Disjunct Medicine: A History of the (Two) Mayapple(s)

by Sasha M. White

mayapplAs early as 1731 Mark Catesby described the medicinal use of American mayapple root in his Natural History of the Carolinas . Image courtesy of the Lloyd Library & Museum.When Europeans came to North America, the mayapple (Podophyllum peltatum), also called mandrake, raccoon berry or wild lemon, was one of the earliest plants to be noticed. Samuel Champlain noted Huron tribes eating the fruit in 1616, and shortly thereafter it was collected and cultivated in gardens in Europe. Linnaeus gave the plant its official scientific name, Podophyllum peltatum, in his 1753 publication Species Plantarum. A perennial herb native to moist woodland edges from southern New England south to Georgia and west to Texas, mayapple became popular not just for its beautiful flower, edible fruit, and horticultural novelty, but also for the medicinal properties of its root.

Medical theory of the 17th and 18th centuries relied on balancing the “humors”, or secretions of the body, to treat disease. Purgatives, bloodletting, sweating, and vomiting were general remedies for all types of illness. The dried or roasted rhizome and roots of mayapple were used by some Native American tribes as a purgative, and the medicine was quickly adopted by early American doctors to treat various types of fever, dropsy, rheumatism, and syphilis. As an indigenous herb, mayapple could replace expensive foreign remedies, such as ipecac (Cephaelis ipecacuanha) and jalap (Ipomoea purga) and also avoid the deleterious side effects of mercury (Barton). In the 19th century Eclectic practitioners developed disease-specific remedies and began using mayapple as a low-dose alterative for glandular disease, rheumatism, chronic hepatitis, and atonic conditions of the digestive system. They also used the compound resin derived from mayapple as a stimulant to the sympathetic nervous system of the solar plexus, to normalize secretions in such afflictions as diarrhea, constipation, gallstones, and gastric catarrh (Felter).

This compound, popularized as podophyllin, became the first commercially produced botanical medicine (Haller).

Along with other herbaceous members of the Berberidaceae found in Eastern North America, mayapple was for many years believed to be the sole member of its genus. In 1824 a second species of mayapple was discovered growing in Asia. Podophyllum hexandrum syn. P. emodi, the Himalayan mayapple, grows in small, widespread populations in the alpine regions of Northern India, Pakistan, Bhutan and western China. Like American mayapple, it has a single flower, ranging from white to pink, born between two lobed and peltate leaves. Both produce an edible fleshy fruit, the American most often yellow, the Himalayan red. Unlike the American species, which varies in both petal and stamen number, Himalayan mayapple consistently has six petals and six stamens and blooms before its leaves are fully open. And while American mayapple grows in large, clonal, generally self-incompatible colonies, spreading by its stoloniferous rhizomes, the Himalayan species is self-pollinating. This characteristic is believed to have evolved when the Himalayan Mountains lifted the mayapple into an alpine zone depauperate in spring pollinators. An effective reproductive strategy for the long-range dispersal of fruits eaten by birds and herbivores, it has also created the great morphological variation documented between the Asian populations (Xiong, Nag).

The two mayapples, one Asian, one American, are part of what is known as the Eastern Asian-Eastern North American Floral Disjunction. In the 1800s, as Western explorers gained greater access to Eastern Asia, their botanical collections displayed a stunning similarity to the flora of Eastern North America. The two regions share more closely related species and genera than either does with Europe, Western North America, or Western Asia. Based on collections made in Japan, botanist Asa Gray outlined the first theory of the EA-ENA Disjunction in 1849. The theory continues to be refined to present day through interdisciplinary research in botany, paleobotany, phytogeography, geology, chemistry, and palynology. Generally it is believed that beginning around 50 million years ago a vast, deciduous boreo-tropical forest spread across the Northern Hemisphere, utilizing land bridges across the North Pacific and the North Atlantic Oceans. During subsequent climatic periods of cooling and glaciation and geological shifts, such as the collision of India with Asia and the rise of the Rockies in America, the forest shifted its range, changed, diversified and, in some places, went extinct (Tiffney, 1985). Eastern Asia and Eastern North America remained relatively hospitable to these ancient plants and hundreds of closely related taxa, now isolated from each other, continued to evolve and grow in these regions. The two mayapple species, called “sister species”, are believed to have diverged from one another around 6 or 7 million years ago, concomitant with the rise of the Himalayan Mountains (Xiong).
Many of the plants that are part of the EA-ENA Disjunction have been used similarly in the traditional systems of medicine in their regions (Duke). Himalayan mayapple is called “bakra” in the vernacular and is thought to be a traditional bile-expelling plant of Sanskrit writings; its fruits are eaten as a mild laxative and for female reproductive issues (Arora). In the 1890s colonial administrators and pharmaceutical companies in British India began exploring the economic possibilities of Himalayan mayapple, hoping to supplant the American domination of the European market for podophyllin. Chemical assays of the Asian root were promising, reporting two to three times the amount of podophyllin as compared to the American mayapple (Thurston). But the remote, mountainous habitat of Himalayan mayapple made the cost of harvest and transport too high to be profitable and the market for it was slow to develop (Chatterjee).

