anti-cancer drugs, were discovered in the 1950s from the Madagascar periwinkle, Catharanthus roseus. Hundreds of compounds have been identified using ethnobotany, investigating plants used by indigenous peoples for possible medical applications. Some important phytochemicals, including curcumin, epigallocatechin gallate, genistein and resveratrol are pan-assay interference compounds, meaning that in vitro studies of their activity often provide unreliable data. As a result, phytochemicals have frequently proven unsuitable as the lead substances in drug discovery. In the United States over the period 1999 to 2012, despite several hundred applications for new drug status, only two botanical drug candidates had sufficient evidence of medicinal value to be approved by the Food and Drug Administration. The pharmaceutical industry has remained interested in mining traditional uses of medicinal plants in its drug discovery efforts. Of the 1073 small-molecule drugs approved in the period 1981 to 2010, over half were either directly derived from or inspired by natural substances. Among cancer treatments, of 185 small-molecule drugs approved in the period from 1981 to 2019, 65% were derived from or inspired by natural substances. Safety Plant medicines can cause adverse effects and even death, whether by side-effects of their active substances, by adulteration or contamination, by overdose, or by inappropriate prescription. Many such effects are known, while others remain to be explored scientifically. There is no reason to presume that because a product comes from nature it must be safe: the existence of powerful natural poisons like atropine and nicotine shows this to be untrue. Further, the high standards applied to conventional medicines do not always apply to plant medicines, and dose can vary widely depending on the growth conditions of plants: older plants may be much more toxic than young ones, for instance. Pharmacologically active plant extracts can interact with conventional drugs, both because they may provide an increased dose of similar compounds, and because some phytochemicals interfere with the body's systems that metabolise drugs in the liver including the cytochrome P450 system, making the drugs last longer in the body and have a more powerful cumulative effect. Plant medicines can be dangerous during pregnancy. Since plants may contain many different substances, plant extracts may have complex effects on the human body. Quality, advertising, and labelling Herbal medicine and dietary supplement products have been criticized as not having sufficient standards or scientific evidence to confirm their contents, safety, and presumed efficacy. A 2013 study found that one-third