Euphorbia Peplus Research Articles

Floristic composition and vegetation analysis in Hail region north of central Saudi Arabia

In this study, 19 sites representing different habitats in Hail region were regularly visited for two years, in each site 2–5 stands were selected for investigating floristic composition and vegetation types in the area. A total of 124 species representing 34 families were recorded. The family Asteraceae is represented by the highest number of species (21 species) followed by the Poaceae (17 species) and the Brassicaceae (10 species) whereas, 15 families including Acanthaceae, Convolvulaceae, Moraceae, Nyctaginaceae and Primulaceae, are represented by a single species each. Chronological analysis of the vegetation in the area revealed the domination of Saharo-Sindian elements in the wild vegetations and of weedy species in the cultivated plots. Therophytes and chamaephytes are the dominating life forms of the vegetation spectra; therophytes represent 49.20% and chamaephytes represent 29.00% of the total species in the study area. Application of TWINISPAN and DECORANA classification and ordination techniques to the data produced seven vegetation groups. Ruderal habitats comprised two small groups A and F dominated by Phragmites australis and Imperata cylindrical (A), Euphorbia peplus and Sisymbrium irio (F), respectively. Two vegetation groups (B and G) have been recognized in the mountains and slopes dominated by Launaea mucronata, Trigonella stellata (B) and Ficus palmate and Fagonia bruguieri (G). Other two groups (C and E) inhabit the desert and mountainous wadies; these are represented by Gymnocarpos decandrus and Ochradenus baccatus (C) and Senecio glaucus subsp. coronopifolius and Rumex equisetiforme (E). On the other hand, one group (D) inhabits the cultivated plots and is represented by Plantago albicans and Rumex vesicarius, the last group also includes species restricted to the sand dune habitat of the Al-Nafud desert north of Hail city and represented by Calligonum polygonoides and Halyxolon salicornicum. The vegetation analysis indicated the invasion of Hail Flora by some foreign weeds such as Solanum nigrum, Lactuca serriola and Amaranthus lividus. The presence of these weeds points out the need to monitor the vegetation change in Hail region, and also other regions of Saudi Arabia, in order to elucidate the human impact on the wild plants diversity as human activities change with the fast development in the kingdom.

The Protein Kinase C Agonist PEP005 (Ingenol 3-Angelate) in the Treatment of Human Cancer: A Balance between Efficacy and Toxicity

The diterpene ester ingenol-3-angelate (referred to as PEP005) is derived from the plant Euphorbia peplus. Crude euphorbia extract causes local toxicity and transient inflammation when applied topically and has been used in the treatment of warts, skin keratoses and skin cancer. PEP005 is a broad range activator of the classical (α, β, γ) and novel (δ, ε, η, θ) protein kinase C isoenzymes. Direct pro-apoptotic effects of this drug have been demonstrated in several malignant cells, including melanoma cell lines and primary human acute myelogenous leukemia cells. At micromolar concentrations required to kill melanoma cells this agent causes PKC-independent secondary necrosis. In contrast, the killing of leukemic cells occurs in the nanomolar range, requires activation of protein kinase C δ (PKCδ) and is specifically associated with translocation of PKCδ from the cytoplasm to the nuclear membrane. However, in addition to this pro-apoptotic effect the agent seems to have immunostimulatory effects, including: (i) increased chemokine release by malignant cells; (ii) a general increase in proliferation and cytokine release by activated T cells, including T cells derived from patients with chemotherapy-induced lymphopenia; (iii) local infiltration of neutrophils after topical application with increased antibody-dependent cytotoxicity; and (iv) development of specific anti-cancer immune responses by CD8+ T cells in animal models. Published studies mainly describe effects from in vitro investigations or after topical application of the agent, and careful evaluation of the toxicity after systemic administration is required before the possible use of this agent in the treatment of malignancies other than skin cancers.

