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The Potentials of Ageratum conyzoides and Other Plants from Asteraceae as an Antiplasmodial and Insecticidal for Malaria Vector: An Article Review
Authors Kusman IT, Pradini GW, Ma'ruf IF, Fauziah N, Berbudi A, Achadiyani A, Wiraswati HL
Received 30 August 2023
Accepted for publication 26 October 2023
Published 7 November 2023 Volume 2023:16 Pages 7109—7138
DOI https://doi.org/10.2147/IDR.S433328
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Suresh Antony
Irfan Taufik Kusman,1 Gita Widya Pradini,2 Ilma Fauziah Ma’ruf,3 Nisa Fauziah,2 Afiat Berbudi,2 Achadiyani Achadiyani,2 Hesti Lina Wiraswati2
1Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; 2Department of Biomedical Science, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, 45363, Jawa Barat, Indonesia; 3Research Center for Climate and Atmosphere, National Research and Innovation Agency, Bandung, 40135 Indonesia
Correspondence: Achadiyani Achadiyani; Hesti Lina Wiraswati, Department of Biomedical Science, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, 45363, Jawa Barat, Indonesia, Tel +6285795183426, Fax +62222037823, Email [email protected]; [email protected]
Background: Malaria is a life-threatening disease prevalent in tropical and subtropical regions. Artemisinin combination therapy (ACT) used as an antimalarial treatment has reduced efficacy due to resistance, not only to the parasite but also to the vector. Therefore, it is important to find alternatives to overcome malaria cases through medicinal plants such as Ageratum conyzoides and other related plants within Asteraceae family.
Purpose: This review summarizes the antimalarial and insecticidal activities of A. conyzoides and other plants belonging to Asteraceae family.
Data Source: Google Scholar, PubMed, Science Direct, and Springer link.
Study Selection: Online databases were used to retrieve journals using specific keywords combined with Boolean operators. The inclusion criteria were articles with experimental studies either in vivo or in vitro, in English or Indonesian, published after 1st January 2000, and full text available for inclusion in this review.
Data Extraction: The antimalarial activity, insecticidal activity, and structure of the isolated compounds were retrieved from the selected studies.
Data Synthesis: Antimalarial in vitro study showed that the dichloromethane extract was the most widely studied with an IC50 value < 10 μg/mL. Among 84 isolated active compounds, 2-hydroxymethyl-non-3-ynoic acid 2-[2,2’]-bithiophenyl-5- ethyl ester, a bithienyl compound from the Tagetes erecta plant show the smallest IC50 with value 0.01 and 0.02 μg/mL in Plasmodium falciparum MRC-pf-2 and MRC-pf-56, respectively. In vivo studies showed that the aqueous extract of A. conyzoides showed the best activity, with a 98.8% inhibition percentage using a 100 mg/kg dose of Plasmodium berghei (NK65 Strain). (Z)- γ-Bisabolene from Galinsoga parviflora showed very good insecticidal activity against Anopheles stephensi and Anopheles subpictus with LC50 values of 2.04 μg/mL and 4.05 μg/mL.
Conclusion: A. conyzoides and other plants of Asteraceae family are promising reservoirs of natural compounds that exert antimalarial or insecticidal activity.
