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Artemisia Annua L. infusion consumed once a week reduces risk of multiple episodes of malaria: A randomised trial in a Ugandan community
Abstract
Purpose: To evaluate the protective effect of Artemisia annua infusion against malaria in a community that uses it as herbal 'tea' for malaria prevention. Methods: 132 flower farm workers who met the study inclusion criteria and were not yet using A. annua infusion were randomized either to A. annua or placebo groups in the ratio of 1:1. Treatments were administered once a week under direct observation to participants. Malaria episodes were documented over a 9-month period while adverse effects were documented over 12 months. Results: A. annua herbal 'tea' significantly reduced the risk of suffering more than one episode of malaria in nine months by 55 % (12/67 vs 26/65, p = 0.005 No participant experienced any serious adverse effect although bitter taste was the most common side effect of the infusion. Conclusion: Artemisia annua infusion consumed once a week was effective in preventing multiple episodes of malaria in humans living in malaria endemic areas. However, its bitter taste and the risk of development of malaria parasite resistance to the artemisinin contained in it remain major challenges for its use in the mass control of malaria. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria.
... This confirms the reported no toxicity at 5000 mg/kg for Artavol® as in (Ogwang et al., 2011). According to the study by Ogwang et al. (2012) it was documented that Artemisia annua tea had a protective effects of 50% in the population of workers in a flower farm who used it over a period of 9 months and it also concluded that the observed effects could be due to the flavonoid content (Ogwang et al., 2012). The findings above which has indicated that the LD 50 is greater than 5000 mg/kg for Artavol®, does not guarantee their safety at doses above these levels and whether their toxicity profiles would remain the same at higher doses. ...
... This confirms the reported no toxicity at 5000 mg/kg for Artavol® as in (Ogwang et al., 2011). According to the study by Ogwang et al. (2012) it was documented that Artemisia annua tea had a protective effects of 50% in the population of workers in a flower farm who used it over a period of 9 months and it also concluded that the observed effects could be due to the flavonoid content (Ogwang et al., 2012). The findings above which has indicated that the LD 50 is greater than 5000 mg/kg for Artavol®, does not guarantee their safety at doses above these levels and whether their toxicity profiles would remain the same at higher doses. ...
... The findings above which has indicated that the LD 50 is greater than 5000 mg/kg for Artavol®, does not guarantee their safety at doses above these levels and whether their toxicity profiles would remain the same at higher doses. The current findings which found both product having a LD 50 greater than 5000 mg/kg thus confirms the earlier results reported (Ogwang et al., 2012). The claim that the product was devoid of artemisinin compounds as in Ogwang et al. (Ogwang et al., 2012) is not true as dihydroartemisinin-3desoxy and deoxyartemisinin with confirmed chemical structures (Figure 1 Artavol® select) were found in the product from the Gas-Chromatography Mass spectrophotometric analysis conducted and a list of other compounds detected in Artavol® (Table 1). ...
... On the other hand, studies have demonstrated that Artemisia annua Tu, 1972 and Artemisia afra Huxley et al., 1992 in the form of infusions or powdered leaves reduce parasitemia and might kill the transmissible gametocyte forms, with characteristic chemoprotective potentials [17][18][19][20][21][22][23]. ...
... While A. annua cultivars have high artemisinin content, cultivars of A. afra are devoid of artemisinin, while other cultivars have negligible contents of artemisinin [17]. Despite it being devoid of artemisinin or having a negligible artemisinin content, A. afra has also demonstrated good anti-plasmodial properties both when it is used in infusions or crude extracts in vitro and in vivo [17][18][19]21,22,30,[35][36][37]. In vitro studies have also confirmed antiparasitic activity of A. afra tea infusions against the different stages of the malaria parasite including the gametocyte stage, with no cytotoxicity [17][18][19]21,22]. ...
... Despite it being devoid of artemisinin or having a negligible artemisinin content, A. afra has also demonstrated good anti-plasmodial properties both when it is used in infusions or crude extracts in vitro and in vivo [17][18][19]21,22,30,[35][36][37]. In vitro studies have also confirmed antiparasitic activity of A. afra tea infusions against the different stages of the malaria parasite including the gametocyte stage, with no cytotoxicity [17][18][19]21,22]. ...
Malaria is the most widespread endemic disease in Cameroon, and asymptomatic Plasmodium (gametocyte) carriers (APCs) constitute more than 95% of infectious human reservoirs in malaria endemic settings. This study assesses the knowledge of asymptomatic malaria (ASM) among health care workers (HCWs) in health facilities (HFs) in the Centre Region of Cameroon and the acceptability of using Artemisia afra tea to treat APCs. A cross-sectional descriptive survey was conducted among 100 HCWs, in four randomly selected HFs in the Centre Region, in the period of 1–20 April 2022, using semi-structured self-administered questionnaires. Logistic regression analyses were performed to determine factors associated with knowledge. More than seven in eight (88%) respondents were aware of the existence of ASM, 83% defined ASM correctly, 75% knew how it was diagnosed, 70% prescribe ACTs for APCs, and 51.1% were informed about ASM transmission. The professional category of HCWs was significantly associated with their knowledge of the existence and transmission of ASM, and longevity of service was associated with knowledge of transmission (p < 0.05). Two-thirds (67%) of respondents knew about Artemisia afra tea, 53.7% believed that it was effective in treating ASM, and 79% were willing to prescribe it if authorized. There was a fair level of knowledge of ASM among HCWs in the study settings.
... Artemisia annua as prophylaxis? Ogwang et al. (2011Ogwang et al. ( , 2012 documented 80% reduction in malaria cases among Ugandan adults who drank a weekly dose of A. annua tea. Those individuals previously had malaria. ...
... Flavonoids in particular have shown importance with respect to efficacy of whole-plant treatment regimens (dried leaves or tea infusion, for example). Since flavonoids can persist in the body for more than 5 days, they could be helpful in promoting prophylactic antimalarial action (Ogwang et al. 2011(Ogwang et al. , 2012 and Table 2). ...
... Non-artemisinin phytochemical activity against artemisinin-resistant malaria and other microbes As described above, there is empirical evidence that there is antimalarial activity in A. annua leaves beyond their artemisinin content. Artemisinin content fails to explain its efficacy as an antimalarial prophylactic well beyond the persistence time of artemisinin in the patient (Birgersson et al. 2016;Gordi et al. 2000;Hien et al. 2011;Ogwang et al. 2012). That conclusion is further supported by the antimalarial efficacy of A. afra, which contains at best traces of artemisinin (Munyangi et al. 2018). ...
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.
... Rutin, the rutinose glycoside of quercetin, showed similar results, indicating that antimalarial activity is not affected by the sugar moiety [62]. Flavonoids can persist in the body for >5 days, so this may explain the antimalarial prophylactic effect of a weekly A. annua tea infusion [65,66]. Although they can inhibit Plasmodium growth in vitro, FLV levels in the diet are reportedly insufficient to offer protection t0010 10005-SNPC52C-9780444639318 ...
... While used historically by the Chinese to treat fever, tea infusion is not recommended as a reliable therapeutic delivery mode mainly because it is impossible to deliver a consistent dose, large volumes of bitter tasting liquid must be consumed, and other potentially important plant phytochemicals may not be stably extracted into the infusion [124,125]. On the other hand, a tea infusion consumed once weekly over months provided an 80% reduction in malaria cases [65,66]. Dried leaf artemisinin delivery (DLA; aka pACT), studied both in rodents and humans is discussed further in subsequent sections. ...
