Composition et mode d’action d’Artemisia annua

Artemisia annua L.

Cet article regroupe les publications scientifiques ayant pour objet la composition phytochimique d’Artemisia annua et les mécanismes d’action de ses composés. Les publications sont citées dans leur ordre chronologique de publication

Composition et mode d’action d’Artemisia annua

Artemisia annua L.

2003

M.M. Abid Ali Khan, D.C. Jain, R.S. Bhakuni, Mohd. Zaim and R.S. Thakur
Occurrence of some antiviral sterols in Artemisia annua.
Plant Science (Ireland) 75, 161-165., 1991

Occurrence of some antiviral sterols in Artemisia annua

Abstract :

Out of the twenty one medicinal plants evaluated for their virus inhibitory activity against tobamoviruses on their test hosts reacting hypersensitively, extracts of Lawsonia alba, Artemisia annua and Cornus capitata showed high virus inhibitory activity. The virus inhibitory agent (s) occurring in A. annus plant was isolated by conventional methods and identified as sterols. The sterols were characterized by spectral methods as sitosterol and stigmaterol.

Key words : tobamoviruses : Artemisia annua ; virus inhibitory agent(s) : /3-sitosterol ; stigmasterol

2005

Bertea CM, Freije JR, van der Woude H, Verstappen FW, Perk L, Marquez V, De Kraker JW, Posthumus MA, Jansen BJ, de Groot A, Franssen MC, Bouwmeester HJ.
Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua
Planta Med. 2005 Jan ;71(1):40-7. doi : 10.1055/s-2005-837749. PMID : 15678372.

Abstract

An important group of antimalarial drugs consists of the endoperoxide sesquiterpene lactone artemisinin and its derivatives. Only little is known about the biosynthesis of artemisinin in Artemisia annua L., particularly about the early enzymatic steps between amorpha-4,11-diene and dihydroartemisinic acid. Analyses of the terpenoids from A. annua leaves and gland secretory cells revealed the presence of the oxygenated amorpha-4,11-diene derivatives artemisinic alcohol, dihydroartemisinic alcohol, artemisinic aldehyde, dihydroartemisinic aldehyde and dihydroartemisinic acid. We also demonstrated the presence of a number of biosynthetic enzymes such as the amorpha-4,11-diene synthase and the—so far unknown—amorpha-4,11-diene hydroxylase as well as artemisinic alcohol and dihydroartemisinic aldehyde dehydrogenase activities in both leaves and glandular trichomes. From these results, we hypothesise that the early steps in artemisinin biosynthesis involve amorpha-4,11-diene hydroxylation to artemisinic alcohol, followed by oxidation to artemisinic aldehyde, reduction of the C11-C13 double bond to dihydroartemisinic aldehyde and oxidation to dihydroartemisinic acid.

2006

Romero Marta, Serrano Maria, Vallejo Marta, Efferth Thomas, Alvarez Marcelino, Marin Jose
Antiviral Effect of Artemisinin from Artemisia annua against a Model Member of the Flaviviridae Family, the Bovine Viral Diarrhoea Virus (BVDV)
Planta Medica 72(13):1169-74, November 2006

Full text submitted to request

Abstract :

The antiviral activity versus flaviviruses of artemisinin, a safe drug obtained from Artemisia annua and commonly used to treat malaria, has been investigated using as an in vitro model bovine epithelial cells from embryonic trachea (EBTr) infected with the cytopathic strain Oregon C24V, of bovine viral diarrhoea virus (BVDV), which is a member of the Flaviviridae family. Antiviral activity was estimated by the degree of protection against the cytopathic effect of BVDV on host cells and by the reduction in BVDV-RNA release to the culture medium. To induce an intermediate cytopathic effect in non-treated cells, EBTr cells were first exposed to BVDV for 48 h and then incubated with virus-free medium for 72 h. Ribavirin and artemisinin (up to 100 µM) induced no toxicity in host cells, whereas a slight degree of toxicity was observed for IFN-α at concentrations above 10 U/mL up to 100 U/mL. Treatment of infected cells with IFN-α, ribavirin and artemisinin markedly reduced BVDV-induced cell death. A combination of these drugs resulted in an additive protective effect. These drugs induced a significant reduction in the production/release of BVDV virions by infected EBTr cells ; there was also an additive effect when combinations of them were assayed. These results suggest a potential usefulness of artemisinin in combination with current pharmacological therapy for the treatment of human and veterinary infections by flaviviruses. Abbreviations BVDV:Bovine Viral Diarrhoea Virus HCV:Hepatitis C Virus IFN:Interferon.

2007

Lommen WJ, Elzinga S, Verstappen FW, Bouwmeester HJ.
Artemisinin and sesquiterpene precursors in dead and green leaves of Artemisia annua L. crops.
Planta Med. 2007 Aug ;73(10):1133-9. doi : 10.1055/s-2007-981567. Epub 2007 Jul 12. PMID : 17628838.

Abstract

This paper analyses the accumulation and concentrations of the antimalarial artemisinin in green and dead leaves of Artemisia annua crops in two field experiments. Concentration differences were analysed as being determined by (a) the total production of artemisinin plus its upstream precursors dihydroartemisinic acid, dihydroartemisinic aldehyde, artemisinic aldehyde and artemisinic alcohol and (b) the conversion of precursors towards artemisinin. Concentrations of the total of artemisinin plus its precursors were higher in green leaves than in dead leaves in the younger crop stages, but were comparable at the final harvests. In every crop stage, the conversion of precursors to artemisinin was more advanced in dead leaves than in green leaves. This resulted in the molar concentrations of artemisinin being higher in dead leaves than in green leaves at the final harvests. The molar quantity of dihydroartemisinic acid, the last enzymatically produced precursor, was higher than that of artemisinin in green leaves, but only 19 - 27% of that of artemisinin in dead leaves. Dead leaves were very important for the final artemisinin yield. They constituted on average 34% of the total leaf dry matter and 47% of the total artemisinin yield at the final harvests. The possibility to convert a larger part of dihydroartemisinic acid into artemisinin during post-harvest handling is discussed.

2008

Khangholil S, Rezaeinodehi A.
Effect of drying temperature on essential oil content and composition of sweet wormwood (Artemisia annua) growing wild in Iran
Pak J Biol Sci. 2008 Mar 15 ;11(6):934-7. doi : 10.3923/pjbs.2008.934.937. PMID : 18814660.

Abstract

Studies were conducted to show the effect of different temperatures in the drying process on the amount and quality of essential oils of sweet wormwood (Artemisia annua L.). The sweet wormwood aerial parts were harvested in full blooming time from an area around the Siahkal city in north of Iran in September 2005. In order to complete drying, the aerial parts were placed at shade (room temperature) and in oven at 35, 45, 55 and 65 degrees C temperatures. The aerial parts essential oil was extracted by hydrodistillation in a Clevenger apparatus and analyzed by GC/MS. Results showed that higher drying temperatures decreased the essential oil content, from 1.12% (room temperature) 0.88% (35 degrees C), 0.55% (45 degrees C) to 0.50% (55 degrees C) and 0.37% (65 degrees C). Thirty-five components were determined in essential oils, which were mostly monoterpenes. The drying temperatures had a significant effect on the essential oils composition and proportion of the various components, as when the temperature increased, the monoterpenes content gradually decreased and vice versa for sesquiterpenes. The major components were artemisia ketone and 1, 8 cineol for room and 45 degrees C ; artemisia ketone, 1, 8 cineol and camphor for 35 and 55 degrees C and beta-caryophyllene and germacrene D for 65 degrees C temperatures.

2009

Xiong YH, Hu K, Wang M.
Analysis of essential oil in herbal pair Artemisia annua, Agastache rugosa by GC-MS and chemometric resolution method.
Yao Xue Xue Bao. 2009 Nov. 44 (11) 1267-72.

Analysis of essential oil in herbal pair Artemisia annua-Agastache rugosa by GC-MS and chemometric resolution method

Abstract :

Gas chromatograph-mass spectrometry, chemometric resolution method (CRM) and overall volume integration method were used to analyze the essential components of herbal pair Artemisia annua-Agastache rugosa (AA-AR) and compare it with that of single herbs AA and AR. The results showed that the components of volatile oil of herbal pair (AA-AR) were different from that of single herb drug in quality and quantity. 70, 69, and 48 essential components in essential oil of herbal pair (AA-AR), AA and AR were determined, accounting for about 85.93%, 88.85% and 93.23% of the total volatile oil, respectively. The volatile active components of the essential oils compounds in number are almost the sum of that of two single herbs, are mainly from herb AA, and the contents of each component from herb AR were relatively high. There are 51 common active constituents shared by herbal pair AA-AR and AA, and 34 common active constituents shared by herbal pair AA-AR and AR. There are 7 new components in the essential oils of herbal pair AA-AR, the relative content of arteannuic acid (2.99%) and p-propenyl-anisole (1.92%) are higher than others.