Annuals sprouting adventitiously from the hypocotyl: their compensatory growth and implications for weed management

Habitats, disturbed severely at least once a year, are often dominated by annual plants, which avoid disturbance by means of a short life span and massive production of seeds. Contrary to perennials, they lack pools of reserve meristems on and storage carbon in below-ground organs necessary for vegetative regeneration after disturbance. However, some annuals are able to initiate a bud bank on the hypocotyl after loss of their shoot. In three experiments, we investigated how the timing of disturbance or population origin affects adventitious bud formation on the hypocotyl for regeneration and compensatory growth in some annual weeds. The best regenerative abilities were observed in Kickxia spuria and K. elatine, with 87% and 80% of individuals regenerating, respectively, followed by Microrrhinum minus with almost 70%. Less than 30% of individuals regenerated in Euphorbia peplus and Anagallis arvensis. The time of injury did not affect the regeneration capacity of species for which the timing was examined, nor their consequent compensatory growth. The best compensation for biomass and fruit production was observed in M. minus, albeit two populations differed in this respect. The injured plants were shorter and produced more shoots than intact plants. Mechanical control of weeds capable of forming adventitious buds on hypocotyl by harrowing, brushing, or cutting may not be sufficient in organically farmed lands.

Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis

There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis. Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring. Local skin responses may have suggested active treatment to investigators. Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.

Jatrophane diterpenes from Euphorbia spp. as modulators of multidrug resistance in cancer therapy

A phytochemical investigation of the aerial parts of Euphorbia spp., considered one of the most common elements of Mediterranean landascape, led to the isolation of a large number of bioactive plant metabolites, belonging to the diterpenes family. Above all, over seventy jatrophane, modified jatrophane, segetane, pepluane, and paraliane diterpenoids, fifty of them reported for the first time, were extracted, purified and characterized from Euphorbia dendroides, Euphorbia characias, Euphorbia peplus, Euphorbia paralias and Euphorbia helioscopia. These compounds showed interesting pharmacological activities. In particular, jatrophanes, modified jatrophanes and lathyranes exhibited a potent inhibitory activity against P-glycoprotein (Pgp), a membrane protein that confers cellular ability to resist lethal doses of certain cytotoxic drugs by pumping them to the outside, thus resulting in a reduced cytotoxicity. Among the others, our chemical survey led to isolation of the most powerful inhibitors of daunomycin-efflux activity isolated to date for this class of inhibitors, named euphodendroidin D and pepluanin A. Their efficiency was found to be at least two-fold higher than the conventional modulator cyclosporin A, taken as a reference. In addition, the isolation of a high number of natural structurally-related analogues allowed us to perform Structure Activity Relationship (SAR) studies, without any chemical modification, which gave information on the key pharmacophoric elements of these new class of promising drugs. A further set of diterpene analogues, very recently isolated from sun spurge, E. helioscopia, individually investigated for their Pgp- and BCRP-inhibiting properties, appeared to be specific inhibitors of Pgp since they showed no significant activity against BCRP, thus resembling to the third-generation class of specific MDR inhibitors.

PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: Results of a randomized, double‐blind, vehicle‐controlled, multicentre, phase IIa study

The sap of the plant Euphorbia peplus is a traditional remedy for skin conditions, including actinic keratosis. The active constituent of the sap is ingenol mebutate (ingenol-3-angelate), formerly known as PEP005. This randomized, double-blind, vehicle-controlled, phase IIa study investigated the safety (and secondarily the efficacy) of two applications of ingenol mebutate gel in 58 patients with biopsy-confirmed actinic keratosis. Five preselected lesions were treated with ingenol mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel, on days 1 and 2 (Arm A) or days 1 and 8 (Arm B). There were no significant differences in tolerability or efficacy between Arms A and B. Treatment was well tolerated. The most common local skin responses were dose-related erythema, flaking/scaling/dryness and scabbing/crusting. Efficacy was greatest with ingenol mebutate gel, 0.05%, which resulted in complete clinical clearance of 71% of treated lesions (P < 0.0001 vs vehicle gel). In addition, 67% of patients treated with ingenol mebutate gel, 0.05% had clinical clearance of at least four of five treated lesions (P = 0.0185 vs vehicle gel). Ingenol mebutate gel is being developed as a short-course topical therapy for actinic keratosis and non-melanoma skin cancer.

