Pyrroloquinolone A, a new alkaloid and other phytochemicals from Atractylis cancellata L. with antioxidant and anticholinesterase activities.

A new alkaloid pyrroloquinolone A (1), along with fifteen known compounds 2-16 were isolated from the petroleum ether, EtOAc and n-BuOH extracts of the whole plant Atractylis cancellata L. Their structures were elucidated on the basis of extensive spectroscopic analysis including 1D- and 2D-NMR and HR-ESI-MS techniques. This is the first report of alkaloids in the genus Atractylis. Some of the isolated compounds and extracts were evaluated for their antioxidant potential (scavenging activity of DPPH and ABTS radicals, and reducing Fe+3 and Cu+2 power assays) and acetylcholinesterase and butyrylcholinesterase inhibitory activities. Compounds 8 and 11 showed good antioxidant capacity compared to ascorbic acid, BHA, and BHT used as standards, whereas compounds 1 and 2 exhibited good anticholinesterase activities compared to galantamine used as standard.

Death in Children After Atractylis gummifera L. Poisoning in Morocco-Report of Three Cases and Review of Literature.

BACKGROUND: Atractylis gummifera L. is a poisonous thistle plant that grows in the Mediterranean regions especially in northern Africa like Morocco and southern Europe. It has been used frequently to treat some diseases in traditional medicine, and its ingestion is a common cause of fatal poisoning. Here, we report 3 death cases in children after accidental ingestion of the Atractylis gummifer L. CASES REPORTS: We report 3 cases of death in children after accidental ingestion of the poisonous plant Atractylis gummifer L. The poisoned children were admitted to hospital in deteriorated general state with clinical symptoms, such as nausea, vomiting, epigastric, and abdominal pain, diarrhea, followed by coma. However, they died a few hours later. The postmortem investigations were performed, and the diagnosis of Atractylis gummifer L. poisoning was confirmed by toxicological examination (chromatography), the latter showed the presence of atractyloside (potassium atractylate), a toxic compound of the plant Atractylis gummifera L.Atractylis gummifer L. poisoning was discussed with review through the literature. CONCLUSIONS: Through the presented cases, we show that Atractylis gummifera L. poisoning remains a health problem that involves children in Morocco, where the plant grows spontaneously. Thus, teaching children to recognize dangerous plants will be helpful to prevent accidental ingestion.

Phytochemical investigation, in vitro and in vivo antioxidant properties of aqueous and organic extracts of toxic plant: Atractylis gummifera L.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylis gummifera is a toxic plant widely used in Mediterranean traditional medicine against colds, dizziness, and headaches, as an antisyphilitic, against boils, as a purgative, emetic and deworming. All studies reported on this plant have been carried out either on the plant and its traditional uses, or on cases of poisoning by this plant. However, few pharmacological studies have readjusted the traditional uses of this plant. AIM OF THE STUDY: The purpose of this article is to carry out a preliminary phytochemical study of Atractylis gummifera and to evaluate in vitro and in vivo antioxidant activity of its aqueous and organic extracts and to provide a complementary analysis of the mechanisms of action of the different antioxidant activity tests studied. METHODS: The phytochemical study consisted of the hot and cold preparation of aqueous extracts: (decocted, infused, macerated), organic extracts: (methanolic, methanolic macerated, chloroformic, ethyl acetate, petroleum ether) and the determination of the secondary metabolites of these extracts. In addition, the biological study consisted of evaluating antioxidant activity in vitro by five different methods (H2O2 radical reduction, DPPH, ABTS, FRAP and RP) and in vivo by SOD and MDA assays. RESULTS: The methanolic macerated is the richest in total polyphenols (102 ±â€¯1.38 mg EAG/gE), tannins (144.09 ±â€¯3.96 mg EC/gE) and flavonoids (17.25 ±â€¯0.06 mg ER/gE). The same extract has the highest percentage to inhibit hydrogen peroxide (19.24 ±â€¯1.10%) and the most potent reducing power of the ABTS radical (122.6 ±â€¯0.63 mg ET/gE). We also noted that aqueous macerated has the most potent anti-radical activity of DPPH with an IC50 of 2.78 ±â€¯1.03 µg/mL, the strongest reducing power of iron 96.15 ±â€¯1.12 mg EAA/gE and which was confirmed by the FRAP test (102.5 ±â€¯1.66 mg ET/gE). These results are in agreement with the in vivo study which showed an increase in SOD secretion in diabetic mice treated with aqueous macerated extract (904.26 ±â€¯29.10 units/g liver and 714.16 ±â€¯24.83 units/g kidney) and methanol macerated extract (813.61 ±â€¯24.03 units/g liver and 719.46 ±â€¯42.10 units/g kidney) with a statistically insignificant difference between these two extracts. Furthermore, we observed a return to normal MDA levels in mice treated with aqueous macerated extract (128.61 ±â€¯15.76 nM/g liver and 103.18 ±â€¯12.67 nM/g kidney) and methanol macerated extract (130.73 ±â€¯10.73 nM/g liver and 34.28 ±â€¯5.73 nM/g kidney). CONCLUSION: The aqueous and organic extracts more particularly those prepared by aqueous and methanolic macerations are rich in polyphenols, flavonoids and tannins, and they represent a rich source of natural antioxidants, also they prevent lipid peroxidation and stimulate the secretion of the enzymatic antioxidant SOD.

