The Potentials of Ageratum conyzoides and Other Plants from Asteraceae as an Antiplasmodial and Insecticidal for Malaria Vector: An Article Review

Irfan Taufik Kusman; Gita Widya Pradini; Ilma Fauziah Ma’ruf; Nisa Fauziah; Afiat Berbudi; Achadiyani Achadiyani; Hesti Lina Wiraswati

doi:10.2147/IDR.S433328

. 2023 Nov 7;16:7109–7138. doi: 10.2147/IDR.S433328

The Potentials of Ageratum conyzoides and Other Plants from Asteraceae as an Antiplasmodial and Insecticidal for Malaria Vector: An Article Review

Irfan Taufik Kusman ¹, Gita Widya Pradini ², Ilma Fauziah Ma’ruf ³, Nisa Fauziah ², Afiat Berbudi ², Achadiyani Achadiyani ^2,^✉, Hesti Lina Wiraswati ²

PMCID: PMC10638911 PMID: 37954507

Abstract

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.

Table 1.

Keyword and Database Used for Ageratum conyzoides

Keyword	Database
(“Ageratum conyzoides” OR “Billy goat weed”) AND (“Antimalarial” OR “Antiplasmodial” OR “Plasmodium” OR “Anopheles” OR “Insecticidal”)	Google Scholar
	PubMed
	Springer Links
	Sciencedirect

Open in a new tab

Table 2.

Keyword and Database Used for Asteraceae

Keyword	Database
(“Asteraceae”) AND (“Antimalarial” OR “Antiplasmodial” OR “Plasmodium” OR “Anopheles” OR “Insecticidal”)	Google Scholar
	PubMed
	Springer Links
	Sciencedirect

Open in a new tab

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.

Table 3.

