Sensitivity of the Indo-Pacific coral Acropora millepora to aromatic hydrocarbons.

The risks posed by petroleum spills to coral reefs are poorly understood and quantifying acute toxicity thresholds for aromatic hydrocarbons to reef-building corals is required to assess their sensitivity relative to other taxa. In this study, we exposed Acropora millepora to toluene, naphthalene and 1-methylnaphthalene (1-MN) in a flow-through system and assessed survivorship and sublethal responses including growth, colour and the photosynthetic performance of symbionts. Median 50% lethal concentrations (LC50s) decreased over the 7-d exposure period, reaching asymptotic values of 22,921, 5,268, 1167 µg L-1 for toluene, naphthalene and 1-MN, respectively. Corresponding toxicokinetic parameters (εLC50) defining the time progression of toxicity were 0.830, 0.692, and 0.256 d-1, respectively. Latent effects after an additional 7-d recovery in uncontaminated seawater were not observed. Effect concentrations (EC50s) for 50% growth inhibition were 1.9- to 3.6-fold lower than the LC50s for each aromatic hydrocarbon. There were no observed effects of aromatic hydrocarbon exposure on colour score (a proxy for bleaching) or photosynthetic efficiency. Acute and chronic critical target lipid body burdens (CTLBBs) of 70.3 ± 16.3 and 13.6 ± 18.4 µmol g-1 octanol (± standard error) were calculated for survival and growth inhibition based on 7-d LC50 and EC10 values, respectively. These species-specific constants indicate adult A. millepora is more sensitive than other corals reported so far but is of average sensitivity in comparison with other aquatic taxa in the target lipid model database. These results advance our understanding of acute hazards of petroleum contaminants to key habitat-building tropical coral reef species.

Insights into toxicity of polychlorinated naphthalenes to multiple human endocrine receptors: Mechanism and health risk analysis.

This study explored the combined disruption mechanism of polychlorinated naphthalenes (PCNs) on the three key receptors (estrogen receptor, thyroid receptor, and adrenoceptor) of the human endocrine system. The intensity of PCN endocrine disruption on these receptors was first determined using a molecular docking method. A comprehensive index of PCN endocrine disruption to human was quantified by analytic hierarchy process and fuzzy analysis. The mode of action between PCNs and the receptors was further identified to screen the molecular characteristics influencing PCN endocrine disruption through molecular docking and fractional factorial design. Quantitative structure-activity relationship (QSAR) models were established to investigate the toxic mechanism due to PCN endocrine disruption. The results showed that the lowest occupied orbital energy (ELUMO) was the most important factor contributing to the toxicity of PCNs on the endocrine receptors, followed by the orbital energy difference (ΔE) and positive Millikan charge (q+). Furthermore, the strategies were formulated through adjusting the nutritious diet to reduce health risk for the workers in PCN contaminated sites and the effectiveness and feasibility were assessed by molecular dynamic simulation. The simulation results indicated that the human health risk caused by PCN endocrine disruption could be effectively decreased by nutritional supplementation. The binding ability between PCNs and endocrine receptors significantly declined (up to -16.45%) with the supplementation of vitamins (A, B2, B12, C, and E) and carotene. This study provided the new insights to reveal the toxic mechanism of PCNs on human endocrine systems and the recommendations on nutritional supplements for health risk reduction. The methodology and findings could serve as valuable references for screening of potential endocrine disruptors and developing appropriate strategies for PCN or other persistent organic pollution control and health risk management.

Intoxication by a synthetic cannabinoid (JWH-018) causes cognitive and psychomotor impairment in recreational cannabis users.

BACKGROUND: Smoking mixtures containing synthetic cannabinoids (SCs) have become very popular over the last years but pose a serious risk for public health. Limited knowledge is, however, available regarding the acute effects of SCs on cognition and psychomotor performance. Earlier we demonstrated signs of impairment in healthy volunteers after administering one of the first SCs, JWH-018, even though subjective intoxication was low. In the current study, we aimed to investigate the acute effects of JWH-018 on several cognitive and psychomotor tasks in participants who are demonstrating representative levels of acute intoxication. METHODS: 24 healthy cannabis-experienced participants took part in this placebo-controlled, cross-over study. Participants inhaled the vapor of 75 µg JWH-018/kg body weight and were given a booster dose if needed to induce a minimum level of subjective high. They were subsequently monitored for 4 h, during which psychomotor and cognitive performance, vital signs, and subjective experience were measured, and serum concentrations were determined. RESULTS: Maximum subjective high (average 64%) was reached 30 min after administration of JWH-018, while the maximum blood concentration was shown after 5 min (8 ng/mL). JWH-018 impaired motor coordination (CTT), attention (DAT and SST), memory (SMT), it lowered speed-accuracy efficiency (MFFT) and slowed down response speed (DAT). CONCLUSION: In accordance with our previous studies, we demonstrated acute psychomotor and cognitive effects of a relatively low dose of JWH-018.