Artemisinin is a molecule crucial for treating malaria. Naturally produced in the plant Artemisia annua, this sesquiterpene lactone has broad therapeutic efficacy against a variety of parasites, viruses, and neoplasms with a diverse effect on the immune system. The molecule has a variety of therapeutic mechanisms, some still under debate. Here we describe the production and regulation of the molecule in A. annua and include a brief discussion of the in planta production of other important phytochemicals that may work synergistically with artemisinin to enhance therapeutic efficacy or bioavailability. This is followed by a discussion of the current state of knowledge in two important areas regarding the mechanism of action of artemisinins on Plasmodium sp. that cause malaria versus mechanisms that affect cancer cells and immune system responses. Last, artemisinins per se, Artemisinin Combination Therapy (ACT), and plant-based Artemisinin Combination Therapy (pACT) will be compared and critically assessed for their therapeutic efficacy in cell cultures, animals, and, where known, humans.
... However, the drop in the demand for artemisinin from Uganda by the industries that make its derivatives led to uncontrolled and wide spread local cultivation and use of the plant in Uganda. The plant is now cultivated and used by communities in Central, Eastern and Northern Uganda which are low land areas (less than 1200m above sea level) initially not recommended for the plant 8,9 . A recent study in Uganda reported that although Ugandan soils are suitable for cultivation of artemisinin, artemisinin levels vary with area of cultivation. ...
... These variations call for quality control and standardization of material for not only of artemisinin levels but also of total flavonoids. This is because flavonoids have been shown to play major role in use of A.annua for malaria treatment and prophylaxis 4,8,9 . ...
Chemical profile of Artemesia annua
... In a randomised clinical trial in Uganda (Ogwang et al. 2011(Ogwang et al. , 2012, Artemisia tea was tested as a prophylaxis against malaria in 132 farm workers for 9 months, and any adverse clinical effects were tracked for 12 months. Tea consumed once a week at a 2.5 g adult infusion dose, had an unadjusted protective efficacy of 37.5% (Ogwang et al. 2012), which is better than that reported for vaccines RTS, S/AS01B and RTS, S/AS02A with protection efficacy of about 30% in adults (Bojang et al. 2001;Polhemus et al. 2009). ...
... In a randomised clinical trial in Uganda (Ogwang et al. 2011(Ogwang et al. , 2012, Artemisia tea was tested as a prophylaxis against malaria in 132 farm workers for 9 months, and any adverse clinical effects were tracked for 12 months. Tea consumed once a week at a 2.5 g adult infusion dose, had an unadjusted protective efficacy of 37.5% (Ogwang et al. 2012), which is better than that reported for vaccines RTS, S/AS01B and RTS, S/AS02A with protection efficacy of about 30% in adults (Bojang et al. 2001;Polhemus et al. 2009). It was also superior to FMP1/AS02 vaccine that was reported to confer no protection and also to vaccines LSA-NRC/AS01 and LSA-NRC/AS02 that elicited antigen-specific antibody and CD4+ T cell responses, but with no protective immunity Cummings et al. 2010). ...
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. © 2014 Springer-Verlag Berlin Heidelberg. All rights are reserved.
... However, the drop in the demand for artemisinin from Uganda by the industries that make its derivatives led to uncontrolled and wide spread local cultivation and use of the plant in Uganda. The plant is now cultivated and used by communities in Central, Eastern and Northern Uganda which are low land areas (less than 1200m above sea level) initially not recommended for the plant 8,9 . A recent study in Uganda reported that although Ugandan soils are suitable for cultivation of artemisinin, artemisinin levels vary with area of cultivation. ...
... These variations call for quality control and standardization of material for not only of artemisinin levels but also of total flavonoids. This is because flavonoids have been shown to play major role in use of A.annua for malaria treatment and prophylaxis 4,8,9 . ...
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.
... Ogwang et al [30,31] tested Artemisia tea as a prophylaxis against malaria in 132 adult farm workers, aged 18-60 years, for 12 mo in a randomized clinical trial in Uganda. Tea infusion was consumed once a week at 2.5 g dried leaves per adult infusion dose with 55-100 mg artemisinin/L. ...
... Rutin, which is a rutinose [α-L-rhamnopyranosyl-(1 →6)-β-D-glucopyranose] glycoside of quercetin, showed similar results, suggesting that the sugar moiety did not significantly affect antimalarial activity (Table 1 [58] ). Flavonoids are known to persist in the body for > 5 d; this may explain the once a week dose inducing a prophylactic effect from A. annua tea infusion that was reported by Ogwang et al [30,31] . Many dietary flavonoids inhibit Plasmodium growth in vitro, but amounts in the diets are reportedly insufficient to offer protection against malaria [54] . ...
Artemisinin from the plant Artemisia annua (A. annua) L, and used as artemisinin combination therapy (ACT), is the current best therapeutic for treating malaria, a disease that hits children and adults especially in developing countries. Traditionally, A. annua was used by the Chinese as a tea to treat "fever". More recently, investigators have shown that tea infusions and oral consumption of the dried leaves of the plant have prophylactic and therapeutic efficacy. The presence of a complex matrix of chemicals within the leaves seems to enhance both the bioavailability and efficacy of artemisinin. Although about 1000-fold less potent than artemisinin in their antiplasmodial activity, these plant chemicals are mainly small molecules that include other artemisinic compounds, terpenes (mainly mono and sesqui), flavonoids, and polyphenolic acids. In addition, polysaccharide constituents of A. annua may enhance bioavailability of artemisinin. Rodent pharmacokinetics showed longer T1/2 and Tmax and greater Cmax and AUC in Plasmodium chabaudi-infected mice treated with A. annua dried leaves than in healthy mice. Pharmacokinetics of deoxyartemisinin, a liver metabolite of artemisinin, was more inhibited in infected than in healthy mice. In healthy mice, artemisinin serum levels were > 40-fold greater in dried leaf fed mice than those fed with pure artemisinin. Human trial data showed that when delivered as dried leaves, 40-fold less artemisinin was required to obtain a therapeutic response compared to pure artemisinin. ACTs are still unaffordable for many malaria patients, and cost estimates for A. annua dried leaf tablet production are orders of magnitude less than for ACT, despite improvements in the production capacity. Considering that for > 2000 years this plant was used in traditional Chinese medicine for treatment of fever with no apparent appearance of artemisinin drug resistance, the evidence argues for inclusion of affordable A. annua dried leaf tablets into the arsenal of drugs to combat malaria and other artemisinin-susceptible diseases.
... In Uganda, A. annua was introduced around 2003 [14] and is mainly grown in Wakiso, Kaberamaido, Kapchorwa, Rukungiri, Kabarole and Kabale districts. The plant contains many antimalarial compounds such as artemisinin, flavonoids and polysaccharides [11,26]. However, the content of these compounds is low compared to other countries for example artemisinin concentration is below 1% yet in other parts of the world it is up to 2% [19]. ...