2-furyl(phenyl)methanol isolated from Atractilis gummifera rhizome exhibits anti-leishmanial activity.

We report for the first time the isolation of 2-furyl(phenyl)methanol (5) from the chloroform extracts of the Atractylis gummifera roots. A. gummifera is a thistle belonging to the Asteraceae family that produces the ent-kaurane diterpenoid glycoside atractyloside (ATR). ATR (1) was isolated and chemically modified to obtain its aglycone atractyligenin (2) and the methylated derivatives ATR-OMe (3) and genine-OMe (4). The compounds 1-5 were structurally characterised and evaluated against the intracellular amastigote, cultured within macrophages, and the extracellular promastigote of Leishmania donovani, the protozoan parasite responsible for the highly infective disease visceral leishmaniasis, which is fatal if untreated. The 2-furyl(phenyl)methanol 5 exhibited notable activity against the promastigote.

Changes in mesophyll element distribution and phytometabolite contents involved in fluoride tolerance of the arid gypsum-tolerant plant species Atractylis serratuloides Sieber ex Cass. (Asteraceae).

Atractylis serratuloides is an abundant native spiny species that grows in the surroundings of superphosphate factories in Tunisia. This plant species is adapted to arid environments and tolerates a high level of fluoride pollution in soils. The aim of this study was to better understand the physiological mechanisms of fluoride tolerance of this species, comparing the fluoride-contaminated sites of Gabes and Skhira with the reference site of Smara. Results demonstrated the involvement of leaf element and phytometabolite balances in the in situ response of A. serrulatoides to fluoride. Calcium, sulphur and magnesium were differently distributed between the sites of Gabes and Smara in all plant organs. No specific tissue fluorine accumulation in root, stem and leaf, even in the most contaminated site at Gabes, was detected by EDAX mapping. Lower anthocyan and flavonol levels but enhanced nitrogen balance index were found in A. serrulatoides leaves from Gabes compared to the two other sites. A. serratuloides appeared as a fluoride excluder and its tolerance involved calcium interactions with fluoride. Moreover, an occurrence of dark septate endophytes and arbuscular mycorhizal fungi in root systems of A. serratuloides was reported for the first time, and these symbioses were present but low at all sites. We suggest the use of this plant species for fluoride-polluted soil stabilization.

A validated method for quantifying atractyloside and carboxyatractyloside in blood by HPLC-HRMS/MS, a non-fatal case of intoxication with Atractylis gummifera L.

Atractyloside (ATR) and carboxyatractyloside (CATR) are diterpene glycosides that are responsible for the toxicity of several Asteraceae plants around the world. Mediterranean gum thistle (Atractylis gummifera L.) and Zulu impila (Callilepis laureola DC.), in particular, are notoriously poisonous and the cause of many accidental deaths, some suicides and even some murders. There is no current method for measuring the two toxins in biological samples that meet the criteria of specificity required in forensic medicine. We have endeavored to fill this analytical gap. Analysis was carried out using a solid-phase extraction and a high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry detection. The method was validated in the whole blood with quantification limits of 0.17 and 0.15 µg/L for ATR and CATR, respectively. The method was applied to a non-fatal case of intoxication with A. gummifera. To the best of the authors' knowledge, this is the first time that a concentration of ATR and CATR in blood (883.1 and 119.0 µg/L, respectively) and urine (230.4 and 140.3 µg/L, respectively) is reported. ATR and CATR were quantified in A. gummifera roots by the standard method addition (3.7 and 5.4 mg/g, respectively).

[Fatal poisoning by Atractylis gummifera L.: a case report]. / Intoxication mortelle au chardon à glu : à propos d'un cas.

