Efficacy of Artemisia afra phytotherapy in experimental tuberculosis.
Artemisia afra [Jacq] (Asteraceae) phytotherapy is widely used for its medicinal properties in traditional practices. In this study we investigated whether extracts of A. afra are capable of controlling mycobacterial replication. For Mycobacterium aurum cultured in the presence of aqueous-, methanol- and dichloromethane (DCM) extracts of A. afra we found that bacterial replication was inhibited by the dichloromethane extract only. Activity of the DCM extract was confirmed in dose-dependent studies against both M. aurum and M. tuberculosis with an IC(50) =270 microg/ml and IC(50) = 290microg/ml, respectively. Fractionation of the DCM extract and evaluation of its efficacy in vitro found that most of the antimycobacterial activity was associated with isolate fraction C8 that contained several sesquiterpene lactones, the most prominent of which are Artemin and Arsubin. Evaluation of the bactericidal efficacy in vitro showed that isolate fraction C8 reduced replication of M. aurum and M. tuberculosis in a dose-dependent manner with IC(50) =1.9 microg/ml and IC(50) = 2.0 microg/ml, respectively, and an MIC = 10 microg/ml. Further, isolate fraction C8 and the DCM extract was administered to M. tuberculosis-infected mice at a tolerated dose of 1000 microg/kg for up to 26 weeks and mycobacterial burdens compared to untreated-, INH/RIF treated- and aqueous-extract-treated animals to assess its bactericidal activity in vivo. Bacterial replication remained unaffected during treatment with either isolate fraction C8 or the DCM extract resulting in pulmonary and splenic bacilli burdens comparable to that of untreated mice. In contrast, INH/RIF treatment cleared M. tuberculosis infection after only 8 weeks to undetectable levels. Interestingly, treatment of M. tuberculosis-infected mice with aqueous extract of A. afra regulated pulmonary inflammation during early infection notwithstanding its inability to inhibit mycobacterial growth. This study clearly demonstrates that A. afra contains in vitro anti-mycobacterial activity, modulates pulmonary inflammation in early mycobacterial infection, and that the mouse experimental tuberculosis model may serve as a useful assay for evaluating the utility of phytotherapy.
Ntutela
Siyabulela
S
Department of Pharmacology, University of Cape Town, South Africa.
Smith
Pete
P
Matika
Lungile
L
Mukinda
James
J
Arendse
Hiram
H
Allie
Nasiema
N
Estes
D Mark
DM
Mabusela
Wilfred
W
Folb
Peter
P
Steyn
Lafras
L
Johnson
Quinton
Q
Folk
William R
WR
Syce
James
J
Jacobs
Muazzam
M
D000818:Animals; D019306:Artemisia; D005260:Female; D008752:Methylene Chloride / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy* / Q000473:pathology
D010936:Plant Extracts; D008752:Methylene Chloride