Introduction: Artemisia annua is a medicinal plant grown by Ugandan farmers in Kabale and Kabarole. It is particularly used in preparation of antimalarial herbal teas used to control and prevent malaria. The content of these antimalarial compounds in A.annua (Anamed) grown in Uganda are low compared to cultivars in other countries but could be enhanced using economical, eco-friendly, and sustainable fertilizers (biofertilizers). Thus, the effect of commercially available biofertilizers in Uganda on A.annua antimalarial components was assessed. Methodology: Seven different commercially available biofertilizers containing nitrogen fixing strains and phosphate solubilizers obtained from the top biofertilizer distributors to Uganda (Shittah Agri and Biotech Pvt Ltd4 106 C22) and manufacturer (Kinyara Sugar Works Ltd.) were used. Their efficiency was assessed by measuring the vegetative growth characters and the content of flavonoids and artemisinin (using High Performance Liquid Chromatography, HPLC) and polysaccharides (using Ultra Violet visible, UV-vis spectrophotometer). Results: Though overall increase in growth was observed upon application of the biofertilizers, there was variation in the concentration of the antimalarial compounds. The highest kaempferol content and artemisinin content were observed in A. annua inoculated with Azotobacter spp. AZT (17.05 µg/ml and 1.43%) and Bacillus subtilis, BS (19.12 µg/ml, 1.42%) while the highest quercetin content was observed in A. annua inoculated with AZT (0.42 µg/ml) and Bacillus megaterium, BM (0.41 µg/ml). Additionally, fertilizers (biofertilizers and chemical fertilizers) decreased polysaccharide content. Conclusion: The findings demonstrate that application of commercially available biofertilizers in Uganda is beneficial in increasing concentration of artemisinin and flavonoids and thus can be utilized by Artemisia annua farmers in Uganda.
... Artemisia annua, a traditional herbal tea utilized for the treatment of various infectious diseases, including malaria, boasts a history spanning over 2,000 years [58] . Moreover, since the awarding of the 2015 Nobel Prize in Physiology or Medicine to Youyou Tu, a Chinese pharmacologist credited with the initial isolation of artemisinin [59] , an effective antimalarial compound found in Artemisia annua, research on this herbal tea has remained a focal point. Scholars have consistently explored its advantages and safety in the context of herbal tea applications [60,61] . ...
Herbal tea, being a beverage with medicinal and edible properties, has served a significant role in promoting health and preventing diseases, leading to ongoing research advancements. This study utilizes bibliometric analysis to examine the comprehensive research status. CiteSpace was employed to conduct an analysis of the literature in the herbal tea field from 2000 to 2023, examining authorship, country and region distribution, institutional affiliations, and keyword relationships using data from the Web of Science database. The findings revealed a fluctuating yet overall upward trend in the volume of publications. China, the USA, Italy, Poland, and Malaysia emerged as the primary drivers of development in this domain. The collaboration network among authors and institutions is still in the developmental stage. Extensive cooperation can facilitate swift and sustained progress, which is urgently needed for the development of this field. Notably, there is substantial interest in the antioxidant properties of herbal tea and its phenolic compounds, particularly flavonoids, while fruit tea is emerging as a new research frontier. Furthermore, the safety aspects of herbal tea have garnered considerable research attention. There are numerous types and complex functions of herbal teas worldwide, and the regulations for their adaptation need to be improved.
... The activity of monocytes alone and immunoglobulins alone was moderate and inconsistent. [59][60][61] Lactoferrin contained in milk selectively segregates into the skin and significantly reduces the sebum content and increases the number of keratinocytes, their migration and reduces their apoptosis. [62][63][64] Human saliva also is rich in lactoferrin. ...
Abstract
Naturally acquired immunity to malaria is a known phenomenon. But little is known about the underlying mechanisms. The majority of adults in sub-Saharan Africa rarely experience overt disease, despite they have a population of parasites in their blood that could prove lethal to a malaria-naïve visitor. The use of Artemisia herbal medicine is spreading in many African countries, in schools, health centers. It was shown 10 years ago in Uganda that regular drinking of infusions from Artemisia plants had a strong prophylactic effect. We were of the belief that this prophylaxis was going to last for a few days, maybe a few weeks. Over the last 2 months we received several surprising inputs indicating that this prophylaxis was lasting for months, even years. But more recently several partners also report that when Artemisia infusions or capsules have been used during 7 days to cure a malaria infection, the people having used this short-term treatment also experience a long-lasting prophylaxis. The most interesting research lead is that specific IgEs induced by Artemisia consumption remain for months in the skin. In this review paper we present several hypotheses to explain this revolutionary property of Artemisia plants, and more particularly Artemisia afra used since generations in many African countries against tropical diseases.
Keywords: artemisia, plasmodium, immunoglobulins, gametocytes, prophylaxis
... This is because, in comparison to previous years, young mothers are more aware of the benefits of using antenatal facilities. Pregnant women are also given free bed nets at such facilities (Masangwi et al., 2012); (Nsagha et al., 2011); (Ogwang et al., 2012). This showed that the mother believes in the efficiency of ITNs to prevent mosquito bites, thereby effectively preventing malaria during pregnancy. ...
There are few guidelines for health workers to follow when providing and managing malaria prevention therapy during pregnancy, but due to a lack of effective treatment options, malaria management during pregnancy has become non-standard in many countries. This study aims to assess the malaria prevention program in pregnancy, including its advantages, challenges, and obstacles. It was carried out using a systematic scoping review of the literature to identify publications that addressed the prevention program. A structured search was conducted on different databases using predefined eligibility criteria for the 17 selected articles. Malaria prevention programs in pregnancy are effective, but they must be integrated and involve the community. Various countries are having difficulty implementing WHO-recommended strategies, such as Long-Lasting Insecticide Nets (LLINs), antimalarial drugs, and Rapid Diagnostic Tests. Therefore it is necessary to develop an integrated program to prevent and treat malaria in pregnancy.
... Artemisia annua is widely grown in different parts of the world as a cheap source of the antimalarial compounds such as artemisinin, flavonoids, aromatic oils and polysaccharides [1,2]. In Uganda, A. annua was introduced around 2003 [3] and is mainly grown in Wakiso, Kaberamaido, Kapchorwa, Rukungiri, Kabarole and Kabale districts. ...
High land areas in Uganda are suitable for the farming of Artemisia annua. However, harvested A. annua from these areas contain varying concentrations of antimalarial components. This may be attributed to variation in soil properties which affect vegetative growth characters, yield and active compounds of A. annua. Thus, bacterial composition and physiochemical properties of soil from Kabale and Kabarole high land areas where A. annua is grown were studied. The study objective was to determine the diversity of bacterial community in the rhizosphere and bulk soil of A. annua grown in highlands of Uganda. Composition of bacterial community was analyzed by amplicon sequencing of 16S rRNA genes on an Illumina Miseq platform. A total of 1,420,688 read counts was obtained and clustered into 163,493 Operational Taxonomic Units ((OTU). Kabarole highland had more OTUs (87,229) than Kabale (76,264). The phylum Proteobacteria (34.2%) was the most prevalent followed by Acidobacteria (17.3%) and Actinobacteria (15.5%). The bacteria community in the two highlands significantly differed (p <0.05) among all phyla except Proteobacteria. The main genera in bulk soil were povalibacter, brevitalea, nocardioides, stenotrophobacter, gaiella and solirubrobacter. Sphingomonas, ramlibacter paludibaculum and pseudarthrobacter were the main genera in A. annua rhizospheric soil.
... Two miscarriages were reported among the pregnant patients. In a randomized Ugandan clinical trial [53], consumption of the A. annua tea infusion (5 g) once a week significantly reduced the risk of suffering more than one episode of malaria in 9 months by 55%. No serious side effects were reported except the bitter taste associated with the plant. ...
Background
Malaria, a treatable disease mainly caused by Plasmodium falciparum has remained a health challenge in Africa, a continent that accounted for 96% of total global cases and deaths in 2021. Uganda, a malaria endemic country is experiencing malaria parasite resistance to some of the drugs used in the artemisinin-based combination therapy (ACT). In an effort to prioritize herbal medicines for new product development, this review synthesized the available safety and efficacy literature on the Ugandan anti-malarial plants to suggest most effective herbal plants.
