Pharmacokinetic and toxicological prediction of the chemical constituents of the essential oil of the leaves of Croton heliotropiifolius Kunth.

The development of new drugs through studies of candidate molecules is a complex undertaking; however, computational or in silico approaches aimed at optimizing molecules with greater development potential are being utilized for predictions of pharmacokinetic properties such as absorption, distribution, metabolism and excretion (ADME) as well as toxicological parameters. The objective of this study was to examine in silico and in vivo pharmacokinetic and toxicological properties of the chemical constituents present in the essential oil of Croton heliotropiifolius Kunth leaves. The following Pubchem platform as well as Software SwissADME and PreADMET software were employed for in silico studies while micronucleus (MN) testing for in vivo determination of mutagenicity, using Swiss adult male Mus musculus mice. In silico findings demonstrated that all chemical constituents presented (1) high oral absorption (2) medium cellular permeability and (3) high blood brain permeability. As for toxicity, these chemical constituents exhibited low to medium risk of occurrence of cytotoxicity. Regarding in vivo evaluation, peripheral blood samples obtained from animals tested with the oil showed no significant differences in number of MN compared to negative controls. Data indicate that further investigations are necessary to corroborate the findings of this study. Our data suggest that essential oil extracted from Croton heliotropiifolius Kunth leaves may serve as a candidate for new drug development.

Evaluation of acute toxicity, 28-day repeated dose toxicity, and genotoxicity of Moringa oleifera leaves infusion and powder.

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. leaves infusion and powder are widely used by population due the nutritional and medicinal potentials, however data regarding safety of use are still inconclusive, leading to prohibition of this plant in some countries. AIM OF THE STUDY: The present work investigated the nutritional and phytochemical composition, acute and 28-day repeated dose toxicity, and genotoxicity of M. oleifera leaves infusion and powder. MATERIALS AND METHODS: For nutritional characterization of leaf powder, it was determined: humidity; mineral residue (ash); total lipid, protein, carbohydrate, and crude fiber contents; and total caloric value. Phytochemical composition was determined by high performance liquid chromatography (HPLC). The acute toxicity assay used Swiss female albino mice and oral administration in a single dose at 2000 and 5000 mg/kg of infusion or powder. The 28-day repeated dose toxicity assay employed female and male mice, with oral administration of infusion or powder at the doses 250, 500 and 1000 mg/kg. The animals were evaluated for body weight, water and feed consumption, biochemical and hematological parameters, and histology of the liver, spleen, and kidneys. In vivo genotoxicity and mutagenicity (2000 mg/kg) were evaluated by the comet assay and the micronucleus test, respectively. RESULTS: Nutritional characterization confirmed that M. oleifera leaves are rich in proteins, carbohydrates, lipids, minerals, and fiber. HPLC indicated the presence of flavonoids and cinnamic derivatives as major polyphenols. Acute toxicity did not reveal alterations in weight gain and water and feed consumptions and no change in biochemical, hematological, and histological parameters. Behavior alterations was observed in the first 2 h after administration at 5000 mg/kg in both treatments. Infusion did not present toxicity when administered for 28 days. Conversely, the powder at 500 and 1000 mg/kg promoted liver and kidney damages observed through biochemical parameters and histopathology. Genotoxicity and mutagenicity were not detected at 2000 mg/kg. CONCLUSIONS: The present study reveals that M. oleifera leaves are an important source of polyphenols and nutrients. Indiscriminate use of both infusion and crude leaf powder above 2000 mg/kg and powder at 500 and 1000 mg/kg are not recommended. Chronic toxicological studies and establishment of preparation protocols are suggested aiming to guarantee the safety in the use of M. oleifera leaves as nutraceutical by population.

Ageratina adenophora Disrupts the Intestinal Structure and Immune Barrier Integrity in Rats.