Species sensitivity assessment of five Atlantic scleractinian coral species to 1-methylnaphthalene.

Coral reefs are keystone coastal ecosystems that are at risk of exposure to petroleum from a range of sources, and are one of the highest valued natural resources for protection in Net Environmental Benefit Analysis (NEBA) in oil spill response. Previous research evaluating dissolved hydrocarbon impacts to corals reflected no clear characterization of sensitivity, representing an important knowledge gap in oil spill preparedness related to the potential impact of oil spills to the coral animal and its photosymbiont zooxanthellae. This research addresses this gap, using a standardized toxicity protocol to evaluate effects of a dissolved reference hydrocarbon on scleractinian corals. The relative sensitivity of five Atlantic scleractinian coral species to hydrocarbon exposure was assessed with 48-h assays using the reference polycyclic aromatic hydrocarbon 1-methylnaphthalene, based on physical coral condition, mortality, and photosynthetic efficiency. The threatened staghorn coral Acropora cervicornis was found to be the most sensitive to 1-methylnaphthalene exposure. Overall, the acute and subacute endpoints indicated that the tested coral species were comparatively more resilient to hydrocarbon exposure than other marine species. These results provide a framework for the prediction of oil spill impacts and impact thresholds on the coral animal and related habitats, essential for informing oil spill response in coastal tropical environments.

Memory deficits induced by chronic cannabinoid exposure are prevented by adenosine A2AR receptor antagonism.

Patients under cannabis-based therapies are usually chronically exposed to cannabinoids. Chronic treatment with a cannabinoid receptor agonist, WIN 55,212-2, affects brain metabolism and modifies functional connectivity between brain areas responsible for memory and learning. Therefore, it is of uttermost importance to discover strategies to mitigate the negative side-effects of cannabinoid-based therapies. Previously, we showed that a single treatment with the synthetic cannabinoid WIN 55,212-2 disrupts recognition memory, an effect mediated by cannabinoid receptor 1 (CB1R) and cancelled by concomitant administration of adenosine A2A receptor (A2AR) antagonists. We herein evaluate if memory deficits induced by chronic exposure to WIN 55,212-2 can also be reverted by A2AR antagonism, and assessed the synaptic mechanisms that could be involved in that reversal. We show that chronic administration of KW-6002 (istradefylline) (3 mg/kg/28days) reverts memory deficits (evaluated through the Novel Object Recognition Test) induced by chronic cannabinoid exposure (WIN 55,212-2, 1 mg/kg/28 days). Long Term Potentiation (LTP) of synaptic potentials recorded from the CA1 area of the hippocampus was impaired by WIN 55,212-2 (300 nM), an effect partially rescued by the A2AR antagonist, SCH 58261 (100 nM). Chronic administration of KW-6002 or WIN 55,212-2 did not affect A2AR or CB1R binding in the hippocampus and in the prefrontal cortex. These results, showing that A2AR antagonism can still revert memory deficits after chronic administration of a cannabinoid, an effect that involves mitigation of synaptic plasticity impairment, strongly indicate that adenosine A2ARs are appropriate targets to tackle side-effects of putative therapies involving the activation of cannabinoid receptors.

Total Synthesis and Structure Revision of Palmarumycin B6.

Palmarumycin B6 and its regioisomer were synthesized via 7- and 13-step routes using 2-chlorophenol and 4-chlorophenyl methyl ether as the starting materials in overall yields of 2.7% and 12%, respectively. Their structures were characterized by 1H and 13C NMR, HRESIMS, and X-ray diffraction data. The structure of palmarumycin B6 was revised as 6-chloropalmarumycin CP17. The bioassay results showed that the larvicidal activity of palmarumycin B6 with an LC50 value of 32.7 µM was significantly higher than that of its 8-chloro isomer, with an LC50 value of 227.3 µM.