Result for Antiplasmodial and Insecticidal from Asteraceae Family

No.	Asteraceae Species	Authors (Year)	Target Species	Study Design	Sample Used	Result	Phytochemical Active
1	Acanthospermum hispidum	Bero et al (2009)³¹	Plasmodium falciparum 3D7 strain	In Vitro	Dichloromethane extract from aerial part	IC 50: 7.5 µg/mL	N/A
		Bero et al (2009)³¹	Plasmodium falciparum W2 strain	In Vitro	Dichloromethane extract from aerial part	IC 50: 4.8 µg/mL	N/A
		Sanon et al (2003)³²	Plasmodium falciparum W2	In Vitro	Alkaloid extract from leaves	IC 50: 5.0 µg/mL	N/A
		Sanon et al (2003)³²	Plasmodium falciparum D6	In Vitro	Alkaloid extract from leaves	IC 50: 4.6 µg/mL	N/A
		Ohashi et al (2018)³³	Plasmodium falciparum 3D7 strain	In Vitro	Ethanol extract from whole plant	IC50: >1,000 µg/mL	N/A
2	Achillea wilhelmsii C. Koch	Soleimani-Ahmadi et al (2017)³⁴	Anopheles stephensi (BandarAbass strain)	In Vivo	Leaves-derived: 1. Methanol extract 2. Essential oil extract	% Mortality: 320 ppm = 100%; LC50: 115.73 160 ppm = 100%; LC50: 39.04	N/A
3	Acmella caulirhiza	Owuor et al (2012)³⁵	Plasmodium falciparum (D6) strain	In Vitro	Dichloromethane extract from whole plant	IC 50: 9.9 µg/mL	N/A
3	Acmella caulirhiza	Owuor et al (2012)³⁵	Plasmodium falciparum (W2) strain	In Vitro	Dichloromethane extract from whole plant	IC 50: 5.2 µg/mL	N/A
4	Acmella ciliata	Silveira et al (2016)³⁶	Plasmodium falciparum (NF54) strain	In Vitro	Subfraction n-Hexane: 1. isobutylamide spilanthol ((2E,6E,8E) -N-isobutyl-2,6,8-decatrienamide 2. N-(2-phenethyl)-2E-en-6,8- nonadiynamide 3. (2E,7Z)-6,9-endoperoxy- N-isobutyl-2,7-decadienamide	IC 50: 1. 0.99 µg/mL 2. 22.1 µg/mL 3. 1.29 µg/mL	Alkamide 1. isobutylamide spilanthol ((2E,6E,8E)-N-isobutyl-2,6,8-decatrienamide 2. N-(2-phenethyl)-2E-en-6,8-nonadiynamide 3. (2E,7Z)-6,9-endoperoxy-N-isobutyl-2,7-decadienamide
4	Acmella ciliata	Silveira et al (2016)³⁶	Plasmodium falciparum (K1) strain	In Vitro	Subfraction n-Hexane: 1. (2E,7Z)-6,9-endoperoxy-N-isobutyl-2,7-decadienamide	IC 50: 1. 0.54 µg/mL
5	Acmella oleracea	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Flower, Leaves, Stem-derived: 1. Ethanol extract 2. Aqueous extract	IC 50: µg/mL 21.5 (f); 28.9 (l); 28.2 (s) 47 (f); 110.7 (l); 536.7 (s)	Flavonoid, Terpenoid, Alkaloid, Saponin, Coumarin
6	Ageratina adenophora	Rajeswary et al (2014)³⁷	Anopheles stephensi egg	In Vivo	Leaves-derived: - n-Hexane extract - Benzene extract - chloroform extract - Ethyl acetate extract - Methanol extract	% Mortality: 450 ppm = 100% 450 ppm = 100% 375 ppm = 100% 300 ppm = 100% 300 ppm = 100%	N/A
7	Ageratum houstonianum Mill.	Tennyson et al (2012)³⁸	Anopheles stephensi	In Vivo	Leaves-derived: - n-Hexane extract - Ethyl acetate extract - Methanol extract	% Repellency activity: 93.4% 93.4% 91.7%	N/A
8	Ambrosia maritima L	Nour AMM et al (2009)³⁹	Plasmodium falciparum K1 strain	In Vitro	Dichloromethane extract	IC 50: 3.08 µg/mL	N/A
9	Anacyclus pyrethrum	Althaus et al (2017)⁴⁰	Plasmodium falciparum NF54 strain	In Vitro	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 5. dodeca-2E,4E-dien acid 4-hydroxy-2-phenylethylamide	IC50: 1. 7.13 μg/mL 2. >5 μg/mL 3. 10.3 μg/mL 4. 7.19 μg/mL 5. 3.18 μg/mL	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 5. dodeca-2E,4E-dien acid 4-hydroxy-2-phenylethylamide