The aim of this study was to investigate the effects of Ageratina adenophora on the intestines morphology and integrity in rat. Rats were randomly divided into two groups and were fed with 10 g/100 g body weight (BW) basal diet and 10 g/100 g BW experimental diet, which was a mixture of A. adenophora powder and basal diet in a 3:7 ratio. The feeding experiment lasted for 60 days. At days 28 and 60 of the experiment, eight rats/group/timepoint were randomly selected, weighed, and sacrificed, then blood and intestinal tissues were collected and stored for further analysis. The results showed that Ageratina adenophora caused pathological changes and injury in the intestine, elevated serum diamine oxidase (DAO), D-lactate (D-LA), and secretory immunoglobulin A (sIgA) levels, reduced occludin levels in intestinal tissues, as well as increased the count of intraepithelial leukocytes (IELs) and lamina propria leukocytes (LPLs) in the intestine (p < 0.05 or p < 0.01). In addition, the mRNA and protein (ELISA) expressions of pro-inflammation cytokines (IL-1ß, IL-2, TNF-α, and IFN-ϒ) were elevated in the Ageratina adenophora treatment groups, whereas anti-inflammatory cytokines such as IL-4 and IL-10 were reduced (p < 0.01 or p < 0.05). Therefore, the results obtained in this study indicated that Ageratina adenophora impaired intestinal function in rats by damaging the intestine structure and integrity, and also triggered an inflammation immune response that led to intestinal immune barrier dysfunction.

Assessment of pharmacological activities of Lygodium microphyllum Cav. leaves in the management of pain, inflammation, pyrexia, diarrhea, and helminths: In vivo, in vitro and in silico approaches.

Lygodium microphyllum Cav. (Family: Lygodiaceae) is a perennial, snake fern and an invasive weed in Florida and also known as old world climbing fern. This study is intended to evaluate the antipyretic, analgesic, anti-inflammatory, antidiarrheal and anthelmintic activity of methanol extract of Lygodium microphyllum Cav. leaves (MELM) by in vivo, in vitro and in silico approaches. In addition, Biovia, PyRx autoDock Vina, UCSF Chimera have been applied to investigate the docking study in order to evaluate the binding interaction and an online tool was used to explore the ADME/T properties of selected bioactive compounds. In acetic acid induced writhing study, MELM inhibited 44.28% and 56.61% of writhes at 200 and 400 (mg/kg) respectively compared to standard drug Diclofenac-Na (10 mg/kg) (74.42% inhibition). In anti-inflammatory experiment by formalin triggered licking method, MELM caused significant (p < 0.05) inhibition of licking in both early phase (42.97%, 63.30%) and late phase (43.35%, 63.03%) at the doses of 200 and 400 mg/kg respectively, whereas reference drug Ibuprofen inhibited paw licking 77.18% in early phase and 76.86% in late phase. MELM also showed promising antipyretic potential where the maximum reduction of fever was produced by MELM 400 mg/kg whose fever lowering capacity is close to the prescribe drug Indomethacin 4 mg/kg, i.p. In Castor oil triggered diarrhea method, MELM delayed the onset time of diarrhea, continuous persistence of wet feces, and decreased the weight of wet feces remarkably. Defection inhibition was achieved 27.56% and 51.72%, for MELM 200 and at 400 (mg/kg) respectively while loperamide 2 (mg/kg) yields 55.17% inhibition of the diarrheal defecation. In anthelmintic bioassay, MELM took 5.83 ± 0.83 and 41.67 ± 1.78 min respectively for paralyzing and death compared to standard drug albendazole; (paralysis time 4.00 ± 0.73 min and death time 31,00 ± 1.71 min). Isoeleutherol, isoquercetin and quercetin were found prominent in molecular docking study and ADME/T analysis verified their drug likeliness. The research validates the moderate analgesic, anti-inflammatory, and remarkable antipyretic, antidiarrheal, anthelmintic activities of the plant extract which can be used an alternative source of novel therapeutics.

Evaluation of ethnopharmacologically selected Vitex negundo L. for In vitro antimalarial activity and secondary metabolite profiling.