Full text in chinese

Ebiamadon Andi Brisibe, Umoren E. Umoren, Fraideh Brisibe, Pedro M. Magalhäes, Jorge F.S. Ferreira, Devanand Luthria, Xianli Wu, Ronald L. Prior
Nutritional characterisation and antioxidant capacity of different tissues of Artemisia annua L.
Food Chemistry 115 (2009) 1240–1246

Nutritional characterisation and antioxidant capacity of different tissues of Artemisia annua L.

Abstract :

Evaluation of different tissues of Artemisia annua for their nutritional contents and antioxidant potential demonstrated that the leaves and inflorescences had the highest percentage of protein, crude fat and in vitro digestible fractions but the lowest levels of detergent fibres. These tissues also had the highest composition of the major elements as well as manganese and copper. Their relatively high amino acid and vitamin profiles equally reflect a desirable nutritional balance adding to their high antioxidant capacities. Collectively, these high levels of the different nutritional constituents and antioxidant activities coupled with the very low and often negligible levels of inherent anti-nutritive factors, especially in the leaves, which are far below recommended toxic levels, establishes A. annua as a good reservoir of nutrients and antioxidants that might favour its use as a potential herbal tonic by humans or an important supplementary feed additive for livestock production systems

Keywords : Antioxidants Artemisia annua Conventional feed Iron Livestock Oxygen radical absorbance capacity (ORAC)

Yang GE, Bao L, Zhang XQ, Wang Y, Li Q, Zhang WK, Ye WC,
Studies on flavonoids and their antioxidant activities of Artemisia annua
Zhong Yao Cai. 2009 Nov ; 32(11) : 1683-6.

Full text submitted to request

Abstract :

To study the flavonoids and their antioxidant activities of Artemisia annua. Isolation and purification were carried out by silica gel and Sephadex LH-20 column chromatographies. Compounds were identified by physicochemical properties and spectral analysis, then their antioxidant activities were evaluated by ORAC assay. Five flavonoids were isolated from the plant. Their structures were identified as 5-hydroxy-3,7,4’-trimethoxyflavone(1), 5-hydroxy-6,7,3’,4’-tetramethoxyflavonol(2), blumeatin(3), 5, 4’-dihydroxy-3,7,3’-trimethoxyflavone(4) and quercetin(5), respectively. Compounds 1-5 could slow up the attenuation rate of the fluorescence induced by AAPH. Compounds 1-3 are isolated from the plant for the first time. Compounds 1-5 all possess the potential antioxidant activities.

2010

J.F.S. Ferreira, Dave Luthria, Tomikazu Sasaki, Arne Heyerick
Flavonoids from Artemisia annua L. as Antioxidants and Their Potential Synergism with Artemisinin against Malaria and Cancer.
Molecules 2010, 15, 3135-3170

Flavonoids from Artemisia annua L. as Antioxidants and Their Potential Synergism with Artemisinin against Malaria and Cancer

Abstract :

Artemisia annua is currently the only commercial source of the sesquiterpene lactone artemisinin. Since artemisinin was discovered as the active component of A. annua in early 1970s, hundreds of papers have focused on the anti-parasitic effects of artemisinin and its semi-synthetic analogs dihydroartemisinin, artemether, arteether, and artesunate. Artemisinin per se has not been used in mainstream clinical practice due to its poor bioavailability when compared to its analogs. In the past decade, the work with artemisinin-based compounds has expanded to their anti-cancer properties. Although artemisinin is a major bioactive component present in the traditional Chinese herbal preparations (tea), leaf flavonoids, also present in the tea, have shown a variety of biological activities and may synergize the effects of artemisinin against malaria and cancer. However, only a few studies have focused on the potential synergistic effects between flavonoids and artemisinin. The resurgent idea that multi-component drug therapy might be better than monotherapy is illustrated by the recent resolution of the World Health Organization to support artemisinin-based combination therapies (ACT), instead of
the previously used monotherapy with artemisinins. In this critical review we will discuss the possibility that artemisinin and its semi-synthetic analogs might become more effective to treat parasitic diseases (such as malaria) and cancer if simultaneously delivered with flavonoids. The flavonoids present in A. annua leaves have been linked to suppression of CYP450 enzymes responsible for altering the absorption and metabolism of artemisinin in the body, but also have been linked to a beneficial immunomodulatory activity in subjects afflicted with parasitic and chronic diseases.

Keywords : Artemisia annua ; artemisinin ; flavonoids ; antimalarial, anticancer ; synergism

Geoffrey D. Brown
The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao)
Molecules 2010, 15, 7603-7698

The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao)

Abstract :

The Chinese medicinal plant Artemisia annua L. (Qinghao) is the only known source of the sesquiterpene artemisinin (Qinghaosu), which is used in the treatment of malaria. Artemisinin is a highly oxygenated sesquiterpene, containing a unique 1,2,4-trioxane ring structure, which is responsible for the antimalarial activity of this natural product. The phytochemistry of A. annua is dominated by both sesquiterpenoids and flavonoids, as is the case for many other plants in the Asteraceae family. However, A. annua is distinguished from the other members of the family both by the very large number of natural products which have been characterised to date (almost six hundred in total, including around fifty amorphane and cadinane sesquiterpenes), and by the highly oxygenated nature of many of the terpenoidal secondary metabolites. In addition, this species also contains an unusually large number of terpene allylic hydroperoxides and endoperoxides. This observation forms the basis of a proposal that the biogenesis of many of the highly oxygenated terpene metabolites from A. annua – including artemisinin itself – may proceed by spontaneous oxidation reactions of terpene precursors, which involve these highly reactive allyllic hydroperoxides as intermediates. Although several studies of the biosynthesis of artemisinin have been reported in the literature from the 1980s and early 1990s, the collective results from these studies were rather confusing because they implied that an unfeasibly large number of different sesquiterpenes could all function as direct precursors to artemisinin (and some of the experiments also appeared to contradict one another). As a result, the complete biosynthetic pathway to artemisinin could not be stated conclusively at the time. Fortunately, studies which have been published in the last decade are now providing a clearer picture of the biosynthetic pathways in A. annua. By synthesising some of the sesquiterpene natural products which have been proposed as biogenetic precursors to artemisinin in such a way that they incorporate a stable isotopic label, and then feeding these precursors to intact A. annua plants, it has now been possible to demonstrate that dihydroartemisinic acid is a late-stage precursor to artemisinin and that the closely related secondary metabolite, artemisinic acid, is not (this approach differs from all the previous studies, which used radio-isotopically labelled precursors that were fed to a plant homogenate or a cell-free preparation). Quite remarkably, feeding experiments with labeled dihydroartemisinic acid and artemisinic acid have resulted in incorporation of label into roughly half of all the amorphane and cadinane sesquiterpenes which were already known from phytochemical studies of A. annua. These findings strongly support the hypothesis that many of the highly oxygenated sesquiterpenoids from this species arise by oxidation reactions involving allylic hydroperoxides, which seem to be such a defining feature of the chemistry of A. annua. In the particular case of artemisinin, these in vivo results are also supported by in vitro studies, demonstrating explicitly that the biosynthesis of artemisinin proceeds via the tertiary allylic hydroperoxide, which is derived from oxidation of dihydroartemisinic acid. There is some evidence that the autoxidation of dihydroartemisinic acid to this tertiary allylic hydroperoxide is a non-enzymatic process within the plant, requiring only the presence of light ; and, furthermore, that the series of spontaneous rearrangement reactions which then convert this allylic hydroperoxide to the 1,2,4-trioxane ring of artemisinin are also non-enzymatic in nature.