10	Anisopappus chinensis	Lusakibanza et al (2010)⁴¹	Plasmodium falciparum 3D7	In Vitro	Whole plant-derived: 1. Dichloromethane extract 2. Methanol extract 3. Aqueous extract	IC 50: 6.53 µg/mL 8.82 µg/mL 76.51 µg/mL	Flavonoid, terpene, tanin, phenolic acid
			Plasmodium falciparum W2	In Vitro	Whole plant-derived: 1. Dichloromethane extract 2. Methanol extract	IC 50: 6.37 µg/mL 12.24 µg/mL	Flavonoid, terpene, tanin, phenolic acid
			Plasmodium berghei	In Vivo	Whole plant-derived: 1. Methanol extract 2. Ethanol extract 3. Dichloromethane extract 4. Aqueous extract	% Growth inhibition: (300mg/kg) 80.5% 65.5% 60.8% 85.6%	N/A
11	Artemisia afra jacq.	Kraft et al(2003)⁴²	Plasmodium falciparum PoW	In Vitro	lipophilic extract (petrol ether/ethylacetate) from aerial part Isolated compound: 1. 7-Metoxyacacetin 2. Acacetin 3.Genkwanin 4. Tamarixetin 5. Apigenin 6 1-desoxy-1α-peroxy-rupicolin A-8-O-acetate 7. Rupicolin A-8-O-acetate 8. Rupicolin B-8-O-acetate 9.11,13-dehydromatricarin 10. 1α,4α-dihydroxybishopsolicepolide 11. 1α,4α-8α-Trihydroxyguaia-2,9,11(13)-triene-12,6α-olide-8-O-acetate 12. Eudesmaafgraucolid	IC 50: 8.9 µg/mL IC 50: 1. 4.3 µg/mL 2. 5.5 µg/mL 3. 5.5 µg/mL 4. 33.9 µg/mL 5. 14.6 µg/mL 6. 8.7 µg/mL 7. 12.5 µg/mL 8. 20.1 µg/mL 9. 17.9 µg/mL 10. 8.6 µg/mL 11. 30.9 µg/mL 12. 47.5 µg/mL	− 7-Metoxyacacetin - Acacetin - Genkwanin - 1-desoxy-1α-peroxy-rupicolin A-8-O-acetate - 1α,4α-dihydroxybishopsolicepolide - A-8-O-acetate
11	Artemisia afra jacq.	Kraft et al(2003)⁴²	Plasmodium falciparum Dd2	In Vitro	1. lipophilic extract (petrol ether/ethylacetate) from aerial part 2. Isolated compound: 1. 7-Metoxyacacetin 2. Acacetin 3.Genkwanin 4. Tamarixetin 5. Apigenin 6 1-desoxy-1α-peroxy-rupicolin A-8-O-acetate 7. Rupicolin A-8-O-acetate 8. Rupicolin B-8-O-acetate 9.11,13-dehydromatricarin 10. 1α,4α-dihydroxybishopsolicepolide 11. 1α,4α-8α-Trihydroxyguaia-2,9,11(13)-triene-12,6α-olide-8-O-acetate 12. Eudesmaafgraucolid	IC 50: 15.3 µg/mL IC 50: 1 7.0 µg/mL 2. 12.6 µg/mL 3. 8.1 µg/mL 4. 33 µg/mL 5. 25 µg/mL 6. 17.5 µg/mL 7. 10.8 µg/mL 8. 31.8 µg/mL 9. 12.5 µg/mL 10. 11.7 µg/mL 11. 20.4 µg/mL 12. >50 µg/mL
12	Artemisia annua	Cheah et al (2013)⁴³	Anopheles sinensis larvae	In Vivo	Acetone extract from plant	% Suppression: 600 ppm = 99%	N/A
13	Artemisia gorgonum	Ortet et al (2011)⁴⁴	Plasmodium falciparun FcB1	In Vitro	Isolated flavonoid compound: 1. Eudesmin 2. Magnolin 3. Epimagnolin A 4. Aschantin 5. Kabusin 6. Sesamin 7. Artemetin	IC 50: 1. >25 µg/mL 2. 22.7 µg/mL 3. 5.7 µg/mL 4. 5.7 µg/mL 5. 7.67 µg/mL 6. 3.37 µg/mL 7. 3.50 µg/mL	1. Eudesmin 2. Magnolin 3. Epimagnolin 4. Aschantin 5. Kabusin 6. Sesamin 7. Artemetin
14	Artemisia nilagirica	Panda et al (2018)⁴⁵	Plasmodium falciparum (FCR-3 strain)	In Vitro	Extract from leaf: 1. Methanol 2. Chloroform 3. n-hexane 4. Petroleum ether 5. Ethanol 6. Aqueous	IC 50: 5.76 μg/mL 7.09 μg/mL 9.88 μg/mL 10.24 μg/mL 11.37 μg/mL 50.15 μg/mL	N/A
		Gogoi et al (2021)⁴⁶	Plasmodium falciparum (3D7)	In Vitro	Extract from leaf: 1. Petroleum ether 2. Chloroform 3. Etyl acetate 4. Methanol 5. Hydro alcoholic	IC 50: 14.24 μg/mL 11.61 μg/mL 5.22 μg/mL 3.28 μg/mL 3.41 μg/mL	N/A
		Gogoi et al (2021)⁴⁶	Plasmodium falciparum (RKL-9) strains	In Vitro	Extract from leaf: 1. Petroleum ether 2. Chloroform 3. Etyl acetate 4. Methanol 5. Hydro alcoholic	IC 50: 18.65 μg/mL 14.51 μg/mL 5.75 μg/mL 3.81 μg/mL 5.51 μg/mL	N/A