ETHANOPHARMACOLOGICAL RELEVANCE: Limited drugs, rise in drug resistance against frontline anti-malarial drugs, non-availability of efficacious vaccines and high cost of drug development hinders malaria intervention programs. Search for safe, effective and affordable plant based anti-malarial agents, thus becomes crucial and vital in the current scenario. The Vitex negundo L. is medicinal plant possessing a variety of pharmaceutically important compounds. The plant is used traditionally worldwide for the treatment of malaria including India and Malaysia by the indigenous tribes. In vitro studies have reported the anti-malarial use of the plant in traditional medicinal systems. AIM OF THE STUDY: The aim of the current study is to evaluate the traditionally used medicinal plants for in vitro anti-malarial activity against human malaria parasite Plasmodium falciparum and profiling secondary metabolite using spectroscopic and chromatographic methods. Chemical profiling of active secondary metabolites in the extracts was undertaken using LC-MS. MATERIALS AND METHODS: Based on the ethno-botanical data V. negundo L. was selected for in vitro anti-malarial activity against P. falciparum chloroquine-sensitive (3D7) and multidrug resistant (K1) strains using SYBR Green-I based fluorescence assay. Cytotoxicity of extracts was evaluated in VERO cell line using the MTT assay. Haemolysis assay was performed using human red blood cells. Secondary metabolites profiling was undertaken using chromatographic and spectroscopic analysis. Liquid chromatography analysis was performed using a C18, 150 X 2.1, 2.6 µm column with gradient mobile phase Solvent A: 95% (H2O: ACN), Solvent B: Acetonitrile, Solvent C: Methanol, Solvent D: 5 mM NH4 in 95:5 (H2O: ACN) at a constant flow rate of 0.250 ml/min. The LC-MS spectra were acquired in both positive and negative ion modes with electrospray ionization (ESI) source. RESULTS: The anti-malarial active extract of V. negundo L. leaf exhibited potent anti-malarial activity with IC50 values of 7.21 µg/ml and 7.43 µg/ml against 3D7 and K1 strains, respectively with no evidence of significant cytotoxicity against mammalian cell line (VERO) and no toxicity as observed in haemolysis assay. The HPLC-LC-MS analysis of the extract led to identification of 73 compounds. We report for the first time the presence of Sabinene hydrate acetate, 5-Hydroxyoxindole, 2(3,4-dimethoxyphenyl)-6, 7-dimethoxychromen-4-one, Cyclotetracosa-1, 13-diene and 5, 7-Dimethoxyflavanone in the anti-malarial active extract of V. negundo L. leaf. Agnuside, Behenic acid and Globulol are some of the novel compounds with no reports of anti-malarial activity so far and require further evaluation in pure form for the development of potent anti-malarial compounds. CONCLUSIONS: The result report and scientifically validate the traditional use of V. negundo L. for the treatment of malaria providing new avenues for anti-malarial drug development. Several novel and unknown compounds were identified that need to be further characterized for anti-malarial potential.

A comprehensive review on phytochemistry, bioactivities, toxicity studies, and clinical studies on Ficus carica Linn. leaves.

The leaves of Ficus carica Linn. (FC) have been widely used for medicine purposes since ancient times, and its decoction is consumed as tea. Many scientific papers have been published in the literature and the researchers across the world are still exploring the health benefits of FC leaves. In this review, we have collected the literature published since 2010 in the databases: Pubmed, Scopus, Web of Science, SciFinder, Google Scholar, Baidu Scholar and local classic herbal literature. The summary of the chemical constituents in FC leaves, biological activities, toxicity studies, and clinical studies carried out on FC leaves is provided in this review. In addition, the molecular mechanisms of the active constituents in FC leaves are also comprehended. FC leaves are reported to 126 constituents out of which the polyphenolic compounds are predominant. Many scientific studies have proven the antidiabetic, antioxidant, anti-inflammatory, anticancer, anticholinesterase, antimicrobial, hepatoprotective, and renoprotective activities. Many studies have carried out to provide the insights on molecular pathways involved in the biological activities of FC leaves. The toxicity studies have suggested that FC leaves exhibit toxicity only at very high doses. We believe this review serve as a comprehensive resource for those who are interested to understand the scientific evidence that support the medicinal values of FC leaves and also the research gaps to further improve the commercial value and health benefits of FC leaves.