Synthesis and characterization of Zr(IV) doped immobilized cross-linked chitosan/perlite composite for acid orange II adsorption.

To enhance the adsorption capacity of chitosan for acid orange II (AOII) adsorption, a novel adsorbent, zirconium(IV) doped immobilized cross-linked chitosan/perlite (Zr(IV)-CS-PT) composite was synthesized and characterized. Batch studies were conducted to analyze the effect of different parameters on AOII adsorption, such as Zr (IV) loading amount, pH, adsorbent dosage and temperature. Also, kinetic data revealed that AOII adsorption was well described by pseudo-second order kinetic model. Langmuir adsorption isotherm model was best described the isotherm data and maximum adsorption capacity was found 476.2 mg/g at natural pH. The thermodynamic data showed that the AOII adsorption occurred spontaneously and endothermic nature. Desorption and recycle experiments showed that after six cycle the adsorption efficiency was decreased from 95.6% to 90.1%, which shows the Zr(IV)-CS-PT is a reusable, cost-effective and high adsorption capacity adsorbent.

Evaluation system for arrhythmogenic potential of drugs using human-induced pluripotent stem cell-derived cardiomyocytes and gene expression analysis.

In recent years, human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) have been widely used to develop evaluation systems for drug cardiotoxicity, including the arrhythmia caused by QT prolongation. To accurately assess the arrhythmogenic potential of drugs, associated with QT prolongation, we developed an evaluation system using hiPS-CMs and gene expression analysis. hiPS-CMs were treated with 8 arrhythmogenic and 17 non-arrhythmogenic drugs at several concentrations for 24 hr to comprehensively analyze gene expression. The results showed that 19 genes were upregulated in the arrhythmogenic drug-treated cells compared with their expression levels in the non-treated and non-arrhythmogenic drug-treated cells. The arrhythmogenic risks of the drugs were evaluated by scoring gene expression levels. The results indicated that arrhythmogenic risks could be inferred when cells were treated at a concentration 100 times higher than the maximum blood concentration of the drug. Thus, we succeeded in developing a system for evaluation of the arrhythmogenic potential of drugs using gene expression analysis.

Relative sensitivity of Arctic species to physically and chemically dispersed oil determined from three hydrocarbon measures of aquatic toxicity.

The risks to Arctic species from oil releases is a global concern, but their sensitivity to chemically dispersed oil has not been assessed using a curated and standardized dataset from spiked declining tests. Species sensitivity to dispersed oil was determined by their position within species sensitivity distributions (SSDs) using three measures of hydrocarbon toxicity: total petroleum hydrocarbons (TPH), polycyclic aromatic hydrocarbon (PAHs), and naphthalenes. Comparisons of SSDs with Arctic/sub-Arctic versus non-Arctic species, and across SSDs of compositionally similar oils, showed that Arctic and non-Arctic species have comparable sensitivities even with the variability introduced by combining data across studies and oils. Regardless of hydrocarbon measure, hazard concentrations across SSDs were protective of sensitive Arctic species. While the sensitivities of Arctic species to oil exposures resemble those of commonly tested species, PAH-based toxicity data are needed for a greater species diversity including sensitive Arctic species.

Species-specific metabolism of naphthalene and phenanthrene in 3 species of marine teleosts exposed to Deepwater Horizon crude oil.

