use the mamala tree to treat hepatitis. Research indicated that prostratin has potential to be useful in the treatment of

HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...

as it could flush viral reservoirs in latently infected CD4+ T-cells. As a modulator of

, it has been shown to exhibit promising therapeutic potential against other diseases such as

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

and Alzheimer's disease. In 2015, study showed that orally administrated prostratin repressed human

pancreatic tumor Pancreatic tumors (Pancreatic cancer Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts o ...

Overview

Prostratin is of interest because of its unique ability to activate latent viral reservoirs, while preventing healthy cells from infection, as well as its discovery through

ethnobotany Ethnobotany is the study of a region's plants and their practical uses through the traditional knowledge of a local culture and people. An ethnobotanist thus strives to document the local customs involving the practical uses of local flora for m ...

. Pioneering agreements to protect indigenous intellectual property rights of the Samoan people were established between the Samoan government and the

AIDS Research Alliance AIDS Research Alliance of America (ARAA) was a national community-based 501(c)(3) non-profit medical research institution that sought to develop a cure for HIV/AIDS, medical strategies to prevent new HIV infections and better treatments for peopl ...

, with 20% of ARA's profits to be returned to the Samoan people, and between the Samoan Government and the

University of California, Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public land-grant research university in Berkeley, California. Established in 1868 as the University of California, it is the state's first land-grant u ...

where a team led by

Jay Keasling Jay D. Keasling is a professor of chemical engineering and bioengineering at the University of California, Berkeley. He is also associate laboratory director for biosciences at the Lawrence Berkeley National Laboratory and chief executive officer ...

is trying to isolate the gene sequence responsible for prostratin biosynthesis.

and UC Berkeley agreed to share equally in any commercial proceeds from the gene product. In 2008, a team at Stanford University led by chemist

Paul Wender Paul A. Wender is an American chemist whose work is focused on organic chemistry, organometallic chemistry, synthesis, catalysis, chemical biology, imaging, drug delivery, and molecular therapeutics. He is currently the Francis W. Bergstrom Pr ...

has published an elegant four-step

chemical synthesis As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In mo ...

of prostratin from

phorbol Phorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. Phorbol was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of the purging croton, '' Crot ...

. This practical synthesis produces gram quantities of prostratin, and is a major step forward in pharmaceutical development of prostratin. In 2010, AIDS Research Alliance in Los Angeles, California announced that it signed a new licensing agreement with Stanford University, transferring exclusive rights of the technology developed by the Stanford research team. Phase I human

clinical trials Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

of prostratin will be carried out by the AIDS ReSearch Alliance in Los Angeles, California.

References

External links

Paul Wender and Stanford Prostratin synthesis
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Prostratin Agreements with SamoaU.S. University Shares Drug Royalties with Samoa for Tree GeneBerkeley searches for AIDS cure in a Samoan indigenous tree
Acetate esters Diterpenes Cyclopropanes Cyclopentenes Phorbol esters