The Contribution of Flavonoids to the Antimalarial Activity ofArtemisia annua

Abstract

Silybin is the main active flavanolignan constituent in the extract of Silybam inarianwn. In order to increase its poor oral absorption, 1dB 1016, a complex with phosphatidylcholine, was synthesized (1, 2).The comparative pharmacokinetics of 1dB 1016 and silybin were investigated by measuring free and total plasma silybin levels, as well as total biliary and urinary excretion in rats following oral administration of a single dose (200 mg/kg as silybin). A specific and sensitive HPLC method (detection limit: 5 ng/ml) for the detection of silybin in biological fluids was developed.Peak levels of free and total silybin (mean values respectively 8 and 74 .tg/ml) were obtained 0.5 and 1 h after 1dB 1016 dosing. The respective AUG values (0-24 h) were 9 and 232 h .tg/ml, demonstrating that about 95 % of the plasma silybin is present in a conjugated from.After the administration of silybin, plasma levels were hardly detectable only during the first hour following the administration.Cumulative biliary excretion after 1dB 1016 administration (0-8 h) was 3.73% and urinary excretion (0-72 h) was 3.26% of the administered dose. As the prolonged urinary excretion indicates, the drug is readsorbed from the bile compartment through an enterohepatic recycle. The quantities excreted were respectively more than 2000 and 300 times higher than after administration of silybin alone.Our results indicate that 1dB 1016 is well absorbed in rats, probably due to its remarkable lipophilic character.Artemisia annua L. is used in traditional Chinese medicine and has been investigated as part of the search for novel antimalarial drugs. The major constituent responsible for the antimalarial activity of this plant is the sesquiterpene lactone artemisinin (QHS, qinghaosu) (1) and this constituent has been found to be particularly active against chloroquine-resistant Plasinodiwn falciparum in the treatment of cerebral malaria (2). We have reported that the antimalarial activity of artemisinin is markedly enhanced by the presence of such methoxylated flavones as casticin (3). Further investigation of R' R2 R' R R1 casticin H3c0 H3CO OCH, OH OCH, artemetin H3CO H3CO OCH, OCH3 OCH, ctirysotplenetin H,CO H3cO OCH, OCH3 OH chrysophenol-D H,CO H,cO OCH, OH OH circilineol H,cO H,CO H OCH, OH eupatorin H,CO H,CO OH OH OCH,the flavonoids of this plant yielded seventeen methoxylated flavonoids, three of which were new naturally occurring flavonoids. The major constituents were chrysosplenol-D (0.1% dw), chrysoplenetin (0.035% dw), eupatorin (0.019% dw) and cirsilineol (0.006% dw) with casticin (0.004% dw) as a minor constituent (4).Cell suspension cultures were developed using seed from plants high yielding in artemisinin. Cultures were maintained at 25°C under continuous illumination and sub-cultured every four weeks. Third generation cells were harvested, freeze-dried, and extracted successively with n-hexane, chloroform, and methanol. These extracts were assayed for antimalarial activity using an assay based on the incorporation of E'RJ-hypoxanthine int...

New evidences of antimalarial activity of Bidens pilosa roots extract correlated with polyacetylene and flavonoids

“…Phytochemical studies of plants used as antimalarial in traditional medicine of different countries revealed the presence of methoxylated aromatic compounds (Nkunya et al, 1993;Reddy et al, 2003;Rao et al, 2002;Cimanga et al, 1995;Kittakoop et al, 2000). The methoxylated flavonoids also enhance the in vitro activity of artemisinin (Elford et al, 1987;Liu et al, 1989;Bilia et al, 2002). In the present study, the 80% ethanol extract and the fraction enriched in flavonoids (ether:methanol fraction) from Bidens pilosa roots proved to be active against malaria also in vivo.…”

Synergy in Herbal Medicines: Part 1

“…in vitro. 26,27 These flavonoids did not reduce Plasmodium resistance to chloroquine. 26,27 While artemisinin is readily and stably extracted by aqueous decoction, flavonoids are best extracted by alcohol.…”

“…26,27 These flavonoids did not reduce Plasmodium resistance to chloroquine. 26,27 While artemisinin is readily and stably extracted by aqueous decoction, flavonoids are best extracted by alcohol. 28 This is interesting in light of in vitro evidence that only ethanolic and not aqueous crude extracts of A. annua are antiplasmodial, and an absence of evidence of synergy in A. annua aqueous extracts in vitro.…”

In vitro antiplasmodial evaluation of medicinal plants from Zimbabwe

“…for A. annua, which contains the 5-hydroxy-3,3',4',6,7-pentamethoxyflavone artemetin and its derivatives: these polymethoxylated flavonoids showed IC 50 values ranging from 9.3 to 25.2 mg/mL (2.4-6.5 Â 10 À5 M; Tan et al, 1998) against P. falciparum and potentiated the antiplasmodial activity of artemisinin (Elford et al, 1987;Liu et al, 1989).…”