Keywords: Ageratum conyzoides, Asteraceae, antimalarial, Plasmodium, insecticidal, Anopheles
Introduction
Malaria has been a worldwide disease since 1800, caused by Plasmodium species through the vector of Anopheles mosquitoes.1 Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi are Plasmodium species that commonly infect humans.2–4 According to World Health Organization (WHO), in 2020, there were around 241 million cases of malaria in the World.5 Caused by various factors such as geographical location, rainfall, and the number of standing water.6 As contained in the WHO guidelines for treating and preventing the incidence of malaria, several efforts have been made, including the use of Artemisinin Combination Therapies (ACT) for treating Plasmodium infections, Insecticide-Treated mosquito Nets (ITN), Insecticides Residual Spraying (IRS), and Larva Source Management (LSM) for preventing the incidence of malaria by controlling the vector.7–10
More than 90% of malaria mortality worldwide was caused by P. falciparum, whereas P. vivax is the most common.11 ACT therapies; by combining artemisinin derivatives and another antimalarial drug, are the current first-line therapy for uncomplicated P. falciparum and second-line therapy for non-P. falciparum. Meanwhile, Quinine derivates are considered the first-line choice for non-P. falciparum infection.12 Plasmodium parasites are now reported to be resistant to several ACT drugs due to mutations in the kelch13 gene reported in the Greater Mekong Subregion (GMS).13,14 Resistance is also experienced by vectors of malaria and Anopheles mosquitoes against insecticides (ITN/IRS) due to mutations of the L1014S gene.15 This phenomenon makes the development of treatment and prevention of malaria continue, which is currently widely reported using natural plant-based ingredients with various secondary metabolite compounds such as flavonoids, terpenoids, and chalcones.16–18 For example, particular species from Asteraceae and Rubiaceae family have been known as sources of antimalarial drugs: Quinine isolated from the Cinchona tree bark (Rubiaceae) and Artemisinin isolated from the leaves and floral buds of Artemisia annua (Asteraceae).19 Since the African continent accounted for >90% of all global malaria cases, various herbaceous plants have been used for traditional remedies in this region.20,21 For example, in Uganda, among the 63 plant families, Asteraceae species are the most widely used, accounting for up to 15% of all plant species followed by Fabaceae (9%), Lamiaceae (8%), Euphorbiaceae (6%), and Mimosaceae (4%) species.21 More specifically, aqueous extract of dried leaf of Ageratum conyzoides, a member of Asteraceae family, has been traditionally used to cure malaria in Nigeria22 Uganda,21 and India.23 Research on the A. conyzoides plant from the Asteraceae family has also been proven to have antiplasmodial and insecticidal activity against Anopheles mosquitoes.24,25 The potency of A. conyzoides is inseparable from the role of its secondary metabolites, such as flavonoids and terpenoids.26 Additionally, this plant is widely used as a source for the adjuvant.27 This review aims to obtain information about the potential of A. conyzoides and other plants from Asteraceae as antiplasmodial and insecticidal from existing studies for better development in the future.
Materials and Methods
This review was conducted using an online database with specific keywords combined with Boolean operators. Studies that met the inclusion criteria in the form of experimental studies (either in vivo or in vitro, articles in English or Indonesian, articles published after 1st January 2000, and full-text articles were included in this review. The exclusion criteria were the articles that only had abstracts available, and other articles that did not correlate with the scope of the discussion in this study.
Articles discussing the potential of A. conyzoides as antiplasmodials and insecticides will be extracted from the author, year of publication, species used, plant extraction methods, and results. To add information regarding the potency of A. conyzoides, this review also presents a similar study to determine the benefits of plants from the Asteraceae family as antiplasmodials and insecticidals, with the hope that they will show good results and be useful for future research on A. conyzoides. Limitation of this study are not including meta-analysis and comprehensive statistical analysis.
Results and Discussion
Results of Literature Review
The literature search analysis is shown in Figure 1. Among the articles retrieved from several databases, such as Google Scholar, PubMed, Science Direct, and Springer links (Tables 1 and 2), 62 articles were found that met the inclusion criteria. Fifteen articles discussed the potential of the A. conyzoides plant, and the remaining 47 discussed the potential of the Asteraceae family plants.
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Figure 1 Literature Study Flowchart. |
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Table 1 Keyword and Database Used for Ageratum conyzoides |
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Table 2 Keyword and Database Used for Asteraceae |
From several studies collected in this review, the results of the A. conyzoides plant and its family (Asteraceae) have varied as antiplasmodial and insecticidal. A part of the plant that is widely used is the leaves of both A. conyzoides and its family (Asteraceae). The most widely used extract is the dichloromethane extract. Several active compounds have been identified, there are 23 species of plants in the Asteraceae family whose active compound(s) have been defined including Acmella ciliata, Anacyclus pyrethrum, Artemisia afra jacq., Artemisia gorgonum, Baccharis dracunculifolia D. C, Dicoma anomala subsp. Gerrardii, Dicoma tomentosa, Distephanus angulifolius, Galinsoga parviflora, Helichrysum gymnocephalum, Kleinia odora, Microglossa pyrifolia, Pechuel-loeschea leubnitziae, Pentacalia desiderabilis (Vell.) Cuatrec, Sinicio smithioides, Sphaeranthus indicus, Symphyopappus casarettoi, Tagetes erecta, Vernonia guineensis Benth., Vernonia fimbrillifera Less., Vernonia colorata, Xanthium brasilicum Vell, and Ageratum conyzoide.
