Pharmacocinétique

Artemisia afra Jacq.

2004

Raymond Muganga
Luteolin Levels in Selected Folkloric Preparations and the Bioavailability of Luteolin from Artemisia afra Aqueous Extract in the Vervet Monkey
University of the Western Cape, 2004, 186 pages

Full text submitted to request

2005

James Tshikosa Mukinda
Acute and chronic toxicity of the flavonoid-containing plant, Artemisia afra in rodents
A thesis submitted in partial fulfillment of the requirements for the degree of Magister Scientiae in the Department of Pharmacology, University of the Western Cape. December 2005

Acute and chronic toxicity of the flavonoid-containing plant, Artemisia afra in rodents

Abstract :

Despite being one of the most popular traditional plant medicines used in South Africa, very little is known about the safety and efficacy of Artemisia afra. The aim of this study was to investigate the possible toxicity of the flavonoid-containing plant, Artemisia afra and especially to establish the safety of the aqueous extract of this plant after acute and chronic administration to mice and rats respectively. To realize this objective, the following were determined : (1) the adverse effects caused by the dried aqueous extract of Artemisia afra in mice and rats, (2) the LD 50 for the aqueous extract of the plant administered acutely in mice using the traditional method of Litchfield and Wilcoxon and a computer-based (AOT425statPgm) method, (3) the doses (i.e. LD 50 ) of the plant causing adverse effects after oral and intraperitoneal acute administration, (4) the general toxicity profile obtained after chronic oral dosing with the extract in rats and (5) the correlation between the plasma levels of luteolin, plant doses and toxic effects obtained after the chronic oral administration of the plant extract to rats. It was hypothesized that : (i) the flavonoids such as luteolin contained in Artemisia afra, if given in high enough doses may be associated with some adverse effects ; (ii) the dose of the plant at which such adverse effects occurred would depend on both the route of administration (oral vs. intraperitoneal) as well as the duration (acute or chronic) of exposure to the plant material ; (iii) the new computer program-based method (i.e. AOT425statPgm) for testing acute toxicity of environmental pollutants, can advantageously be used to evaluate the acute toxicity of A. afra extract, and (iv) plasma levels of luteolin could be used as a marker to monitor A. afra toxicity and/or its bioavailability (ingestion) in rats.

Plant material (i.e. leaves & aerial parts) was collected from Montague Museum, Western Cape Province, South Africa and the freeze-dried aqueous extract prepared. Mice were administered single oral doses of A. afra (0.175 to 24 g/kg) or intra-peritoneal doses (0.175 to 5,5g/kg) and were monitored for mortality and toxic symptoms for two weeks. The LD 50 values for each route were determined according to the methods of “Litchfield and Wilcoxon” and the “Acute Oral Toxicity (Guideline 425) statistical program” (AOT425statPgm). In another study, rats were given oral doses (0,1 or 1g/kg) of A. afra for : (a) three months (92 days), after which blood was withdrawn for measurement of several haematological and biochemical parameters and plasma levels of luteolin by HPLC assay, and selected tissues inspected for histopathological changes, or (b) seven days, after which the levels of luteolin in the blood of rats were measured. In addition, the luteolin level in the Artemisia afra aqueous extract was determined using HPLC.

The LD 50 of A. afra extract after acute intraperitoneal injection in mice was 27% of that after oral administration (i.e. 2450 mg/kg vs. 8960mg/kg). The AOT425statPgm method, while giving the same symptom profile and LD 50 results and having the same study time to conduct, however involved substantially fewer mice, in fact only 20 and 50% of that used in the Litchfield and Wilcoxon method for the acute p.o. and i.p. toxicity testing, respectively. In the chronic toxicity study, all the rats survived the duration of the treatment (i.e. LD 50 was much higher than 1000mg/kg), with no significant changes in physical signs, haematological and biochemical parameters, except for a transient decrease in aspartate aminotransferase (AST) activity. There were also no significant differences in the organs weights, and the histopathological results showed normal architecture suggesting no morphological disturbances. The luteolin levels in the Artemisia afra and rat plasma were 0,923± 0,015 µg/mg extract and less than 0,2 µg/ml plasma, respectively.

Collectively, the results indicate that acute doses of A. afra are relatively non-toxic in mice irrespective of the route of administration used, chronic doses of A. afra are very safe in the rat, that the AOT425statPgm is a potentially useful tool for the evaluation of acute toxicity of plant medicines and, finally, that luteolin may be a good marker for A. afra bioavailability, but not likely for its toxicity.

Keywords : Acute and chronic toxicity, Artemisia afra, Hydrolyzed extract, Flavonoids, Luteolin, HPLC, Rodents, Adverse effects, Oral and intra-peritoneal routes, Heamatological parameters, Biochemical parameters, Histopathological examination

2010

James T. Mukinda a,∗ , James A. Syce a , David Fisher b , Mervin Meyer
Effect of the Plant Matrix on the Uptake of Luteolin Derivatives-containing Artemisia afra Aqueous-extract in Caco-2 cells
Journal of Ethnopharmacology 130 (2010) 439–449

Full text submitted to request

2015

Pierre Lutgen
Artemisia afra and luteolin
malariaworld.org, June 26, 2015

Online Article

Mis en ligne par La vie re-belle
 6/04/2020
 http://lavierebelle.org/artemisia-afra-pharmacocinetique

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 Acute and chronic toxicity of the flavonoid-containing plant, Artemisia afra in rodents
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 James Tshikosa Mukinda
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Pharmacologie

Revue des études sur la composition, les mécanismes d’action, les formes galéniques, la toxicologie et l’épidémiologie d’Artemisia afra

Les articles 3

IMG: Formes galéniques Cet article regroupe les publications consacrées aux formes pharmaceutiques d’Artemisia afra Jaq.
2005James Tshikosa Mukinda Acute and chronic toxicity of the flavonoid- containing plant, Artemisia afra in rodents A thesis submitted in partial (...)
IMG: Composition et modes d'action Cet article regroupe les publications scientifiques ayant pour objet la composition phytochimique d’Artemisia afra et les mécanismes d’action de ses composés. (...)
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