The 2 most abundant polycyclic aromatic hydrocarbons (PAHs) measured in Deepwater Horizon crude oil, naphthalene and phenanthrene, and their associated homologs have both been shown to be acutely toxic in fish. Although fish have a relatively high metabolic capacity for PAHs, hydroxylated PAH (OH-PAH) derivatives formed during the initial metabolic response can negatively impact the health of fish. Species-specific metabolism of naphthalene and phenanthrene was evaluated in 3 marine teleosts, red drum (Scianops ocellatus), Florida pompano (Trachinotus carolinus), and southern flounder (Paralichthys lethostigma). Fish were exposed to Deepwater Horizon crude oil by intraperitoneal injections at time 0 and 48 h, with bile sampling events at 24 and 72 h post injection. The data suggested metabolic induction in Florida pompano and red drum, whereas southern flounder may have demonstrated metabolic fatigue. By 24 h post injection, overall profiles of red drum and southern flounder were dominated by hydroxylated phenanthrene metabolites; conversely, the Florida pompano profiles were dominated by monohydroxylated naphthalenes. In addition, Florida pompano had faster overall relative biotransformation rates, suggesting their potential decreased susceptibility to adverse effects. Red drum and southern flounder had much lower relative biotransformation rates, indicating their probable susceptibility to adverse outcomes after naphthalene and phenanthrene exposures. To our knowledge, the present study is the first to investigate monohydroxylated PAHs in fish exposed to Deepwater Horizon oil. Environ Toxicol Chem 2017;36:3168-3176. © 2017 © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Use of selenium to alleviate naphthalene induced oxidative stress in Trifolium repens L.

Polycyclic aromatic hydrocarbons (PAHs) are among the most dangerous of environmental contaminants, due to their toxicity, carcinogenicity and mutagenicity. This study investigated the use of selenium (Se) to protect plants from the toxic effects of naphthalene (NPH). Exposing Trifolium repens L. (white clover) to a high concentration of NPH (soil spiked to 500mgkg-1) for 60 d significantly decreased biomass, CO2 assimilation rate (Pn), stomatal conductance (Gs) and intercellular CO2 concentration (Ci), while inducing production of H2O2 and malondialdehyde (MDA). Application of Se (soil spiked to 0.5mgkg-1) to plants exposed to NPH clearly protected the plants; biomass, Pn, Gs and Ci were significantly higher and contents of MDA and H2O2 decreased. The protection provided to Trifolium repens L. by Se is attributed primarily to an increase in photosynthesis and a decrease in oxidative stress. This study demonstrates that a low concentration of Se protects plants against oxidative stress induced by NPH and can provide a means for improving phytoremediation in PAHs contaminated soils.

Developmental toxicity in flounder embryos exposed to crude oils derived from different geographical regions.

Crude oils from distinct geographical regions have distinct chemical compositions, and, as a result, their toxicity may be different. However, developmental toxicity of crude oils derived from different geographical regions has not been extensively characterized. In this study, flounder embryos were separately exposed to effluents contaminated by three crude oils including: Basrah Light (BLO), Pyrenees (PCO), and Sakhalin Vityaz (SVO), in addition to a processed fuel oil (MFO-380), to measure developmental toxicity and for gene expressions. Each oil possessed a distinct chemical composition. Edema defect was highest in embryos exposed to PCO and MFO-380 that both have a greater fraction of three-ring PAHs (33% and 22%, respectively) compared to BLO and SVO. Observed caudal fin defects were higher in embryos exposed to SVO and MFO-380, which are both dominated by naphthalenes (81% and 52%, respectively). CYP1A gene expressions were also highest in embryos exposed to SVO and MFO-380. Higher incidence of cardiotoxicity and lower nkx 2.5 expression were detected in embryos exposed to PCO. Unique gene expression profiles were observed in embryos exposed to crude oils with distinct compositions. This study demonstrates that crude oils of different geographical origins with different compositional characteristics induce developmental toxicity to different degrees.

New naphthalene derivatives and isoquinoline alkaloids from Ancistrocladus cochinchinensis with their anti-proliferative activity on human cancer cells.

Five new compounds, named ancistronaphtosides A and B (1 and 2), anciscochine (3), anciscochine 6-O-ß-d-glucopyranoside (4), and 4'-methoxy-5-epi-ancistecrorine A1 (5), together with tortoside A (6) and 4-hydroxy-2-methoxyphenyl-6-O-syringoyl-ß-d-glucopyranoside (7) were isolated from the methanolic extract of Ancistrocladus cochinchinensis. Their chemical structures were established using HR-ESI-MS, NMR spectroscopic, and chiroptical methods. Compound 5 significantly exhibited anti-proliferation against HL-60, LU-1, and SK-MEL-2 cells with IC50 values of 5.0±1.2, 6.5±1.6, and 6.8±2.0µg/mL, respectively.

Acute ecotoxicology of natural oil and gas condensate to coral reef larvae.