Activity of Some Plant Extracts Against Multi-Drug Resistant Human Pathogens

Plants used for traditional medicine contain a wide range of substances which can be used to treat various infectious diseases. Hence, antibacterial activities of ethanolic extracts of 19 plant species were studied against multi-drug resistant clinical isolates using agar well diffusion method. Extracts of Liquidambar orientalis, Vitis vinifera,?? ?????????????????????? ????????????????????, Punica granatum, Cornus sanguinea, Euphorbia peplus, Ecballium elaterium, Inula viscosa and Liquidambar orientalis showed broad-spectrum antibacterial activity with inhibition zones ranging from 8 to 26 mm. The most resistant organisms were Escherichia coli (E. coli) (Ampicillin-, amoxycillin- and sulfamethoxazole-resistant), Stenotrophomonas maltophilia (S. maltophilia) (Amoxycillin- and nalidixic acid-resistant) and Klebsiella pneumoniae (K. pneumoniae) (Ampicillin-, amoxycillin- and aztreonam-resistant), and the most susceptible species were Staphylococcus aureus (S. aureus) (Penicillin G- and oxacillin-resistant), Streptococcus pyogenes (S. pyogenes) (Penicillin G-, erythromycin- and clindamycin-resistant) and Pseudomonas aeruginosa (P. aeruginosa) (Sulfamethoxazole- and novobiocin-resistant), respectively. Minimum Inhibitory Concentrations (MIC) of crude extracts were determined for the seven highly active plants showing activity against methicillin resistant S. aureus (MRSA), E. coli, P. aeruginosa, S. pneumoniae and the reference bacteria (E. coli ATCC 11229 and Kocuria rhizophila ATCC 9341 NA). MICs of active extracts ranged from 8 to 14.2 mg/mL against one or other test bacteria.

Rare, endangered and protected plant species of synanthropic flora of the Kampinos National Park (Central Poland)

The aim of this paper is to present the rare, endangered and protected plant taxons growing in the synanthropic habitats of the Kampinos National Park. The research was conducted on agricultural fields (still maintained) and in ruderal habitats in over a dozen abandoned villages in the Kampinos Forest. Among species considered to be endangered are: Agrostemma githago, Asperugo procumbens, Atriplex rosea, Camelina microcarpa, Centunculus minimus, Filago arvensis, Fumaria officinalis, Gagea pratensis, Holosteum umbellatum, Myosurus minimus, Pulicaria vulgaris and Radiola linoides. To the category of rare plant species belong: Anthemis ruthenica, Arabis glabra, Arnoseris minima, Chenopodium ficifolium, Ch. pedunculare and Euphorbia peplus. Species protected by law, found during the study, include: Epipactis helleborine, Jovibarba sobolifera and Helichrysum arenarium. According to our observations some of the segetal plant species, for example Filago arvensis, Centaurea cyanus and Papaver rhoeas, have tendencies to habitat change. These plant species move from agricultural fields to ruderal habitats. In the Kampinos Forest’s synanthropic habitats the species from seminatural non-forest habitats such as Sedum sexangulare, Eryngium planum, Cerastium semidecandrum, find their place.

Effects of protein kinase C modulation by PEP005, a novel ingenol angelate, on mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling in cancer cells