Traditional Use of Asteracea Family as Antimalaria
Since ancient times, certain plants have been recognized to offer therapeutic effects to cure malaria. The use of plants as medicine has grown in popularity since they are more economical, efficient, and safe.28 The extract is mostly prepared by using single herbal plants (monoteraphy) or from combination of two herbal plants for example Tamarindus indica and Mangifera indica.21,29 The most commonly used plant parts were leaves (67.3%), followed by roots (13.5%), root bark (5.8%), and fruits (5.8%). The herbal medicines were majorly administered orally (86.7%) follow by topical baths (11.1%), and steam baths (2.2%).20 The most common herbal medicine preparation is water extracts in the form of decoction and infusion or as steam baths.21 For example traditional remedy preparation of A. conyzoides to cure malaria was performed as follows: the water from boiling of A. conyzoides leaf was drunk thrice a day for seven days.21 Besides treating malaria, medicinal herbs from Asteraceae also has promising prophylactic use or malaria prevention. The most prevalent technique of preparing plant species for malaria prevention was to dry the plant material and burn it to make smoke, as well as to boil the plant material and consume it as a sauce.29
In vitro and in vivo Assay of Antiplasmodial Potency of Asteraceae Family
The emergence of drug resistance in Plasmodium parasites and unwanted side effects from certain chemical drugs have fueled the search for new plant-derived antimalarials. Consequently, the antimalarial properties of herbal plants have increasingly been reported. Specifically, the antimalarial activity of various extracts, fractions, and active compounds was tested as a starting point to become an alternative that can be used as a potential source of new antimalarial agents in the future.
In vitro and in vivo efficacy tests against Plasmodium parasites in vitro or in vivo have been performed on several plants belonging to the Asteraceae family (Tables 3 and 4). According to Deharo et al30 a compound with an IC50 value <5 μg/mL is considered a very effective antimalarial agent based on the results of in vitro tests and is very effective if the in vivo test shows an inhibition percentage >50% at a dose of 100 mg/kg/day.30 Therefore, 37 plants from the Asteraceae family showed antiplasmodial effects that could be tested in the future.
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Table 3 Result for Antiplasmodial and Insecticidal from Asteraceae Family |
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Table 4 Result for Antiplasmodial and Insecticidal from Ageratum conyzoides |
Among the 37 potential plants, the majority of the extract used in this study was dichloromethane extract, and the plants that had the highest activity were Microglossa pyrifolia and Vernonia guineensis Benth The dichloromethane extract from the leaves showed IC50 values of 1.5, 2.4, 1.8, and 1.6 μg/mL for P. falciparum 3D7, W2, Dd2, and Hb3 species, respectively.52,77 Meanwhile, the results showed little difference from in vivo testing on mice, dichloromethane extract from the whole plant Anisopappus chinensis gave medium yield with a suppression percentage of 60% at a dose of 300 mg/kg against Plasmodium berghei.41 However, this cannot be equated considering that the species tested in the two studies are different, no study states that this extract has been tested against Plasmodium other than P. berghei, therefore research on the effects of dichloromethane extract on mice infected with parasites other than P. berghei needs to be carried out.
Studies on the isolation of secondary metabolites from the Asteraceae family have also been conducted. In this review, 21 plants of the Asteraceae family were investigated for their antiplasmodial activity, as listed in Table 3. Of these 21 plants, there were 78 active antiplasmodial metabolites from various plants. The isolated compounds were very diverse, but the active compound that had the best antiplasmodial activity was 2-hydroxymethyl-non-3-ynoic acid 2-[2,2’]-bithiophenyl-5- ethyl ester, a bithienyl compound from the T. erecta plant which shows IC50 value 0.01 and 0.02 µg/mL against P. falciparum MRC -pf-2 and MRC-pf-56 respectively.70 In addition, the active compound from the terpenoid group, namely hautriwaic acid extracted from the plant B. dracunculifolia, also had high activity on P. falciparum D6 with IC50 0.8 µg/mL.47 Other types of terpenoids are also reported to have good effects as antiplasmodial from plants of the Laminaceae family.87
Insecticidal Activity from Asteraceae Family
Table 3 shows that the Asteraceae family; not only shows its activity against Plasmodium, but also has the potential insecticidal activity against malaria vector, Anopheles. Although there are only a few studies mention its activity, in this review the majority of the results that have been tested on Anopheles produce good results.
