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The traditionally used Central American medicinal plant Pluchea odorata, known as an anti-inflammatory and cancer cell growth-inhibiting remedy, was subjected to bioassay-guided isolation. Structure elucidation by 1D- and 2D-NMR and MS techniques supported by ECD and UV spectroscopic data revealed seven structurally previously undescribed and eight known eudesmane-type sesquiterpenes. Furthermore, one previously undescribed and one known phytol-like alcohol were identified. All compounds were tested for their cytotoxicity in cancer cells and for their anti-invasive effects. Among the eudesmanes, 3α-(2',3'-epoxy-2'-methylbutyryloxy)-4α-hydroxy-11-hydroperoxy-eudesm-6-en-8-one exhibited the most potent cytotoxic activity with an IC50 value of 8.8 μM (after 48 h). Also in an in vitro model measuring the tumor-triggered breaching of the adjacent lymph endothelial cell barrier (3S*,4R*,5S*,10S*,2'R*,3'R*)-3-(2',3'-epoxy-2'-methylbutyryloxy)-4,7-dihydroxy-eudesm-11-en-8-one (IC75 = 47 μM) and (3S*,4R*,5R*,10S*,2'R*,3'R*)-3-(2',3'-epoxy-2'-methylbutyryloxy)-4-acetyloxy-6-methoxy-11-hydroxy-eudesm-6-en-8-one (IC75 = 73 μM) showed inhibitory activities. Furthermore, preliminary structure-activity relationships (SARs) of the eudesmanes were developed.

Objective To evaluate the antileishmanial activity of different extracts from three Cuban Pluchea species. Methods In in vitro assays the IC 50 was calculated in the promastigotes and amastigotes forms as cytotoxicity in murine macrophages. In leishmaniasis cutanea experiment, mortality, weight loss, lesion size and burden parasite were measured. Results Extracts evaluated showed inhibitive effect on growing of promastigote form; however, active extracts caused a high toxicity. Ethanol and n -hexane extracts demonstrated specific antileishmanial activity. Ethanol and n -hexane extracts from Pluchea carolinensis (P. carolinensis) caused similar inhibition against amastigote form. The intraperitoneal administration of the ethanol extract of P. carolinensis at 100 mg/kg prevented lesion development compared with control groups. Conclusions The antileishmanial experiment suggests that ethanol extracts from P. carolinensis is the most promising. Further studies are still needed to evaluate the potential of this plant as a source of new antileishmanial agents.

Leaves of three Cuban species of the genus Pluchea: Pluchea carolinensis, Pluchea odorata and Pluchea rosea were extracted with various solvents and analyzed. Highest values of phenolic compounds were detected after ethyl acetate (EtOAc) and n-butyl alcohol (n-BuOH) extractions. Flavonoids were detected after chloroform, EtOAc and n-BuOH extractions of the species Pluchea and three aglycone flavonol forms (quercetin, kaempferol and myricetin) were also quantified after EtOAc and n-BuOH extractions, using high performance liquid chromatography. The total antioxidant capacity (TAC), expressed as Trolox equivalents per gram of leaf dry weight (TE/g dw) was analyzed using 2,2-diphenyl-1-picrylhydrazyl (DPPH·), 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and the oxygen radical absorbance capacity. The highest values of TAC were detected after EtOAc and n-BuOH extractions of the three species. P. carolinensis was the most promising species, being the n-BuOH extraction with the most bioactive compounds: 15.3 mg TE/g dw using DPPH·. PRACTICAL APPLICATIONS The study of the chemical and biological properties of natural crude extracts from plant sources constitutes an important way for discovering new chemical compounds beneficial for human health. Many disorders in humans are associated with the accumulation of free radicals in the body, as it is the case in atherosclerosis, arthritis, ischemia, central nervous system injury and some cancers among others. In the three Cuban species of the genus Pluchea, high amounts of natural compounds and especially phenolics have been detected. The antioxidant capacity of the plants has been tested by means of three different methods. These three species have high quantities of antioxidant substances that could be used in the treatment of different pathologies. In addition, these three species are well distributed in Cuba and they can be found in dense patches of individuals, so we have also access to high quantities of these natural sources.

