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Artemisia Annua L., Potential Source of Molecules with Pharmacological Activity in Human Diseases Luz Estella Mesa*1,2, Pierre Lutgen3, Ivan D

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Artemisia Annua L., Potential Source of Molecules with Pharmacological Activity in Human Diseases Luz Estella Mesa*1,2, Pierre Lutgen3, Ivan D Original Article Artemisia annua L., Potential Source of Molecules with Pharmacological Activity in Human Diseases Luz Estella Mesa*1,2, Pierre Lutgen3, Ivan D. Velez1, Angela M. Segura2 and Sara M. Robledo1 1PECET- Medical Research Institute, School of Medicine, University of Antioquia-UdeA. Calle 70 # 52-21, Medellin-Colombia 2Epidemiology and Biostatistic, Universidad CES Calle 10 A No. 22 - 04. Medellin-Colombia 3IFBV-BELHERB, PO Box 98, L-6905 Niederanven, Luxembourg ABSTRACT Objective: This review intends to motivate and encourage researchers to explore new alternatives to treat different diseases with Artemisia annua L., an important plant of traditional Chinese pharmacopoeia that has been used for more than 2.000 years in the treatment of different diseases, mainly malaria. Methods: Data include currently available information about A. annua, its origin, traditional use in medicine, pharmacological activity, toxicity and main metabolites with reported clinical activity. The information was collected by literature search on web databases such as Pubmed and Google Scholar up to 2014 on publications about the medicinal uses of A. annua L., in the treatment of different diseases that affect humans but also some animals. Results: Pharmacological activity against chronic and infectious diseases of various metabolites from A. annua, artemisinin and its derivatives, flavonoids and essential oils, reported in this review, is supported by preclinical experimental evidence both in vivo and in vitro and clinical observations in human beings of different parts of Address for the plant, mainly leaves, in the treatment of malaria. Leaves, seeds Correspondence and whole plant of A. annua have also proved pharmacological activity against parasites responsible of leishmaniasis and Chagas PECET- Medical disease. Recently, the first report of in vivo efficacy of A. annua research Institute, against dengue fever was published. School of Medicine, University of Conclusions: This review highlights the pharmacological potential Antioquia-UdeA. Calle of the A. annua plant in the treatment of several infectious diseases 70 # 52-21, Medellin- and unveils its suitable profile of safety and tolerability. Colombia. Keywords: Artemisia annua, Antibacterial activity, Antiparasitic E-mail: activity, Anti-inflammatory activity, Antiviral potential, Anthelmintic [email protected] activity. American Journal of Phytomedicine and Clinical Therapeutics www.ajpct.org Mesa et al___________________________________________________ ISSN 2321 – 2748 INTRODUCTION Artemisia annua L., is a plant Scientific name included in the Chinese Pharmacopeia that Artemisia annua L. (Latin name) has been used since more than 2000 years to belongs to Asteraceae Family (also known cure a broad array of diseases. During the as Compositae), Genus: Artemisia and Vietnam war the whole plant was supplied Especie: A. annua. Carl von Linnaeus to the Vietcong as a remedy against malaria. already listed the plant in his Species In 1972 a Chinese research team discovered Plantarum in 1793. in the leaves of the plant a molecule, which they called artemisinin or quinhaosu. This Common name molecule and its derivatives were initially A. annua is commonly known in used in monotherapy against malaria. But English as “sweet wormwood”, “annual after 30 years of use severe resistance wormwood”, “sweet sagewort” or “sweet developed. WHO recommended to combine annie”. In Chinese is named “qinghao” or artemisinin with other long lasting “huag hua hao” while in French is called antimalarials like lumefantrine, mefloquine “armoise annuelle”. or amodiaquine. These combinations are called ACT (artemisin combined therapy). Origin The discovery of the plant A. annua was a A. annua is an annual plant of major breakthrough in the fight against Chinese origin. It spread in Europe and malaria. America in river valleys as offspring of There are however some problems seeds imported by merchant vessels but it relating to the use of artemisinin. The main grows preferably at altitudes of 1000 to problem is that it is a very fast acting drug 1500 m. It has a vegetation period of six with a very short half-life. It therefore needs months. Its leaves are extensively used in to be combined with a slower acting drug in Chinese Traditional Medicine (TCM) for the order to assure the effective elimination of treatment of malaria, fever, tuberculosis, all the parasitaemia. Another problem is the nematodes, ulcers, diarrhea1. assurance of an adequate supply of artemisinin. Due to its complex chemical Distribution structure the synthesis and/or