Six studies discussed insecticidal activity, and the extract or active compound showed promising results. The methanol extract and essential oil from the Achillea wilhelmsii plant resulted in 100% mortality for Anopheles stephensi from both extractions. However, with different doses of 320 ppm and 160 ppm, with LC50 values of 115.73 ppm and 39.04 ppm respectively, indicating that the essential oil from this plant is more potent against Anopheles, as seen from the results, the essential oil has 3 times the activity of methanol extract.34
More advanced research has shown that the active compound from the Galinsoga parviflora plant tested by in vivo method against A. stephensi and Anopheles subpictus vectors showed excellent LC50 values of 2.04 μg/mL and 4.05 μg/mL for the active compound in the form of (Z)-γ- bisabolene, indicating that this compound is even more active than the essential oils tested on this plant, which only showed LC50 values of 31.04 μg/mL and 45.55 μg/mL respectively.59 This compound also has better larvicidal activity compared to essential oils from plants from other areas where malaria is prevalent: Juniperus virginiana with LC50 10.75–9.06 μg/mL (Anopheles gambiae), Pelargonium roseum with LC50 13.63–8.98 μg/mL (A. gambiae)88 and Lantana camara with LC50 7.73 μg/mL (A. gambiae Susceptible strain (Kisumu)) and 25.63 μg/mL (A. gambiae Field strain (VK7)).89 (Z)-γ-Bisabolene is a monocyclic sesquiterpene hydrocarbon belonging to the bisabolene type, which is found in several evoluted plant families such as Lamiaceae that have good results against Anopheles.90 However, research on this compound needs to be reviewed considering there has been no further research about its toxicity test.
In addition to testing the larvae and eggs of the Anopheles vector, studies on Ageratum houstonianum and Blumea lacera have also tested the effectiveness of the adult vector as a repellent. The study used n-hexane and petroleum extracts from leaves, and the results showed that these two plants were good repellents with results of 93.4%38 and 97%,3 respectively, as shown in Table 3. In the A. houstonianum experiment, the plant extract was mixed with coconut oil, which is also believed to ward off several species of mosquitoes, resulting in good efficacy as well, but in B. lacera extract it was tried without any mixture but produced low efficacy (1 hour).3,38 Most of the plant-based repellents are shown to repel mosquitoes, but their effect lasts from few minutes to some hours since their active ingredients tend to be highly volatile, so although they are effective repellents for a short period after application, they rapidly evaporate, leaving the user unprotected.90 Therefore, in the future research coconut oil or compounds can be used as a mixture to inhibit evaporation.