Keywords : artemisinin ; dihydroartemisinic acid ; sesquiterpene ; biosynthesis ; Artemisia annua ; phytochemistry ; oxidation ; allylic hydroperoxide

2011

Van der Kooy Frank, Verpoorte Robert
The content of artemisinin in the Artemisia annua tea infusion
Planta medica 2011

The content of artemisinin in the Artemisia annua tea infusion

Abstract :

The traditional use of the medicinal plant Artemisia annua for the treatment of malaria entails the preparation of a tea infusion. In the scientific literature there have been some discrepancies on the quantity of the active principle, artemisinin, in the tea infusion. Due to these discrepancies, we decided to quantify artemisinin in tea infusions prepared according to different methods. We also studied the water solubility of pure artemisinin at room temperature and at 100  °C and compared it to the solubility of artemisinin from the plant material. We found that the extraction efficiency is very sensitive to temperature and that efficiencies of above 90 % can be reached. We also showed that the solubility of artemisinin is not improved by other components in the extract but that a supersaturated solution of artemisinin might be formed, which is stable for at least 24 hours.

Key words : Artemisia annua L. - Asteraceae, artemisinin, supersaturation, tea infusion. MeSH terms : Anti-Infective Agents/analysis, Anti-Infective Agents/isolation & purification, Artemisia annua/chemistry, Artemisinins/analysis, Artemisinins/isolation & purification, Beverages/analysis, Drugs, Chinese Herbal/analysis, Drugs, Chinese Herbal/isolation & purification, Chinese Traditional Medicine, Plants, Medicinal/chemistry, Solubility, Temperature, Time Factors
Substances : Anti-Infective Agents, Artemisinins, Drugs, Chinese Herbal, artemisinine

Philippe Rasoanaivo, Colin W Wright, Merlin L Willcox, Ben Gilbert
Whole plant extracts versus single compounds for the treatment of malaria : synergy and positive interactions
Malaria Journal 2011, 10 (Suppl 1) : 54

En médecine traditionnelle, on utilise des plantes entières ou des mélanges de plantes plutôt que des composés isolés. Il existe des preuves que les extraits bruts de plantes ont souvent une activité antiplasmodiale in vitro ou/et in vivo plus importante que les constituants isolés à dose équivalente.

L’objectif de cet article était d’examiner les interactions positives entre les composants des extraits de plantes entières, qui peuvent expliquer ces observations. Plusieurs types d’interactions positives ont été identifiées entre les différents composants des plantes médicinales utilisées dans le traitement du paludisme.
Une synergie pharmacodynamique a été démontrée entre les alcaloïdes de Cinchona et entre divers extraits de plantes traditionnellement combinés. Des interactions pharmacocinétiques se produisent, par exemple entre les constituants de l’infusion d’Artemisia annua, de sorte que son artémisinine est plus rapidement absorbée que le médicament pur. Certains extraits de plantes peuvent avoir un effet immunomodulateur ainsi qu’un effet antiplasmodique direct. Plusieurs extraits contiennent des inhibiteurs de la multirésistance aux médicaments, bien qu’aucun d’entre eux n’ait été testé cliniquement sur le paludisme. Certains constituants végétaux sont ajoutés principalement pour atténuer les effets secondaires d’autres, par exemple le gingembre pour prévenir les nausées.

Davantage de recherches cliniques sont nécessaires sur tous les types d’interaction entre les constituants des plantes. Cela pourrait inclure des essais cliniques sur des combinaisons de composés purs (comme l’artémisinine + la curcumine + la pipérine) et des combinaisons de remèdes à base de plantes (comme les feuilles d’Artemisia annua + la racine de Curcuma longa + les graines de Piper nigum). Les premières peuvent renforcer l’activité des préparations pharmaceutiques existantes, et les secondes peuvent améliorer l’efficacité des remèdes à base de plantes existants pour une utilisation dans des régions éloignées où les médicaments modernes ne sont pas disponibles.

Résumé publié :

Background : In traditional medicine whole plants or mixtures of plants are used rather than isolated compounds. There is evidence that crude plant extracts often have greater in vitro or/and in vivo antiplasmodial activity than isolated constituents at an equivalent dose. The aim of this paper is to review positive interactions between components of whole plant extracts, which may explain this.

Methods : Narrative review.

Results : There is evidence for several different types of positive interactions between different components of medicinal plants used in the treatment of malaria. Pharmacodynamic synergy has been demonstrated between the Cinchona alkaloids and between various plant extracts traditionally combined. Pharmacokinetic interactions occur, for example between constituents of Artemisia annua tea so that its artemisinin is more rapidly absorbed than the pure drug. Some plant extracts may have an immunomodulatory effect as well as a direct antiplasmodial effect. Several extracts contain multidrug resistance inhibitors, although none of these has been tested clinically in malaria. Some plant constituents are added mainly to attenuate the side-effects of others, for example ginger to prevent nausea.

Conclusions : More clinical research is needed on all types of interaction between plant constituents. This could include clinical trials of combinations of pure compounds (such as artemisinin + curcumin + piperine) and of combinations of herbal remedies (such as Artemisia annua leaves + Curcuma longa root + Piper nigum seeds). The former may enhance the activity of existing pharmaceutical preparations, and the latter may improve the effectiveness of existing herbal remedies for use in remote areas where modern drugs are unavailable.

2012

Masoumeh Mazandarani, Zahra Majidi, Parastoo Zarghami Moghaddam, Mehdi Abroudi, Azerbaijan Shahid Madani
Total Phenol, Flavonoid, Anthocyanin and Antioxidant Activities in Different Parts of Artemisia annua L. in Two Localities (North of Iran)
Journal of Medicinal Plants and By-products (2012) 1 : 13-21

Total Phenol, Flavonoid, Anthocyanin and Antioxidant Activities in Different Parts of Artemisia annua L. in Two Localities (North of Iran)

Abstract :

In this study, we evaluate the different biological activities of Artemisia annua L., locally known as "Moureh", in various altitudes in North of Iran, which has been used as sedative, fever few, anti inflammation, insecticide and anti infection to treat many current diseases. Parts of plants were collected from two different localities (23-1000 m) in Mazandaran province, North of Iran. The most important of secondary metabolites of total phenolics (TP), total flavonoids (TF) and total anthocyanin (TA) content of extracts were investigated by spectrophotometry method and their antioxidant activity were obtained by Total Antioxidant Capacity (TAC), Reducing Power (RP) and 1,1-diphenyl-2-picryl hydrazyl radical scavenging (DPPH). The essential oils were obtained by hydro distillated in a Clevenger-type apparatus for 5h and analyzed by GC/MS. Results indicate that the main components in essential oils were identified as Artemisia ketone (25.54-13.6%), followed by 1,8-cineole (11.98-13.26%), camphor (11.89-13.68%), α-pinene (10.11-9.29%) in AFRACHAL (1000m) and DOLAT ABAD (23m) regions , respectively. TP content had significant variation in different plant parts and regions, ranging from (11.22 to 16.94) mgGAEg-1 , TF content (11.62 to 63.74) mgQUE g-1 and quantity of TA (0.03 to 3.59) mgCGEg-1. The highest contents of secondary metabolites were found in aerial parts when compared with the other parts. Amount of antioxidant activity (IC50) in various parts of A. annua L. was measured (1.98 to 4.2) in DPPH, (7.07 to 7.46) in TAC and (5.26 to 8.04) in RP methods. In general, the highest contents of activities were found in aerial parts when compared with the other parts, whereas this part with the highest amount of IC 50 had the weakest antioxidant activity.

Iqbal S, Younas U, Chan KW, Zia-Ul-Haq M, Ismail M. 
Chemical composition of Artemisia annua L. leaves and antioxidant potential of extracts as a function of extraction solvents
Molecules. 2012 May 21 ;17(5):6020-32. doi : 10.3390/molecules17056020. PMID : 22614857 ; PMCID : PMC6268588.

Abstract

This study was conducted to investigate the chemical and nutritional composition of Artemisia annua leaves in addition to determination of antioxidant potential of their extracts prepared in different solvents. Chemical composition was determined by quantifying fat, protein, carbohydrate, fiber, tocopherol, phytate, and tannin contents. Extraction of A. annua leaves, for antioxidant potential evaluation, was carried out using five solvents of different polarities, i.e., hexane, chloroform, ethyl acetate, methanol and water. Antioxidant potential was evaluated by estimating total phenolic (TPC), flavonoid (TFC) contents, ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), DPPH radical scavenging activity and lipid peroxidation. Efficiency of different solvents was compared for the yield of antioxidant extracts from leaf samples and a clear variation was observed. The highest TPC, TFC, TEAC, DPPH radical scavenging and lowest lipid peroxidation were observed in MeOH extracts, whereas aqueous extract exhibited high ferric reducing antioxidant power ; suggesting MeOH to be the most favorable extractant.