Methods
Literature was exhaustively searched using engines and databases, such as Google scholar, Pubmed, and Scopus-indexed journals during the period of June 2020–December 2021. In the first phase, information on ethnobotanical uses of anti-malarial plants in Uganda was gathered and synthetized to generate a list of plants, followed by data on anti-malarial efficacy (both in vitro and in vivo) on each listed plant. Minimum inhibitory concentrations (µg/ml), and % parasite suppression for every plant were scored using The Research Initiative on Traditional and Antimalarial Methods (RITAM) scoring system. The best twenty (20) plants were evaluated for acute safety (LD50) data in rat model, plant parts used, ease of cultivation, presence of clinical studies and other relevant factors for suggesting the best three (3) plants for future anti-malarial product development.
Results
Over one hundred twenty-six (126) plant species are used in Uganda for treatment of malaria in local communities. Out of these, about 33% (41) have been studied for efficacy and safety, with Artemisia annua and Vernonia amygdalina being the most extensively studied and among the best twenty (20) anti-malarial plants in Uganda. Both are limited by parasite recrudescence in clinical studies. Microglossa pyrifolia, a very potent plant (IC50 = 0.03 – 0.05 µg/ml has potential to penetrate the liver and could ameliorate the challenge of recrudescence if combined with A. annua and V. amygdalina in a polyherbal formulation.
Conclusion
There are many plants with promising potential for malaria treatment in Uganda and a herbal combination of A. annua, V. amydalina and M. pyrifolia could offer the next herbal ACT if carefully studied and developed.
... Concerning its clinical activity in humans, A. annua tea in a curative scheme has not shown sufficient efficacy to be recommended (Mueller et al., 2004). But some efficacy in the prevention of malaria has been demonstrated through a clinical trial which reported 40% of more than one clinical malaria attacks during the 9months follow-up in the control group, compared to 17.9% in the A. annua group (Ogwang et al., 2012). A. afra, a plant of the same genus, is found naturally in South and East Africa; it is one of the most popular and commonly used herbal medicines in Southern Africa. ...
Malaria has always been a major public health problem in sub-Saharan Africa. To limit malaria morbidity and mortality, people traditionally use plants. This chapter, focused on West Africa, aims to give an overview of the use of traditional medicine in this area, and of the main plants used and scientifically validated in vitro, on murine models and through clinical trials. The main compounds from West African plants with good antimalarial activity are also listed. For this purpose, a bibliographical review by country was carried out to identify the local plants used and scientifically validated. The issue of the quality of plant-based products (composition, efficacy, safety) and of the diversity of methods used by the teams to validate their use is also addressed. Finally, the antimalarial use of the plant Artemisia annua and A. afra, in West Africa is discussed, although this plant is not endemic to this region.
... The activity of monocytes alone and immunoglobulins alone was moderate and inconsistent. [59][60][61] Lactoferrin contained in milk selectively segregates into the skin and significantly reduces the sebum content and increases the number of keratinocytes, their migration and reduces their apoptosis. [62][63][64] Human saliva also is rich in lactoferrin. ...
... There is also evidence of a potential interaction between the host immune system and DLA in the difference in efficacy of DLA as a prophylactic against malaria in malaria-naïve vs exposed individuals. DLA was not an effective preventative measure against malaria for EU travelers [53], but Artemisia teas appeared to be prophylactic in those that have already had malaria [54,55]. The experiments in this paper probed for these interactions by examining the simultaneous effects of various human sera and DLA and may offer some insight into those prophylactic discrepancies. ...
Dried-leaf Artemisia annua L. (DLA) antimalarial therapy was shown effective in prior animal and human studies, but little is known about its mechanism of action. Here IC50s and ring-stage assays (RSAs) were used to compare extracts of A. annua (DLAe) to artemisinin (ART) and its derivatives in their ability to inhibit and kill Plasmodium falciparum strains 3D7, MRA1252, MRA1240, Cam3.11 and Cam3.11rev in vitro. Strains were sorbitol and Percoll synchronized to enrich for ring-stage parasites that were treated with hot water, methanol and dichloromethane extracts of DLA, artemisinin, CoArtem™, and dihydroartemisinin. Extracts of A. afra SEN were also tested. There was a correlation between ART concentration and inhibition of parasite growth. Although at 6 hr drug incubation, the RSAs for Cam3.11rev showed DLA and ART were less effective than high dose CoArtem™, 8 and 24 hr incubations yielded equivalent antiparasitic results. For Cam3.11, drug incubation time had no effect. DLAe was more effective on resistant MRA-1240 than on the sensitive MRA-1252 strain. Because results were not as robust as observed in animal and human studies, a host interaction was suspected, so sera collected from adult and pediatric Kenyan malaria patients was used in RSA inhibition experiments and compared to sera from adults naïve to the disease. The sera from both age groups of malaria patients inhibited parasite growth ≥ 70% after treatment with DLAe and compared to malaria naïve subjects suggesting some host interaction with DLA. The discrepancy between these data and in-vivo reports suggested that DLA’s effects require an interaction with the host to unlock their potential as an antimalarial therapy. Although we showed there are serum-based host effects that can kill up to 95% of parasites in vitro, it remains unclear how or if they play a role in vivo. These results further our understanding of how DLAe works against the malaria parasite in vitro.
... The plant derived drugs need also to be safe and tolerated by the consumers [7,8]. For example, Artemesia annua infusion preserved cerebral malaria complication associated with P. falciparium [9]. However it is necessary to detect news drugs with higher half-life than A. annua infusion [10]. ...
... An attractive approach is repurposing drugs already licensed for other diseases. Teas of A. annua plants have been employed to treat malaria in Traditional Chinese Medicine, as well as in clinical trials, 7,8 and are used widely in many African countries, albeit against WHO recommendations. Artemisinin (Figure 1, 1), a sesquiterpene lactone with a peroxide moiety and one of many bioactive compounds present in A. annua, is the active ingredient to treat malaria infections. ...
Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs.
Proof-of-concept for prophylactic efficacy of the extracts was obtained using a plaque-reduction assay in VeroE6 cells. Subsequent concentration-response studies using a high-throughput antiviral assay, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that pretreatment and treatment with extracts, artemisinin, and artesunate inhibited SARS-CoV-2 infection of VeroE6 cells. In treatment assays, artesunate (50% effective concentration (EC50): 7 μg/mL) was more potent than the tested plant extracts (128-260 μg/mL) or artemisinin (151 μg/mL) and artemether (>179 μg/mL), while generally EC50 in pretreatment assays were slightly higher. The selectivity index (SI), calculated based on treatment and cell viability assays, was highest for artemisinin (54), and roughly equal for the extracts (5-10), artesunate (6) and artemether (<7). Similar results were obtained in human hepatoma Huh7.5 cells. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.
... Eleven known saponins were detected in the leaves and stems ( This study showed the artemetin content of C. aconitifolius leaves to be comparable to Artemisia annua [50]. Artemetin possesses anti-inflammatory, antioxidant, antihypertensive, cardio-protective, immune-modulatory, cell cycle and lipoxygenase inhibitory properties [51,52,53,54]. Digitoxin and digoxin are used in managing atrial fibrillation, congestive cardiac insufficiency, congestive heart failure and cardiac arrhythmias [55,56]. ...
