Toxicologie

Artemisia annua L.

Sont regroupées dans cet article les études toxicologiques publiées concernant Artemisia annua L.

2011

Gaëlle Audrey Chuipet Njamkep
Étude préliminaire à l’utilisation d’une phytothérapie à base d’Artemisia annua chez l’enfant de 6 mois à 5 ans : dosage de l’artémisinine et étude de la toxicité de la tisane et de la limonade
Thèse présentée et soutenue en vue de l’obtention du Diplôme de Docteur en Pharmacie, Université des montagnes de Bangangté, Cameroun et Université Paul Sabatier Toulouse, France.

Étude préliminaire à l’utilisation d’une phytothérapie à base d’{Artemisia annua} chez l’enfant de 6 mois à 5 ans : dosage de l’artémisinine et étude de la toxicité de la tisane et de la limonade

Résumé :
Introduction : Le paludisme est une endémie parasitaire qui est à l’origine de nombreux décès, surtout chez les enfants de moins de 5 ans et dont la chimiorésistance à plusieurs antipaludiques a conduit à la mise au point des ACT. Ce sont une association d’antipaludiques conventionnels avec l’artémisinine ou l’un de ses dérivés. Mais ils coutent chers. Alors, certaines populations utilisent la plante d’Artemisia annua, dont est extraite l’artémisinine, sous forme de tisane pour traiter le paludisme. Chougouo et al ont montré que cette tisane est toute aussi efficace que les ACT après 7 jours de traitement. Mais peu d’enfants ont pris part à cette étude à cause de la forme galénique employée (tisane amère). C’est ainsi que notre projet de recherche a été initié avec pour but de valider une forme galénique acceptable par les enfants.
Matériels et méthodes : Nous avons déterminé la teneur en artémisinine de différentes préparations d’Artemisia annua d’origine différente (Bangangté, Bandjoun, Dschang et Luxembourg) et dans des préparations de tisane et limonade conservées sur 7 jours en utilisant la CCM – densitométrie. Avec Artemisia annua de Bangangté, nous avons réalisé des études de toxicité aigüe de l’extrait sec de la tisane ainsi que la toxicité subaigüe de la tisane et de la limonade. Pour ce dernier test, nous avons évalué les transaminases, la créatinine et l’urée sérique.
Résultats : D’après les résultats que nous avons obtenus, A. annua du Luxembourg contient nettement moins d’artémisinine que ceux de l’Ouest Cameroun confirmant ainsi les résultats de Chougouo et al sur CPG. De plus, la limonade et la tisane conservées sur 7 jours perde 20 % de leur teneur en artémisinine par jour. La tisane et la limonade de A. annua n’ont pas présenté de toxicité aigüe ni subaigüe notable.
Conclusion : La limonade d’A. annua est une forme mieux adaptée pour les enfants que la tisane, mais l’inconvénient est la grande quantité d’eau à prendre. Cependant, ces formes ne sont pas toxiques pour les rongeurs aux doses usités.

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Merlin L Willcox1, Shelly Burton, Rosalia Oyweka, Rehema Namyalo, Simon Challand and Keith Lindsey
Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria
Malaria Journal 2011, 10:84

Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria

Abstract :
Background : Several non-governmental organisations (NGOs) are promoting the use of Artemisia annua teas as a home-based treatment for malaria in situations where conventional treatments are not available. There has been controversy about the effectiveness and safety of this approach, but no pharmacovigilance studies or evaluations have been published to date.
Method : A questionnaire about the cultivation of A. annua, treatment of patients, and side-effects observed, was sent to partners of the NGO Anamed in Kenya and Uganda. Some of the respondents were then selected purposively for more in-depth semi-structured interviews.
Results : Eighteen partners in Kenya and 21 in Uganda responded. 49% reported difficulties in growing the plant, mainly due to drought. Overall about 3,000 cases of presumed malaria had been treated with A. annua teas in the previous year, of which about 250 were in children and 54 were in women in the first trimester of pregnancy. The commonest problem observed in children was poor compliance due to the bitter taste, which was improved by the addition of sugar or honey. Two miscarriages were reported in pregnant patients. Only four respondents reported side-effects in other patients, the commonest of which was vomiting. 51% of respondents had started using A. annua tea to treat illnesses other than malaria.
Conclusions : Local cultivation and preparation of A. annua are feasible where growing conditions are appropriate. Few adverse events were reported even in children and pregnant women. Where ACT is in short supply, it would make sense to save it for young children, while using A. annua infusions to treat older patients who are at lower risk. An ongoing pharmacovigilance system is needed to facilitate reporting of any adverse events.

