The hepatoprotective effect and mechanism of lotus leaf on liver injury induced by Genkwa Flos.

OBJECTIVES: As a traditional Chinese medicine, lotus leaf was reported to have significant hepatoprotective effect. To explore the hepatoprotective mechanism of lotus leaf, a rapid and reliable UPLC-MS/MS method was conducted to simultaneously determine six specific endogenous substances including 5-oxoproline, phenylalanine, tryptophan, C18 -phytosphingosine, lysophosphatidylcholine (16 : 0) and lysophosphatidylcholine (18 : 1). METHODS: With the help of HPLC-FT-ICR-MS, the chemical constituents of louts leaf extract were elucidated. By observing histopathological changes and determining hepatotoxicity-related biochemical indicators, rat model of liver injury was developed and the hepatoprotective effect of lotus leaf was verified. With the developed UPLC-MS/MS method, six endogenous metabolites related to hepatotoxicity were monitored to investigate the hepatoprotective mechanism of lotus leaf. KEY FINDINGS: In the qualitative analysis, a total of twenty compounds including ten flavonoids, nine alkaloids and one proanthocyanidin were identified. Based on the results of determining six endogenous metabolites related to hepatotoxicity, it was predicted that the hepatoprotective mechanism of lotus leaf might be related to glutathione metabolism, phenylalanine metabolism, tryptophan metabolism, sphingolipid metabolism and phospholipid metabolism. CONCLUSIONS: This study could be a meaningful investigation to provide mechanistic insights into the hepatoprotective effect of lotus leaf and further lay a theoretical basis for the clinical application of lotus leaf.

Reproductive toxicity of the hydroethanolic extract of the flowers of Acmella oleracea and spilanthol in zebrafish: In vivo and in silico evaluation.

Hydroethanolic preparations of Acmella oleracea is used in the north of Brazil as a female aphrodisiac. Thus, the objective of this study was to evaluate the action of the hydroethanolic extract of Acmella oleracea (EHFAo) flowers (21.873 and 44.457 mg/kg) and spilanthol (3 mg/kg) administered orally on reproductive performance and effects on the embryonic development of zebrafish F1 generation. It was observed that in the groups in which males and females received EHFAo and spilanthol, the spawning was interrupted, whereas in the groups in which only the females were treated, spawning occurred during the 21 days. Thus, in the histopathological evaluation of the gonads, it was possible to observe that the percentage of mature cells in the spermatozoa and females was significantly reduced. Only the embryo groups in which parental generation was treated with EHFAo showed lethal and teratogenic effects. On the other hand, the parental groups treated with the spilanthol presented only the lethality. Spilanthol and some metabolites showed good oral availability and important toxicological properties. Thus, it is suggested that the treatment of parental generation of zebrafish with EHFAo and spilanthol caused severe changes in the gonads and on fertility. However, on the embryo, the most striking effects in the development were recorded in the groups in which the parental generation was treated with the EHFAo, while the spilanthol influenced the lethality of the embryos.

Are wild and cultivated flowers served in restaurants or sold by local producers in Denmark safe for the consumer?

New Nordic Food has within the last decade received much media coverage with chefs of top restaurants using wild plants for foods. As part of a control campaign, the Danish Veterinary and Food Administration visited 150 restaurants and local food producers from May-October 2016 and investigated their use of plants picked from the wild, cultivated in private gardens or market gardens. Among the species used were the flowers from 23 plants. Here we present a safety evaluation of these flowers based on published phytochemical investigations and toxicological data in humans, farm animals, pets, or experimental animals. Of the 23 flowers reviewed, nine contained compounds with toxic or potentially toxic effects if eaten, two contained unidentified toxic compound(s), and four were flowers from plants with potentially toxic compounds present in other plant parts or related species. Many of the flowers may be considered novel, since a use to a significant degree in Europe prior to 15 May 1997 before Regulation (EC) 258/97 on novel food and novel food ingredients came into force could not be established. In conclusion, this review illuminates a striking lack of chemical and toxicological data of many of the proposed wild or cultivated flowers for food use.

Acute and subacute toxicity of aqueous extract of the tuber of Kedrostis africana (L.) Cogn in Wistar rats.