15	Baccharis dracunculifolia D. C	da Silva Filho et al (2009)⁴⁷	Plasmodium falciparum D6 strain	In Vitro	Extract: 1. Hydroalcoholic green propolis extract 2. Dichloromethane extract isolated compound: 1. Ursolic acid 2. 2α-hydroxy-ursolic acid 3. Uvaol 4. Ermanin 5. Hautriwaic acid lactone 6. Clerodane diterpene 7. Viscidone	IC 50: 1. 25 µg/mL 2. 20 µg/mL IC 50: 1. 1 µg/mL 2. 3.2 µg/mL 3. 3.3 µg/mL 4. 2.6 µg/mL 5. 0.8 µg/mL 6. 3.0 µg/mL 7. 1.9 µg/mL	1. 2α-hydroxy-ursolic acid 2. uvaol 3. ermanin 4. Hautriwaic acid lactone 5. clerodane diterpene 6. viscidone
15	Baccharis dracunculifolia D. C	da Silva Filho et al (2009)⁴⁷	Plasmodium falciparum W2 strain	In Vitro	Extract: 1. Hydroalcoholic green propolis extract 2. Dichloromethane extract isolated compound: 1. 2α-hydroxy-ursolic acid 2. Uvaol 3. Ermanin 4. Hautriwaic acid lactone 5. Clerodane diterpene 6. Viscidone	IC 50: 1. 13 µg/mL 2. 13 µg/mL IC 50: 1. 3.0 µg/mL 2. 1.9 µg/mL 3. 2.2 µg/mL 4. 2.2 µg/mL 5. 2.6 µg/mL 6. 2.3 µg/mL
16	Bidens pilosa L.	Andrade-Neto et al (2004)⁴⁸	Plasmodium berghei strain NK-65,	In Vivo	Ethanol extract from root	% Inhibition: 1000 mg/kg = 60%	Flavonoid
			Plasmodium falciparum clone W2	In Vitro	Ethanol extract from root	IC 50: 12.6 µg/mL
			Plasmodium falciparum clone D6	In Vitro	Ethanol extract from root	IC 50: 10.4 µg/mL
			Isolate BHz	In Vitro	Ethanol extract from root	IC 50: 17 µg/mL
		Nadia et al (2020)⁴⁹	Plasmodium berghei ANKA strain	In Vivo	1. Ethyl acetate extract 2. Fraction 12	% Suppression: 250 mg/kg = 79.20% 125 mg/kg = 100%	N/A
		Lacroix et al (2011)⁵⁰	Plasmodium falciparum FcB1	In Vitro	Ethyl acetate extract	IC 50: 45.8 µg/mL	N/A
17	Blumea aurita (L. f.) DC	Nour et al (2009)³⁹	Plasmodium falciparum K1 strain	In Vitro	Dichloromethane extract	IC 50: 2.8 µg/mL	N/A
18	Blumea balsamifera	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Leaves & Stem-derived: 1. Ethanol extract 2. Aqueous extract	IC 50: 9.7 µg/mL (l); 35.5 µg/mL (s) 30 µg/mL (l); 206 µg/mL (s)	Oleamide, α-amyrin, β-eudesmol, 3,3a epoxydicyclopenta [a,d]cyclo octan-4.beta.-ol, and 9,10a-dimethyl-6-methylene-3.beta.-isopropyl-, sakuranin, quercetin, pilloin, 5,7-dihydroxy, 30,40,50-trimethoxyflavone, retusin and 7,30-dimethylquercetin
19	Blumea lacera	Singh et al (2014)⁵¹	Anopheles stephensi Liston	In Vivo	Petroleum extract from leaf	% Repellency activity: 2% doses: 84.6% 4% doses: 91.4% 6% doses: 97.0%	N/A
20	Chromolaena odotarum	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Leaves & Stem-derived: 1. Ethanol extract 2. Aqueous extract	IC 50: 42.8 µg/mL (l); 112.3 µg/mL (s) 137.3 µg/mL (l); 488.9 µg/mL (s)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin, Coumarin
21	Chrysanthemum morifolium	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Flower, Leaves, Stem-derived: 1. Ethanol extract 2. Aqueous extract	IC 50: µg/mL 54.4 (f); 27.6 (l); 107.5 (s) 110.2 (f); 97.7 (l); 503.3 (s)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin, Coumarin
22	Conyza aegyptiaca (L.) Ait.	Nour et al (2009)³⁹	Plasmodium falciparum K1 strain	In Vitro	Dichloromethane extract	IC 50: 3.59 µg/mL	N/A
		Muganga et al (2010)⁵²	Plasmodium falciparum 3D7	In Vitro	Extraction from leave: 1. Methanol extract 2. Dichloromethane extract	IC 50: 22.7 µg/mL 36.8 µg/mL	N/A
		Muganga et al (2010)⁵²	Plasmodium falciparum W2	In Vitro	Methanol extract from leave	IC 50: 24.66 µg/mL	N/A
23	Cosmos sulphureus	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Ethanol extract from flowers	IC 50: 41.2 µg/mL (flowers)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin, Coumarin