2012

Eteng M. Ubana, Amos O. Abolaji, Patrick E. Ebong, Ebiamadon Andi Brisibe, Ahsana Dar, Nurul Kabir and M. Iqbal Choudhary, « Biochemical and Haematological Evaluation of Repeated Dose Exposure of Male Wistar Rats to an Ethanolic Extract of Artemisia annua L.
Phytotherapy research : PTR, 2012

Biochemical and Haematological Evaluation of Repeated Dose Exposure of Male Wistar Rats to an Ethanolic Extract of Artemisia annua

Abstract :
Artemisia annua is widely used for the treatment of malaria and other disorders. In a previous study, the artemisinin concentration in the dry leaves of A. annua grown under humid tropical conditions was determined to be 1.098% using reversed phase high performance liquid chromatography. In the current study, biochemical and haematological evaluations of ethanolic leaf extracts derived from such plants (EAA) were carried out in 20 male Wistar rats. Rats were divided into four study groups of saline-treated (control) and test groups exposed orally to graded doses of EAA for 28 days. The results showed that the liver function and haematological indices, and testosterone levels were not adversely affected. High density lipoprotein -cholesterol was reduced at 100mg/kg of EAA, atherogenic index as well as low density lipoprotein -cholesterol was raised, and glucose concentration was reduced significantly at the 100 and 200mg/kg of EAA (p<0.05).> / ?page=nous-contacter]

Abstract :
Ethnopharmacological relevance : Artemisia annua contains the well-known antimalarial compound artemisinin, which forms the backbone of the global malaria treatment regime. In African countries a tea infusion prepared from Artemisia annua has been used for the treatment of malaria only for the past 10–20 years. Several informal claims in Africa exist that the Artemisia annua tea infusions are also able to inhibit HIV. Since HIV is a relatively newly emerged disease, the claims, if substantiated, could provide a very good example of “ethnopharmacology in overdrive”.
Objective : The objective of this study was to provide quantitative scientific evidence that the Artemisia annua tea infusion exhibits anti-HIV activity through in vitro studies. A second objective was to determine if artemisinin plays a direct or indirect (synergistic) role in any observed activity. This was done by the inclusion of a chemically closely related species, Artemisia afra, known not to contain any artemisinin in our studies. Materials and Methods : Validated cellular systems were used to test Artemisia annua tea samples for anti-HIV activity. Two independent tests with different formats (an infection format and a co-cultivation format) were used. Samples were also tested for cellular toxicity against the human cells used in the assays.
Results : The Artemisia annua tea infusion was found to be highly active with IC50 values as low as 2.0 g/mL. Moreover we found that artemisinin was inactive at 25 g/mL and that a chemically related species Artemisia afra (not containing artemisinin) showed a similar level of activity. This indicates that the role of artemisinin, directly or indirectly (synergism), in the observed activity is rather limited. Additionally, no cellular toxicity was seen for the tea infusion at the highest concentrations tested.
Conclusion : This study provides the first in vitro evidence of anti-HIV activity of the Artemisia annua tea infusion. We also report for the first time on the anti-HIV activity of Artemisia afra although this was not an objective of this study. These results open the way to identify new active pharmaceutical ingredients in Artemisia annua and thereby potentially reduce the cost for the production of the important antimalarial compound artemisinin.