We report the case of a 13-year-old child admitted to the ICU because of Atractylis gummifera poisoning. This plant is poisonous, with a liver tropism and is a public health problem in the pediatric population. Beyond this observation, we review this intoxication, whose diagnosis is clinical, treatment is symptomatic and prevention is crucial.

Anti-proliferative effects of Atractylis lancea (Thunb.) DC. via down-regulation of the c-myc/hTERT/telomerase pathway in Hep-G2 cells.

Atractylis lancea (Thunb.) DC. (AL), an important medicinal herb in Asia, has been shown to have anti-tumor effects on cancer cells, but the involved mechanisms are poorly understood. This study focused on potential effects and molecular mechanisms of AL on the proliferation of the Hep-G2 liver cancer cell line in vitro. Cell viability was assessed by MTT test in Hep-G2 cells incubated with an ethanol extract of AL. Then, the effects of AL on apoptosis and cell cycle progression were determined by flow cytometry. Telomeric repeat amplification protocol (TRAP) assays was performed to investigate telomerase activity. The mRNA and protein expression of human telomerase reverse transcriptase (hTERT) and c-myc were determined by real-time RT-PCR and Western blotting. Our results show that AL effectively inhibits proliferation in Hep-G2 cells in a concentration- and time-dependent manner. When Hep-G2 cells were treated with AL after 48h,the IC50 was about 72.1 µg/ mL. Apoptosis was induced by AL via arresting the cells in the G1 phase. Furthermore, AL effectively reduced telomerase activity through inhibition of mRNA and protein expression of hTERT and c-myc. Hence, these data demonstrate that AL exerts anti-proliferative effects in Hep-G2 cells via down-regulation of the c-myc/hTERT/ telomerase pathway.

Prognostic factors of Atractylis gummifera L. poisoning, Morocco.

In Morocco, acute Atractylis gummifera L. poisoning represents the leading cause of death by plant poisoning especially for children. All cases received in the Moroccan poison control centre from January 1981 to December 2009 (n = 467) were included in a retrospective study of the characteristics and risk factors of A. gummifera L. poisoning. The most vulnerable age group was children (63.4% of cases). Most cases were due to accidental exposure (75.5%), but some were from therapeutic use (18.1%) or attempted abortion (7.4%). Patients presented with moderate poison severity signs (grade 2) in 22.3% of cases or severe signs (grade 3) in 21.0%. The mortality rate was 39.2%. The majority of deaths (81.1%) occurred in children aged < 15 years following accidental exposure. Multivariate logistic regression analysis revealed that risk factors for mortality were coma (OR = 20.5); hepatitis (OR = 52.7) and rural residence (OR = 7.26), while gastric decontamination was a protector factor (OR = 0.26).

[Atractylis gummifera: from poisoning to the analytic methods]. / Atractylis gummifera : de l'intoxication aux méthodes analytiques.

Atractylis L gummifera is a plant that causes every year serious and often deadly poisonings. In Morocco, 153 cases of poisoning have been recorded between January 1980 and June 1995 by the Moroccan Antipoison Centre. The ignorance by the clinicians, the fast evolution and the frequency of these poisonings are the origin of diagnosis problems. The solution of those problems is to detect atractyloside and carboxyatractyloside in the biologic liquids. Since several decades, some toxicological analytical methods were established in view of an assay. The aim of our paper is to describe the poisoning by this plant and to review the methods of toxicological analysis used from the colorimetric technique until the news recent chromatographic methods.

[Poisoning by Atractylis gummifera L. Morocco poison control center data]. / Intoxication par Atractylis gummifera L. Données du centre antipoison et de pharmacovigilance du Maroc.

To assess the extent and severity of poisoning by Atractylis gummifera L. in Morocco, a descriptive retrospective study was conducted on all the poisoning cases listed between 1981 and 2004 to the Morocco Poison Control Center. During this period, 240 people were hospitalized for glue thistle poisoning, 72% of which are children under 16 years. The severity of the poisoning has been affirmed by significant intrahospital lethality. Indeed, among the 182 patients for whom the outcomes were known, 98 died (54%).

Hepatorenal injury induced by cutaneous application of Atractylis gummifera L.