Teresa Carbonara, Maria Pia Argentieri, Paride Papadia, Paride Papadia, Francesco Paolo Fanizzi, Luciano Villanova, Pinarosa Avato
Phytochemical analysis of a herbal tea from Artemisia annua L.
J Pharm Biomed Anal. 2012 Mar 25 ;62:79-86. doi : 10.1016/j.jpba.2012.01.015. Epub 2012 Jan 18. PMID : 22305080.

Abstract

Strategies to control diffusion of malaria needs to account for the increase of resistance of the parasite to the conventional antimalarial drugs. It has been proposed that a traditional aqueous preparation from Artemisia annua, with a low content of the active compound, artemisinin, may reduce the risk of resistance of the protozoa and be relatively more effective in the treatment of the disease. The solubility properties of the molecule have been the matter of concern about the therapeutic usefulness of herbal teas from A. annua. The present study aimed at analysing the chemical profile of a tea infusion from A. annua. Tea from A. annua was prepared through infusion of the plant aerial parts in water for 1, 24 and 48 h. Content of artemisinin was determined by HPLC-ELSD. Overall chemical characterization of the extracts was carried out by a combination of metabolomic techniques. The artemisinin content varied only slightly in the three different extracts (about 0.12%). A series of mono-caffeoyl- and mono-feruloyl-quinic acids, di-caffeoyl- and di-feruloyl-quinic acids was identified as main components of the tea infusion, together with some flavonoids. Reconstitution of the same extracts in less polar or apolar solvents resulted in a different composition with no phenolics and a much lower concentration of artemisinin.

2013

John O. Suberu, Alexander P. Gorka, Lauren Jacobs, Paul D. Roepe, Neil Sullivan, Guy C. Barker, Alexei A. Lapkin
Anti-Plasmodial Polyvalent Interactions in Artemisia annua L. Aqueous Extract – Possible Synergistic and Resistance Mechanisms
PLoS ONE 8(11) : e80790. Published : November 14, 2013

Anti-Plasmodial Polyvalent Interactions in Artemisia annua L. Aqueous Extract – Possible Synergistic and Resistance Mechanisms

Abstract :

Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L-1), dihydroartemisinic acid (70.0±0.3 mg L-1), arteannuin B (1.3±0.0 mg L-1), isovitexin (105.0±7.2 mg L-1) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B’s potentiation of artemisinin.

Praveen Kumar Ashok, Kumud Upadhyaya
Preliminary Phytochemical Screening and Physico-Chemical Parameters of Artemisia absinthium and Artemisia annua.
Journal of Pharmacognosy and Phytochemistry, Vol. 1 No. 6, 2013

Preliminary Phytochemical Screening and Physico-Chemical Parameters of Artemisia absinthium and Artemisia annua

Abstract :

The family Asteraceae or compositae known as the ester, daisy or sunflower family is the largest family of flowering plants. Artemisia is a large diverse genus of plants with between 100 to 150 species belonging to the family asteraceae (compositae). It comprises hardy herbs and shrubs known for their volatile oils. They grow in temperate climate of the northern hemisphere and southern hemisphere usually in dry or, semidry habitats. The collected herbs were authenticated, dried and extracted to calculate the percentage of yield. Phytochemical studies of the Hexane and alcoholic extracts showed the presence of various phytoconstituents i.e. carbohydrate, saponins, phytosterol, proteins and amino acid, tannin, phenolic compounds and flavonoids. It was observed that all the extracts show more important chemical constituents for various pharmacological activities. The determination of these characters will aid future investigators in their Pharmacological analysis of this species.

Keyword : Artemisia, Phenol, Phytochemical screening, Tannin

J Mouton, O Jansen M Frédérich, Fr van der Kooy
Is artemisinin the only antiplasmodial compound in the Artemisia annua tea infusion
Planta Med 2013, 79, 468-470.

Is Artemisinin the Only Antiplasmodial Compound in the Artemisia annua Tea Infusion ? An in Vitro Study

Abstract :

In our ongoing investigation into Artemisia annua for the treatment of malaria, we decided to study the possibility that synergism might enhance the efficacy of artemisinin. Our main objective was to test tea infusions and nonpolar extracts prepared from different A. annua varieties against Plasmodium falciparum in vitro in order to determine if synergism will increase the effectiveness of artemisinin in the samples as compared to pure artemisinin. We found that the IC50 of artemisinin in the tea and nonpolar extracts was not significantly different to the IC50 of pure artemisinin. We could show that the year and country of harvest or storage conditions did not have any influence on the activity and that it narrowly followed the concentration of artemisinin in all the extracts. In conclusion, based on these in vitro results, artemisinin seems to be the only active antiplasmodial compound in A. annua.

Key words : Artemisia annua L. Asteraceae · artemisinin · tea infusion · Plasmodium falciparum

Nageeb A, Al-Tawashi A, Mohammad Emwas AH, Abdel-Halim Al-Talla Z, Al-Rifai N.
Comparison of Artemisia annua Bioactivities between Traditional Medicine and Chemical Extracts
Curr Bioact Compd. 2013 Dec ;9(4):324-332. doi : 10.2174/157340720904140404151439. PMID : 24761137 ; PMCID : PMC3992861.

Abstract

The present work investigates the efficacy of using Artemisia annua in traditional medicine in comparison with chemical extracts of its bioactive molecules. In addition, the effects of location (Egypt and Jericho) on the bioactivities of the plant were investigated. The results showed that water extracts of Artemisia annua from Jericho have stronger antibacterial activities than organic solvent extracts. In contrast, water and organic solvent extracts of the Artemisia annua from Egypt do not have anti-bacterial activity. Furthermore, while the methanol extract of EA displayed high anticancer affects, the water extract of Egypt and the extracts of Jericho did not show significant anticancer activity. Finally, the results showed that the methanol and water extracts of Jericho had the highest antioxidant activity, while the extracts of Egypt had none. The current results validate the scientific bases for the use of Artemisia annua in traditional medicine. In addition, our results suggest that the collection location of the Artemisia annua has an effect on its chemical composition and bioactivities.

Keywords : Artemisia ; NMR ; antibacterial ; anticancer. ; bioactivities.

Habibi Z, Ghanian S, Ghasemi S, Yousefi M. 
Chemical composition and antibacterial activity of the volatile oil from seeds of Artemisia annua L. from Iran
Nat Prod Res. 2013 ;27(2):198-200. doi : 10.1080/14786419.2012.662652. Epub 2012 Feb 21. PMID : 22348222.

Abstract

The composition of essential oil of the seeds of Artemisia annua L. was analysed by GC-MS. Overall, 16 volatile components were identified on the basis of their mass spectra characteristics and retention indices representing 95.5% of the total oil. Trans-3(10)-caren-4-ol (22.3%), artemisia ketone (18.6%), 1,8-cineole (14.9%), δ-selinene (13.0%) and α-pinene (8.2%) were the major compounds. Oxygenated monoterpenes were the main compounds with 51.6% followed by sesquiterpene hydrocarbons (13.3%), monoterpene hydrocarbons (9.9%) and other compounds (8.3%). The essential oil was highly active against Escherichia coli and Enterococcus faecalis.

2014

Anna Rita Bilia, Francesca Santomauro, Cristiana Sacco, Maria Camilla Bergonzi, Rosa Donato
Essential Oil of Artemisia annua L. : An Extraordinary Component with Numerous Antimicrobial Properties
Evidence-Based Complementary and Alternative Medicine, 2014 : 159819

Résumé publié :

Artemisia annua L. (Asteraceae) is native to China, now naturalised in many other countries, well known as the source of the unique sesquiterpene endoperoxide lactone artemisinin, and used in the treatment of the chloroquine-resistant and cerebral malaria. The essential oil is rich in mono- and sesquiterpenes and represents a by-product with medicinal properties. Besides significant variations in its percentage and composition have been reported (major constituents can be camphor (up to 48%), germacrene D (up to 18.9%), artemisia ketone (up to 68%), and 1,8 cineole (up to 51.5%)), the oil has been subjected to numerous studies supporting exciting antibacterial and antifungal activities. Both gram-positive bacteria (Enterococcus, Streptococcus, Staphylococcus, Bacillus, and Listeria spp.), and gram-negative bacteria (Escherichia, Shigella, Salmonella, Haemophilus, Klebsiella, and Pseudomonas spp.) and other microorganisms (Candida, Saccharomyces, and Aspergillus spp.) have been investigated. However, the experimental studies performed to date used different methods and diverse microorganisms ; as a consequence, a comparative analysis on a quantitative basis is very difficult. The aim of this review is to sum up data on antimicrobial activity of A. annua essential oil and its major components to facilitate future approach of microbiological studies in this field.