2016

Rosine Desiree Nkuitchou-Chougouo, Jonas Kouamouo, Johnson Titilayo, Dalia Fomekong Fotsop, Gilbert Hansen, Pierre Lutgen, Marc Flies, Marc Fisher, Simon Sven, Lysette Kouemeni, Mathieu Tene, Denis Wouessidjewe, Jean Tekam, Lazare Kaptue, Pierre Tane
Comparative Study of Chemical Composition of Artemisia annua Essential Oil Growing Wild in Western Cameroon and Luxembourg By Μ-Cte/Td/Gc/Ms
North Asian International Research Journal of Multidisciplinary, Vol. 2, n° 4 : pp 1-20, April 2016

Comparative Study of Chemical Composition of {Artemisia annua} Essential Oil Growing Wild in Western Cameroon and Luxembourg By Μ-Cte/Td/Gc/Ms

Abstract : The composition of essential oils of Artemisia annua from seven localities of West Cameroon and from Luxembourg were determined. The essential oils were extracted by micro-chamber thermal extractor (µ-CTE) and analyzed by Thermal Desorption plus Gas Chromatography coupled to Mass Spectrum (TD/GC/MS). According to the results obtained in this study, artemisia ketone was present only in the samples from Luxembourg. Limonene, eucalyptol and copaene were also found to be present in higher concentration in the Luxembourg samples while various localities of Cameroon were found to be richer in camphor and menthol. Camphor was the major compound among the thirteen identified and quantified from the extracts of both countries even though its yield was>60% in the Cameroon samples and 35.67% in that of Luxembourg. Climatic and culture conditions could be responsible for the variation in chemical composition of the samples studied. This work was carried out in an accredited laboratory (ISO 17025) by using validated method.

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Nkuitchou-Chougouo K. Rosine D., Kouamouo Jonas, Titilayo O. Johnson, Djeungoue P. Marie-Ange, Chuisseu Pascal, Jaryum, Kouemeni Lysette, Lutgen Pierre, Tane Pierre, Moudipa F. Paul
Comparative study of Hepatoprotective and Antioxidant Activities of Artesunate and Artemisia annua Flavonoids on rats hepatocytes
4th International Conference and Exhibition on Pharmacognosy, Phytochemistry & Natural Products Research August 29-31, 2016 Sao Paulo, Brazil

Comparative study of hepatoprotective properties of artesunate and A. annua flavonoids on rat hepatocytes

Abstract : Artesunate is a semi-synthetic derivative of artemisinin, the active compound of the Chinese herb Artemisia annua. It is a drug commonly used to treat malaria, especially chloroquine resistant malaria. Past works on A annua show many hepatoprotectives effects of the plant. Further to these works, the present study was aimed at investigating the fractions in charge of A annua’s antihépatotoxics activities and, searching the activities of artesunate on rat’s hepatocytes. The antioxidants activities of flavonoïds extract and artesunate was assessed by antiradical and reduction experiments. Free radical scavenging activity was determined by measuring the decrease in the visible absorbance of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and artesunate showed an EC50 >100 μg/ml. This result was lower than the flavonoïds one (EC50 = 8, 23 ± 0, 56 μg/ml). Likewise, reduction test showed a poor activity of artesunate. Hepatoprotectives activities were analyzed on two hepatitis models induced. Hepatocyte’s viability according to the extract’s concentrations was studied by the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) test , the estimation of ALT activities and the MDA level. There was no significant difference between poisoned cells (by CCL4 and Paracetamol) and cells treated by artesunate contrary to aqueous extracts and flavonoïds extract which showed a significant difference (p<0,001). The outcome suggests that Artesunate toxicity may possibly cause damages to the hepatocytes and liver function ; effect contrary to that of A annua, who keeps cells alive. A. annua has Hepatoprotective effect.

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Nkuitchou-Chougouo K. Rosine D., Kouamouo Jonas, Titilayo O. Johnson, Djeungoue P. Marie-Ange, Chuisseu Pascal, Jaryum, Kouemeni Lysette, Lutgen Pierre, Tane Pierre, Moudipa F. Paul
Comparative Hepatoprotective and Antioxidant Activities of Artesunate and Flavonoids extracts from Artemisia annua grown in Cameroon

Comparative Hepatoprotective and Antioxidant Activities of Artesunate and Flavonoids extracts from Artemisia annua grown in Cameroon

Abstract : The hepatoprotective activites of Artesunate, an antimalarial compound derived from artemisinin and the flavonoids extracts of Artemisia annua was investigated. The antioxidants activities of artesunate and Artemisia annua flavonoids were assessed using 1,1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging activity and ferric reducing/antioxidant power (FRAP). Hepatoprotective activities were analyzed on two induced hepatitis models. Hepatocyte’s viability according to the extract’s concentrations was studied by the MTT test, the estimation of ALT activities and the MDA level. Likewise, reduction test showed a poor activity of artesunate. There was no significant difference between poisoned cells and cells treated by artesunate contrary to aqueous extracts and flavonoids extract which showed a significant difference (p<0.001).>