23	Cosmos sulphureus	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Aqueous extract from flowers	IC 50: 515.3 µg/mL (flowers)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin, Coumarin
24	Crassocephalum vitellinum	Lacroix et al (2011)⁵⁰	Plasmodium falciparum FcB2	In Vitro	Ethyl acetate extract from leave	IC 50: 40.6 µg/mL	N/A
25	Dicoma anomala subsp. gerrardii	Becker et al (2011)⁵³	Plasmodium falciparum D10 strain	In Vitro	Plant root isolated compound: 1. sesquiterpene lactone dehydrobrachylaenolide.	IC 50: 1. 0.455 µg/mL	Dehydrobrachylaenolide
25	Dicoma anomala subsp. gerrardii	Becker et al (2011)⁵³	Plasmodium falciparum K1 strain	In Vitro	Plant root isolated compound: 1. sesquiterpene lactone dehydrobrachylaenolide.	IC 50: 1. 1 µg/mL	Dehydrobrachylaenolide
26	Dicoma tomentosa	Jansen et al (2012)⁵⁴	Plasmodium falciparum 3D7	In Vitro	Crude extract whole plant: 1. Petroleum ether 2. Hexane 3. Dichloromethane 4. Diethyl ether 5. Ethyl acetate 6. Methanol isolated compound: 1. urospermal A-15-O-acetate	IC 50: 1. 23.2 µg/mL 2. 18.7 µg/mL 3. 3.4 µg/mL 4. 3.9 µg/mL 5. 4.4 µg/mL 6. 5.8 µg/mL IC 50: 1. 0.92 µg/mL	Urospermal A-15-O-acetate
26	Dicoma tomentosa	Jansen et al (2012)⁵⁴	Plasmodium falciparum W2	In Vitro	Crude extract whole plant: 1. Petroleum ether 2. Hexane 3. Dichloromethane 4. Diethyl ether 5. Ethyl acetate 6. Methanol isolated compound: 1. urospermal A-15-O-acetate	IC 50: 1. 21.2 µg/mL 2. 17.7 µg/mL 3. 1.9 µg/mL 4. 4.8 µg/mL 5. 4.6 µg/mL 6. 3.0 µg/mL IC 50: 1. 0.77 µg/mL	Urospermal A-15-O-acetate
27	Distephanus angulifolius	Pedersen et al (2009)⁵⁵	Plasmodium falciparum D10 strain	In Vitro	Isolated compound sesquiterpene lactone: 1. Vernangulide A 2. Vernangulide B 3. Vernodalol 4. Vernodalin	IC 50: 1. 0.764 µg/mL 2. 0.626 µg/mL 3. 1.513 µg/mL 4. 0.635 µg/mL	- Vernangulide A [(6S,7R,8S)-14-acetoxy-8-[2-hydroxymethylacrylat]- 15-helianga-1(10),4,11(13)-trien-15-al-6,12-olid] - Vernangulide B [(5R,6R,7R,8S,10S)-14-acetoxy-8-[2-hydroxymethylacrylat]-elema-1,3,11(13)-trien-15-al-6,12-olid] - vernodalol - vernodalin
27	Distephanus angulifolius	Pedersen et al (2009)⁵⁵	Plasmodium falciparum W2 strain	In Vitro	Isolated compound sesquiterpene lactone: 1. Vernangulide A 2. Vernangulide B 3. Vernodalol 4. Vernodalin	IC 50: 1. 1.302 µg/mL 2. 0.848 µg/mL 3. 1.956 µg/mL 4. 0.974 µg/mL
28	Echinops kebericho	Toma et al (2015)⁵⁶	Plasmodium falciparum ANKA strain	In Vivo	Methanol extract from root	LD 50: >5000 mg/kg % Suppression: 57.29%	N/A
28	Echinops kebericho	Biruksew et al (2018)⁵⁷	Plasmodium falciparum ANKA strain	In Vivo	70% methanol rhizome extracts	% Inhibition: 250 mg/kg = 22% 500 mg/kg = 34% 1000 mg/kg = 49%	N/A
29	Eclipta prostrata	Rajakumar et al (2015)⁵⁸	Plasmodium falciparum (Nk 65) strain	In Vivo	1. Aqueous leave extract 2. Palladium acetate 3. Synthesize palladium nanoparticle	% Inhibition: (150 mg/kg) 38.34% 58.32% 78.13%	N/A
30	Francoeuria crispa (Forssk.) Cass.	Nour et al (2009)³⁹	Plasmodium falciparum K1 strain	In Vitro	Dichloromethane extract	IC 50: 4.66 µg/mL	N/A
31	Galinsoga parviflora	Govindarajan et al (2018)⁵⁹	Anopheles stephensi	In Vivo	1. Essential oil from leave extract Isolated compound: 1. (Z)-γ-bisabolene compound	LC 50: 31.04 μg/mL (EO), 2.04 μg/mL % Motrality: 75 µg/mL~100% (EO), 5 μg/mL~100%	(Z)-γ-bisabolene