victorVictor Jacquement’s Voyage dans l’Inde of 1844 established the scientific name for Himalayan mayapple. Image courtesy of the Lloyd Library and Museum.Mayapple is not a medicine to be used without caution. The fresh root is a violent, sometimes fatal emeto-cathartic, used among some Native American peoples for suicides and poisonings (Erichsen-Brown).

Even dried, a large dose can be fatal. In early American medicine its purgative or cathartic doses were usually modulated by the addition of such botanicals as hyoscyamus (Hyoscyamus niger) and belladonna (Atropa belladonna) to dull the pain of intestinal griping (Felter). The Physio-Medicalist William H. Cook came to eschew the use of mayapple almost altogether. He describes it in his 1869 Dispensatory as a powerful stimulant to the secretory organs, useful perhaps in moderation for atony of the digestive organs, but exacerbating and debilitating even in small amounts to disease states. It is escharotic to the skin, and workers with the powdered drug have reported severe inflammation in mucous membranes and other sensitive areas. This property has been put to use both historically and contemporarily as a topical treatment for various types of skin lesions including genital warts (Hartwell). In 1947 mayapple was investigated for its anti-cancer properties and was found both to be anti-tumoural and to cause toxic side effects in the patient. By the late 1960s, semi-synthetic drugs, such as etoposide and teniposide, were being derived from podophyllotoxin, one of the lignans found in podophyllin and mayapple. These anti-cancer drugs have mitigated some, but not all, side effects. In addition to possible gastro-intestinal distress, studies have shown that podophyllotoxin is damaging to the bone marrow, liver, and central nervous system, as well as tetragenic and detrimental to the development of the fetus. Still, these drugs are being used extensively and effectively against cancers of the lymph, lungs, brain, breast, and testes (Arora).

Anti-cancer drugs are now the driving force behind the wild harvest of mayapple. In 1970, 130 tons of American mayapple were dug from the wild (Meijer). The higher amounts of podophyllotoxin found in the Himalayan species, however, quickly shifted pharmaceutical manufacturers’ interest to Asia.

Today, far from being the “abundant” and “plentiful” plant promoted by British colonial administrators, Himalayan mayapple is an endangered species. It is listed in the Convention on International Trade in Endangered Species Appendix II, along with goldenseal (Hydrastis canadensis) and American ginseng (Panax quinquefolius) (both of which are also part of the EA-ENA Floral Disjunction). These plant species may not be immediately threatened with extinction, but it is feared they soon may be if their trade is not closely regulated. Despite this status, Himalayan mayapple’s dwindling wild populations continue to be the main pharmaceutical source of podophyllotoxin.* Harvest data are difficult to obtain, as the market from digger to buyer is secretive, but Asian Internet wholesalers offer supply abilities of Podophyllum extract of up to 10 tons per month. With 50 plants of Himalayan mayapple required to make a single kilogram of dried root, the harvest rates are “well over natural regeneration” (Rai, Nadeem).

One recent author lamented the disappearance of plants from their Himalayan study populations: in the area of Prashar the average number of plants per quadrant decreased from 2 to .6 over the course of two growing seasons (Nag). Attempts at cultivation of this alpine plant have been hampered by poor seed viability and germination, as well as a maturation time of anywhere from 6 to 12 years from planting to harvest of marketable rhizomes (Krishnamurthy, Troup). The uses of tissue culture and fungi to synthesize podophyllotoxin are still in early stages of investigation (Chaudhari).

Possibly, what may save Himalayan mayapple is the American mayapple. Recent assays on the leaves of the American species report levels of podophyllotoxin in some populations equal to or greater than the amounts found in the Himalayan roots. Growers are finding American mayapple does not require the use of shadecloth and that it thrives under cultivation (Moraes). Thus, it could provide a renewable source of podophyllotoxin and allow for the recovery of the Asian species. Simultaneous to cultivation efforts, the restoration of savanna and fire-dependent woodland ecosystems would also ensure that wild American mayapple populations have ideal habitat, increasing fruit set and genetic diversity (Erichsen-Brown, Crants). Mayapple has graced the earth for millions of years. If protected from overexploitation, these sister species, one of alpine meadows, one of open woodlands and savannas, will continue to give us powerful medicine.