INTRODUCTION: In Mediterranean countries, intoxication by Atractylis gummifera L. is frequent and characterized principally by hepatorenal injury, often fatal. Its toxicity after a cutaneous application is unknown. We report a case of poisoning by A. gummifera L. induced by repeated cutaneous application. CASE REPORT: A 30-month-old boy was admitted in our pediatric intensive care unit in coma (Glasgow Coma Scale 8). Investigations showed hepatic cellular injury, cholestasis, decreased prothrombin level, and increased creatinine. History from the parents revealed repeated and occlusive cutaneous application of A. gummifera L. on a skin burn. Qualitative analysis of urine confirmed the diagnosis of A. gummifera poisoning. The child was discharged after 16 days of hospitalization with residual renal insufficiency. DISCUSSION: Poisoning by A. gummifera L. after cutaneous application has not previously been reported in the literature. The prevention of this poisoning, particularly frequent in Mediterranean countries, is mainly based on the education of the public concerning the dangers of this plant.

Atractylis gummifera and Centaurea ornata in the Province of Badajoz (Extremadura, Spain)-Ethnopharmacological importance and toxicological risk.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylis gummifera L. and Centaurea ornata Willd. are locally marketed herbal remedies, even though in Spain it is forbidden to sell toxic plants like Atractylis gummifera. Intoxications in Spain are mainly due to accidental substitution of Centaurea ornata with Atractylis gummifera which may be fatal. AIM OF STUDY: The aim of this article is to analyse the current use and marketing of Atractylis gummifera and Centaurea ornata in Badajoz and analyse the ethnopharmacological relevance of two recent cases of Atractylis gummifera poisoning. BACKGROUND AND METHODS: An ethnopharmacological survey was conducted in the area where one of the poisoned patients lives and in Guadiana del Caudillo. The use, knowledge and naming of the species involved in the poisoning was assessed. This information was complemented with an exhaustive search in Spanish ethnobotanical works on the ethnopharmacological uses of both species. RESULTS: Intoxications are due to species' substitutions. The two species are similar in name and use in the area, and both are locally marketed. AG is mainly used to heal wounds and calcaneal spurs, and CO to treat gastric ulcers and wounds. CONCLUSIONS: New intoxications are likely since consumers often have limited knowledge of the plants they consume. Also, it is common to think that all medicinal plants are harmless. As the use of Atractylis gummifera seems to increase in the area, preventive measures need to be taken.

Uso medicinal de Atractylis gummifera en Guadiana del Caudillo (Badajoz, España), toxicidad y especies afines / Medicinal use of Atractylis gummifera L. in Guadiana del Caudillo (Badajoz, Spain): toxici- ty and related species

Un estudio etnomédico llevado a cabo en Guadiana del Caudillo, pueblo de colonización de Badajoz, detectó el uso de la planta Atractylis gummifera L. que entre los años 1983 y 1984 provocó graves intoxicaciones en esta provincia. Dicha especie vegetal fue confundida con Centaurea ornata Willd., una planta de morfología similar, carente de toxicidad, de la cual se utiliza popularmente la decocción de la raíz y el rizoma para el tratamiento de afecciones gástricas.En el presente trabajo se analizan las especies que pueden ser confundidas con Atractylis gummiferapor parte de los usuarios de la medicina popular de dicha localidad. Igualmente se realiza una estimación del riesgo de confusión y la consiguiente posibilidad de intoxicaciones, en el área de estudio. Se presentan también las actividades programadas para contribuir a la planificación de la salud pública y a la asistencia médica en la zona (AU)

A study on Ethnomedicine in Guadiana del Caudillo, a colonization village located in the province of Badajoz, Spain, registerered the use of Atractylis gummifera L., which in the years 1983 and 1984 caused serious poisoning in the province. This plant species was confused with Centaurea ornata Willd., a similar non-toxic plant, the root and rhizome of which are used as infusion or decoction as a popular remedy against gastric disorders. In this paper we analyze the species that users of folk medicine in this locality could confuse with the mentioned toxic plant. It also provides an estimate on the potential risk of poisoning in the studied area. Finnally, the paper also aims to contribute to the planning of public health and medical care actions in the area (AU)

Fingerprinting of complex mixtures with the use of high performance liquid chromatography, inductively coupled plasma atomic emission spectroscopy and chemometrics.

The molecular and metal profile fingerprints were obtained from a complex substance, Atractylis chinensis DC-a traditional Chinese medicine (TCM), with the use of the high performance liquid chromatography (HPLC) and inductively coupled plasma atomic emission spectroscopy (ICP-AES) techniques. This substance was used in this work as an example of a complex biological material, which has found application as a TCM. Such TCM samples are traditionally processed by the Bran, Cut, Fried and Swill methods, and were collected from five provinces in China. The data matrices obtained from the two types of analysis produced two principal component biplots, which showed that the HPLC fingerprint data were discriminated on the basis of the methods for processing the raw TCM, while the metal analysis grouped according to the geographical origin. When the two data matrices were combined into a one two-way matrix, the resulting biplot showed a clear separation on the basis of the HPLC fingerprints. Importantly, within each different grouping the objects separated according to their geographical origin, and they ranked approximately in the same order in each group. This result suggested that by using such an approach, it is possible to derive improved characterisation of the complex TCM materials on the basis of the two kinds of analytical data. In addition, two supervised pattern recognition methods, K-nearest neighbors (KNNs) method, and linear discriminant analysis (LDA), were successfully applied to the individual data matrices-thus, supporting the PCA approach.