31	Galinsoga parviflora	Govindarajan et al (2018)⁵⁹	Anopheles subpictus	In Vivo	1. Essential oil from leave extract Isolated compound: 1. (Z)-γ-bisabolene compound	LC 50: 45.55 μg/mL (EO), 4.50 μg/mL % Motrality: 100 µg/mL~97,3% (EO), 10 μg/mL~98%	(Z)-γ-bisabolene
32	Gerbera jamesonii	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Flowers & Stem-derived: 1. Ethanol extract 2. Aqueous extract	IC 50: 112.4 µg/mL (f); 123.3 µg/mL (s) 207.8 µg/mL (f); 479.4 µg/mL (s)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin
33	Helichrysum declinatum (L. f.) Less	Nour et al (2009)³⁹	Plasmodium falciparum K1 strain	In Vitro	Dichloromethane extract	IC 50: 7.6 µg/mL	N/A
34	Helichrysum gymnocephalum	Ranaivoarisoa et al (2020)⁶⁰	Plasmodium falciparum FCM29	In Vitro	1. Crude ethanol extract 2. Hexane extract 3. Dichloromethane extract 4. Aqueous fraction Isolated compound: 1. Pinocembrin 2. 3-O-Acetylpinobanksin 3. 5,7-Dihydroxyisoflavone	IC 50: 1. 39 µg/mL 2. 38.35 µg/mL 3. 8.81 µg/mL 4. 46.24 µg/mL IC 50: 1. 26.308 µg/mL 2. 4.905 µg/mL 3. 18.999 µg/mL	- Pinocembrin - 3-O-Acetylpinobanksin - 5,7-Dihydroxyisoflavone
35	Kleinia odora	Al Musayeib et al (2013)⁶¹	Plasmodium falciparum K1	In Vitro	1. Petroleum ether extract: 2. Chloroform extract Isolated compound: 1. Ursolic acid 2. Urs-12-ene-3β,16β-diol 3. 3β 11α-dihydroxy urs-12-ene 4. 3-Hydroxy-13,28-epoxyurs-11-en-28-one	IC 50: 1. 8.6 µg/mL 2. 8.2 µg/mL IC 50: 1. 13.068 µg/mL 2. 4.132 µg/mL 3. 10.182 µg/mL 4. >28.928 µg/mL	- Ursolic acid - Urs-12-ene-3β,16β-diol - 3β 11α-dihydroxy urs-12-ene - 3-Hydroxy-13,28-epoxyurs-11-en-28-one
36	Launea taraxacifolia (wild)	Nour et al (2009)³⁹	Plasmodium falciparum K1 strain	In Vitro	Dichloromethane extract	IC 50: 16.39 µg/mL	N/A
37	Leonotis nepetifolia	Lacroix et al (2011)⁵⁰	Plasmodium falciparum FcB3	In Vitro	Ethyl acetate extract from leave	IC 50: 27.0 µg/mL	N/A
38	Microglossa pyrifolia	Kohler et al (2002)⁶²	Plasmodium falciparum PoW	In Vitro	Extract: 1. Ethyl ether extract isolated compound: 1. Linoleic acid (octadeca-9,12-dienoic acid) 2. E-Phytol 3. Benzyl 2,6-dimethoxybenzoate 4. 13-Hydroxy-octadeca-9Z,11E,15Z-trienoic acid 5. 6E-Geranylgeraniol-19-oic-acid	IC 50: 10.5 µg/mL IC 50: 1. 6.1 µg/mL 2. 2.5 µg/mL 3. 9.0 µg/mL 4. 6.7 µg/mL 5. 4.3 µg/mL	2. Linoleic acid (octadeca-9,12-dienoic acid) 3. E-Phytol 4. Benzyl 2,6-dimethoxybenzoate 5. 13-Hydroxy-octadeca-9Z,11E,15Z-trienoic acid 6. 6E-Geranylgeraniol-19-oic-acid
		Kohler et al (2002)⁶²	Plasmodium falciparum Dd2	In Vitro	Extract: 1. Ethyl ether extract isolated compound: 1. Linoleic acid (octadeca-9,12-dienoic acid) 2. E-Phytol 3. Benzyl 2,6-dimethoxybenzoate 4. 13-Hydroxy-octadeca-9Z,11E,15Z-trienoic acid 5. 6E-Geranylgeraniol-19-oic-acid	IC 50: 1. 13.1 µg/mL 2. 8.7 µg/mL 3. 3.4 µg/mL 4. >25 µg/mL 5. 13.7 µg/mL 6. 5.2 µg/mL
		Muganga et al (2010)⁵²	Plasmodium falciparum 3D7	In Vitro	Extraction from leave: 1. Methanol extract 2. Dichloromethane extract	IC 50: 4.2 µg/mL 1.5 µg/mL	N/A
		Muganga et al (2010)⁵²	Plasmodium falciparum W2	In Vitro	Dichloromethane extract from leave	IC 50: 2.4 µg/mL	N/A
39	Pechuel-loeschea leubnitziae	Kadhila et al (2020)⁶³	Plasmodium falciparum strain (3D7)	In Vitro	Extract: 1. Dichloromethane extract Isolated compound 1. xerantholide	IC 50: 1. 7.24 µg/m IC 50: 1. 2.42 µg/mL or 2.29 µg/mL	- Npk1 F70-77 - Npk1 F78-90
40	Pentacalia desiderabilis (Vell.) Cuatrec	Morais et al (2012)⁶⁴	Plasmodium falciparum K1 strain	In Vitro	Plant leaf isolated compound: 1. Jacaronone	IC 50: 1. 7.82 μg/mL	Jacarone