Kedrostis africana (L.) Cogn (Cucurbitaceae) is used in South African traditional medicine and pharmacopoeia as an emetic, purgative and diuretic, and it is used against dropsy in the management of obesity. Aim of the study In this study, acute and subacute toxicity of aqueous extract of K. africanatuber was evaluated in male and female Wistar rats in order to assess its safety profile. Materials and methods In acute toxicity, the effects of a single oral dose (2,000 and 5,000 mg/kg) of aqueous extract was determined in both sexes. General behavior, adverse effects and mortality were determined for 3 h and then periodically for 14 days. The subchronic toxicity test was performed in rats. The effects of the extract in daily single oral administration at the doses of 200, 400 and 600 mg/kg for 28 days were determined. Food and water intakes were monitored daily while body weight was monitored on a weekly bases. Hematological, biochemical and organ parameters were determined at the end of the 28-day administration. Results In the acute study, a single administration of the aqueous extract at the doses of 2,000 and 5,000 mg/kg did not induce mortality. Thus, the LD50 of the aqueous extract of K. africana (AEKA) has been estimated to be higher than 5,000 mg/kg. In the subchronic study, daily oral administration of the AEKA did not result in death of the rats or significant changes in hematological or biochemical parameters at the highest dose of 600 mg/kg. No alteration was observed in body weight, food and water intake. Liver, kidney and heart histopathology did not reveal morphological alteration. Conclusions The results showed that the aqueous tuber extract of K. africana did not cause any death, nor did it cause abnormalities in necropsy and histopathology findings. There were no acute or subchronic toxicity observed, and this indicates that the plant extract could be considered safe for oral medication.

Geranium intoxication induces detoxification enzymes in the Japanese beetle, Popillia japonica Newman.

Popillia japonica is a generalist herbivore that feeds on >300 host plant species in at least 72 plant families. It is unknown why P. japonica, despite possessing active detoxification enzymes in its gut, is paralyzed when feeding on the petals of one of its preferred host plant, Pelargonium×hortorum, or on artificial diet containing quisqualic acid (QA), the active compound in zonal geranium. We hypothesized that Pelargonium×hortorum or QA do not induce activity of the cytochrome P450, glutathione S transferase (GST), and carboxylesterase (CoE) detoxification enzymes in P. japonica. In this study, P. japonica were fed petals of zonal geranium or agar plugs containing QA, or rose petals, another preferred but non-toxic host. Midgut enzyme activities of P450, GST, and CoE were then assayed after 6, 12, or 24h of feeding. In most cases, P450, GST, and CoE activities were significantly induced in P. japonica midguts by geranium petals and QA, though the induction was slower than with rose petals. Induced enzyme activity reached a peak at 24h after consumption, which coincides with the period of highest recovery from geranium and QA paralysis. This study shows that toxic geranium and QA induce detoxification enzyme activity, but the induced enzymes do not effectively protect P. japonica from paralysis by QA. Further investigation is required through in vitro studies to know if the enzymes induced by geranium are capable of metabolizing QA. This study highlights a rare physiological mismatch between the detoxification tool kit of a generalist and its preferred host.

Evaluation of the cytotoxicity (HepG2) and chemical composition of polar extracts from the ruderal species Coleostephus myconis (L.) Rchb.f.

Coleostephus myconis (L.) Rchb.f. (Asteraceae) is a highly disseminated plant species with ruderal and persistent growth. Owing to its advantageous agronomic properties, C. myconis might have industrial applications. However, this species needs to be comprehensively characterized before any potential use. In a previous study, the phenolic composition and antioxidant activity of different C. myconis tissues were characterized. This investigation was extended to examine the cytotoxic potential of selected plant tissues (flowers and green parts) using a HepG2 cell line by utilizing the lysosomal neutral red uptake assay or mitochondrial (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. In addition, the macronutrients content, lipophilic compounds (fatty acids, tocopherols), and amino acids were also determined. C. myconis flowers were used in the senescence stage, which was previously identified as the stage that presented maximal phenolic content and highest antioxidant activity. In contrast, stems and leaves were employed due to their high biomass proportion. Regarding cytotoxicity, mitochondrial and lysosomal damage was only significant when HepG2 cells were exposed to the highest extract concentrations (stems and leaves, 0.9 mg/ml; senescent flowers, 0.3 mg/ml). Chemically, the senescent flowers were mostly characterized by their high levels of fat, amino acids (especially threonine), oleic acid, ß-, and γ-tocopherol, while stems and leaves contained high concentrations of carbohydrates, linolenic acid, and α-tocopherol. In general, these results provide information regarding the threshold concentrations of C. myconis extracts that might be used in different applications without toxicity hazards.