semi-synthesis Currently, A. annua grows in all remains to be difficult and therefore the continents and climates. The plant however main source of artemisinin remains to be prefers countries with pronounced summers isolation and purification from the A. annua and winters and does not like equatorial plant. In addition, the annual production of days with a constant daylight duration of 12 A. annua varies from a boom and bust cycle hours. It is cultivated at large scale in Asia with overproduction and low prices the one and Africa for the extraction and supply of year to underproduction and high prices the artemisinin. Other countries are adopting next year due to environmental and their own plantations to promote the use of economic influences. The cost of this this plant in the traditional medicine2. Western style treatment is also far too high for where it is used, predominantly in non- Constituents of A. annua L. of Western countries1. pharmacological use or interest The best known of these constituents is the sesquiterpenoid artemisinin and its chemical derivatives artesunate, artemether, AJPCT[3][05][2015] 436-450 Mesa et al___________________________________________________ ISSN 2321 – 2748 arteether. The plant not only has a high the mitochondria of the parasite, and more content of polyphenols, flavonoids, proteins, specifically the protein TCTP or the coumarins, phytosterols, polysaccharides but PfATP6, an ATP localized in the also in potassium, selenium and nitrate sarcoplasma of the parasite5. More recent inorganic salts. Volatile essential oils are studies with yeast indicate that artemisinins present at concentrations of 0.20-0.25%. change the potential of the mitochondrial Other important constituents include membrane if the glycolysis of ethanol, camphene, ketone, camphor, beta- glycerol and other sugars are inhibited. caryophyllene, pinene and 1, 8-cineole2. There are several other approaches trying to explain the action of artemisin. Artemisinin However, after three decades these theories Artemisin is a sesquipterpene lactone are still conflicting and how artemisinins containing an endoperoxyde bridge that is work remains to be understood5. present in many other species of Artemisia3, although at very low concentrations. In vitro Flavonoids artemisinin has one of the lowest LD50 Over the last 40 years hundreds of against Plasmodium spp. In vivo it is also peer reviewed papers have concentrated very active against various stages of their research on the antiparasitic effect of Plasmodium of different species. The artemisinin and its chemical derivatives toxicity of the molecule is negligable at while other constituents have deserved less therapeutic doses; however, repeated use at attention. Particularly polyphenols and high doses of artemisinin has been flavonoids are now considered as key actors associated with haemolysis and toxicities in in the efficiency of A. annua and other liver, spleen, nervous and cardiovascular plants of this family. Flavonoids such as system; artemisinin is also considered artemetin, rutin, quercetin, casticin, eupatin, genotoxic, ototoxic and embryotoxic4. luteolin and their glucosides have a variety of biological activities many of them Artemisinin derivatives synergizing the effects of artemisinin. Artemisinin has been chemically Luteolin has shown antimalarial and modified by pharmaceutical companies to antioxidant activities6. In general flavonoids enhance its solubility either in water inhibit CYP3A4 which is responsable for the (artesuante) or in lipids (artemether). It is rapid metabolism of artemisinin. Flavonoids claimed that these derivatives are 5 times are known to persist in the body for > 5 more efficient than artemisinin although days; this may explain that a once a week scientific data to substantiate this claim are dose induces a prophylactic effect from A scarce. They are rapidly metabolized into annua tea infusion7,8. dihydroartemisinin and their half live in the human body is very short. One of the first Coumarins mechanisms which was proposed for the A. annua contains several coumarins action of the artemisinins was that they and most Artemisia species contain interfered with digestion of hemoglobin in predominantly scopoletin which is the food vacuole. This theory is based on the considered hepatoprotective. Scopoletin has Fenton reaction in which the endoperoxide also immunomodulatory and anti- reacts with iron and creates a flurry of inflammatory activities9. The concentration radicals which kill the parasite. Other of scopoletin in several samples of A. annua studies indicate that the artemisinins attack as measured at Luxembourg is around 0.2% AJPCT[3][05][2015] 436-450 Mesa et al___________________________________________________ ISSN 2321 – 2748 (w/w). Coumarins have anti-coagulatory In turn, saponins, common in many properties10,11. plants, have been described in A. abrotanum19 and A. sphaerocephala20.
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