41	Pluchea dioscoridis (L.) DC	Nour et al (2009)³⁹	Plasmodium falciparum K1 strain	In Vitro	Dichloromethane extract	IC 50: 31.59 µg/mL	N/A
42	Praxelis clematidea	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Leaves & Stem- derived: 1. Ethanol extract 2. Aqueous extract	IC 50: 173.8 µg/mL (l); 12.8 µg/mL (s) 417.3 µg/mL (l); 308.3 µg/mL (s)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin
43	Psiadia amygdalina	Ledoux et al (2018)⁶⁵	Plasmodium falciparum 3D7 strain	In Vitro	Leaves & bark-derived: 1. Ethyl acetate	IC 50: >50 µg/mL (leaves) 16.61 µg/mL (bark)	N/A
44	Psiadia bovini	Ledoux et al (2018)⁶⁵	Plasmodium falciparum 3D7 strain	In Vitro	Leaves & bark-derived: 1. Ethyl acetate	IC 50: 23.69 µg/mL (leaves) >50 µg/mL (bark)	N/A
45	Psiadia dentata	Ledoux et al (2018)⁶⁵	Plasmodium falciparum 3D7 strain	In Vitro	Leaves & bark-derived: 1. Ethyl acetate	IC 50: 22.99 µg/mL (leaves) >50 µg/mL (bark)	N/A
46	Psiadia retusa	Ledoux et al (2018)⁶⁵	Plasmodium falciparum 3D7 strain	In Vitro	Leaves & bark-derived: 1. Ethyl acetate	IC 50: 12.09 µg/mL (leaves) >50 µg/mL (bark)	N/A
47	Pulicaria undulata (L.) C. A. Mey	Nour et al (2009)³⁹	Plasmodium falciparum K1 strain	In Vitro	Dichloromethane extract	IC 50: 3.87 µg/mL	N/A
48	Sinicio smithioides	Mollinedo et al (2016)⁶⁶	Plasmodium falciparum	In Vitro	Extract from plant: 1. Petroleum ether extract 2. Dichloromethane extract 3. Ethyl acetate 4. Hydroethanolic Isolated compound 1. 9-oxoeuryopsin	IC 50: 1. < 1.0 µg/mL 2. > 2.0 µg/mL 3. > 2.0 µg/mL 4. > 2.0 µg/mL IC 50: 1. 1.2 µg/mL	9-oxoeuryopsin
49	Solanecio mannii	Muganga et al (2010)⁵²	Plasmodium falciparum 3D7	In Vitro	Extraction from leave: 1. Methanol extract 2. Dichloromethane extract	IC 50: 21.6 µg/mL 18.2 µg/mL	N/A
49	Solanecio mannii	Muganga et al (2010)⁵²	Plasmodium falciparum W2	In Vitro	Extraction from leave: 1. Methanol extract 2. Dichloromethane extract	IC 50: 26.2 µg/mL 12.7 µg/mL	N/A
50	Sphaeranthus indicus	Sangsopha et al (2016)⁶⁷	Plasmodium falciparum K1 strain	In Vitro	Sesquiterpene isolated compound: 1. Indicusalactone 2. (-)-oxyfrullanolide 3. (-)-frullanolide 4. 7-hydroxyfrullanolide 5. Squalene 6. 3,5-di-O-caffeoylquinic acid methyl ester 7. 3,4-di-O-caffeoylquinic acid methyl ester	IC 50: 1. 2.87 µg/mL 2. 3.82 µg/mL 3. 6.47 µg/mL 4. 2.49 µg/mL 5. 2.32 µg/mL 6. 2.39 µg/mL 7. 2.90 µg/mL	- indicusalactone - (-)-enantiomer - (-)-frullanolide - 7-hydroxyfrullanolide ( - squalene - 3,5-di-O-caffeoylquinic acid methyl ester - 3,4-di-O-caffeoylquinic acid methyl ester
51	Symphyopappus casarettoi	Zani et al (2020)⁶⁸	Plasmodium falciparum W2 strain	In Vitro	1. Ethanol extract 2. Fr-A 3. Fr-B 4. BP-181-6 Isolated compound: 1. Caryatin BP204	IC 50: 1. 4.8 µg/mL 2. 2.5 μg/mL 3. 26 μg/mL 4. 7.2 μg/mL IC 50: 1. 2.5 μg/mL	N/A
52	Synedrella nodiflora	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Leaves & Stem- derived: 1. Ethanol extract 2. Aqueous extract	IC 50: 37.8 µg/mL (l); 142.2 µg/mL (s) 153.9 µg/mL (l); 539.9 µg/mL (s)	N/A
52	Synedrella nodiflora	Chaniad et al (2021)⁶⁹	Plasmodium berghei var. Anka I strain	In Vivo	Ethanol extract from leaves	% Suppression: 200 mg/kg = 38.57% 400 mg/kg = 57.67% 600 mg/kg = 62.65%	N/A