Chemical Composition and Allelopathic Potential of Essential Oils from Citharexylum spinosum L. Grown in Tunisia.

Citharexylum spinosum L. (Verbenaceae) also known as Citharexylum quadrangulare Jacq. or Citharexylum fruticosum L. is an exotic tree introduced many years ago in Tunisia, specially used as a street and park ornamental tree. Essential oils (EOs) were obtained by hydrodistillation of the different parts (roots, stems, leaves, flowers and fruits; drupes) collected from trees grown in the area of Monastir (Tunisia). In total, 84 compounds, representing 90.1 - 98.4% of the whole oil composition, were identified by GC-FID and GC/MS analyses. The root EO was distinguished by its high content in monoterpene hydrocarbons (α-phellandrene; 30.8%) whereas that obtained from stems was dominated by sesquiterpene hydrocarbons (cuparene; 16.4%). The leaf oil was rich in an apocarotenoid derivative (hexahydrofarnesylacetone; 26%) and an aliphatic hydrocarbon (nonadecane; 14.5%). Flowers oil was rich in esters (2-phenylethyl benzoate; 33.5%). Finally, drupes oil was rich in oxygenated sesquiterpenes (ß-eudesmol; 33.1%). Flowers oil showed a significant phytotoxic effect against lettuce seeds germination, it induces a total inhibition when tested at 1 mg/ml. Root and shoot elongation seemed to be more affected than germination. The inhibition of the shoot length varied from 3.6% to 100% and that of the root from 16.1% to 100%. The highest inhibition of 100% was detected for flower oil tested at 1 mg/ml. Our in vitro studies suggest a possible and new alternative use of C. spinosum EOs in herbicidal formulations, further experiments involving field conditions are necessary to confirm its herbicidal potential.

Toxicological evaluation of the flavonoid-rich extract from Maydis stigma: Subchronic toxicity and genotoxicity studies in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Maydis stigma (corn silk) has a long history of use as a traditional herbal medicine or functional food in China and many other countries and has been listed in the Chinese Pharmacopea. However, little data about its potential toxicity is available. AIM OF THE STUDY: In this study, we evaluated the subchronic toxicity and genotoxicity of the flavonoid-rich extract from Maydis stigma (FMS) in mice. MATERIALS AND METHODS: In the subchronic toxicity study, the FMS was administered orally to mice at doses of 2.50, 5.00 and 10.00g/kg/day for 28 consecutive days. At the end of experiment, general clinical signs, mortality, haematological, biochemical and histopathological parameters were examined. The genotoxicity of FMS was also evaluated by the micronucleus assay and the sperm malformation assay. RESULTS: All animals survived until the scheduled necropsy, and no statistically significant or toxicologically relevant differences were observed in any of the FMS-treatment groups, compared with the control group. The no-observed-adverse-effect level (NOAEL) was determined as 10.00g/kg/day. Based on the results of the micronucleus assay and the sperm malformation assay, no evidence of genotoxicity was found either in somatic cells or germ cells even at an experimental upper limit dose (10.00g/kg/day). CONCLUSIONS: The results of the present studies might support the safe use of FMS as a functional food, food additive and natural remedy.

Dual Effect of Phenolic Nectar on Three Floral Visitors of Elsholtzia rugulosa (Lamiaceae) in SW China.