PEP005 (ingenol-3-angelate) is a novel anticancer agent extracted from Euphorbia peplus that was previously shown to modulate protein kinase C (PKC), resulting in antiproliferative and proapoptotic effects in several human cancer cell lines. In Colo205 colon cancer cells, exposure to PEP005 induced a time- and concentration-dependent decrease of cells in S phase of cell cycle and apoptosis. In Colo205 cells exposed to PEP005, a variety of signaling pathways were activated as shown by increased phosphorylation of PKCdelta, Raf1, extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (MAPK), c-Jun NH(2)-terminal kinase, p38 MAPK, and PTEN. PEP005-induced activation of PKCdelta was associated with its translocation from the cytosol to the nucleus and other cellular membranes. Interestingly, PEP005 treatment also resulted in reduced expression of PKCalpha and reduced levels of phosphorylated active form of AKT/protein kinase B. These data suggest that PEP005-induced activation of PKCdelta and reduced expression of PKCalpha resulted in apoptosis by mechanisms mediated by activation of Ras/Raf/MAPK and inhibition of the phosphatidylinositol 3-kinase/AKT signaling pathways. This study supports ongoing efforts targeting PKC isoforms in cancer therapy with PEP005 alone and in combination with other cytotoxic agents.

Proceedings of the First International Conference on PEP005

The sap of Euphorbia peplus, commonly know as 'petty spurge', 'radium weed' or 'milkweed' has been used for centuries as a traditional treatment for skin conditions, including warts, corns and cancers of the skin. Documentation of its use by medical professionals to treat basal cell carcinoma (BCC) dates from the early 19 century. Individuals who participated in a 1988 survey of home treatments for cancer indicated the sap of E. peplus was an effective cure for actinic lesions leading the investigators to suggest that this potential utility should be further explored in controlled clinical trials. The fractionation of the sap E. peplus using solvents of varying polarity yielded several macrocyclic diterpenes, many of which were found to have cytotoxic activity or the ability to influence cellular differentiation. Ultimately, ingenol 3-angelate (I3A) of PEP005, emerged as a promising potential new anti-cancer treatment. Here we report the proceedings from the First International Conference on PEP005, covering the exciting potential of PEP005 as the therapeutic agent for the treatment of skin cancer, leukemia and bladder cancer.

Discovery and Biological Evaluation of the Novel Naturally Occurring Diterpene Pepluanone as Antiinflammatory Agent

From the whole plant of Euphorbia peplus L., a new diterpene based on a rare pepluane skeleton, named pepluanone (1), was isolated together with a known pepluane diterpene (2). The stereostructure of pepluanone was determined on the basis of an extensive NMR study, MS data, and chemical reaction. The ability of these compounds to act as antiinflammatory agents has been evaluated for the first time by in vivo tests on carrageenin-induced rat paw edema, an experimental model of acute inflammation. Comparison of the bioactivity of pepluanone and compound 2 in terms of chemical structure, evidenced the high efficiency of pepluanone and the absence of appreciable activity for compound 2, thus giving a first insight into the structure-activity relationship. Further in vitro experiments performed on pepluanone let us hypothesize that its activity could be explained in reducing the production of nitric oxide, prostaglandin E(2), and TNF-alpha by inhibiting the expression of inducible nitric oxide synthase, cyclooxygenase-2, and TNF-alpha mRNA through the down-regulation of NF-kappaB binding activity.

PEP005, a selective small-molecule activator of protein kinase C, has potent antileukemic activity mediated via the delta isoform of PKC

AbstractIngenol 3-angelate (PEP005) is a selective small molecule activator of protein kinase C (PKC) extracted from the plant Euphorbia peplus, whose sap has been used as a traditional medicine for the treatment of skin conditions including warts and cancer. We report here that PEP005 also has potent antileukemic effects, inducing apoptosis in myeloid leukemia cell lines and primary acute myeloid leukemia (AML) cells at nanomolar concentrations. Of importance, PEP005 did not induce apoptosis in normal CD34+ cord blood myeloblasts at up to 2-log concentrations higher than those required to induce cell death in primary AML cells. The effects of PEP005 were PKC dependent, and PEP005 efficacy correlated with expression of PKC-delta. The delta isoform of PKC plays a key role in apoptosis and is therefore a rational potential target for antileukemic therapies. Transfection of KG1a leukemia cells, which did not express PKC-delta or respond to PEP005, with enhanced green fluorescent protein (EGFP)-PKC-delta restored sensitivity to induction of apoptosis by PEP005. Our data therefore suggest that activation of PKC-delta provides a novel approach for treatment of acute myeloid leukemia and that screening for PKC-delta expression may identify patients for potential responsiveness to PEP005. (Blood. 2005;106:1362-1368)