Cnidoscolus aconitifolius is consumed as a vegetable in many parts of Southern Nigeria. Presently, there is no information regarding the allicins alkaloids, carotenoids, glycosides, phytosterols, saponins and terpenoids profiles of the leaves and stems of this vegetable. The proximate, minerals, vitamins, amino acid, carotenoids, saponins, glycosides, phytosterols, terpenoids, alkaloids and allicins profiles of the leaves and stems of Cnidoscolus aconitifolius were determined using standard methods. The leaves and stems had high fibre (14.0-15.2 g/100g), carbohydrate (40.2-41.2 g/100g) and protein (22.2-24.5 g/100g). These were equivalent to about 56.0-66.9% daily value for fibre, 44.4-49.0% daily value protein and 13.4-15.1% daily value carbohydrate. They had high contents of selenium, copper, manganese, iron, cobalt, magnesium (leaves only) and vitamins E, B9, C and K (stems only), carotenoids, saponins and glycosides; and moderate phytosterols and terpenoids. Their proteins were rich in essential amino acids (42.7-45.6%). Ten known carorenoids were detected in the stems and leaves, consisting mainly of carotene (43.7-46.1%), lutein (20.8-22.5%) and neo-xanthin (10.92-12.99%). Sapogenin (62.99-64.56%) and saponine (24.5-28. 9%) were the most abundant of the eleven saponins detected. Of the twelve known glycosides were detected, artemetin (65.8-67.6%) and digitoxin (24.8-27.7%) were the most abundant. Seven phytosterols were detected, and consisted mainly of sitosterol (63.6-71.3%), stigmasterol (10.9-13.6%) and 5-avenasterol (10.6-11.4%). Beta-amyrin (52.2-66.3%), alpha-amyrin (18.5-31.6%) and lupeol (14.8-15.9%) were the most abundant of the five phytosterols detected. This result indicates that the leaves and stems of Cnidoscolus aconitifolius are good sources of nutrients and bioactive phytochenicals that can support human health and nutrition. This rich profile makes them potential sources of nutraceuticals.
... The in vivo effects of Artemisia annua and Artemisia afra on Plasmodium falciparum have been documented in scientific publications since 2005 in Kenya, Cameroon, Mozambique, Uganda, Togo, Senegal, Ethiopia, Mali, Benin and RDCongo. [1][2][3][4][5][6][7][8][9][10][11][12][13] In this most recent clinical trial a team of medical doctors in RDCongo, J. Munyangi and M. Idumbo, have run randomized clinical trials on a large scale in the Maniema province with the participation of some 1000 malaria infected patients. The trials were run in conformity with the WHO procedures and compared Artemisia annua and Artemisia afra with ACTs (Coartem and ASAQ). ...
... Artemisinin in form of artemisinin-based combination therapies (ACTs) is recommended for treatment of malaria caused by resistant Plasmodium species (WHO, 2006). The flavonoids have been reported to have synergistic effect with artemisinin against malaria (Bilia, De Malgalhaes, Bergonzi, & Vincieri, 2006;Ferreira, Luthria, Sasaki, & Heyerick, 2010;Liu, Yang, Roberts, Elford, & Phillipson, 1992;Weathers & Towler, 2012) and are believed to be responsible for the malaria prophylactic effect of Artemisia annua herbal teas (Jansen, 2006;Ogwang et al., 2012). Lastly, the A. annua aromatic oil is a mosquito repellant (Engeu, Omujal, Agwaya, Kyakulaga, & Celestino, 2015). ...
The antimalarial active compounds in Artemisia annua include artemisinin, flavonoids, and aromatic oils. Artemisinin is the main antimalarial compound in A. annua, it used in the formulation of artemisinin-based combined therapies used to treat malaria. Artemisinin is largely obtained from A. annua plant but the content in it is very low and its production commercially is not cost effective worldwide. Flavonoids have a synergistic effect with artemisinin against malaria and are partly responsible for the prophylactic effect of A. annua herbal tea. Essential oils from A. annua are effective mosquito repellents. Most attempts have been made to try to raise artemisinin content. However, few or none has been tried to increase the flavonoids and aromatic oils. This article presents a review of various efforts that have been carried out to increase these antimalarial compounds.
... The activity of monocytes alone and immunoglobulins alone was moderate and inconsistent. 21,22 Immunoglobulins protect efficiently by targeting α-gal on sporozoites immediately after inoculation by Anopheles mosquitoes; but not against the disease once ...
... A prophylactic effect as Artemisia annua infusions had been noticed in 2012 in a study of the Ministry of Health in Uganda. 3 Patrick Ogwang (personal communication) found that when asymptomatic carriers started taking Artemisia infusion, the parasites are kind of forced to progress quickly, to cause fever and disease, and once persons are treated and continue taking Artemisia they don't catch malaria easily. A similar positive effect of Artemisia annua powdered leaves in the form of capsules had been noticed by a study in Bangui. ...
... The clinical assays of Jerome Munyangi in RDC [1,2] following those of Patrick Ogwang in Uganda [3] have clearly shown that Artemisia annua has prophylactic properties against malaria, but it is not known how and why. Artemisia plants are rich in polyunsaturated fatty acids (PUFA) which generate prostaglandins and stimulate monocytes. ...
... Recent research from the Al Quds University has shown that aqueous infusions of several Artemisia species strongly inhibit beta-hematin, like chloroquine did [8]. But the most important finding in several of the clinical trials, especially in Kenya and Uganda, was that people who drink one or two cups of Artemisia annua tea per week become immune against malaria [9]. At Lubumbashi, RDCongo Dr C Kansango Tchandema has shown in 2014 that Artemisia annua and Artemisia afra raised CD 4+ [2]. ...
... In this paper V. amygdalina which is widely available in Uganda and used as a herbal antimalarial was studied in combination with A. annua using rodent malaria. Although A. annua was used for malaria treatment in Ancient China and also still used in some communities in Africa for both cure and prevention of malaria [10,11], recent studies have demonstrated that A.annua preparation's major drawback is the occurrence of parasite recrudescence and the fear of widespread artemisinin resistance occurring when used as single plant [12]. It is therefore thought that a combination of A. annua with another antimalarial plant may be able to overcome the challenge of recrudescence and provide an option to the inaccessible ACTs. ...
... Artemisia annua has several other potential uses namely, as an insect repellant (Tripathi, 2000), in the treatment of schistosomiasis and gastrointestinal tract infections , treatment of coccidiosis in poultry (Ebiamadon et al., 2008) and treatment of cancer (Efferth et al., 2001;Ferreira, 2004). An infusion of the leaves is used for malaria prophylaxis and in the treatment of fevers, colds, diarrhea and some other illinesses, while Artemisia oil is used in perfumery, cosmetics and dermatology (Bhutani et al., 2003;Ogwang et al., 2011Ogwang et al., , 2012. ...
... The drug also needs to be palatable and tolerable, facets absent in most prophylaxis drugs with phytochemical origins [4,5]. In Uganda, an infusion of Artemisia annua consumed once weekly reduced risk of Plasmodium falciparum infection episodes due to as yet an unidentified constituent [6] with a longer half-life than artemisinin. However, its only drawback is the bitterness [7]. ...
Background
Malaria prevention has remained a critical area in the absence of efficacious vaccines against malaria. Drugs currently used as chemotherapeutics are also used in chemoprophylaxis increasing possible drug resistance. Asiatic acid is a natural phytochemical with oxidant, antioxidant and anti-inflammatory properties with emerging anti-malarial potential. The influence of asiatic acid administration prior to Plasmodium berghei infection of Sprague-Dawley rats on parasitaemia induction is here reported.