Risks posed by oil spills to coral reefs are difficult to evaluate, partially due to the absence of studies that adequately assess toxicity to relevant coral reef species. Here we experimentally tested the acute toxicity of condensate, representing a fraction of light crude oil, to coral (Acropora tenuis) and sponge (Rhopaloeides odorabile) larvae. The metamorphosis of coral larvae was inhibited at total petroleum aromatic hydrocarbon (TPAH) concentrations of water accommodated fractions (WAF) as low as 103 µg l(-1), similar to concentrations detected in seawater following large spills. The sensitivity of coral larvae increased by 40% when co-exposed to UV light that they might encounter in shallow reefal systems. Condensate WAF was more toxic to coral larvae than predicted by summing the toxicity of its main components (benzene, toluene, p-xylene and napthalene). In contrast, the sensitivity of sponge larvae to condensate WAF (>10,000 µg l(-1) TPAH) was far less than coral in the presence and absence of UV, but similar to that of other marine invertebrates. While these results highlight the relative sensitivity of coral larvae to oil, further research is needed to better understand and predict the impacts and risks posed by hydrocarbons to tropical reef systems.

Metabolomics coupled with pattern recognition and pathway analysis on potential biomarkers in liver injury and hepatoprotective effects of yinchenhao.

Metabolomics can provide an opportunity to develop the systematic analysis of the metabolites in biological samples and has been increasingly applied to discovering and identifying biomarkers and perturbed pathways. It enables us to better understand the metabolic pathways which can clarify the mechanism of traditional Chinese medicines (TCM). Yinchenhao (YCH, Artemisia annua L), a famous TCM plant, has been used clinically for more than a thousand years to relieve liver diseases in Asia, and its mechanisms are not still completely clear. Here, metabolomic techniques may provide additional insight, and our investigation was designed to assess the effects and possible mechanisms of YCH on α-naphthylisothiocyanate (ANIT)-induced liver injury. Metabolite profiling was performed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) combined with pathway analysis and pattern recognition approaches including independent component analysis (ICA) and partial least squares-discriminant analysis (PLS-DA). Biochemistry test was also performed for the liver tissue and plasma samples. The changes in metabolic profiling were restored to their baseline values after YCH treatment according to the ICA score plots. Of note, YCH has a potential pharmacological effect through regulating multiple perturbed pathways to normal state, correlating well to the assessment of biochemistry test. Five different potential biomarkers in the positive mode contributing to the treatment of YCH were discovered. Pathway analysis showed that these metabolites were associated with perturbations in pyrimidine metabolism, primary bile acid biosynthesis, and propanoate metabolism, which may be helpful to further understand the action mechanisms of YCH. It showed that changed biomarkers and pathways may provide evidence to insight into drug action mechanisms and drug discovery.

CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and memory deficits following treatment with JWH-081, a new component of spice/K2 preparations.

Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as "Spice" or "K2" to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of "Spice/K2", including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of JWH-081 on pCaMKIV, pCREB, and pERK1/2 signaling events followed by long-term potentiation (LTP), hippocampal-dependent learning and memory tasks using CB1 receptor wild-type (WT) and knockout (KO) mice. Acute administration of JWH-081 impaired CaMKIV phosphorylation in a dose-dependent manner, whereas inhibition of CREB phosphorylation in CB1 receptor WT mice was observed only at higher dose of JWH-081 (1.25 mg/kg). JWH-081 at higher dose impaired CaMKIV and CREB phosphorylation in a time-dependent manner in CB1 receptor WT mice but not in KO mice and failed to alter ERK1/2 phosphorylation. In addition, SR treated or CB1 receptor KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio compared with vehicle or WT littermates. In hippocampal slices, JWH-081 impaired LTP in CB1 receptor WT but not in KO littermates. Furthermore, JWH-081 at higher dose impaired object recognition, spontaneous alternation and spatial memory on the Y-maze in CB1 receptor WT mice but not in KO mice. Collectively our findings suggest that deleterious effects of JWH-081 on hippocampal function involves CB1 receptor mediated impairments in CaMKIV and CREB phosphorylation, LTP, learning and memory in mice.

Can crude oil toxicity on phytoplankton be predicted based on toxicity data on benzo(a)pyrene and naphthalene?

