Pollio A, De Natale A, Appetiti E, Aliotta G, Touwaide A. Continuity and change in the Mediterranean medical tradition: Ruta spp. (rutaceae) [sic] in Hippocratic medicine and present practices. J Ethnopharmacol. 3 Jan 2008;116: 469-482.

With over 100 traditional uses, rue (Ruta spp, especially R. angustifolia, R. chalepensis, R. corsica, and R. graveolens), a strong-smelling, bitter-tasting shrub, is "among the most-used genera in contemporary Italian traditional medicine, economic botany, and folk life." Extensive use has been documented for other Mediterranean areas as well. Rue was "abundantly used" when the Corpus Hippocraticum was compiled, between the 5^th century BCE and 2^nd century CE. The authors compared uses documented then with current use throughout the Mediterranean and, where they found "numerous and significant" similarities, tried to determine if such uses have been continuous since ancient times.

Nine Hippocratic treatises contain therapeutic indications for rue. Other ancient works were consulted to complement them. Touwaide and Appetiti compiled a database of medicinal plants in the Corpus Hippocraticum. Modern ethnobotanical literature was searched, and a database compiled of contemporary uses of rue in the region. While the ancients were aware not only of various species of rue, but also of differences due to conditions of cultivation or wild growth, they seem to have called all rue pêganon. Today as well, rue's "species limits are not... well known, but are the object of a continuing study of species boundaries and biogeographic patterns."

In ancient times, rue was used primarily for pulmonary diseases, against "throat angina", for swelling of the spleen, and, externally, in wound care. Gynecologically, rue was used for any disturbance of the menses, to aid both abortion and conception, and "to treat all the possible disturbances during pregnancy, during the delivery, to expel the placenta, and against puerperal fever." Rue preparations, usually macerated leaves, often included wine or honey. Rue was frequently taken with other herbs, such as coriander (Coriandrum sativum), cardamom (Elettaria cardamomum), and cumin (Cuminum cyminum). Non-Greek natives, as well as the changing uses in ancient texts, indicate that knowledge of rue expanded and evolved over time. Rue has both "hot" and "dry" properties, in Hippocratic physiological terms. It could be used, according to the principle of similarity, against inflammation (heat against heat); or, according to the principle of contrariness, against "any excess of fluids" (heat and dryness against cold and moisture). The herbs used with it were also credited with hot and dry qualities. Their use might have aimed to reinforce rue's drying, warming effects.

Contemporary uses of rue vary within the region around De Natale. Focusing on Spain, Italy, and Turkey, where "a conspicuous corpus of ethnopharmacological data" exists, the authors found that in Spain, rue is still used for menstrual disorders, as an abortifacient, and for digestive problems. In Italy, its antihelmenthic and vermifuge properties "are by far the most common[ly]" sought, with anti-inflammatory and analgesic effects second. Turkish herbalists mainly prescribe rue as a laxative, but other indications are known from province to province. Infusions or decoctions of fresh leaves are most commonly used. Leaves fried in olive oil (from Olea europaea) are used externally for rheumatism in Spain and Italy, and severe coughs in Turkey. Throughout the region, rue is frequently mixed with mint and oregano, as well as members of the Thymus and Nepeta genera, and garlic (Allium sativum). Nigella (Nigella sativa) seeds are used with rue in Turkey.

Commenting on similarities and differences in use from ancient to modern times, the authors note that hot water extracts may damage thermo-labile compounds and, maceration in wine, "might ensure the preservation of [rue's]... constituents." Rue, used constantly in Western medicine since the Hippocratic era, as well as early Arabic medicine, gained new popularity in the West with the 16^th century reintroduction of ancient Greek texts. Some early medicinal uses have been preserved in part, others were lost (or found over time to be inefficacious), and new ones emerged. Ascendancy of Christianity in the Mediterranean gave a new, symbolic, value to rue. Rue is used to bless holy water, and was thus among the first herbs brought by Europeans to the New World. It has been suggested that this promoted therapeutic uses of rue in Latin America. The authors add that modern Mediterranean use shows "greater awareness of the potential toxicity" of rue, and "seem[s] to suggest that a shift towards a safer application occurred at a certain point."