A. conyzoides, a Medicinal Plant with Potential Antimalarial Activity
A. conyzoides is a plant belonging to the Asteraceae family with a height that can reach 100 cm and is characterized by the growth of flowers at the ends of the stems. This plant is also known as billy goat weed.91 Comes in tropical America, Southeast Asia, South China, India, and West Africa.26 The stems and leaves are covered with fine white hairs, and the leaves are conical in shape and reach 7.5 cm in length, the flowers are sometimes found purplish-blue or white. A. conyzoides can sometimes be found in yards, rice fields, and mountains, and can thrive anywhere.92 This plant has been traditionally used to treat many diseases, such as skin diseases, inflammation, diarrhea, and malaria.93
In this study, the 15 articles listed in Table 4 discuss the efficacy tests of these plants both in vitro and in vivo. Eleven of these studies tested the effect of this plant on Plasmodium, and the remaining four discussed the effect of this plant on the Anopheles malaria vector. There were 4 out of 5 studies testing dichloromethane extract on Plasmodium which produced good and moderate results.30 It was stated that the values obtained from the in vitro test results of the three studies were 2.1, 3.4, 9.95, and 7.9 µg/mL which were tested on Plasmodium parasite types D6, W2, FCB, and K1. In addition to the dichloromethane extract, research from Nour et al24 also suggested active compounds from the flavonoid group that produced positive activity as antiplasmodials, which were tested against Plasmodium K1 with results of 4.57, 4.26, 2.99 and 3.59 µg/ mL. In addition, research from Ukwe et al22 tested the aqueous extract from the leaves of this plant combined with malaria drugs, such as artesunate and chloroquine, to produce excellent values with a suppression percentage reaching 100% at a dose of 100 mg/kg on P. berghei. The results of this study are remarkably similar to those of previous studies on various antimalarial herb-drug interactions, which showed the potential effect of herbs on the antimalarial action of some common medications.94 Besides that, methanol extract and n-hexane were also reported to have a good effect on Plasmodium from in vivo test results. However, the dichloromethane extraction that is mostly carried out on both A. conyzoides and their families (Asteraceae) requires further research regarding its efficacy in test animals, considering that this extract produces many good scores in tests on A. conyzoides and their families.
The insecticidal potency of A. conyzoides was reported to be derived from the petroleum extract of its leaves, which resulted in a 93% mortality rate of A. stephensi larvae. This extract was reported to have a moderate antiplasmodial effect in the Asteraceae family, as shown in Table 3. However, testing its vector has also been reported to be successful as a repellent from the B. lacera plant, as described previously. Further research by Adelaja et al25 showed that the isolation of the active compound from the terpenoid group in an oil extract dose of 0.3 mg/mL resulted in 100% mortality against A. gambiae.25 These results could rival the positive control of deltamethrin which is a common spray insecticide used for malaria vectors.
In the research included in this review, extracts were taken from plants, both from the Asteraceae family and A. conyzoides itself; the majority came from dichloromethane extracts, although there were several studies that stated that the results were not as good, all of these could not be separated from the part of the plant used for extraction and from the tested Plasmodium species.
The antimalarial activity of A. conyzoides and its family (Asteraceae) is closely related to the presence of secondary metabolites, as seen in the majority of studies in Tables 3 and 4, showing that the phytochemicals that play a role include flavonoids and terpenoids. The mechanism of action of flavonoids as antimalarials is by inhibiting fatty acid biosynthesis, inhibiting the entry of L-glutamine, and targeting important functional biomolecules such as enzymes and DNA in plasmodium.95 Whereas the terpenoid group with the sesquiterpene lactone type inhibits the process of sporogonic development in gametogenesis and/or macrogamete fertilization. Another mechanism of the terpenoid group is the inhibition of protein synthesis in cells, which inhibits parasite growth.96
Antimalaria an Insecticidal Natural Compounds Isolated from Asteraceae
In vitro antimalarial activities of the compounds were classified into four categories: high (IC50 < 5 μg/mL), promising (5 < IC50 < 15 μg/mL), moderate (15 < IC50 < 50 μg/mL), and inactive (IC50 > 50 μg/mL).97 Based on the summary in Tables 3 and 4, the natural compounds from Asteraceae (including A. conyzoides) were classified based on their IC50 values. Among 84 compounds, there were 50 compounds with high antimalarial activity (Figure 2) (59.52%), 26 with promising antimalarial activity (Figure 3) (30.95%), 15 with moderate antimalarial activity (Figure 4) (17.86%), and only two with inactive antimalarial activity (Figure 5) (2.38%). Therefore, plants from the Asteraceae family are excellent reservoirs for antimalarial drugs of natural origin. Among the compounds with high antimalarial activity, 2-hydroxymethyl-non-3-ynoic acid 2-[2,2’]-bithiophenyl-5-ethyl ester exhibited the best antimalarial activity with an IC50 0.01–0.02 µg/mL (10–20 ng/mL). This compound has better antimalarial activity than the established antimalarial drug, chloroquine (IC50 232.65 ng/mL98), and has comparable IC50 with artemisinin (with ic50 1.5–7.5 ng/mL99). Resistance to chloroquine and artemisinin is the main obstacle to global malaria elimination/eradication programs.100 The discovery of natural antimalarial drugs provides new hope for combating the emergence of antimalarial drug resistance worldwide. Furthermore, the structures of these natural compounds listed in Figures 2–5 could also be used as reference backbones for novel antimalarial drug synthesis, docking studies of various enzymes to reveal the mechanism of action of each compound, or to estimate ADMET (adsorption, distribution, metabolism, excretion, and toxicity) parameters before in vivo testing.
