Composition et mode d’action sur le Plasmodium falciparum

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

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

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.

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

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.

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

2014

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

Full text submitted to request

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

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 ».

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

 Documents

 Deleterious effects of Artemisia infusions on Paramecium, Vibrio and Plasmodium
PDF 
 Pharmacy & Pharmacology International Journal
 The content of artemisinin in the Artemisia annua tea infusion
PDF 
 Planta medica
 Commercial drugs containing flavonoids are active in mice with malaria and in vitro against chloroquine-resistant Plasmodium falciparum
PDF 
 Instituto Oswaldo Cruz
 Anti-Plasmodial Polyvalent Interactions in Artemisia annua L. Aqueous Extract – Possible Synergistic and Resistance Mechanisms
PDF 
 PLoS ONE

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 (...)
Cet article regroupe et rend disponible les publications relatives aux étude du devenir d’Artemisia annua dans l’organisme.
Cet article présente les études publiées concernant l’activité in vitro d’Artemisia annua L sur le le Plasmodium falciparum
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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