Ecotoxicology of Heavy Metal(loid)-Enriched Particulate Matter: Foliar Accumulation by Plants and Health Impacts.

Atmospheric contamination by heavy metal-enriched particulate matter (metal-PM) is highly topical nowadays because of its high persistence and toxic nature. Metal-PMs are emitted to the atmosphere by various natural and anthropogenic activities, the latter being the major source. After being released into the atmosphere, metal-PM can travel over a long distance and can deposit on the buildings, water, soil, and plant canopy. In this way, these metal-PMs can contaminate different parts of the ecosystem. In addition, metal-PMs can be directly inhaled by humans and induce several health effects. Therefore, it is of great importance to understand the fate and behavior of these metal-PMs in the environment. In this review, we highlighted the atmospheric contamination by metal-PMs, possible sources, speciation, transport over a long distance, and deposition on soil, plants, and buildings. This review also describes the foliar deposition and uptake of metal-PMs by plants. Moreover, the inhalation of these metal-PMs by humans and the associated health risks have been critically discussed. Finally, the article proposed some key management strategies and future perspectives along with the summary of the entire review. The abovementioned facts about the biogeochemical behavior of metal-PMs in the ecosystem have been supported with well-summarized tables (total 14) and figures (4), which make this review article highly informative and useful for researchers, scientists, students, policymakers, and the organizations involved in development and management. It is proposed that management strategies should be developed and adapted to cope with atmospheric release and contamination of metal-PM.

Antidiabetic effects of Syzygium cumini leaves: A non-hemolytic plant with potential against process of oxidation, glycation, inflammation and digestive enzymes catalysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant materials are commonly used in traditional medicine in order to treat various diseases such as Diabetes mellitus. Some plants, such as Syzygium cumini, have the capability to act controlling oxidative stress and protein glycation besides their potential to decrease hyperglycemia and hyperlipidemia by the inhibition of the catalysis of digestive enzymes. The aim of this study was to evaluate the antioxidant and antiglicant activity of S. cumini leaves fractions, their capacity to inhibit hydrolases and lipase enzymes, as well as the cytotoxicity effects against erythrocytes and comparate these results with isolate quercetin flavonoid. MATERIAL AND METHODS: Ethnobotanical researches, carried out by academic studies at the Federal University of Uberlandia, led us to choose S. cumini as a potential plant for treatment of Diabetes mellitus. Fractions from ethanolic extract of S. cumini (hexane/Hex, dichloromethane/DCM, ethyl acetate/EtOAc, n-butanol/ButOH and water/H2O) were used to evaluate their antioxidant (DPPH, ORAC and FRAP) and antiglycant (BSA/fructose, BSA/methylglyoxal and Arginine/Methylglyoxal) activity as well as the inhibitory potential against α-amylase, α-glucosidase and lipase. In addition, identification of the main bioactive compounds of S. cuimini leaves by HPLC-ESIMS/MS analysis was carried out. RESULTS: Our results indicate that all fractions, for exception Hex, present noteworthy antioxidant activity, mainly in EtOAc and ButOH fractions (FRAP 1154.49 ± 67.37 and 1178.27 ± 21.26 µmol trolox eq g-1, respectively; ORAC 1224.63 ± 58.16 and 1313.53 ± 85.23 µmol trolox eq g-1, respectively; DPPH IC50 15.7 ± 2.4 and 23.5 ± 2.7 µg mL-1, respectively). Regarding the antiglycant activity (BSA/fructose and Arginine/Methylglyoxal models), all fraction, for exception Hex, presented inhibition higher than 85%. All fractions were capable to inhibit 100% of α-amylase and the fractions DCM, EtOAc and ButOH inhibited α-glucosidase more than 50%. Regarding the lipase assay, DCM and Hex had the best activity (31.5 ± 14.3 and 44.3 ± 4.5 µg mL-1, respectively). Various biomolecules known as potent antioxidants were identified in these fractions, such as quercetin, kaempferol, luteolin and (Epi)catechin. CONCLUSION: S. cumini fractions and quercetin presented promising antioxidant and antiglycation properties as well as the ability to inhibit digestive enzymes. This study presents new biological activities not yet described for S. cumini which provide new possibilities for further studies in order to assess the antidiabetic potential of S. cumini fractions especially EtOAc and ButOH.