Some plants secrete toxic nectar to appeal to most effective pollinators and deter non-pollinators or nectar thieves; however available information about ecological function of toxic nectar remains scarce. Elsholtzia rugulosa stands out as a plant with toxic nectar recorded in SW China. We focused on the functional significance of the phenolic compound that imparts toxic to the nectar of E. rugulosa. The effects of phenolic nectar were studied in three visitors of the flowers of the winter-blooming E. rugulosa Hemsl. (Lamiaceae) in SW China. The pollinating species Apis cerana Fabricius (Apidae; Asian honey bee) and two occasional visitors, Vespa velutina Lepeletier (Vespidae; yellow-legged Asian hornet) and Bombus eximius Smith (Apidae; a bumble bee) were tested for their preferences for low and high concentrations of 4-hydroxybenzoic acid in hexose and sucrose solutions. The pollinator is important for the plant, which is dependent on pollinator visits to attain a higher seed production and it is most likely that the combination of phenolic toxic nectar and the adaptation to phenolic nectar by A. cerana delivers an evolutionary advantage to both actors. The low and high concentrations of the phenolic acid were nearly totally refused by both occasional visitors V. velutina and B. eximius and were preferred by the pollinator A. cerana. E. rugulosa gains by having a much higher seed production and the pollinating honey bee by having an exclusive and reliable food source during the winter season at high altitudes in SW China. We found that the function of the toxic phenolic compound has dual roles by appealing to legitimate pollinators and deterring non-pollinators of E. rugulosa.

Neonicotinoid-Coated Zea mays Seeds Indirectly Affect Honeybee Performance and Pathogen Susceptibility in Field Trials.

Thirty-two honeybee (Apis mellifera) colonies were studied in order to detect and measure potential in vivo effects of neonicotinoid pesticides used in cornfields (Zea mays spp) on honeybee health. Honeybee colonies were randomly split on four different agricultural cornfield areas located near Quebec City, Canada. Two locations contained cornfields treated with a seed-coated systemic neonicotinoid insecticide while the two others were organic cornfields used as control treatments. Hives were extensively monitored for their performance and health traits over a period of two years. Honeybee viruses (brood queen cell virus BQCV, deformed wing virus DWV, and Israeli acute paralysis virus IAPV) and the brain specific expression of a biomarker of host physiological stress, the Acetylcholinesterase gene AChE, were investigated using RT-qPCR. Liquid chromatography-mass spectrometry (LC-MS) was performed to detect pesticide residues in adult bees, honey, pollen, and corn flowers collected from the studied hives in each location. In addition, general hive conditions were assessed by monitoring colony weight and brood development. Neonicotinoids were only identified in corn flowers at low concentrations. However, honeybee colonies located in neonicotinoid treated cornfields expressed significantly higher pathogen infection than those located in untreated cornfields. AChE levels showed elevated levels among honeybees that collected corn pollen from treated fields. Positive correlations were recorded between pathogens and the treated locations. Our data suggests that neonicotinoids indirectly weaken honeybee health by inducing physiological stress and increasing pathogen loads.

Safety assessment of Vitis vinifera (grape)-derived ingredients as used in cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of 24 Vitis vinifera (grape)-derived ingredients and found them safe in the present practices of use and concentration in cosmetics. These ingredients function in cosmetics mostly as skin-conditioning agents, but some function as antioxidants, flavoring agents, and/or colorants. The Panel reviewed the available animal and clinical data to determine the safety of these ingredients. Additionally, some constituents of grapes have been assessed previously for safety as cosmetic ingredients by the Panel, and others are compounds that have been discussed in previous Panel safety assessments.

Mining the brain metabolome to understand behavioural disruptions induced in mouse fed Hypochoeris radicata (L.), a neurotoxic plant for horse.