Pluchea odorata is ethno pharmaceutically used to treat inflammation-associated disorders. The dichloromethane extract (DME) was tested in the carrageenan-induced rat paw oedema assay investigating its effect on inflammation that was inhibited by 37%. Also an in vitro anti-neoplastic potential was reported. However, rather limited information about the bio-activity of purified compounds and their cellular mechanisms are available. Therefore, two of the most abundant eudesmanes in P. odorata were isolated and their anti-neoplastic and anti-intravasative activities were studied. HL-60 cells were treated with P. odorata compounds and metabolic activity, cell number reduction, cell cycle progression and apoptosis induction were correlated with relevant protein expression. Tumour cell intravasation through lymph endothelial monolayers was measured and potential causal mechanisms were analyzed by Western blotting. Compound PO-1 decreased the metabolic activity of HL-60 cells (IC 50 = 8.9 μM after 72 h) and 10 μM PO-1 induced apoptosis, while PO-2 showed just weak anti-neoplastic activities at concentrations beyond 100 μM. PO-1 arrested the cell cycle in G1 and this correlated with induction of JunB expression. Independent of this mechanism 25 μM PO-1 decreased MCF-7 spheroid intravasation through the lymph endothelial barrier. Hence, PO-1 inhibits an early step of metastasis, impairs unrestricted proliferation and induces apoptosis at low micromolar concentrations. These results warrant further testing in vivo to challenge the potential of PO-1 as novel lead compound.

Introduction. Several studies demonstrated that anti-inflammatory remedies exhibit excellent anti-neoplastic properties. An extract ofPluchea odorata(Asteraceae), which is used for wound healing and against inflammatory conditions, was fractionated and properties correlating to anti-neoplastic and wound healing effects were separated.Methods. Up to six fractionation steps using silica gel, Sephadex columns, and distinct solvent systems were used, and eluted fractions were analysed by thin layer chromatography, apoptosis, and proliferation assays. The expression of oncogenes and proteins regulating cell migration was investigated by immunoblotting after treating HL60 cells with the most active fractions.Results. Sequential fractionations enriched anti-neoplastic activities which suppressed oncogene expression of JunB, c-Jun, c-Myc, and Stat3. Furthermore, a fraction (F4.6.3) inducing or keeping up expression of the mobility markers MYPT, ROCK1, and paxillin could be separated from another fraction (F4.3.7), which inhibited these markers.Conclusions. Wound healing builds up scar or specific tissue, and hence, compounds enhancing cell migration support this process. In contrast, successful anti-neoplastic therapy combats tumour progression, and thus, suppression of cell migration is mandatory.

Many traditional healing plants successfully passed several hundred years of empirical testing against specific diseases and thereby demonstrating that they are well tolerated in humans. Although quite a few ethno-pharmacological plants are applied against a variety of conditions there are still numerous plants that have not been cross-tested in diseases apart from the traditional applications. Herein we demonstrate the anti-neoplastic potential of two healing plants used by the Maya of the Guatemala/Belize area against severe inflammatory conditions such as neuritis, rheumatism, arthritis, coughs, bruises and tumours. Phlebodium decumanum and Pluchea odorata were collected, dried and freeze dried, and extracted with five solvents of increasing polarity. We tested HL-60 and MCF-7 cells, the inhibition of proliferation and the induction of cell death were investigated as hallmark endpoints to measure the efficiency of anti-cancer drugs. Western blot and FACS analyses elucidated the underlying mechanisms. While extracts of P. decumanum showed only moderate anti-cancer activity and were therefore not further analysed, particularly the dichloromethane extract of P. odorata inhibited the cell cycle in G2-M which correlated with the activation of checkpoint kinase 2, and down-regulation of Cdc25A and cyclin D1 as well as inactivation of Erk1/2. In HL-60 and MCF-7 cells this extract was a very strong inducer of cell death activating caspase-3 followed by PARP signature type cleavage. The initiating death trigger was likely the stabilization of microtubules monitored by the rapid acetylation of alpha-tubulin, which was even more pronounced than that triggered by taxol. The dichloromethane extract of P. odorata contains apolar constituents which inhibit inflammatory responses and exhibit anti-cancer activity. The strong proapoptotic potential warrants further bioassay-guided fractionation to discover and test the active principle(s).