Methods
Sprague-Dawley rats (90–120 g) were administered with asiatic acid (10 mg/kg) 48 h before intraperitoneal infection with P. berghei. Parasitaemia induction and progression, food and water intake as well as weight were compared to 30 mg/kg chloroquine-treated and infected control rats during sub-chronic studies (21 days).
Results
Asiatic acid pre-infection administration preserved food and water intake as well as increase in percentage weight gain of infected animals. In pre-infection treated animals, the pre-patent period was extended to day 6 from 72 h. Asiatic acid suppressed parasitaemia while oral chloroquine (30 mg/kg) did not influence malaria induction.
Conclusions
Per-oral, pre-infection, asiatic acid administration influenced parasitaemia patency and parasitaemia progression, food, water, and weight gain percentage. This may suggest possible chemoprophylaxis effects of asiatic acid in malaria.
... It is widely dispersed throughout the temperate region [1]. A. annua is the source of artemisinin, an antimalarial drug which is effective against multidrug resistant strains of plasmodium, the malarial parasite [2] [3]. Artemisinin and its derivatives have been found to be effective against all stages of resistant strains of Plasmodium falciparum [4] [5]. Although it has been found to be a useful medicine; its production is very low in comparison with what is actually needed to treat the worldwide threat of malaria. ...
... Indeed recent studies show that in animal models consumption of the dried leaves of the plant is more effective than the pure drug in reducing parasitemia (Elfawal et al., 2012). Likewise prophylactic use of an A. annua tea infusion in Uganda showed an 80% reduction in malaria cases (Ogwang et al., 2012), and some preliminary human trials in Africa of oral consumption of dried A. annua leaves showed excellent reduction in parasitemia (see review by Weathers et al., 2014). Local cultivation and production of dried leaves from high quality A. annua cultivars would provide Africans with an opportunity to establish small enterprises resulting in jobs, which would also allow people to become more self-sufficient and less reliant on the West for their healthcare needs (Weathers et al. 2011). ...
This paper introduces the work and diversity of the Council for Frontiers of Knowledge (CFK). In a series of vignettes relating to the intellectual interests of some of the leading academics working with the CFK, both the mission and the trans- disciplinary oversight of the agency are explored.
... However, they also suggested a treatment plan of 5-6 days followed by a secondary dosage another 5-6 days later to eliminate slow maturing parasites within the bloodstream. A similar strategy using the tea infusions rather than the dried plant material capsules was proposed by Ogwang et al. (2012), where it was shown that the prophylactic ingestion of Artemisia annua tea infusions once per week lowered the risk of contracting malaria by 55%. Ogwang et al. (2011) performed a similar study in which a Ugandan community ingested Artemisia annua tea once per week prophylactically to reduce the occurrence of malaria and fevers, resulting in 80% less clinical identifications of malaria. ...
In Asia, Artemisia annua L. tea and press juice are used to cure malaria and its associated symptoms. Artemisia annua comes under the Anthemideae tribe, which includes the roughly 500 species of Artemisia L., is primarily distributed in Asia, Europe, and North America. Due to the presence of numerous active components or secondary metabolites, artemisia typically exhibits a wide range of bioactivity. The drug’s active component, Artemisinin (ARS), was created as an antimalarial and is used all over the world. It’s interesting to note that the bioactivity is not just used to cure malaria. It is discovered that medications of the ARS type also exhibit anti-cancerous activity in vivo and in vitro. Artemisinin and its analogues have been demonstrated to reduce intracellular free iron levels in cancer cells, which are substantially higher than those in normal cells. Apoptosis, necrosis, necroptosis, tumour-related signal transduction pathways are responses to oxidative stress in cancer cells that are triggered by ARS and its derivatives. Artemisia annua L. extracts contain anti-inflammatory, antioxidant, and antifungal antimicrobial substances. The purpose of this review is to illustrate how artemisinin retrieves various illnesses and conditions. Another objective of ours is to compile an up-to-date report on the various activities of artemisinin
Malaria in Benin is a real public health problem, causing thousands of deaths every year, particularly among young children. To combat this disease, the Beninese population uses both conventional and traditional medicine. At the frontier between these two medicines are products that are neither part of age-old traditions nor scientific standards. Products based on Artemisia annua and Artemisia afra belong to this category, and have recently appeared in Benin. Our team conducted a survey in 2022 to determine the type of products sold, their origin, price, audience, and the knowledge and practices of those involved in the "Artemisia market". We interviewed 128 people in 8 of Benin's 12 departments. Four profiles of people were interviewed: producers, retailers, consumers and traditional practitioners. Thanks to this study, we were able to trace the origins of the craze for these plants, identify the key players in the sector, notably the Maison de l'Artemisia, and demonstrate the virtual absence of traditional practitioners in this sector during the survey. The diversity of products sold and their indications was also noted. The two species A. afra and A. annua seem to be used for malaria in a similar way, with no real distinction in efficacy between the two. From an economic point of view, we have not noted any clear benefit linked to the use of Artemisia teas compared with therapeutic combinations based on artemisinin derivatives. Their efficacy and safety in humans have yet to be demonstrated. In conclusion, our study provides initial data on the use of Artemisia in Benin, and also identifies various aspects to be clarified, such as the extent of use, the health impact, and the economic interest for users of Artemisia-based products sold in Benin.
Artemisia annua L. has been diagnosed as a potent medicinal herb and has been well documented in the historical pharmacopoeias of distinctive Asian and European nations. The WHO has suggested Artemisia annua as a potential pharmacological agent and as an antimalaria drug. The entire plant has been recognized to possess antipyretic, antihelminthic, antispasmodic, antiseptic, stimulant, carminative, and stomachic properties. In African, Artemisia annua brew has been used to deal with malaria. A. annua has a key ingredient known as artemisinin, which serves as the chemical basis for the world’s antimalarial programmes and combinatorial curative therapy. Current research indicates that artemisinin is active in killing human breast cancer cells. As a result, the characterization and separation of artemisinin from Artemisia annua L. has received augmented global interest.
Background
Initiation of HAART among people living with HIV (PLWH) having a CD4 count ≤ 350cells/µl, produces poor immunological recovery, putting them at a high risk of opportunistic infections. Artemisia annua and Moringa oleifera are among the herbs commonly consumed by PLWH on HAART to boost their immunity, but their clinical benefits and potential interactions with ARVs remain unknown. This study investigated the effect of A.annua and M.oleifera on CD4 count, viral load, and other clinical and haematological indices among PLWH on HAART at an HIV clinic in Uganda.
Methods
282 HIV-positive participants on HAART with a CD4 count ≤ 350cells/µl were randomized in a double-blind clinical trial to receive daily, in addition to their routine standard of care; 1) A.annua leaf powder, 2) A.annua plus M.oleifera, and 3) routine standard of care only. Our primary outcome was change in the CD4 count at 12 months. Secondary outcomes included change in viral load, complete blood count, renal function tests, liver function tests, ARV plasma levels, and quality of life (QoL). Participants were followed up for a year and outcomes were measured at baseline, 6 and 12 months.
Results
At 12 months of patient follow-up, administration of A.annua + M.orifera plus routine standard of care produced an absolute mean CD4 increment of 105.06 cells/µl, (P < 0.001), while administration of A.annua plus routine standard of care registered an absolute mean CD4 increment of 60.84 cells/µl, (P = 0.001) compared to the control group. The viral load reduced significantly (P = 0.022) for participants on the A.annua + M.orifera compared to those receiving standard of care only. There were significant differences in White blood cell count (P = 0.03), platelet count (P = 0.025), perceived QoL (P < 001) among participants who received A.annua + M.oleifera compared to those who received standard of care only. There were no significant differences in the other secondary outcomes.