The larvicidal activity of a compound against the Anopheles mosquito is classified into six categories: extremely active (LC50<1 µg/mL), highly active (1 µg/mL <LC50 <5 µg/mL), active (5 µg/mL<LC50 <50 µg/mL), moderately active (50 µg/mL <LC50 <100 µg/mL), slightly active (100 µg/mL <LC50 <200 µg/mL), and inactive (LC50 >200 µg/mL).101 Among natural compounds isolated from Asteraceae family, (Z)-γ-bisabolene from the essential oil of G. parviflora (Figure 6) exerts high larvicidal activity with LC50 values of 2.04 μg/mL and 4.05 μg/mL against A. stephensi and A. subpictus vectors.59 This compound might be a novel insecticide of natural origin with low toxicity because established synthetic compounds, such as permethrin or deltamethrin, usually pose potential hazards to humans and the environment because of their high toxicity and may lead to resistance development.102,103
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Figure 2 Natural Compounds Isolated from Asteraceae with High Antimalaria Activity. 1: isobutylamide spilanthol ((2E,6E,8E) -N-isobutyl-2,6,8-decatrienamide, 2: (2E,7Z)-6,9-endoperoxy- N-isobutyl-2,7-decadienamide,36 3: dodeca-2E,4E-dien acid 4-hydroxy-2-phenylethylamide,40 4: 7-Metoxyacacetin,42 5: Sesamin, 6: Artemetin,44 7: Ursolic acid, 8, 2α-hydroxy-ursolic acid, 9: Uvaol, 10: Ermanin, 11: Hautriwaic acid lactone, 12: Clerodane diterpene, 13: Viscidone,47 14: sesquiterpene lactone dehydrobrachylaenolide,53 15: urospermal A-15-O-acetate,54 16: Vernangulide A, 17: Vernangulide B, 18: Vernodalol, 19: Vernodalin,55 20: 3-O-Acetylpinobanksin,60 21: Urs-12-ene-3β,16β-diol,61 22: E-Phytol, 23: 6E-Geranylgeraniol-19-oic-acid, 24: Benzyl 2.6-dimethoxybenzoate,62 25: xerantholide,63 26: 9-oxoeuryopsin,66 27: Indicusalactone, 28: (-)-oxyfrullanolide, 29: 7-hydroxyfrullanolide, 30: Squalene, 31: 3,5-di-O-caffeoylquinic acid methyl ester,67 32: 3.4-di-O-caffeoylquinic acid methyl ester, 33: Caryatin BP204,68 34: 2-hydroxymethyl-non-3-ynoic acid 2-[2,2’]-bithiophenyl-5-ethyl ester,70 35: Vernopicrin, 36: Vernomelitensi), 37: Sucrose ester,77 38: s 8-(4’-hydroxymethacrylate)-dehydromelitensin, 39: onopordopicrin, 40: 8α-[4’-hydroxymethacryloyloxy]-4-epi-sonchucarpolide,78 41: vernodalol, 42: 11β,13-dihydrovernodalin,42 43: 8-Epixanthatin, 44: 8-Epixanthatin 1β,5β-epoxide, 45: Pungiolide A, 46: Pungiolide B,39 47: 5,6,7,8,5-pentamethoxy-3,4-methylenedioxyflavone (eupalestine), 48: 5,6,7,5-tetramethoxy3,4-methylenedioxyflavone, 49: 5,6,7,3,4,5-hexamethoxyflavone, 50: 4-hydroxy-5,6,7,3,5-pentamethoxyflavone (ageconyflavone C).24 |
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Figure 3 Natural Compounds Isolated from Asteraceae with Promising Antimalaria Activity. 