Mining the brain metabolome to understand behavioural disruptions induced in mouse fed Hypochoeris radicata (L.), a neurotoxic plant for horse. C57BL/6J mice orally exposed to 9% H. radicata (HR) are metabolically competent laboratory animals which can be used as model of Australian stringhalt, a neurological horse disease induced by HR ingestion. So, the present study was conducted to assess the brain metabolome and the behavioural performances of mice fed with a 9%-HR-based diet for 21 days. By the end of the period of exposure, mice were investigated for motor activity and coordination, anxiety level, learning and memory performances, social behaviour and rewarding properties of for the plant. Thus, the animals were sacrificed and the brain metabolome was studied using (1)H NMR spectroscopy. HR-exposed mice displayed a motor hyperactivity in several tasks, a less resignation in the forced swimming test, and paradigm place preference for the plant. A bootstrap-based regularized canonical analysis performed on merged behavioural and metabolic datasets showed a clear relationship in HR-treated mice between an increase in cerebral scyllo-inositol, an increased motor activity, and seemingly rewarding properties of HR. These results underlie the interest of such a dual approach to characterize functional end-points of a pathophysiological model of the Australian stringhalt in equine species.

Metabonomic study of genkwa flos-induced hepatotoxicity and effect of herb-processing procedure on toxicity.

A urinary metabonomic approach based on ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS) was developed to study the metabolic disturbances caused by the administration of Genkwa Flos (GF) to rats. Potential biomarkers of GF-induced toxic effects were screened out and identified, and the underlying toxicological mechanism as well as the detoxification of vinegar-processing procedure on this herb was discussed. Urine samples were analyzed by the established UPLC-MS method. With the help of serum biochemistry and histopathology results, metabolic disturbances induced by the exposure to GF and the detoxification of processing procedure were confirmed. The differences in the metabolic profiles of healthy and treated rats were clearly discriminated with the principal component analysis of the chromatographic data. Eight significantly changed metabolites were identified and interpreted as biomarkers for the hepatotoxicity and detoxification of processing procedure. This study indicated that a UPLC-MS-based metabonomic analysis of urine samples could be considered as a promising tool to predict the hepatotoxicity induced by the GF and the detoxification of traditional vinegar-processing procedure on this herb.

The day of the triffids?

This is a case report of two children who presented with a widespread bullous erythematous rash secondary to exposure to the hogweed plant.

Application of the threshold of toxicological concern approach for the safety evaluation of calendula flower (Calendula officinalis) petals and extracts used in cosmetic and personal care products.

Calendula flower (Calendula officinalis) (CF) has been used in herbal medicine because of its anti-inflammatory activity. CF and C. officinalis extracts (CFE) are used as skin conditioning agents in cosmetics. Although data on dermal irritation and sensitization of CF and CFE's are available, the risk of subchronic systemic toxicity following dermal application has not been evaluated. The threshold of toxicological concern (TTC) is a pragmatic, risk assessment based approach that has gained regulatory acceptance for food and has been recently adapted to address cosmetic ingredient safety. The purpose of this paper is to determine if the safe use of CF and CFE can be established based upon the TTC class for each of its known constituents. For each constituent, the concentration in the plant, the molecular weight, and the estimated skin penetration potential were used to calculate a maximal daily systemic exposure which was then compared to its corresponding TTC class value. Since the composition of plant extracts are variable, back calculation was used to determine the maximum acceptable concentration of a given constituent in an extract of CF. This paper demonstrates the utility and practical application of the TTC concept when used as a tool in the safety evaluation of botanical extracts.

A toxic cyanobacterial bloom in an urban coastal lake, Rio Grande do Sul state, Southern Brazil / Uma floração de cianobacterias em um lago costeiro urbano, Rio Grande do Sul, Brasil

Reports of cyanobacterial blooms developing worldwide have considerably increased, and, in most cases, the predominant toxins are microcystins. The present study reports a cyanobacterial bloom in Lake Violão, Torres, Rio Grande do Sul State, in January 2005. Samples collected on January 13, 2005, were submitted to taxonomical, toxicological, and chemical studies. The taxonomical analysis showed many different species of cyanobacteria, and that Microcystis protocystis and Sphaerocavum cf. brasiliense were dominant. Besides these, Microcystis panniformis, Anabaena oumiana,Cylindrospermopsis raciborskii, and Anabaenopsis elenkinii f. circularis were also present. The toxicity of the bloom was confirmed through intraperitoneal tests in mice, and chemical analyses of bloom extracts showed that the major substance was anabaenopeptin F, followed by anabaenopeptin B, microcystin-LR, and microcystin-RR.