Conyza odorata Linnaeus, Systema Naturae, ed. 10, 2: 1213. 1759. ["Habitat in America meridionali."] Sp. Pl., ed. 2, 2: 1208 (1763). RCN: 6233. Lectotype (Britten in J. Bot. 36: 54. 1898): [icon] " Conyza major, odorata seu baccharis, floribus purpureis nudis " in Sloane, Voy Jamaica 1: 258, t. 152, f. 1. 1707. - Typotype: Herb. Sloane 5: 18 (BM-SL). Current name: Pluchea odorata (L.) Cass. (Asteraceae)., Published as part of Jarvis, Charlie, 2007, Chapter 7: Linnaean Plant Names and their Types (part C), pp. 370-473 in Order out of Chaos. Linnaean Plant Types and their Types, London :Linnaean Society of London in association with the Natural History Museum on page 443, DOI: 10.5281/zenodo.291971

Die Untersuchung der Wurzeln ergibt neben bereits bekannten Verbindungen ein neues Carvotageton-Derivat (9) und das Phthalsaurederivat 11. Die oberirdischen Teile enthalten neben dem bereits bekannten Eudesman-Derivat 12 zwei weitere dieses Typs (13 und 14) Die Konstitutionen werden durch spektroskopische Methoden geklart. Naturally Occurring Terpene Derivatives, 66: On New Constituents of Pluchea odorata Cass. The Investigation of the roots yields besides already known compounds a new carvotagetone derivative (9) and the phthalic acid derivative 11, while the aerial parts contain besides the already known eudesmane derivative 12 two further compounds of this type (13 and 14). The constitutions are elucidated by spectroscopic methods.

From the leaves of Pluchea odorata three previously known compounds have been isolated. In addition, four new derivatives of 3α,4α,11-trihydroxy-6,7-dehydroeudesman-8-one have also been obtained from the same source. Their structures have been established by spectroscopic means.

Natural products continue to represent the main source for therapeutics, and ethnopharmacological remedies from high biodiversity regions are a rich source for the development of novel drugs. Hence, in our attempt to find new anti-neoplastic activities we focused on ethno-medicinal plants of the Maya, who live in the world's third richest area in vascular plant species. Pluchea odorata (Asteraceae) is traditionally used for the treatment of various inflammatory disorders and recently, the in vitro anti-cancer activities of different extracts of this plant were described. Here, we present the results of bioassay-guided fractionations of the dichloromethane extract of P. odorata that aimed to enrich the active principles. The separation resulted in fractions which showed the dissociation of two distinct anti-neoplastic mechanisms; firstly, a genotoxic effect that was accompanied by tubulin polymerization, cell cycle arrest, and apoptosis (fraction F2/11), and secondly, an effect that interfered with the orchestrated expression of Cyclin D1, Cdc25A, and Cdc2 and that also led to cell cycle arrest and apoptosis (fraction F3/4). Thus, the elimination of generally toxic properties and beyond that the development of active principles of P. odorata, which disturb cancer cell cycle progression, are of interest for potential future therapeutic concepts against proliferative diseases.

13C NMR data are presented for plucheinol and its ester derivatives obtained from Pluchea odorata (L) Cass. A comparison with the data reported for cuauhtemone derivatives was carried out. An unexpected deshielding for C-4 in diester derivatives was observed.