Cited References:

Arora, Rajesh, Shikha singh, S.C. Puri, R.K. Sharma. 2008. Himalayan Mayapple: traditional uses, clinical indications and future prospects in Botanical Medicine in Clinical Practice (R.R. Watson and V.R. Preedy, eds.) CAB International, Wallingford UK.
Barton, B.S. 1810. Collections for an Essay towards a Materia Medica of the United States. Edward Earle and Company, Philadelphia.
Chatterjee, Ramgopal. 1952. Indian Podophyllum. Economic Botany 6: 342-354.
Chaudhari, Sunbal Khalil, Yamin Bibi, Muhammad Arshad. 2014 Podophyllum hexandrum: an endangered medicinal plant from Pakistan. Pure Appl. Bio. 3(1): 19-24
Cook, Wm. H. 1869. Physio-Medical Dispensatory. Wm. H. Cook, Cincinnati OH.
Crants, James E. 2008. Pollination and pollen limitation in Mayapple (Podophyllum peltatum L.), a nectarless spring ephemeral. PhD thesis, University of Michigan, Ann Arbor.
Duke, James A. and Ayensu, Edward S. 1985. Medicinal Plants of China. Reference Publications, Inc., Algonac MI.
Erichsen-Brown, Charlotte. 1989, 1979. Medicinal and other uses of North American Plants: a historical survey with special reference to the eastern Indian Tribes. Dover, New York.
Felter, Harvey Wickes and Lloyd, John Uri. 1909. King’s American Dispensatory. Vol. 2. The Ohio Valley Company, Cincinnati OH.
Haller, John S. 1994. Medical Protestants: The Eclectics in American Medicine, 1825-1939. Southern Illinois University Press, Carbondale and Edwardsville IL.
Hartwell, Jonathon L. 1982. Plants Used Against Cancer: A Survey. Quarterman Publications, Lawrence MA.
Krishnamurthy, T., G.V. Karira, B.K. Sharma, Kuldip Bhatia. 1965.
Cultivation and exploitation of Podophyllum hexandrum Royle. Indian Forester 91(7): 470-475.
Meijer, Willem. 1974. Podophyllum peltatum, Mayapple: A potential new cash crop of Eastern North America. Economic Botany 28: 68-72.
Moraes, Rita M., Hemant Lata, Ebru Bedir, Muhammad Maqbool, Kent Cushman. 2002. The American Mayapple and its Potential for Podophyllotoxin Production in Trends in New Crops and New Uses. J. Janick and A whipkey, eds. ASHS Press, Alexandria VA.
Nadeem, M., L.M.S. Palni, A.N. Purohit, H. Pandey, S.K. Nandi. 2000. Propagation and conservation of Podophyllum hexandrum royle: an important medicinal herb. Biological Conservation. 92: 121-129.
Nag, A., P.S. Ahuja, R.K. Sharma. 2015. Genetic diversity of high-elevation populations of an endangered medicinal plant. AoB PLANTS 7: plu076; doi: 10.1093/aobpla/plu076.
Rai, L.K., Pankaj Prasad, E. Sharma. 2000. Conservation threats to some important medicinal plants of the Sikkim Himalaya. Biological Conservation 93: 27-33.
Shaw, Julian M. H. 2002. The Genus Podophyllum in The Genus Epimedium and other Herbaceous Berberidaceae. William T. Stearn. Timber Press, Portland OR.
Thurston, E., ed. 1892. Hand-books of Commercial Products, Indian Section: No. 3 Podophyllum emodi. Office of the Superintendent of Government Printing, Calcutta.
Tiffney, Bruce H. 1985. Perspectives on the Origin of the Floristic Similarity Between Eastern Asia and Eastern North America. J. Arnold Arbor. 66: 73-94.
Tiffney, Bruce H. 1985. The Eocene North Atlantic Land Bridge: Its Importance in Tertiary and Modern Phytogeography of the Northern Hemisphere. J. Arnold Arbor. 66: 243-273.
Troup, R.S. 1915. A note on the cultivation of Podophyllum emodi. Indian Forester 41(10): 361-365.
Xiong, Ying-Ze, Fang Qiang, Shuang-Quan Huang. 2013. Pollinator scarcity drives the shift to delayed selfing in Himalayan mayapple Podophyllum hexandrum (Berberidaceae). AoB PLANTS 5:plt037; doi:10.1093/aobpla/plt037.