Pamela J Weathers, Kirsten Reed, Ahmed Hassanali, Pierre Lutgen, Patrick Owang Engeu
Whole Plant Approaches to Therapeutic Use of Artemisia annua L. (Asteraceae)
in Tariq Aftab, ‎Jorge F.S. Ferreira, ‎M. Masroor A. Khan, Artemisia annua - Pharmacology and Biotechnology, - 2013 - ‎Science

Abstract :

Long used as a therapeutic tea by the Chinese to treat fever, Artemisia annua is more recently being studied and used for eventual treatment for not only malaria, but also many other diseases. This chapter describes studies using in vitro systems, animal models, and humans to evaluate use of not only combinations of pure compounds from the plant, but also tea infusions and the dried leaves of the plant.

Keywords : Artemisinin Combination Therapy, Parasite Clearance, Antiplasmodial Activity, Artemisinin Content, Trophozoite Stage (These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves)

2014

Akkawi M, Jaber S, Abu-Remeleh Q, Engeu OP, Lutgen P
Investigations of Artemisia annua and Artemisia sieberi Water Extracts Inhibitory Effects on β-Hematin Formation
Medicina and Aromatic Plants 3 : 150. doi : 10.4172/2167-0412.1000150)

Investigations of Artemisia Annua and Artemisia Sieberi Water Extracts Inhibitory Effects on β-Hematin Formation

Abstract :

Malaria is the most prevalent infectious disease in the world, killing 1-2 million people each year. New drugs are urgently needed to treat drug-resistant strains of malaria. In a previous study we found that extracts from Salvia palestinia leaves inhibited the formation of β-hematin with efficiency similar to that of chloroquine. The objective of this study was to investigate the effect of other plant extracts on hemozoin formation. A comparison between the efficiency of aqueous extracts or infusions of Artemisia annua from Luxembourg and Artemisia sieberi from Palestine in inhibiting β-hematin formation was done. Although it was found that the Artemisia sieberi leaf tea infusion was less effective than that of the Artemisia annua, the stem infusion of Artemisia sieberi was found to be better than that of Artemisia annua stems. Results obtained with infusions prepared with tap or well water may be different from results obtained in the laboratory with distilled water. Artemisia annua leaf infusions prepared using salt water (0.5g salt/150ml water) had higher efficiency in inhibiting β-hematin formation than those infusions done with distilled water. Mixing equal amounts of Artemisia annua leaf and Artemisia sieberi stem water extract showed an increase in their inhibitory effect on β-hematin formation. An important finding in this investigation was that the Artemisia annua lyophilized extracts lost activity with time, which may have an impact not only on in vitro laboratory results but also on in vivo treatment efficiency obtained with old extracts. In light of this finding it might be advisable to use Artemisia annua in the form of dried leaf powder and not in the form of extracts or infusion. Stored in dry, ventilated conditions the plant keeps its properties for many years.

2015

Engeu Patrick Ogwang, Francis Omujall, Moses Agwaya, Hassan Kyakulaga, Celestino Obua
Variations in antimalarial components of Artemisia annua Linn from three regions of Uganda
African Health Science. 2015 Sep ;15(3):828-34. doi : 10.4314/ahs.v15i3.17.

Variations in antimalarial components of Artemisia annua Linn from three regions of Uganda

Abstract :

Introduction : Artemisia annua plant from the family Asteracea is a powerful antimalarial plant introduced to Uganda around 2003. In addition to the artemisinin component, the plant also contains flavonoids which work in synergy to artemisinin against malaria parasites. The plant also contains aromatic oils which repel mosquitoes. In this paper we report the variations in antimalarial components of A. annua samples from the regions cultivating it in Uganda.

Methods : Artemisia annua samples were obtained from three regions that cultivated the plant at the time of this study. The samples were brought to laboratory, authenticated and processed. The levels of artemisinin, total flavonoids and aromatic components were quantified using high performance thin layer chromatography, ultra violet spectrophotometry and gas chromatography respectively.

Results : Artemisinin and total flavonoids levels were higher in samples obtained from high land areas (western and south western region) compared to that obtained from lowland regions (central) i.e 0.8% Vs 0.4% and 2.6% Vs 1.5% respectively. The aromatic oils (mosquito repellent components) were similar with camphor component being highest and levels ranging from 75.4% to 79.0%. Conclusion : Our findings show that the active components in Artemisia annua cultivated and used in the Uganda vary with geographical regions and this calls for standardisation by source.

Key words : Variations, Antimalarial components, Artemisia annua, Uganda

Éric Yarnell, ND, RH(AHG)
Synergy in Herbal Medicines : Part 1
Journal of Restorative Medicine 2015 ; 4 : 60 pages

Synergy in Herbal Medicines : Part 1

Abstract :

In the following paper, we will review the available literature on synergy and additive effects involving medicinal herbs and herbal extracts. Several types of synergistic interactions are discussed, including apparently inactive constituents enhancing the effects of apparently active constituents within and between herbal medicines, various herbal compounds altering the absorption of others, reduction in toxicity of some herbal constituents by others, and direct synergistic therapeutic effects when active constituents are combined within and between many medicinal herbs. Species discussed include Artemisia annua (sweet Annie, qing hao), Ammi visnaga (khella), Glycyrrhiza glabra (licorice), Glycyrrhiza uralensis (Chinese licorice, g an cao), Panax ginseng (Asian ginseng, rén shen), Mahonia aquifolium (Oregon grape), Berberis aetnensis (Mt. Etna barberry), Boquila trifoliolata (algerita), B. fendleri (Colorado barberry), and Coptis chinensis (goldthread, huáng lián). Part 2 of this article will continue this review on other medicinal herb species.

Keywords : Synergy ; Medicinal plants ; Artemisia annua ; Glycyrrhiza ; Coptis.

2017

Pierre Lutgen
Prophylaxis with Artemisia annua is very efficient : the role of chelators
Pharmacy & Pharmacology International Journal, Volume 5 Issue 5 – 2017

Prophylaxis with Artemisia Annua is very efficient : the role of chelators

Texte sans résumé

Xiaobo Zhang, Yuping Zhao, Lanping Guo, Zhidong Qiu, Luqi Huangn and Xiaobo Qu
Differences in chemical constituents of Artemisia annua L from different geographical regions in China
PLOS ONE, September 7, 2017

Résumé publié

Background : Daodi-herb is a part of Chinese culture, which has been naturally selected by traditional Chinese medicine clinical practice for many years. Sweet wormwood herb is a kind of Daodiherb, and comes from Artemisia annua L. Artemisinin is a kind of effective antimalarial drug being extracted from A. annua. Because of artemisinin, Sweet wormwood herb earns a reputation. Based on the Pharmacopoeia of the People’s Republic of China (PPRC), Sweet wormwood herb can be used to resolve summerheat-heat, and prevent malaria. Besides, it also has other medical efficacies. A. annua, a medicinal plant that is widely distributed in the world contains many kinds of chemical composition. Research has shown that compatibility of artemisinin, scopoletin, arteannuin B and arteannuic acid has antimalarial effect. Compatibility of scopoletin, arteannuin B and arteannuic acid is conducive to resolving summerheatheat. Chemical constituents in A. annua vary significantly according to geographical locations. So, distribution of A. annua may play a key role in the characteristics of efficacy and chemical constituents of Sweet wormwood herb. It is of great significance to study this relationship.

Objectives : We mainly analyzed the relationship between the chemical constituents (arteannuin B, artemisinin, artemisinic acid, and scopoletin) with special efficacy in A. annua that come from different provinces in china, and analyzed the relationship between chemical constituents and spatial distribution, in order to find out the relationship between efficacy, chemical constituents and distribution.

Methods : A field survey was carried out to collect A. annua plant samples. A global positioning system (GPS) was used for obtaining geographical coordinates of sampling sites. Chemical constituents in A. annua were determined by liquid chromatography tandem an atmospheric pressure ionization-electrospray mass spectrometry. Relationship between chemical constituents including proportions, correlation analysis (CoA), principal component analysis (PCA) and cluster analysis (ClA) was displayed through Excel and R software version2.3.2 (R), while the one between efficacy, chemical constituents and spatial distribution was presented through ArcGIS10.0, Excel and R software.