1: deca-2E,4E,9-trienoic acid isobutylamide, 2: deca-2E,4E-dienoic acid 2-phenylethylamide, 3: undeca-2E,4E-dien-8,10-diynoic acid isopentylamide, 4: tetradeca-2E,4E,12Z-trien-8,10-diynoic acid isobutylamide,40 5: 7-Metoxyacacetin, 6: Acacetin, 7: Genkwanin, 8: Apigenin, 9: 1-desoxy-1α-peroxy-rupicolin A-8-O-acetate, 10: Rupicolin A-8-O-acetate, 11: 11,13-dehydromatricarin, 12: 1α,4α-dihydroxybishopsolicepolide.42 13: Epimagnolin A, 14: Aschantin, 15: Kabusin,44 16: Ursolic acid, 17: 3β 11α-dihydroxy urs-12-ene,61 18: Linoleic acid (octadeca-9,12-dienoic acid), 19: Benzyl 2.6-dimethoxybenzoate, 20: 13-Hydroxy-octadeca-9Z,11E,15Z-trienoic acid, 21: E-Phytol, 22: 6E-Geranylgeraniol-19-oic-acid,62 23: Jacaronone,64 24: (-)-frullanolide,67 25: 5,6,7,8,3’,4’,5’-heptamethoxyflavone (5’-methoxynobiletine,), 26: encecalol methyl ether.24 |
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Figure 4 Natural Compounds Isolated from Asteraceae with Moderate Antimalaria Activity. 1: N-(2-phenethyl)-2E-en-6,8- nonadiynamide,36 2: Tamarixetin, 3: Apigenin, 4: 1-desoxy-1α-peroxy-rupicolin A-8-O-acetate, 5: Rupicolin B-8-O-acetate, 6: 11,13-dehydromatricarin, 7: 1α,4α-8α-Trihydroxyguaia-2,9,11(13)-triene-12,6α-olide-8-O-acetate, 8: Eudesmaafgraucolid,42 9: Eudesmin, 10, Magnolin,44 11: Pinocembrin, 12: 5,7-Dihydroxyisoflavone,60 13: 3-Hydroxy-13,28-epoxyurs-11-en-28-one,61 14: 11β,13-dihydrovernolide,42 15: Xanthipungolide.39 |
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Figure 5 Natural Compounds Isolated from Asteraceae with Inactive Antimalaria Activity. 1: Eudesmaafgraucolid, 2: 11β,13-dihydrovernolide.42 |
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Figure 6 Z-γ-bisabolene from the essential oil of Galinsoga parviflora (Asteraceae) with insecticidal activity.59 |
Conclusion
There are 64 plant species with antimalarial or insecticidal activities were included in this study. For the antimalarial in vitro study, the dichloromethane extract was the most widely studied, with most of the extracts showing high and moderate activity (IC50 value <10 μg/mL). There are 84 compounds isolated from 22 plant species, 59.52% of compounds have high antimalarial activity, of which 2-hydroxymethyl-non-3-ynoic acid 2-[2,2’]-bithiophenyl-5- ethyl ester from T. erecta showed the best activity with IC50 value 0.01 of 0.02 µg/mL against P. falciparum MRC-pf-2 and MRC-pf-56 respectively, this compound has comparable IC50 with established antimalaria drug artemisinin (0.0015 and 0.0075 µg/mL). The in vivo antimalarial study showed that the aqueous extract of A. conyzoides showed the best activity, with a 100 mg/kg dose exerting 98.8% inhibition against P. berghei (NK65 Strain). In contrast, in a study on insecticidal activity, (Z)- γ-bisabolene from G. parviflora showed excellent activity against A. stephensi and A. subpictus with LC50 values of 2.04 μg/mL and 4.05 μg/mL. In conclusion, A. conyzoides and other plants from the Asteraceae family are promising reservoirs for natural compounds that exhibit antimalarial or insecticidal activity.
Acknowledgments
The authors acknowledge the support of the Faculty of Medicine Universitas Padjadjaran, particularly the supervising team, and the support of the Directorate of Research, Community Service, and Innovation Universitas Padjadjaran.
Disclosure
The authors report no conflicts of interest in this work.
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