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Most studies of horse chestnut extract or its active ingredients escin and esculin were done in animals or tissue cultures.

The agency also advises never to use homemade preparations, and points out on its Web site that while the extract is safe when properly processed, raw horse chestnut seeds, leaves, bark and flowers contain a chemical called esculin that is toxic.

In 1870, according to Dymock, Broughton analyzed the fresh bark and reported that the bitter taste was due to esculin, which after drying and coming in contact with decomposing organic matter is transformed into the almost tasteless esculetin.

The species Aesculus hippocastanum has been studied and has been found to contain saponin, tannin, and the glycoside, esculin.

Esculin is used in patent remedies in the form of ointments and pastes to protect the skin from sunburn.