Results : According to the results of CoA, arteannuin B content presented a strong positive correlation with artemisinic acid content (p = 0), and a strong negative correlation with artemisinin content (p = 0). Scopoletin content presented a strong positive correlation with artemisinin content (p = 0), and a strong negative correlation with artemisinic acid content (p = 0). According to the results of PCA, the first two principal components accounted for 81.57% of the total accumulation contribution rate. The contribution of the first principal component is about 45.12%, manly including arteannuin B and artemisinic acid. The contribution of the second principal component is 36.45% of the total, manly including artemisinin and scopoletin. According to the ClA by using the principal component scores, 19 provinces could be divided into two groups. In terms of provinces in group one, the proportions of artemisinin are all higher than 80%. Based on the results of PCA, ClA, percentages and scatter plot analysis, chemical types are defined as "QHYS type", "INT type" and "QHS type."

2018

Jorge F. S. Ferreira , Vagner A. Benedito , Devinder Sandhu , José A. Marchese and Shuoqian Liu
Seasonal and Differential Sesquiterpene Accumulation in Artemisia annua Suggest Selection Based on Both Artemisinin and Dihydroartemisinic Acid may Increase Artemisinin in planta
Frontiers in Plant Science. 13 August 2018

Seasonaland Differential Sesquiterpene Accumulation in Artemisia annua Suggest Selection Based on Both Artemisinin and Dihydroartemisinic Acid may Increase Artemisinin in planta.

Abstract :

Commercial Artemisia annua crops are the sole source of artemisinin (ART) worldwide. Data on seasonal accumulation and peak of sesquiterpenes, especially ART in commercial A. annua, is lacking while current breeding programs focus only on ART and plant biomass, but ignores dihydroartemisinic acid (DHAA) and artemisinic acid (AA). Despite past breeding successes, plants richer in ART are needed to decrease prices of artemisinin-combination therapy (ACT). Our results show that sesquiterpene concentrations vary greatly along the growing season and that sesquiterpene profiles differ widely among chemotypes. Field studies with elite Brazilian, Chinese, and Swiss germplasms established that ART peaked in vegetative plants from late August to early September, suggesting that ART is related to the photoperiod, not flowering. DHAA peaks with ART in Chinese and Swiss plants, but decreases, as ART increases, in Brazilian plants, while AA remained stable through the season in these genotypes. Chinese plants peaked at 0.9% ART, 1.6% DHAA ; Brazilian plants at 0.9% ART, with less than 0.4% DHAA ; Swiss plants at 0.8% ART and 1% DHAA. At single-date harvests, seeded Swiss plants produced 0.55–1.2% ART, with plants being higher in DHAA than ART ; Brazilian plants produced 0.33–1.5% ART, with most having higher ART than DHAA. Elite germplasms produced from 0.02–0.43% AA, except Sandeman-UK (0.4– 1.1% AA). Our data suggest that different chemotypes, high in ART and DHAA, have complementary pathways, while competing with AA. Crossing plants high in ART and DHAA may generate hybrids with higher ART than currently available in commercial germplasms. Selecting for high ART and DHAA (and low AA) can be a valuable approach for future selection and breeding to produce plants more efficient in transforming DHAA into ART in planta and during post-harvest. This novel approach could change the breeding focus of A. annua and other pharmaceutical species that produce more than one desired metabolite in the same pathway. Obtaining natural variants with high ART Ferreira et al. High ART/DHAA Important for Artemisia Breeding content will empower countries and farmers who select, improve, and cultivate A. annua as a commercial pharmaceutical crop. This selection approach could enable ART to be produced locally where it is most needed to fight malaria and other parasitic neglected diseases.

This article is part of the research topic « Artemisinin - from traditional chinese medicine to artemisinin combination therapies ; four decades of research on the biochemistry, physiology, and breeding of Artemisia annua ».

View all 11 Articles

Julia Penna-Coutinho, Anna CC Aguiar, and Antoniana Ursine Krettli
Commercial drugs containing flavonoids are active in mice with malaria and in vitro against chloroquine-resistant Plasmodium falciparum
Memórias do Instituto Oswaldo Cruz », Instituto Oswaldo Cruz, Received 2018 Jun 6 ; Accepted 2018 Oct 5.

Commercial drugs containing flavonoids are active in mice with malaria and in vitro against chloroquine-resistant Plasmodium falciparum

Abstract :

Background : The main strategy to control human malaria still relies on specific drug treatment, limited now by Plasmodium falciparum-resistant parasites, including that against artemisinin derivatives. Despite the large number of active compounds described in the literature, few of them reached full development against human malaria. Drug repositioning is a fast and less expensive strategy for antimalarial drug discovery, because these compounds are already approved for human use.

Objectives : To identify new antimalarial drugs from compounds commercially available and used for other indications.

Methods : Accuvit®, Ginkgo® and Soyfit®, rich in flavonoids, and also the standard flavonoids, hesperidin, quercetin, and genistein were tested against blood cultures of chloroquine-resistant P. falciparum, as well as chloroquine, a reference antimalarial. Inhibition of parasite growth was measured in immunoenzymatic assay with monoclonal anti-P. falciparum antibodies, specific to the histidine-rich protein II. Tests in mice with P. berghei malaria were based on percent of parasitaemia reduction. These compounds were also evaluated for in vitro cytotoxicity.

Findings : The inhibition of parasite growth in vitro showed that Accuvit® was the most active drug (IC50 5 ± 3.9 μg/mL). Soyfit® was partially active (IC50 13.6 ± 7.7 μg/mL), and Ginkgo® (IC50 38.4 ± 14 μg/mL) was inactive. All such compounds were active in vivo at a dose of 50 mg/kg body weight. Accuvit® and quercetin induced the highest reduction of P. berghei parasitaemia (63% and 53%, respectively) on day 5 after parasite inoculation. As expected, the compounds tested were not toxic.

Main conclusions : The antimalarial activity of Accuvit® was not related to flavonoids only, and it possibly results from synergisms with other compounds present in this drug product, such as multivitamins. Multivitamins in Accuvit® may explain its effect against the malaria parasites. This work demonstrated for the first time the activity of these drugs, which are already marketed.

Key words : malaria, Plasmodium falciparum, antimalarial, drug resistance, flavonoid, new drugs

Jerome Munyangi, Lucile Cornet Vernet, Constant Tchandema, Pierre Lutgen
Deleterious effects of Artemisia infusions on Paramecium, Vibrio and Plasmodium
Pharmacy & Pharmacology International Journal 2018 ; 6(6) : 462-466.

Deleterious effects of Artemisia infusions on Paramecium, Vibrio and Plasmodium

Abstract :

Paramecium is an alveolate closely related to apicomplexan parasites (Plasmodium, Toxoplasma). As in vivo trials with antimalarial drugs are difficult to perform, mostly for ethical reasons, and as in vitro trials may be meaningless because the protozon Plasmodium, which needs a specific culture medium which interfers itself with the antimalarial drug, may react in a completely different way in vivo, where antimalarial drugs are dismantled by metabolism. Cultures of Paramecium tetraurelia are easy to cultivate and to handle. In vitro trials were run in 2014-2015 at the Laboratoire de Biologie cellulaire et moléculaire de l’Université Paris 11 with infusions of Artemisia annua and Artemisia afra and showed several detrimental effects on the behaviour of this parasite. This confirms similar effects on Vibrio fischeri and Vibrio cholerae which had been identified earlier.