Abstract :
Background : Malaria is prevalent in Nigeria, and artemether + lumefantrine (artemisinin‑based combination therapy [ACT]) is drug of choice in treatment of uncomplicated cases. ACT is contraindicated in early pregnancy. They release‑free radicals that can compromise female fertility. Infertility and its associated complications such as miscarriages, abnormal gestation, and unstable marriages seem to be on the increase. This study aims at evaluating the effect of ACT on female fertility. The significance of this research is to draw the attention of fertility care givers to this possible cause of infertility and fertility challenges.
Subjects and Methods : Creighton Model Fertility Care Systemand NaProTECHNOLOGY are simply technologies that can be used to assess female fertility. They are used in this study to assess the effect of ACT administered at different stages of menstrual cycles of three selected fertile adult females. The results are interpreted on the background of standard Creighton model chart.
Results : This study has shown that ACT has a significant fertility deteriorating effect on the women. It caused ovulation defect and diagnosed as partial rupture syndrome in the very cycle of use and in the first cycle after use. It also significantly reduced cervical mucus production and significantly reduced luteal phase progesterone production with an associated significant increase of luteal phase estrogen production. Conclusion : ACT use as antimalarial may be a possible cause of infertility and fertility challenges in women.
Keywords : Artemether + lumefantrine, Creighton Model FertilityCare System, infertility, NaProTECHNOLOGY

2018

Rene de Wit, Stephen Underwood
Is Arthrem safe ?
Promisia, 19 February 2018

Is Arthrem safe ?

No abstract

2019

Francisco Javier Ruperti-Repilado, Simon Haefliger, Sophia Rehm, Markus Zweier, Katharina M. Rentsch, Johannes Blum, Alexander Jetter, Markus Heim, Anne Leuppi-Taegtmeyer, Luigi Terracciano and Christine Bernsmeier
Danger of Herbal Tea : A Case of Acute Cholestatic Hepatitis Due to Artemisia annua Tea
Frontiers in Medicine, 1 October 2019, Volume 6 ; Article 221

Danger of Herbal Tea : A Case of Acute Cholestatic Hepatitis Due to Artemisia annua Tea

Abstract :
Background : Artemisia annua is a Chinese medicinal herb. Artemisinin-derivatives are recommended as part of a combination treatment for uncomplicated malaria. Herbal and dietary supplements (HDS) are increasingly used worldwide and HDS-induced liver injury is becoming a growing concern.
Case Report : We present the first case of severe acute cholestatic hepatitis due to the intake of Artemisia annua tea as chemoprophylaxis for malaria in a patient returning from Ethiopia. The patients presented with jaundice, elevated transaminases, and parameters of cholestasis (total bilirubin 186.6 μmol/L, conjugated bilirubin 168.5 μmol/L). A liver biopsy showed a portal hepatitis with lymphocytic infiltration of the bile ducts and diffuse intra-canalicular and intra-cytoplasmic bilirubinostasis. The toxicologic analysis of the Artemisia tea revealed the ingredients arteannuin b, deoxyartemisin, campher, and scopoletin. There were no other identifiable etiologies of liver disease. The Roussel Uclaf Causality Assessment Method (RUCAM) score assessed a “probably” causal relationship. Sequencing of genes encoding for hepatic transporters for bile acid homeostasis (BSEP, MDR3, and FIC1) found no genetic variants typically associated with hereditary cholestasis syndromes. Normalization of bilirubin occurred 3 months after the onset of disease.
Conclusion : The use of artemisinin-derivatives for malaria prevention is ineffective and potentially harmful and should thus be discouraged. Moreover, the case demonstrates our as yet inadequate understanding of the pathophysiology and susceptibility to HDS induced liver injury.
Keywords : acute, cholestatic liver disease, drug induced liver injury, Artemisia annua tea, artemisinin, herbal and dietary supplement, malaria