Conclusion
A combination of A.annua and M.oleifera leaf powders taken once a day together with the routine standard of care produced significant improvement in CD4 count, viral load suppression, WBCs, platelets, and quality of life among individuals on HAART.
As the world desperately searches for ways to treat the coronavirus disease 2019 (COVID-19) pandemic, a growing number of people are turning to herbal remedies. The Artemisia species, such as A. annua and A. afra, in particular, exhibit positive effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and COVID-19 related symptoms. A. annua is a source of artemisinin, which is active against malaria, and also exhibits potential for other diseases. This has increased interest in artemisinin’s potential for drug repurposing. Artemisinin-based combination therapies, so-called ACTs, have already been recognized as first-line treatments against malaria. Artemisia extract, as well as ACTs, have demonstrated inhibition of SARS-CoV-2. Artemisinin and its derivatives have also shown anti-inflammatory effects, including inhibition of interleukin-6 (IL-6) that plays a key role in the development of severe COVID-19. There is now sufficient evidence in the literature to suggest the effectiveness of Artemisia, its constituents and/or artemisinin derivatives, to fight against the SARS-CoV-2 infection by inhibiting its invasion, and replication, as well as reducing oxidative stress and inflammation, and mitigating lung damage.
Chronic inflammation is involved in many pathological conditions such as rheumatoid arthritis, atherosclerosis, type 2 diabetes, asthma, obesity, inflammatory bowel diseases, neurodegenerative diseases, and cancer. Currently, there is a demand for effective anti-inflammatory drugs with low toxicity and reduced side effects. In this context, A. annua appears to be a promising source of anti-inflammatory compounds, as numerous studies on different models of inflammation certify. Further research is needed in order to understand the underlying mechanism of action for each compound. The anti-inflammatory activity of extracts is also promising, considering the fact they have been demonstrated to be more efficient than isolated compounds, although they raise the problem of reproducibility and standardization. In addition, no clinical trials were yet undertaken to assert the anti-inflammatory effect of A. annua in the human body.
Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs. Concentration–response antiviral treatment assays, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that treatment with all studied extracts and compounds inhibited SARS-CoV-2 infection of VeroE6 cells, human hepatoma Huh7.5 cells and human lung cancer A549-hACE2 cells, without obvious influence of the cell type on antiviral efficacy. In treatment assays, artesunate proved most potent (range of 50% effective concentrations (EC50) in different cell types: 7–12 µg/mL), followed by artemether (53–98 µg/mL), A. annua extracts (83–260 µg/mL) and artemisinin (151 to at least 208 µg/mL). The selectivity indices (SI), calculated based on treatment and cell viability assays, were mostly below 10 (range 2 to 54), suggesting a small therapeutic window. Time-of-addition experiments in A549-hACE2 cells revealed that artesunate targeted SARS-CoV-2 at the post-entry level. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.
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 anti-inflammatory 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, anti-nociceptive 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.
The genus Artemisia belongs to the family Asteraceae which has now become the subject of great attraction because of its rich species diversity and phytochemical composition. This genus has a very long history of use in the treatment of human diseases in different parts of the world. This medicinally important genus has promising therapeutic potential which includes antimalarial, anti-parasitic, hepato-protective, anti-nociceptive, anti-inflammatory, anti-ulcerogenic, antimicrobial, antitumour, antioxidant, anticancer, anticonvulsant, anti-leishmanial, anti-diabetic, anti-promastigote, antidepressant and anticonvulsant. A total of 839 chemical compounds (volatile and non-volatile) have been reported in different species of this genus. These chemical compounds can be categorised into major classes such as flavonoids, lignans, terpenes, fatty acids, phenylpropanoids, sterols, fatty esters, phenolics, hydrocarbons and miscellaneous compounds. Strategic conservation of Artemisia species shall continue to provide molecules of pharmaceutical importance in future.
Introduction
Malaria is one of the most common major health problems in tropical low-and middle-income countries, with antimalarial drugs being highly effective but also threatened by increasing drug resistance. Clinically efficacious, well-tolerated antimalarial plants could be an important alternative treatment. This systematic review aims at identifying and critically appraising clinical trials testing plants with antimalarial properties for malaria treatment and/or prophylaxis.
Methods
Studies were identified through PubMed, Elsevier Scopus and Cochrane Central, and scanning article reference lists. Records were published in English between 01/01/2005 and 15/01/2018. A framework for analysis based on the CONSORT statement was used for data extraction. Risk of bias was assessed. A meta-analysis could not be conducted due to data heterogeneity.
Results
Nine studies met inclusion criteria. Extracts from Argemone mexicana, Artemisia annua, Citrus aurantifolia, Nauclea pobeguinii, Nycthanthes arbor-tristis and Vernonia amygdalina were examined. Methodological rigorosity varied. Adequate clinical response on day 14 with A. mexicana was 81% (p = 0.027) in one study and 89% (95% CI 84.1–93.2) on day 28 in another study. Similarly, 87.9% of participants taking N. pobeguinii had an adequate clinical response on day 14 (p = 0.003). The risk of bias and study quality varied. Two studies had a Jadad score of 3 and all others but one had a score of 1. All herbal preparations were safe with no moderate or severe adverse events being reported.
Conclusions
Studies have demonstrated that antimalarial plants show promise for malaria treatment and prophylaxis. A. mexicana and N. pobeguinii extracts were supported by the best evidence. More work should be undertaken to better understand relevant approaches.
INTRODUCTION:
Cutaneous leishmaniasis (CL) is a tropical disease that affects millions of individuals worldwide. The current drugs for CL may be effective but have serious side effects; hence, alternatives are urgently needed. Although plant-derived materials are used for the treatment of various diseases in 80% of the global population, the validation of these products is essential. Gelatin capsules containing dried Artemisia annua leaf powder were recently developed as a new herbal formulation (totum) for the oral treatment of malaria and other parasitic diseases. Here, we aimed to determine the usefulness of A. annua gel capsules in CL.
METHODS:
The antileishmanial activity and cytotoxicity of A. annua L. capsules was determined via in vitro and in vivo studies. Moreover, a preliminary evaluation of its therapeutic potential as antileishmanial treatment in humans was conducted in 2 patients with uncomplicated CL.
RESULTS:
Artemisia annua capsules showed moderate in vitro activity in amastigotes of Leishmania (Viannia) panamensis; no cytotoxicity in U-937 macrophages or genotoxicity in human lymphocytes was observed. Five of 6 (83.3%) hamsters treated with A. annua capsules (500mg/kg/day) for 30 days were cured, and the 2 examined patients were cured 45 days after initiation of treatment with 30g of A. annua capsules, without any adverse reactions. Both patients remained disease-free 26 and 24 months after treatment completion.
CONCLUSION:
Capsules of A. annua L. represent an effective treatment for uncomplicated CL, although further randomized controlled trials are needed to validate its efficacy and safety.
Artemisia annua L. has been recognized as important ethanomedicinal herb since two millennia. It has been included in ancient pharmacopoeias of various Asian and European countries. World Health Organization has recommended A. annua as antimalarial drug. Its most common ethnobotanical practice involves the use of whole plant decoction for the treatment of malaria, cough, and cold. Diarrhea is also reported to be cured by taking its dry leaves powder. Whole flowering plant is known to be antihelminth, antipyretic, antiseptic, antispasmodic, carminative, stimulant, tonic, and stomachic. The tincture was formally used to treat nervous diseases and crushed plants in liniments. A. annua tea infusion has been used for the treatment of malaria in African countries. A. annua contains vital compound known as artemisinin that provide structural chemical base for combinatorial treatment therapy for world antimalarial program. Research studies also report that artemisinin is effective for killing human breast cancer cells. Therefore, isolation and characterization of artemisinin has increased the interest in A. annua worldwide. Several ethnobotanical uses in Africa claim that the A. annua tea is also effective against HIV. Recently, research investigations are more focused to evaluate its antiviral potential against HIV, as it is highly emerging disease throughout the world. Therefore, scientific validation can provide the support to the concept of ethnopharmacology in overdrive. © 2014 Springer-Verlag Berlin Heidelberg. All rights are reserved.