Pierre Lutgen
Tannins in Artemisia : the hidden treasure of prophylaxis
Pharmacy & Pharmacology International journal, Volume 6 Issue 3, 2018

Tannins in Artemisia : the hidden treasure of prophylaxis

No abstract

2019

Tomasz Czechowski, Mauro A. Rinaldi, Mufuliat Toyin Famodimu, Maria Van Veelen, Tony R. Larson, Thilo Winzer, Deborah A. Rathbone, David Harvey, Paul Horrocks and Ian A. Graham
Flavonoid Versus Artemisinin Anti-malarial Activity in Artemisia annua Whole-Leaf Extracts
Frontiers in Plant Science, 30 July 2019 »

Flavonoid Versus Artemisinin Anti-malarial Activity in Artemisia annua Whole-Leaf Extracts

Abstract :

Artemisinin, a sesquiterpene lactone produced by Artemisia annua glandular secretory trichomes, is the active ingredient in the most effective treatment for uncomplicated malaria caused by Plasmodium falciparum parasites. Other metabolites in A. annua or related species, particularly flavonoids, have been proposed to either act as antimalarials on their own or act synergistically with artemisinin to enhance antimalarial activity. We identified a mutation that disrupts the CHALCONE ISOMERASE 1 (CHI1) enzyme that is responsible for the second committed step of flavonoid biosynthesis. Detailed metabolite profiling revealed that chi1-1 lacks all major flavonoids but produces wildtype artemisinin levels, making this mutant a useful tool to test the antiplasmodial effects of flavonoids. We used whole-leaf extracts from chi1-1 and mutant lines impaired in artemisinin production in bioactivity in vitro assays against intraerythrocytic P. falciparum Dd2. We found that chi1-1 extracts did not differ from wild-type extracts in antiplasmodial efficacy nor initial rate of cytocidal action. Furthermore, extracts from the A. annua cyp71av1-1 mutant and RNAi lines impaired in amorpha-4,11-diene synthase gene expression, which are both severely compromised in artemisinin biosynthesis but unaffected in flavonoid metabolism, showed very low or no antiplasmodial activity. These results demonstrate that in vitro bioactivity against P. falciparum of flavonoids is negligible when compared to that of artemisinin.

Keywords : malaria, Artemisia annua, artemisinin, flavonoids, Plasmodium falciparum, chalcone isomerase.

Adjogblé Messan Koffi, Bakoma Batomayena, Metowogo Kossi, Amouzou Kodjovi Dotsè, Potchoo Yao, Eklugadegbeku Kwashie, Aklikokou Kodjo A, Gbeassor Menssanvi
Pharmacognostic Studies and Artemisinin Content of Artemisia annua L. Grown in Togo
Pharmacognosy Journal. 2019 ; 11(6):1331-1335

Pharmacognostic Studies and Artemisinin Content of Artemisia Annua L. Grown in Togo

Abstract :

Objective : Artemisia annua grown in Togo is used as an antimalaria drug. The present study shows a detailed analysis of pharmacognostic evaluation of leaf powder and root that will be used for the purpose of identification, authentication, and consequent standardization. Materials and Methods : Both the leaf and root were evaluated for their macroscopic and microscopic features. The physicochemical parameters of the leaf powder and its phytochemical screening were done based on its total phenols and flavonoïd content. Artemisinin content was also performed using weigh method after extraction.

Results : Physicochemical evaluation yielded water, alcohol, acetone, methanol, chloroform, and petroleum ether soluble extractive values which are 2.25%, 1.25%, 4.22%, 8.12% and 3.77% (w/w), respectively. Fluorescence analysis imparted characteristic colors to the leaf powder when observed under visible, UV light 254 and 365 nm. Phytochemical screening of leaf powder showed the presence of alkaloïds, flavonoïd, and anthracene derivatives. Total phenols and flavonoïd content were 32.5 ± 0.67 mEq Gallic Acid/100 mg and 11.3 ± 1.52. mgEq Quercetin/100 mg, respectively. Artemisinin content value was 0.009% (w/w). Conclusion : Various pharmacognostic parameters which were evaluated assisted in identification and standardization of A. annua leaf in powder and crude form.

Key words : Artemisia, Pharmacognostic, Artemisinin, Total phenols, Flavonoid.

Pierre Lutgen
Luteolin in the Artemisia family
Malariaworld.com, 16 mars 2019

Luteolin in the artemisia family

No abstract

Tu Youyou
Études sur les actions pharmacologiques de l’Artemisia annua. Action antivirale
[Chapitre 6] de Youyou Tu, Prix Nobel de médecine. De Artemisia annua L. aux artémisinines. La découverte et le développement des artémisinines et des agents antipaludiques, QuintSciences, ECP Sciences, Chemical Industry Press
2019 Chemical Industry Press, published by Elsevier Inc., with Chemical Industry Press, in association with the B&R Book Program.

Full text not free of copyright. Except submitted on request.

Action antivirale (de l’artemisinine)

Zhigzhitzhapova SV, Dylenova EP, Gulyaev SM, Randalova TE, Taraskin VV, Tykheev ZA, Radnaeva LD.
Composition and antioxidant activity of the essential oil of Artemisia annua L.
Nat Prod Res. 2020 Sep ;34(18):2668-2671. doi : 10.1080/14786419.2018.1548461. Epub 2019 Jan 19. PMID : 30663350.

Abstract

Artemisia annua L. is an annual Eurasian desert-steppe plant. The composition of essential oils found in Artemisia annua from Russian (Buryatian) flora was analyzed in this work using gas chromatography mass-spectrometry method. Artemisia ketone, β-selinene, caryophyllene, caryophyllene oxide, germacrene D were the main components of the analyzed essential oils. The comparison of own and literature data showed that the essential oils of A. annua conditionally could be divided into "Asian" and "European" groups. Our samples, referring to "Asian" profile, exhibited higher antiradical activity in comparison with data from previously published studies.

Keywords : Artemisia annua L. ; Buryatian flora ; DPPH ; antiradical activity ; essential oils ; gas chromatography mass-spectrometry ; principal component analysis.

Pacheco AC, de Oliveira Petkowicz CL.
Changes in the composition and structure of cell wall polysaccharides from Artemisia annua in response to salt stress
Carbohydr Res. 2019 Sep 1 ;483:107753. doi : 10.1016/j.carres.2019.107753. Epub 2019 Jul 23. PMID : 31362136.

Abstract

Artemisia annua is cultivated mainly for isolation of artemisinin, a potent antimalarial compound. Moderate salt stress has been proved to increase the artemisinin synthesis by the plant. The aim of this study was to evaluate the influence of salt stress on physiological parameters and cell wall polysaccharides of A. annua. Plants subjected to salt stress displayed reduction in the biomass and length and showed high damage of cellular membranes. Cell wall polysaccharides extracted from aerial parts with hot water, EDTA and NaOH also exhibited modifications in the yield and monosaccharide composition. The main changes were found in the pectic polysaccharides : increase of homogalacturonan domain, increase of neutral side chains and increase in the methyl esterification. 1H NMR analyses of pectins indicated that for A. annua, arabinans have an important role in coping with salt stress. Hemicellulose domain was also modified under salt stress, with increased xylose contents. The results indicated adaptations in the cell wall of A. annua under salt stress.

Keywords : Abiotic stress ; Arabinose ; Hemicellulose ; Pectin ; Salinity ; Xylan.

B. M. Gruessner, L. Cornet-Vernet, M. R. Desrosiers, P. Lutgen, M. J. Towler, P. J. Weathers
It is not just artemisinin : Artemisia sp. for treating diseases including malaria and schistosomiasis
Phytochem Rev. 2019 December ; 18(6) : 1509–1527. doi:10.1007/s11101-019-09645-9.

Abstract

Artemisia sp., especially A. annua and A. afra, have been used for centuries to treat many ailments. While artemisinin is the main therapeutically active component, emerging evidence demonstrates that the other phytochemicals in this genus are also therapeutically active. Those compounds include flavonoids, other terpenes, coumarins, and phenolic acids. Artemisia sp. phytochemicals also improve bioavailability of artemisinin and synergistically improve artemisinin therapeutic efficacy, especially when delivered as dried leaf Artemisia as a tea infusion or as powdered dry leaves in a capsule or compressed into a tablet. Here results from in vitro, and in vivo animal and human studies are summarized and critically discussed for mainly malaria, but also other diseases susceptible to artemisinin and Artemisia sp. including schistosomiasis, leishmaniasis, and trypanosomiasis.