O número de relatos de ocorrências de florações de cianobactérias em todo o mundo vem aumentando consideravelmente e na maioria desses episódios, as toxinas dominantes são as microcistinas. O presente estudo relata a ocorrência de floração na Lagoa do Violão, município de Torres, RS, em janeiro de 2005. As amostras coletadas em 13/01/2005 foram submetidas a estudos taxonômicos, toxicológicos e químicos. O exame microscópico do fitoplancton mostrou a dominância das espécies Microcystis protocystis e Sphaerocavum cf. brasiliense; foram observadas, também, Microcystis panniformis, Anabaena oumiana,Cylindrospermopsis raciborskii e Anabaenopsis elenkinii f. circularis. A toxicidade da floração foi confirmada através de ensaio intraperitonial em camundongos e a análise química de extratos obtidos da biomassa liofilizada mostrou que a substância majoritária era a anabaenopeptina F, seguida por anabaenopeptina B, microcistina-LR e microcistina-RR.

["Spring-summer-fall dermatitis" in a florist. Consequences for workmen's compensation insurance]. / "Frühjahr-Sommer-Herbst-Ekzem" einer Floristin. Versicherungsrechtliche Konsequenzen.

Compositae dermatitis in florists is generally occupational. The result of airborne exposure is a serious skin reaction and an objective medical requirement to stop work, since the conditions for an occupational disease required by section 5101 of the appendix to the Ordinance on Industrial Disease are fulfilled. We report on a florist, who suffered over a period of 27 years from chronic, repetitive and finally continuous eczema on air-exposed skin areas. Despite evidence of a highly sensitive type IV response to compositae, it was only after she stopped working, with the resulting elimination of the continuous exposure to allergens that the airborne trigger became apparent. This was a spring-summer-fall dermatitis resulting from airborne pollen exposure to compositae. As contact with airborne compositae constituents is almost impossible to avoid, her prognosis was poor and we estimated that she was at least 40% disabled for general employment market.

Toxicity profile of lutein and lutein ester isolated from marigold flowers (Tagetes erecta).

Lutein is a carotenoid with antioxidant properties and is commonly present in many fruits, vegetables, and egg yolk. Lutein affords protection against the development of the two common eye diseases of aging: cataract and macular degeneration. As the dietary lutein concentration is much lower compared to the actual requirement to reduce macular degeneration, supplementation of lutein is under consideration. There are very few data on the toxicity of lutein. In the present study, the authors have evaluated the short-term and long-term toxicity profile of lutein and its esterified form isolated from marigold flowers (Tagetes erecta) in young adult male and female Wistar rats. Lutein and its ester form administered orally at doses of 4, 40, and 400 mg/kg body weight for 4 weeks for short-term toxicity study and 13 weeks for a subchronic toxicity study did not produced any mortality, change in body weight, food consumption pattern, organ weight, and other adverse side reactions. Administration of lutein and ester form did not alter the hepatic and renal function, and did not produce any change in the hematological parameters and in lipid profile. Histopathological analysis of the organs supported the nontoxicity of lutein and its ester form.

Comparative effects of prolonged administration of cyanide, thiocyanate and chokecherry (Prunus virginiana) to goats.

The aim of the present study was to determine and compare the clinical, hematological, biochemical and histopathological changes induced by cyanide, thiocyanate and chokecherry (Prunus virginiana) in goats. Sixteen Boer-Spanish cross-bred female goats were divided into four treatment groups: (1) control, (2) potassium cyanide (KCN) at 3.8 mg kg(-1) day(-1), (3) potassium thiocyanate (KSCN) at 4.5 mg kg(-1) day(-1) and (4) ground frozen chokecherry leaves and flowers at a target dose of 2.5 mg HCN kg(-1) day(-1), all for 4 weeks. Clinical signs were observed in two goats treated with chokecherry. Only sporadic changes were found in the hematological and blood chemical panel. Goats treated with chokecherry and thiocyanate had an increased number of vacuoles in the colloid of thyroid glands. Spongiosis and spheroids were found in the mesencephalon from goats treated with KCN and chokecherry. These findings suggest the thyroid lesions can be attributed to thiocyanate, whereas the effects on the nervous system were most likely caused by cyanide.