Toxic Potential and Metabolic Profiling of Two Australian Biotypes of the Invasive Plant Parthenium Weed (Parthenium hysterophorus L.).

Parthenium weed (Parthenium hysterophorus L.) is an invasive plant species in around 50 countries and a 'Weed of National Significance' in Australia. This study investigated the relative toxicity of the leaf, shoot and root extracts of two geographically separate and morphologically distinct biotypes of parthenium weed in Queensland, Australia. Parthenium weed exhibited higher phytotoxic, cytotoxic and photocytotoxic activity in leaf tissue extracts in contrast to shoot and root. The germination and seedling growth of a dicot species (garden cress) were inhibited more than those of a monocot species (annual ryegrass) using a phytotoxicity bioassay. The cytotoxicity of leaf extracts was assessed in a mouse fibroblast cell suspension assay and increased under high ultraviolet A(UV-A) radiation. A major secondary metabolite, parthenin, was found in abundance in leaf extracts and was positively correlated with cytotoxicity but not with photocytotoxicity or phytotoxicity. Ambrosin and chlorogenic acid were also detected and were positively correlated with germination inhibition and the inhibition of radicle elongation, respectively. In addition, other currently unidentified compounds in the leaf extracts were positively correlated with phytotoxicity, cytotoxicity and photocytotoxicity with two to three molecules strongly correlated in each case. Both parthenium weed biotypes investigated did not differ with respect to their relative toxicity, despite their reported differences in invasive potential in the field. This suggests that secondary chemistry plays a limited role in their invasion success.

Evaluation of carbon tetrachloride fraction of Actinodaphne angustifolia Nees (Lauraceae) leaf extract for antioxidant, cytotoxic, thrombolytic and antidiarrheal properties.

Actinodaphne angustifolia Nees (Family: Lauraceae) is commonly used in folk medicine against urinary disorder and diabetes. The objective of the present study was to evaluate the antioxidant, cytotoxic, thrombolytic, and antidiarrheal activities of carbon tetrachloride (CCl4) fraction of leaves of A. angustifolia (CTFAA) in different experimental models. Antioxidant activity was evaluated by using qualitative and quantitative assays, while antidiarrheal effects assessed with castor oil-induced diarrheal models in mice. The clot lysis and brine shrimp lethality bioassay were used to investigate the thrombolytic and cytotoxic activities, respectively. CTFAA showed antioxidant effects in all qualitative and quantitative procedures. The fraction produced dose-dependent and significant (P<0.05 and P<0.01) activities in castor oil-induced diarrheal models. Moreover, CTFAA significantly (P<0.05) demonstrated a 15.29% clot lysis effect in the thrombolytic test, and the brine shrimp lethality assay LC50 value was 424.16 µg/ml bioassay. In conclusion, the current study showed CTFAA has significant antidiarrheal effects along with modest antioxidant and thrombolytic effects, and these data warrant further experiment to justify and include CTFAA as a supplement to mitigate the onset of diarrheal and cardiovascular disease.

Toxicological Studies of Hydroethanolic Leaf Extract of Launaea taraxacifolia (Willd) Amin Ex C. Jeffrey on Wistar Rats.

Launaea taraxacifolia (Asteraceae) is a widely used vegetable in West Africa. It is used in traditional healing of many diseases such as hypertension, anemia, diabetes, and bleeding. The aim of this study is to investigate the cytotoxicity and the acute and subacute (28 days) oral toxicity of L. taraxacifolia hydroethanolic leaves extract on male Wistar rats. The LC50 values of L. taraxacifolia on brine shrimp were 0.142 ± 0.11 mg/mL. The limit test dose of 5000 mg/kg did not provoke death or toxicity signs in the rats tested during the observation period. For 28 days subacute toxicity at 500 and 1000 mg/kg body weight, no signs of toxicity or mortality were observed during the experiment. There was no significant difference between the treated groups and the control group concerning the body and the relative organs weight (P > .05). Results of biochemical and hematological parameters did not show any treatment-related abnormalities. According to our results, the hydroethanolic extract of L. taraxacifolia leaves, at 500 and 1000 mg/kg body weight, is safe when administrated to male Wistar rats for 28 days.

