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Ethnopharmacological relevance Cissus verticillata (L.) Nicolson and C.E. Jarvis is best known for its hypoglycaemic and anti-lipemic action. In Brazilian ethnopharmacy it is called “plant-insulin” and used mostly against diabetes, as well as in abscesses, haemorrhage and epilepsy. In the present paper we study the past significance of this plant recorded between 1571 and 1829 both in ethnic (Mexico, Haiti) and official (European) pharmacies. Aim of the study (1) We are able to identify Carolus Sanctus and Lupulus Mechiocanus from Renaissance and later sources as Cissus verticillata . The specific identity of its historical herbal stock has not been proposed yet. (2) The identification we propose enables us to extract a number of historical ethnopharmacological usages from historical texts, not mentioned so far. (3) We try to find links between historical and present popular usages of C. verticillata . Material and methods The identity of Carolo Sancto and Lupulus Mechiocanus as Cissus verticillata has been proposed on the grounds of: (1) analysis of pre-Linnaean synonymic polynomials, (2) critical evaluation of old illustrations in botanical and pharmaceutical works, compared to living plants, (3) comparison of morphological, anatomical and histochemical characters of C. verticillata with old pharmacognostical descriptions of the plant and the herbal stock which it delivered. Results We have recognised the specific identity on the basis of: (1) subsequent botanical works published between 1574 and 1763; (2) Hans Sloane׳s herbarium specimen No. BM589925; (3) morphology and organoleptic characteristics of the bark and roots published in the 16th and 17th century which are confirmable in living plants. Cissus verticillata was discovered by Nicolás Monardes in Mexico in 1571 and first published in Europe under the name Carolo Sancto in 1574. In European pharmacy the plant was also called Lupulus Mechiocanus. In official European pharmacy the root ( Radix Caroli Sancti = Rad. Indica , later its sole bark) was appreciated for its action to teeth and gums when chewed. Internal usages (ascribed initially to this medicament) were gradually discarded in the late 1700s. Roots were met in the European trade until 1795. Conclusions Cissus verticillata is common in Americas and could have been imported to Europe since the 16th century. Complete plants were not seen knowingly in European pharmacy; taxonomical investigation of this species developed independently. Ethnopharmacological usages described between 1582 and 1829 were not adopted in Europe with the exception of two recommendations: “weakness of the stomach” and fevers. Gastroprotective and anti-inflammatory actions were re-discovered in the 2000s. Two other historical usages: antiepileptic and styptic, are observed in today׳s ethnomedicine of Brazil. [ABSTRACT FROM AUTHOR]