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Ruth L. Savage, Geraldine R. Hill, Joanne Barnes, Susan H. Kenyon and Michael V. Tatley
Suspected Hepatotoxicity With a Supercritical Carbon Dioxide Extract of Artemisia annua in Grapeseed Oil Used in New Zealand
In "Hepatotoxicity and Hepatocarcinogenicity of Herbal Medicines : Clinical and Pharmacoepidemiological Perspectives"
Frontiers in pharmacology

Suspected hepatotoxicity with supercritical carbon dioxide extract of artemisia annua in grapeseed oil used in New Zealand

Abstract : A case series of hepatotoxicity associated with an extract of Artemisia annua L. was identified through the New Zealand spontaneous adverse drug reaction reporting system. A. annua extract, produced using a supercritical carbon dioxide extraction method and formulated with grapeseed oil, has been marketed in New Zealand as a natural product for joint health. As of 31 January 2019, the New Zealand Pharmacovigilance Centre had received 29 reports of hepatic adverse reactions occurring in patients taking A. annua extract in grapeseed oil. The case reports were assessed for patient and adverse reaction characteristics, patterns of A. annua extract use and causality (based on the WHO-UMC system for standardized case causality assessment). Patients were aged 47 to 93 years (median 67). Time to onset of hepatotoxicity from starting A. annua extract was 7 days to approximately 12 months in the 23 reports with this information. Nineteen of these reports indicated onset within 12 weeks. A. annua extract was the sole suspect medicine in 27 reports. A few patients had possible predisposing conditions. Twenty-seven patients were reported to have recovered or improved on stopping A. annua extract. Nine patients required hospital admission. The pattern of hepatic injury varied. Jaundice, often with pruritus and dark urine, was experienced by 16 patients. There was considerable consistency across case reports from various reporters. We assessed the case reports as a series using the Bradford Hill guidelines for causal inference and concluded that there was a safety signal of a causal association between the A. annua extract and hepatotoxicity sufficient to be communicated and investigated further.
Keywords : Artemisia annua, herb-induced liver injury (HILI), herbal medicines, pharmacovigilance, adverse reaction reporting

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Pierre Lutgen
Review
« No toxicity detected for Artemisia annua or afra »
Malaria world
Malariaworld.org/blog, Review published on August 5, 2019 - 19:06

Article online

Mis en ligne par La vie re-belle
 1er/04/2020
 http://lavierebelle.org/artemisia-annua-l-toxicologie

 Documents

 Étude préliminaire à l’utilisation d’une phytothérapie à base d’{Artemisia annua} chez l’enfant de 6 mois à 5 ans : dosage de l’artémisinine et étude de la toxicité de la tisane et de la limonade
PDF 
 Gaëlle Audrey Chuipet Njamkep
 Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria
PDF 
 Malaria Journal
 Biochemical and Haematological Evaluation of Repeated Dose Exposure of Male Wistar Rats to an Ethanolic Extract of Artemisia annua
PDF 
 Phytotherapy research
 Comparative Study of Chemical Composition of {Artemisia annua} Essential Oil Growing Wild in Western Cameroon and Luxembourg By Μ-Cte/Td/Gc/Ms
PDF 
 North Asian International Research Journal of Multidisciplinary

Artemisia annua L..

Artemisia annua, connue en Chine sous le nom qing hao est utilisée dans sa région d’origine depuis plus de 2000 ans.

Les recherches contemporaines démontrent ses propriétés antipaludiques et plus largement antiparasitaires, ainsi que bien d’autres propriétés antivirales, immunoprotectrices...

Les articles 12

Cet article présentent les revues d’études bibliographiques et les méta-analyses concernant Artemisia annua L.
2006Jorge F.S. Ferreira, K. D. Ritchey, K.L. Cassida, K.E. Turner, J. M. Gonzalez Agrotechnological aspects of the anti-malarial plant Artemisia annua (...)
2014Seid Yimer and Omprakash Sahu Anti-mosquito repellent from Artemisia Annua L. International Journal of Medical and Clinical Sciences. Vol 1(1) : pp (...)
Cet article recensent les Publications relatives aux historiques, ethnobotaniques et ethnopharmacologiques sur Artemisia annua (...)
Cet article regroupe et rend disponible les publications relatives aux étude du devenir d’Artemisia annua dans l’organisme.
Cet article recense et met à disposition les études relatives aux formes galéniques d’Artemisia annua c’est-à-dire aux formes sous lesquelles sont mis les (...)
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