Malaria is major public health problem in Uganda endemic in 95% contributing up to 40% of hospital outpatient attendances. Approaches to controlling the disease include; environmental, entomological and medicinal interventions. Some communities use medicinal plants to control the disease. In this paper we report the use of Artemisia annua L. for malaria prophylaxis at a Ugandan floricultural farm. We conducted a survey of the farm workers to determine extent of use of A. annua 'tea', their clinic attendance patterns and also quantified the levels of artemisinin and flavonoids in A. annua. We further tested the effect of artemisinin devoid extract in laboratory animal models. Findings from the survey showed that 84.2% of the managers and 62% of field workers in this farm consumed A. annua 'tea' once a week to prevent malaria and related fevers. Clinic attendance due to fevers or symptoms associated with malaria was reduced by 80% while cases of laboratory confirmed diagnosis of malaria reduced by 16.7%. Laboratory test of A. annua leaf powder used in community indicated the presence of artemisinin (0.4% to 0.5%) and flavonoids (9% to 11%). A. annua extract devoid of artemisinin was found to significantly boost monocyte counts in albino rats Research Article British Journal of Pharmaceutical Research, 1(4): 124-132, 2011 125 (p<0.001).The action of these flovonoids could explain the mechanism of prophylaxis of A. annua 'tea'. A. annua variety or product thereof rich in flavonoids but devoid of artemisinin should be developed and tried for mass prevention of malaria as a beverage or food taken regularly.
A new, simple, rapid, accurate and precise HPTLC method was developed. The detector response was linear for concentrations between 100-600 ng/spot (r =0.9931). The limits of detection and quantitation were 25 ng/spot and 75 ng/spot, respectively. The recovery study was carried out by standard addition method and was found to be 99.60+/-0.27. Statistical analysis proved that the method was precise, accurate and reproducible, and hence was suitable for the routine analysis of artemisinin.
The stage-dependent phagocytosis of Plasmodium falciparum-infected erythrocytes (IRBC) opsonized with nonimmune serum has been investigated. An average of 2.9 red blood cell (RBC) harboring ring-forms (RIRBC) and 7.5 RBC infected with trophozoites (TIRBC) or schizonts (SIRBC) were ingested per monocyte, in comparison with 0.8 noninfected RBC (NRBC) or 5 RBC oxidatively damaged with diamide. Abrogation of generation of complement component C3b or blockage of its binding to the phagocyte inhibited phagocytosis of RIRBC by 78% to 95% and of TIRBC by 25% to 50%. Blockage of immunoglobulin G (IgG) binding reduced phagocytosis of both RIRBC and TIRBC nonsignificantly by 14%. Preincubation of monocytes with phosphatidylserine (PS)-containing liposomes reduced phagocytosis of TIRBC by 22%, but had little effect on RIRBC. Residual, noncomplement, non-IgG-, and non-PS-dependent phagocytosis amounted to 6% to 18% of total phagocytosis in RIRBC and TIRBC, respectively. RIRBC bound 2.5 times more protein A and 3.1 times more anti-C3c (a stable derivative of C3b) antibodies, and TIRBC bound 20 times more protein A and 6.8 times more anti-C3c antibodies than NRBC. Phagocytosis of oxidatively damaged RBC and RIRBC are similar, whereas a higher portion of phagocytosis appears to be noncomplement-dependent and PS-suppressible in TIRBC. It is concluded that RIRBC generate recognition signals similar to those present in oxidatively damaged or senescent RBC. Extensive membrane modifications in TIRBC produce additional, hitherto undefined signals that induce much higher and qualitatively distinct phagocytosis.
Artemisinin and its derivatives have been used for falciparum malaria treatment in China since late 1970s. Monotherapy and uncontrolled use of artemisinin drugs were common practices for a long period of time. In vitro tests showed that the susceptibility of Plasmodium falciparum to artemisinins was declining in China. A concern was raised about the resistance to artemisinins of falciparum malaria in the country. It has been reported that in vitro artemisinin resistance was associated with the S769N mutation in the PfATPase6 gene. The main purpose of this study was to investigate whether that mutation has occurred in field isolates from China.
Plasmodium falciparum field isolates were collected in 2006-2007 from Hainan and Yunnan provinces, China. A nested PCR-sequencing assay was developed to analyse the genotype of the PfATPase6 S769N polymorphism in the P. falciparum field isolates.
The genotyping results of six samples could not be obtained due to failure of PCR amplification, but no S769N mutation was detected in any of the 95 samples successfully analysed.
The results indicate that the S769N mutation in the PfATPase6 gene is not present in China, suggesting that artemisinin resistance has not yet developed, but the situation needs to be watched very attentively.
Cell suspension cultures developed from Artemisia annua exhibited antimalarial activity against Plasmodium faldparum in vitro both in the n-hexane extract of the plant cell culture medium and in the chloroform extract of the cells. Trace amounts of the antimalarial sesquiterpene lactone artemisinin may account for the activity of the n-hexane fraction but only the methoxylated flavonoids artemetin, chrysoplenetin, chrysosplenol-D and cirsilineol can account for the activity of the chloroform extract. These purified flavonoids were found to have IC50 values at 2.4 - 6.5 × 10(-5)M against P. falciparum in vitro compared with an IC50 value of about 3 × 10(-8)M for purified artimisinin. At concentrations of 5 × 10(-6)M these flavonoids were not active against P. falciparum but did have a marked and selective potentiating effect on the antiplasmodial activity of artemisinin.
Interaction between the flavones casticin and artemetin and the antimalarial activity of chloroquine and qinghaosu (QHS) was
examined using an in vitro growth assay based on [3H]hypoxanthine incorporation in synchronized cultures of a cloned line of Plasmodium falciparum. Casticin, and to a lesser extent artemetin, selectively enhanced the inhibition of growth by QHS, but had little effect
on the activity of chloroquine. The findings suggest that flavones indigenous to Artemisia annua, from which QHS is isolated, might significantly alter the clinical potential of this novel antimalarial drug in the treatment
of chloroquine-resistant malaria.
Artemisia annua L. (Qinghao) is a promising and potent antimalarial herbal drug. This activity has been ascribed to its component artemisinin, a sesquiterpene lactone that is very effective against drug-resistant Plasmodium species with a low toxicity. Our studies indicate that several flavonoids of A. annua can promote and enhance the reaction of artemisinin with hemin. These data are in good agreement with previous investigations on the in vitro potentiation of antimalarial activity of artemisinin by such flavonoids. As a consequence, in view of a possible use of the phytocomplex rather than pure artemisinin, an HPLC/DAD/MS method is proposed for the simultaneous detection and quantification of both flavonoids and artemisinin. Different extracts, obtained from two different herbal drugs, a commercial sample and a selected cultivar, were analyzed in order to determine which solvents provide the best yields of both artemisinin and flavonoids. Qualitative and quantitative results obtained using an HPLC method are described, which will be useful for developing highly effective herbal drug preparations.