Polycyclic aromatic hydrocarbons (PAHs), which are major components of crude oil, are responsible in large part for the toxicity of crude oil to phytoplankton. This study addressed the following question. Can reliable predictions of the aquatic toxicity of crude oil, a multi-component mixture, be described from toxicity data on individual PAH compounds? Naphthalene, the most abundant PAH compound, and benzo(a)pyrene, a highly toxic PAH compound, were selected as model compounds to quantify toxicity of crude oil on two phytoplankton species, Ditylum brightwellii and Heterocapsa triquetra, by analyzing the effects of different concentrations of these PAHs on growth rate. EC50 values suggested that the diatom D. brightwellii was more vulnerable to both toxicants than the dinoflagellate H. triquetra. However, a previous study, which investigated the impact of crude oil on the same two species, had opposite results. The differences in response from these phytoplankton species to naphthalene and benzo(a)pyrene toxicity compared to their response to crude oil suggest that they may not be solely used as surrogates to assess crude oil toxicity on phytoplankton.

Protective effect of Coleus aromaticus Benth (Lamiaceae) against naphthalene-induced hepatotoxicity.

OBJECTIVE: To investigate protective effect of Coleus aromaticus leaf extract against naphthalene induced hepatotoxicity in rats. METHODS: Eighteen male rats were divided into three groups. Group I rats were treated as control. Group II rats were intraperitoneally administered with naphthalene (435 mg/kg b.wt) dissolved in corn oil once a day for a period of 30 days. Group III rats were treated with leaf extract (100 mg/kg b.wt) dissolved in 0.9% saline and naphthalene (435 mg/kg b.wt) dissolved in corn oil once a day for a period of 30 days. RESULTS: Significant protective effect was observed against naphthalene induced liver damage, which appeared evident from the response levels of marker enzymes (aspartate transaminase, alanine transaminase, acid phosphatase, alkaline phosphatase and lactate dehydrogenase). The biochemical components viz. triglycerides, free fatty acids, cholesterol acyl transferase, high-density lipoprotein, low-density lipoprotein, cholesterol and bilirubin were found to be increased in liver and serum of naphthalene stressed rats when compared to control. CONCLUSION: Treatment of naphthalene intoxicated rats with plant extract reversed these distorted parameters to near normal levels. Liver histology showed supportive evidence regarding the protective nature of plant extract against fatty changes induced by naphthalene. The present study provides a scientific rationale for using C. aromaticus in the management of liver disorders.

Antimalarial activity of nepodin isolated from Rumex crispus.

The purpose of this study is to define the antimalarial activity of Rumex crispus. To identify an active compound that is isolated from R. crispus, bioassay-based chromatographic fractionation and purification is carried out from 70 % ethanol extract of R. crispus; then, an active compound, nepodin, is identified by spectroscopic analysis. Anitmalarial activity is measured by PfNDH2 assay, cytotoxicity, and animal test. From NADH:quinone oxidoreductase enzyme (PfNDAH2) assay, nepodin exhibited significant IC50 values that were 0.74 ± 0.07 and 0.79 ± 0.06 µg/ml against P. falciparum chloroquine-sensitive (3D7) and P. falciparum chloroquine-resistant (S20), respectively. Nepodin showed a potential selective inhibition (SI index: ratio of 50 % cytotoxic concentration to 50 % effective anti-plasmodial concentration) of 161.6 and 151.4 against P. falciparum 3D7 and P. falciparum S20. In the animal test, all groups of nepodin treatment of 10, 50, and 250 mg/kg were active with a parasitemia suppression of 97.1 ± 3.3, 99.1 ± 3.7, and 99.1 ± 2.6 %, respectively. The survival time with nepodin treatment was increased by 14.6 ± 2.5, 16.2 ± 1.5, and 19.8 ± 1.7 days at each dose, respectively. This study newly identified the plant R. crispus containing nepodin, which is a potential antimalarial compound. It exhibited the inhibitory activity of PfNDH2 and prolonged the survival time on the group of nepodin treatment; moreover, it inhibited the parasitemia in the animal test.

Eremophilane derivatives from Senecio dianthus.

From the aerial parts of Senecio dianthus, five eremophilane glucosides (1, 2, 4-6) and one new eremophilenolide (7) were isolated, together with sixteen known compounds (3, 8-22). Their structures and relative configurations were elucidated on the basis of extensive spectroscopic analysis, including HR-ESI-MS, X-ray, CD, 1D- and 2D-NMR experiments.