Ingenol 3-angelate induces dual modes of cell death and differentially regulates tumor necrosis factor–related apoptosis-inducing ligand–induced apoptosis in melanoma cells

Ingenol 3-angelate (PEP005), one of the active ingredients in an extract from Euphorbia peplus, was shown in preclinical studies to have activity against human melanoma xenografts in nude mice. In the present study, we have tested its ability to induce the apoptosis of melanoma cells in vitro in the absence or presence of tumor necrosis factor-related apoptosis inducing ligand (TRAIL). The results showed that at relatively high concentrations (100 microg/mL), PEP005 killed melanoma cells mainly by induction of necrosis. In 20% of cell lines, evidence of apoptosis was observed. Apoptosis was caspase-dependent and associated with changes in mitochondrial membrane potential that were not inhibitable by overexpression of Bcl-2 or inhibition of caspases but were blocked by inhibition of protein kinase C (PKC). Low concentrations (1 or 10 microg/mL) of PEP005 either increased or decreased TRAIL-induced apoptosis in a cell line-dependent manner. These changes in TRAIL-induced apoptosis seemed to be due to activation of PKC and varying levels of PKC isoenzymes in different melanoma cell lines. PEP005-mediated enhancement of apoptosis seemed to be associated with low expression of the PKCepsilon isoform. These results indicate that PEP005 may enhance or inhibit sensitivity of melanoma to treatments associated with TRAIL-induced apoptosis depending on the PKC isoform content of melanoma cells.

Jatrophane Diterpenes as Modulators of Multidrug Resistance. Advances of Structure—Activity Relationships and Discovery of the Potent Lead Pepluanin A.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Characterization of the interaction of ingenol 3-angelate with protein kinase C.

Ingenol 3-angelate (I3A) is one of the active ingredients in Euphorbia peplus, which has been used in traditional medicine. Here, we report the initial characterization of I3A as a protein kinase C (PKC) ligand. I3A bound to PKC-alpha in the presence of phosphatidylserine with high affinity; however, under these assay conditions, little PKC isoform selectivity was observed. PKC isoforms did show different sensitivity and selectivity for down-regulation by I3A and phorbol 12-myristate 13-acetate (PMA) in WEHI-231, HOP-92, and Colo-205 cells. In all of the three cell types, I3A inhibited cell proliferation with somewhat lower potency than did PMA. In intact CHO-K1 cells, I3A was able to translocate different green fluorescent protein-tagged PKC isoforms, visualized by confocal microscopy, with equal or higher potency than PMA. PKC-delta in particular showed a different pattern of translocation in response to I3A and PMA. I3A induced a higher level of secretion of the inflammatory cytokine interleukin 6 compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction. I3A was unable to cause the same extent of association of the C1b domain of PKC-delta with lipids, compared with PMA or the physiological regulator diacylglycerol, and was able to partially block the association induced by these agents, measured by surface plasmon resonance. The in vitro kinase activity of PKC-alpha induced by I3A was lower than that induced by PMA. The novel pattern of behavior of I3A makes it of great interest for further evaluation.

Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death.

