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Himatanthus Willd. ex Schult. (Apocynaceae): Review

The genus Himatanthus Wild. ex Schult. (Apocynaceae) includes about 13 species and five subspecies widely distributed in South America, especially Brazil. The phytochemical reports on this genus have revealed mainly triterpenes and iridoids. The plants are traditionally used as anthelmintic, antitumor, and antiinflammatory agents. The most used parts of the plant are its bark, leaves, and latex. This review emphasizes the phytochemical constituents and medicinal properties, which may help in future research. The research was conducted with data obtained from books about medicinal plants, theses, dissertations, and articles in refereed journals.


INTRODUCTION
The Apocynaceae family includes approximately 550 genuses and 3700-5100 species distributed in all continents except Antarctica. It is a rich source of secondary metabolites, because of which many of the genuses belonging to it, such as Rauwolfia, Catharanthus, Allamanda, Strophantus, and Himatanthus, are used on a large scale for medicinal use by small communities and/or pharmaceutical industry. [1] In this review, we will be focused on the folk medicine uses, biological effects, and phytochemistry of the genus Himatanthus Willd. Ex Schult., in order to provide a basis for several different research areas, such as the botanic, pharmaceutical, medical, and chemical fields.

MATERIALS AND METHODS
The method used for this study was based on bibliographical research into books about medicinal plants, theses, dissertations, and articles in refereed journals. Presentations at conferences and symposia were not considered. We performed extensive research in the Periodicals Portal of Capes (Coordination for the Improvement of Higher Education Personnel), which has several databases such as Chemical Abstracts, PubMed, Web of Science and Science Direct (consultation period: February to May 2014). The key word used in the research was Himatanthus; information on the plant parts used, the uses in folk medicine, the biological activities, and the chemical constituents was collected. Data were compiled and organized into a table [Table 1], and the Himatanthus species have been arranged in alphabetical order.

RESULTS AND DISCUSSIONS
The genus Himatanthus Willd. Ex Schult., initially included in the genus Plumeria, has large bracts involving the floral buttons, determinants for the separation of genus. The presence of these bracts has inspired the naming of this genus, which means "flower robe. " [59] It  [60] They all occur in Brazil and some other countries in South and Central America. [22,60] From among the 13 species of Himatanthus, four did not have any research records concerning their chemical composition and medicinal properties: H. attenuatus, H. semilunatus, H. speciosus, and H. tarapotensis. The research results with the other species are summarized in Table 1. The H. bracteatus, H. fallax, and H. stenophyllis species have only reports of chemical composition studies, and the presence of the iridoid plumieride in the bark of these species is common. [10,21] This substance and the isoplumieride, generally, are present in the bark, latex, leaves, and/or roots of the species of Himatanthus. [2,10,21,23,36,38,41] This kind of spirolactone iridoid is not commonly found in nature. Some studies revealed that plumieride exhibits antimicrobial [61] and antioxidant effects, [62] arrests spermatogenesis in male rats without noticeable side effects, and presents cytotoxicity. [3] The H. articulatus, H. drasticus, H. lancifolius, H. obovatus, H. phagedaenicus, and H. sucuuba species presented chemical and biological studies, and in general the barks are the most studied, followed by the leaves. Although the presence of alkaloids in the barks of H. articulates is reported, [2] only from the barks of H. lancifolius were they isolated and identified, [24,25] and   [26][27][28][29][30] However, there are no data on the ethnopharmacological use of the plant as an antitumor agent. [23,30,31] H. articulatus latex is popular as an antifungal and antitumor agent, these effects evidenced by biological studies. [4] Their barks showed cytotoxic and trypanocidal and leishmanicidal effects, also reported in folk medicine. [2,3,5,6] Leishmaniasis is a parasitic disease responsible for considerable mortality and morbidity, affecting many people every year. [4] Leishmania donovani is the causative agent of visceral leishmaniasis, which is fatal in the absence of treatment. [63] Its various side effects and resistance to available drugs, in addition to the increase in new cases, have led to an urgent need for new therapeutic agents. This activity was also determined in H. articulatus leaves, H. obovatus roots, and H. sucuuba latex, [4,36,42] which are certainly promising sources of treatment.
There are studies of H. drasticus latex evaluating its antiulcerogenic, antitumor, analgesic, and antiinflammatory activities, which somehow justify their popular uses in the treatment of cancer, gastric disorders, rheumatism, and bruises. [1,[11][12][13][14][15][16][17][18] H. sucuuba is the most studied species, with a record of chemical composition of the latex, bark, leaves, roots and leaves, and the presence of triterpene amyrin cinnamate. [41,[43][44][45][46] Latex, bark, and leaves have antitumor action, justifying the popular use for the same purpose. [41,[46][47][48][49][50] The latex and bark showed antiinflammatory and analgesic effects, which are reasons for some popular uses of the plant: In treatment of arthritis, boils, and edema. [41,44,46,[48][49][50] Biological studies on H. obovatus roots have no relation with the ethnopharmacological information about the plant. [36] However, the popular use of the leaves as antitumor agent [36] can be justified by the presence of iridoids and triterpene esters. The triterpenoids are considered promising anticancer drugs due to their diverse pharmacological activities, including antiangiogenic, antiinflammatory, and antioxidant effects and the ability to increase cell differentiation. [64] These compounds, along with iridoids, are certainly responsible for most of the plant's medicinal properties reported in both folk medicine and biological studies.

CONCLUSION
Among the nine species studied, six species were evaluated chemically and biologically. The most studied species was H. sucuuba.
In general, the species are traditionally used as an anthelmintic, antitumor, and antiinflammatory agent. There were no evaluation studies of anthelmintic activity for any species of the genus; however, there are several studies evaluating antitumor and antiinflammatory activities.
Regarding the chemical composition, the genus is distinguished by the presence of triterpene esters and iridoids, predominantly in the bark and leaves. These compounds exhibit valuable pharmacological properties such as antimicrobial, antioxidant, antiinflammatory, and antitumor properties, which warrant further exploration. The chemical and pharmacological data presented in this study should inspire further study of the species of Himatanthus for future use in therapies, including treatment of leishmaniasis.