Risk assessment via genotoxicity, metabolism, apoptosis, and cell growth effects in a HepG2/C3A cell line upon treatment with Rubus rosifolius (Rosaceae) leaves extract.

RUBUS ROSIFOLIUS: Sm. (Rosaceae) is a plant traditionally used in Brazil and some other countries to treat diarrhea, stomach diseases, and as an analgesic, antimicrobial, antihypertensive, and as well as other pharmacological properties. The aim of this study was to examine cytotoxic and genotoxic effects of R. rosifolius leaves extract on HepG2/C3A cells and correlate these findings with the expression of mRNA to underlying mechanisms of action. At concentrations between 0.01 and 100 µg/ml, cytotoxic effects were not detected by the MTT assay. This was confirmed by mRNA induction of the CYP3A4 gene (by RT-qPCR assay). However, genotoxic effects occurred at treatments from 1 µg/ml extract (comet and micronucleus test). An increase in the number of cells in S phase was observed at 100 µg/ml, and an elevation in apoptotic cell number was found for all tested concentrations (10, 20, or 100 µg/ml) (cell cycle and apoptosis analysis by flow cytometry). The genotoxicity induced by the extract was the main cause of the rise in the number of cells undergoing apoptosis, as indicated by rise in mRNA of CASP7 gene, and elevation of cells in the S phase of the cell cycle at the higher tested concentrations, as an attempt to repair genetic damage that occurred. These observations suggest that, despite its pharmacological potential, the use of R. rosifolius leaves extract may pose a risk to the integrity of the genetic material of human cells.

Genotoxic Assessment of the Dry Decoction of Myracrodruon urundeuva Allemão (Anacardiaceae) Leaves in Somatic Cells of Drosophila melanogaster by the Comet and SMART Assays.

Medicinal plants are worldwide used as an efficient treatment of many diseases. Myracrodruon urundeuva Allemão (Anacardiaceae) is widely used Brazilian folk medicine to treat inflammations and infections of the female genital tract, conditions of the stomach and throat, and to heal wounds on the skin and mucous membranes. Several pharmacological properties of extracts and compounds isolated from M. urundeuva are found in the literature, corroborating its uses as antiulcer and gastroprotective, anti-inflammatory and analgesic, as well as antimicrobial. Despite these many uses in traditional herbal medicine, there are few reports of its toxic-genetic effect. This work aimed to investigate the genotoxic and mutagenic potential in vivo of the dry decoction of M. urundeuva leaves on somatic cells of Drosophila melanogaster, through the Comet assay and somatic mutation and recombination test (SMART). Six concentrations (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 mg/mL) were studied after feeding individuals for 24 hr in culture medium hydrated with extracts of M. urundeuva. In the Comet assay, all concentrations showed a genotoxic effect significantly higher than the negative control group, treated with distilled water. The two highest concentrations were also superior to the positive control group, treated with cyclophosphamide (1 mg/mL). In the SMART, there was a mutagenic effect at all concentrations tested, with a clear dose-dependent relationship. Both recombination and mutation account for these mutagenic effects. The set of results indicate that the dry decoction of M. urundeuva leaves is genotoxic and mutagenic for D. melanogaster under the experimental conditions of this study. Environ. Mol. Mutagen. 61:329-337, 2020. © 2019 Wiley Periodicals, Inc.