Keywords : Artemisia annua and Artemisia afra ; Artemisinin resistance ; Bioavailability ; Leishmaniasis ; Malaria ; Schistosomiasis ; Trypanosomiasis

2020

Xinchi Feng, Shijie Cao, Feng Qiu, Boli Zhang
Traditional application and modern pharmacological research of Artemisia annua L.
Pharmacology & Therapeutics, https://doi.org/10.1016/j.pharmthera.2020.107650

Abstract

As a Traditional Chinese Medicine, Artemisia annua L. (A. annua) has been used for the treatment of various diseases since ancient times, including intermittent fevers due to malaria, bone steaming and heat/ fever arising from exhaustion, tuberculosis, lice, wounds, scabies, dysentery et al. With the discovery of artemisinin and its excellent anti-malarial activity, A. annua has received great attention. Recently, A. annua has been revealed to show inhibitory effects against parasites (e.g. Plasmodium, Toxoplasma gondii, Leishmania, Acanthamoeba, Schistosoma), viruses (e.g. hepatitis A virus, herpes simplex viruses 1 and 2, human immunodeficiency virus), fungi (Candida, Malassezia, Saccharomyces spp.) and bacteria (Enterococcus, Streptococcus, Staphylococcus, Bacillus, Listeria, Haemophilus, Escherichia, Pseudomonas, Klebsiella, Acinetobacter, Salmonella, Yersinia spp.). A. annua has also been reported to possess antiinflammatory and anti-cancer actions and been employed for the treatment of osteoarthritis, leukemia, colon cancer, renal cell carcinoma, breast cancer, non-small cell lung cancer, prostate cancre and hepatoma. Besides, the immunoregulation, anti-adipogenic, anti-ulcerogenic, anti-asthmatic, antinociceptive and anti-osteoporotic activities of A. annua were also evaluated. Along these lines, this review summarizes the traditional application and modern pharmacological research of A. annua, providing novel insights of A. annua in the treatment of various diseases.

Mirbehbahani FS, Hejazi F, Najmoddin N, Asefnejad A.
Artemisia annua L. as a promising medicinal plant for powerful wound healing applications.
Prog Biomater. 2020 Sep ;9(3):139-151. doi : 10.1007/s40204-020-00138-z. Epub 2020 Sep 28. PMID : 32989678 ; PMCID : PMC7544745.

Abstract

Artemisia annua L. has been utilized for the first time in a nanofibrous wound dressing composition. The extract of this valuable plant provides anti-inflammatory, anti-bacterial and anti-microbial properties which can be considered as a promising medicinal component in therapeutic applications. In the present work, Artemisia annua L. was picked up from Gorgan forest area of Northern Iran and its extract was prepared by methanol as the extraction solvent. In the fabrication of wound dressing, Artemisia annua L. extract was mixed with gelatin and a nanofibrous structure was formed by electrospinning technique. To have a wound dressing with acceptable stability and optimum mechanical properties, this biologically active layer was formed on a PCL nanofibrous base layer. The fabricated double-layer wound dressing was analyzed chemically, structurally, mechanically and biologically. ATR-FTIR spectra of the prepared wound dressing contain functional groups of Artemisia annua L. as peroxide groups, etc. SEM micrographs of electrospun gelatin/Artemisia annua L. confirmed the successful electrospinning process for producing Artemisia annua L.-containing nanofibers with mean diameter of 242.00 ± 67.53 nm. In vitro Artemisia annua L. release study of the fabricated wound dressings suggests a sustain release over 7 days for the crosslinked sample. In addition, evaluation of the in vitro structural stability of the prepared wound dressings confirmed the stability of the crosslinked nanofibrous structures in PBS solution environment. Biological study of the Artemisia annua L.-containing wound dressing revealed no cytotoxicity, good proliferation and attachment of the seeded fibroblasts cells and acceptable antibacterial property against Staphylococcus aureus bacteria.

Keywords : Antibacterial property ; Artemisia annua L. ; Electrospinning ; Gelatin–Artemisia annua L. nanofibers ; Wound dressing.

Huo J, Lu Y, Xia L, Chen D.
Structural characterization and anticomplement activities of three acidic homogeneous polysaccharides from Artemisia annua.
J Ethnopharmacol. 2020 Jan 30 ;247:112281. doi : 10.1016/j.jep.2019.112281. Epub 2019 Oct 7. PMID : 31600559.

Abstract

Ethnopharmacological relevance : Artemisia annua L. is a heat-clearing Chinese medicine and well-known for its antimalarial constituent, artemisinin. It has gained increasing attention for its anti-inflammatory and immunoregulatory activities. Interestingly, the crude polysaccahrides of A. annua exhibited potent anticomplement activity. This study was to isolate and characterize its anticomplement homogeneous polysaccharides from A. annua, and reveal the relationship between structures and anticomplement activities of the isolated polysaccharides.

Materials and methods : Water-soluble crude polysaccharides from the aerial parts of A. annua were extracted and fractionated by DEAE-cellulose and Sephacryl S-300 gel permeation chromatography. Homogeneity, molecular weight, monosaccharide composition, methylation and NMR analysis were performed to characterize the structures of homogeneous polysaccharides. Their anticomplement activities and targeting components in the complement activation cascade were evaluated by hemolytic assays.

Results : Three homogeneous polysaccharides (AAP01-1, AAP01-2 and AAP01-3) were obtained from A. annua. AAP01-1 was composed of seven monosaccharides, including mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose. AAP01-2 and AAP01-3 had similar monosaccharides with AAP01-1, except the absence of glucuronic acid. They were all branched acidic heteropolysaccharides with different contents of galacturonic acid (8%, 28% and 15% for AAP01-1, AAP01-2 and AAP01-3, respectively). AAP01-2 showed potent anticomplement activity with CH50 value of 0.360 ± 0.020 mg/mL through the classical pathway and AP50 value of 0.547 ± 0.033 mg/mL through the alternative pathway. AAP01-3 exhibited slightly weaker activity (CH50 : 1.120 ± 0.052 mg/mL, AP50 : 1.283 ± 0.061 mg/mL), while AAP01-1 was inactive. Moreover, AAP01-2 acted on C1q, C3, C4, C5 and C9 components and AAP01-3 interacted with C3, C4 and C5 components in the activation cascade of complement system.

Conclusion : These results indicated that the relatively high contents of galacturonic acid were important for anticomplement activities of the polysaccharides from A. annua. The anticomplement polysaccharides are another kind of bioactive constituents conferring heat-clearing effects of A. annua.

Keywords : Anticomplement ; Artemisia annua ; Galacturonic acid ; Polysaccharide ; Structure.

2021

Liu H, Guo SS, Lu L, Li D, Liang J, Huang ZH, Zhou YM, Zhang WJ, Du S.
Essential oil from Artemisia annua aerial parts : composition and repellent activity against two storage pests.
Nat Prod Res. 2021 Mar ;35(5):822-825. doi : 10.1080/14786419.2019.1599887. Epub 2019 Apr 8. PMID : 30961365.

Abstract

As a medicinal plant, Artemisia annua is widely distributed in China. The purpose of this work was to analyze the chemical composition of essential oil from A. annua aerial portions, as well as to assess its repellent activity against Lasioderma serricorne and Tribolium castaneum adults. GC-FID and GC-MS analyses enabled the identification of 15 components representing 90.1% of the essential oil. The main components included artemisia ketone (70.6%), α-caryophyllene (5.1%) and germacrene D (3.8%). The essential oil was found to possess considerable ability to repel the two storage pests. This paper provided some evidence for the exploitation and utilization of A. annua resources as a natural repellent.

Keywords : Artemisia annua ; Lasioderma serricorne ; Tribolium castaneum ; artemisia ketone ; repellent.

Mis en ligne par La vie re-belle
 27/03/2020
 https://lavierebelle.org/composition-et-mode-d-action-sur

 Documents

 Tannins in Artemisia : the hidden treasure of prophylaxis
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 Pharmacy & Pharmacology International journal
 Preliminary Phytochemical Screening and Physico-Chemical Parameters of Artemisia absinthium and Artemisia annua
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 Journal of Pharmacognosy and Phytochemistry
 Flavonoid Versus Artemisinin Anti-malarial Activity in Artemisia annua Whole-Leaf Extracts
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 Frontiers in Plant Science
 Whole Plant Approaches to Therapeutic Use of Artemisia annua L. (Asteraceae)
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 Pharmacology and Biotechnology, Springer-Verlag Berlin Heidelberg

Pharmacologie

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

Les articles 9

Sont regroupées dans cet article les études toxicologiques publiées concernant Artemisia annua L.
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 (...)
IMG: Pharmacocinétique d'Artemisia annua L. Cet article regroupe et rend disponible les publications relatives aux étude du devenir d’Artemisia annua et de ces composés dans (...)
Cet article présente les études publiées concernant l’activité in vitro d’Artemisia annua L. sur les Plasmodiums, agents pathogènes à l’origine du (...)
IMG: Etudes in vivo de la tisane d'Artemisia annua sur le Plasmodium falciparum Cet article recense et donne accès aux études relatives aux études in vivo propriétés antipaludiques d’extraits d’Artemisia annua. Les publications sont ordonnés (...)
Ce document rassemble les études relatives aux activités anti-infectieuses d’Artemisia annua autres qu’antipaludique, et à l’utilité potentielle des extraits de (...)
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