Options for skin cancer treatment currently include surgery, radiotherapy, topical chemotherapy, cryosurgery, curettage, and electrodessication. Although effective, surgery is costly and unsuitable for certain patients. Radiotherapy can leave a poor cosmetic effect, and current chemotherapy is limited by low cure rates and extended treatment schedules. Here, we describe the preclinical activity of a novel topical chemotherapeutic agent for the treatment of skin cancer, 3-ingenyl angelate (PEP005), a hydrophobic diterpene ester isolated from the plant Euphorbia peplus. Three daily topical applications of 42 nmol (18 micro g) of PEP005 cured a series of s.c. mouse tumors (B16 melanoma, LK2 UV-induced squamous cell carcinoma, and Lewis lung carcinoma; n = >14 tumors/group) and human tumors (DO4 melanoma, HeLa cervical carcinoma, and PC3 and DU145 prostate carcinoma; n = >4 tumors/group) previously established (5-10 mm(3)) on C57BL/6 or Foxn1(nu) mice. The treatment produced a mild, short-term erythema and eschar formation but, ultimately, resulted in excellent skin cosmesis. The LD(90) for PEP005 for a panel of tumor cell lines was 180-220 micro M. Electron microscopy showed that treatment with PEP005 both in vitro (230 micro M) and in vivo (42 nmol) rapidly caused swelling of mitochondria and cell death by primary necrosis. (51)Cr release, uptake of propidium iodide, and staining with the mitochondria dye JC1, revealed that PEP005 (230 micro M) treatment of tumor cells in vitro resulted in a rapid plasma membrane perturbation and loss of mitochondrial membrane potential. PEP005 thus emerges as a new topical anti-skin cancer agent that has a novel mode of action involving plasma membrane and mitochondrial disruption and primary necrosis, ultimately resulting in an excellent cosmetic outcome.

Pectin distribution pattern in the apertural intine of Euphorbia peplus L. (Euphorbiaceae) pollen

The apertural inner layer (intine) of Euphorbia L. pollen grains has a characteristic but original structure that has paired thickenings, one on either side of the colpus. To determine the nature and role of this intine layer, pollen grains of Euphorbia peplus L. were germinated in vivo and in vitro. The germination process involves wall changes that facilitate formation of the pollen tube and its subsequent growth. In the thickenings of the intine of E. peplus, the unesterified pectin epitopes are more densely localised in the inner part of the middle intine. No such epitopes are located in the intine portion adjacent to the plasma membrane (cellulosic endintine). Unesterified pectin epitopes are also localised in the outer part of the intine but are restricted to the centre of the aperture, around and in the pore. The de-esterification of pectins is very advanced at the time of dehiscence and pollen germination. The stratification of the aperture intine may take the following pathway at the time of germination: the thin outer zone of the intine in the pore region becomes disorganised and undergoes dissolution with liberation of unesterified and esterified pectins; the middle intine thickenings undergo an important elastic modification, but without liberation of unesterified pectins; the cellulosic inner intine is the progenitor of the pollen tube wall. This special intine of E. peplus is an adaptation to the hydration process preceding germination, increasing intine and pollen grain wall elasticity.

Nonpolar components of the latex of Euphorbia peplus.

The less polar fractions of the latex of Euphorbia peplus were found to contain obtusifoliol, cycloartenol, 24-methylenecycloartanol, lanosterol, and 24-methylenelanosterol in the free and esterified triterpene alcohol fractions; 9-cis-tricosene as the major component of the hydrocarbon fraction; and a new acyclic triterpene alcohol named peplusol (1). The structure of 1 was determined as the R-isomer of (all-E)-2-(5,9-dimethyl-1-methylene-4,8-decadienyl)-5,9, 13-trimethyl-4,8,12-tetradecatrien-1-ol by spectral and chemical methods.

Jatrophane diterpenoids from Euphorbia peplus.

From the pro-inflammatory active extract of Euphorbia peplus, a new diterpene polyester (1) based on the jatrophane skeleton was isolated together with the known compounds 2-5. The irritant activities of some jatrophane diterpenes (2, 3 and 6-9) were also investigated: only compound 2 was found to exert a weak pro-inflammatory activity on mouse ear.

Isolation and structure revision of pepluane diterpenoids from euphorbia peplus

A new pepluane diterpene polyester (2) was isolated from a CH2Cl2 extract of the whole, undried plant of Euphorbia peplus, together with the known compound 1. The structures were established by high-field spectroscopic methods, including 2D NMR techniques, and by X-ray crystallography, and the stereostructure of the first member of the pepluane diterpenoids (1) was revised.