Potential antimalarial activity of Coccinia barteri leaf extract and solvent fractions against Plasmodium berghei infected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Coccinia barteri (Hook. F.) is traditional used in Southeast of Nigeria in management of fever. This study aimed to evaluate the antimalarial activities of hydro-methanol crude extract and solvent fractions of Coccinia barteri leaf. MATERIALS AND METHODS: Two animal models employed for the study were, 4-day suppressive and curative assays against chloroquine sensitive Plasmodium berghei NK65. Level of parasitaemia, mean survival time (MST), anal temperature and weight loss were measured to assess antimalarial efficacy of the extract/fractions. Chloroquine (10 mg kg-1) was used as positive control. Chemo-profile of extract was evaluated using GC-MS, HPLC techniques and standard phytochemical analysis. Preliminary toxicity test was done using modified Lorke's method. RESULTS: The crude extract (100-400 mg kg-1) and solvent fractions (20-80 mg kg-1) demonstrated antimalarial activity in both models compared to controls. Semi purified fractions of the extract produced stronger percentage chemosuppression and inhibition of parasite. The % inhibition of the fractions, hexane, chloroform, ethyl acetate and aqueous at 80 mg kg-1 were 96.0 0, 95.29, 89.86 and 96.00% respectively on day 8 (D8). While on D14, 100% parasite clearance, indicating cure was obtained for hexane, chloroform and aqueous fraction treatment groups, no death occurred in these groups. Ethyl acetate fraction treated groups lived longer but were not fully protected. Some marker compounds were identified. CONCLUSIONS: These results support the use of C. barteri as malaria remedy and potential source of antimalarial templates. Long acting parasitaemia reduction effect indicates its possible combination potential in poly-herbal combination therapy.

Dust accumulation due to anthropogenic impact induces anatomical and photochemical changes in leaves of Centranthus ruber growing on the slope of the Vesuvius volcano.

In Mediterranean ecosystems, some natural areas are exposed to severe anthropogenic impact. Especially in summer, the considerable number of tourists visiting such areas, often with vehicles, causes deposition of dust over the vegetation due to formation of powder clouds, also favoured by wind erosion, high temperature, low precipitation and incoherent soil structure. The main aim of this study was to analyse whether the deposition of dust can induce changes in leaf anatomical functional traits and in the efficiency of photosynthetic apparatus in Centranthus ruber, a species widespread in Mediterranean ecosystems. Leaf morpho-functional traits were quantified in plants growing at sites characterised by high (HD) and low (LD) dust deposition, in periods with high anthropogenic impact. Analyses included quantification of chlorophyll fluorescence emission parameters, photosynthetic pigment concentration as well as stomatal size and frequency, leaf lamina thickness, quantification of intercellular spaces and phenolics in the mesophyll through microscopy. The overall analysis suggested that the different conditions of dust deposition induced different adjustment of morpho-functional traits in leaves of C. ruber. High dust deposition shielded the leaf lamina, protecting the photosynthetic apparatus from excess light and favoured plant photochemical efficiency. Leaves exposed to low dust deposition showed higher accumulation of phenolic compounds, protecting chloroplast membranes and characterised by high thermal dissipation of excess light. Such adaptive phenomena can affect vegetation dynamics due to possible different species-specific plant responses, resulting in different plant competitiveness under the limiting conditions of Mediterranean environments.

Safety evaluation of orally-administered methanol extract of Muntingia calabura Linn. leaves: A sub-chronic toxicity study in Sprague Dawley rats.

Muntingia calabura (M. calabura), locally known as "kerukup siam" or "buah ceri" belongs to the family Muntingiaceae and has been scientifically demonstrated to exert various pharmacological activities. The objectives of the current study are to evaluate the antioxidant activities and to determine the subchronic toxicity of 90 days orally-administered methanol extract of M. calabura (MEMC) in male Sprague Dawley rats. The rats were randomly divided into four groups (n=6). Vehicle control received 8% tween 80 and treatment group received 50, 250 and 500 mg/kg of MEMC orally administered daily for 90 days. Blood collection was carried out to obtain the hematological and biochemical profile of the rats. The organs harvested were subjected to histopathological analysis. For the antioxidant test, the extract was subjected to antioxidant study using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide anion-radical scavenging activity, total phenolic content (TPC) and phytochemical screening. Results obtained show that no adverse effects were observed during the experimental period. Hematological and biochemical analysis also showed no significant changes in this toxicity study. Besides, antioxidant analyses revealed that MEMC has higher DPPH- and SOD-radical scavenges activity as well as higher TPC value. In conclusion, M. calabura is safe for consumption and possesses beneficial antioxidant effect.