[Study of four cases of poisoning by Atractylis gummifera L. in Morocco]. / Etude de quatre cas d'intoxication par Atractylis gummifera L. au Maroc.

Atractylis gummifera L., a poisonous thistle responsible for frequent and sometimes mortal poisonings is known in Mediterranean region and in occident as this plant is used in alternative medicine. The clinical and biological data of four cases of poisoning in Morocco by Atractylis gummifera L. reported and discussed in this study will have to help to review this poisoning in order to inform better and to take care of the poisoned persons. Also this study may contribute to prevent the use of this plant in traditional medicine.

[Atractylis gummifera poisoning in a pregnant woman]. / Intoxication par le chardon à glu chez une femme enceinte.

BACKGROUND: Atractylis gummifera is poisonous and its ingestion causes illness, characterized principally by hepatorenal injury, often fatal. The toxicity of this plant to the fetus is not known. We report a case of poisoning during pregnancy. CASE REPORT: A 28 year-old woman was admitted to our intensive care unit for Atractylis gummifera poisoning during her 24th week of pregnancy. She showed gastrointestinal symptoms, impaired consciousness, hypoglycemia, hepatic cytolysis and decreased factor V blood levels. The mother recovered after symptomatic treatment. A healthy boy was delivered vaginally at 39 weeks and his clinical findings and laboratory results were normal at birth and a week later. DISCUSSION: Poisoning by Atractylis gummifera has not previously been reported during pregnancy. The favorable course of our patient and her infant do not rule out possible fetal damage from which he recovered, as his mother did.

Atractylis gummifera L. poisoning: an ethnopharmacological review.

Atractylis gummifera L. (Asteraceae) is a thistle located in the Mediterranean regions. Despite the plant's well-known toxicity, its ingestion continues to be a common cause of poisoning. The toxicity of Atractylis gummifera resides in atractyloside and carboxyatractyloside, two diterpenoid glucosides capable of inhibiting mitochondrial oxidative phosphorylation. Both constituents interact with a mitochondrial protein, the adenine nucleotide translocator, responsible for the ATP/ADP antiport and involved in mitochondrial membrane permeabilization. Poisoned patients manifest characteristic symptoms such as nausea, vomiting, epigastric and abdominal pain, diarrhoea, anxiety, headache and convulsions, often followed by coma. No specific pharmacological treatment for Atractylis gummifera intoxication is yet available and all the current therapeutic approaches are only symptomatic. In vitro experiments showed that some compounds such as verapamil, or dithiothreitol could protect against the toxic effects of atractyloside, but only if administered before atractyloside exposure. New therapeutic approaches could come from immunotherapy research: some studies have already tried to produce polyclonal Fab fragments against the toxic components of Atractylis gummifera.

A review of acute poisoning from Atractylis gummifera L.

Atractylis gummifera is a poisonous plant widely found in North Africa. The thistle grows commonly in dry areas, and the juice of the rhizome is poisonous. It provokes frequent poisoning, especially of children. Toxic glucosides have been isolated and their identified as atractyloside and carboxyatractyloside. Tissues of high metabolic activity are the main target organs. Atractylis gummifera glucosides cause a severe hepatitis with fatal liver failure common. The plant's poisonous compounds interact with detoxication and/or transformation systems in the liver even at doses not likely to induce cytolysis by blocking ADP-ATP conversion through inhibition of P450 cytochrome. Clinical manifestations are related to an induced hypoglycemia and neurovegetative disorders or subsequent renal failure. Liver transplantation or immunotherapy may improve the often fatal prognosis.

[Atractylis gummifera L. poisoning: a case report]. / L'intoxication par le chardon à glu (Atractylis gummifera L.); à propos d'un cas clinique.

Intoxication by Atractylis gummifera L. frequently happens in Morocco. It's often accidental and mortal if no precocious and effective treatment. In order to take stock of this intoxication of which diagnosis is clinical and treatment symptomatic, we suggest to analyze one clinical case of the intoxication by Atractylis gummifera L. on a 12 year old child who accidentally ingested this plant.