53	Tagetes erecta	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Flowers, Leaves, Stem- derived: 1. Ethanol extract 2. Aqueous extract	IC 50: µg/mL 32.8 (f); 70.6 (l); 86.6 (s) 35.6 (f); 229.5 (l); 450.9 (s)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin, Coumarin
		Chaniad et al (2021)⁶⁹	Plasmodium berghei var. Anka I strain	In Vivo	Aqueous extract from flower	% Suppression: 200 mg/kg = 26.33% 400 mg/kg = 50.82% 600 mg/kg = 65.65%	N/A
		Gupta et al (2010)⁷⁰	Plasmodium falciparum strain (MRC-pf-2)	In Vitro	Plant extract from root: 1. Petroleum ether 2. Chloroform 3. Ethyl acetate 4. Methanol 5. Aqueous Isolated compound: 1. 2-hydroxymethyl-non-3-ynoic acid 2-[2,2’]-bithiophenyl-5- ethyl ester	IC 50: 1. 0.22 µg/mL 2. 0.05 µg/mL 3. 0.02 µg/mL 4. 0.09 µg/mL 5. 0.31 µg/mL IC 50: 1. 0.01 µg/mL	N/A
		Gupta et al (2010)⁷⁰	Plasmodium falciparum strain(MRC-pf-56)	In Vitro	Plant extract from root: 1. Petroleum ether 2. Chloroform 3. Ethyl acetate 4. Methanol 5. Aqueous Isolated compound: 1. 2-hydroxymethyl-non-3-ynoic acid 2-[2,2’]-bithiophenyl-5- ethyl ester	IC 50: 1. 0.37 µg/mL 2. 0.09 µg/mL 3. 0.07 µg/mL 4. 0.15 µg/mL 5. 0.49 µg/mL IC 50: 1. 0.02 µg/mL	N/A
54	Tithonia diversifolia	Elufioye et al (2004)⁷¹	Plasmodium berghei var. Anka I strain	In Vivo	Ethanol extract from aerial part	% Suppression: 200 mg/kg = 54%	N/A
		Nour et al (2009)³⁹	Plasmodium falciparum K1 strain	In Vitro	Dichloromethane extract	IC 50: 6.1 µg/mL	N/A
		Ajayi et al (2020)⁷²	Plasmodium berghei ANKA strain	In Vivo	Aqueous extract from leaves	% Suppression: 200 mg/kg = 64.3% 400 mg/kg = 65.78%	N/A
55	Tridax procumbens	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Leaves & Stem- derived: 1. Ethanol extract 2. Aqueous extract	IC 50: 57.9 µg/mL (l); 52.6 µg/mL (s) 461.6 µg/mL (l); 775.4 µg/mL (s)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin
55	Tridax procumbens	Nour et al (2009)³⁹	Plasmodium falciparum (K1) strain	In Vitro	Dichloromethane extract	IC 50: 4.13 µg/mL	N/A
56	Tagetes minuta	Lacroix et al (2011)⁵⁰	Plasmodium falciparum FcB4	In Vitro	Ethyl acetate extract from leave	IC 50: 61.0 µg/mL	N/A
57	Vernonia amygdalina Del.	Quartey et al (2020)⁷³	Plasmodium berghei NK 65	In Vivo	Hydroethanolic stem bark extract	% Suppression: 100 mg/kg = 20.30% 200 mg/kg = 38.34% 400 mg/kg = 54.11% 600 mg/kg = 81.80%	Tannins, glycoside, saponin, alkaloid, flavonoid, terpenoids
		Ajayi et al (2020)⁷²	Plasmodium berghei ANKA strain	In Vivo	Aqueous extract from leaves	% Suppression: 200 mg/kg = 63.92% 400 mg/kg = 75.13%
		Lacroix et al (2011)⁵⁰	Plasmodium falciparum FcB5	In Vitro	Ethyl acetate extract from leave	IC 50: 97.8 µg/mL	N/A
		Obbo et al (2019)⁷⁴	Plasmodium falciparum K1 strain	In Vitro	Extract from leave: 1. Petroleum ether 2. Methanol	IC 50: >30 µg/mL >30 µg/mL	N/A
58	Vernonia cinerea	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Ethanol extract from leaves & stem	IC 50: 30.4 µg/mL (leaves) 143.4 µg/mL (stem)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin
		Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Aqueous extract from leaves & stem	IC 50: 63.0 µg/mL (leaves) 917.1 µg/mL (stem)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin
		Soma et al (2017)⁷⁵	Plasmodium falciparum (K1) strain	In Vitro	Whole plant extract: 1. Dichloromethane 2. Methanol 3. Water methanol 4. Alkaloid extracts	IC 50: 1. 5.85 µg/mL 2. 21.08 µg/mL 3. 41.56 µg/mL 4. 2.56 µg/mL	Alkaloid, triterpens
		Soma et al (2017)⁷⁵	Plasmodium falciparum (3D7) strain	In Vitro	Whole plant extract: 1. Dichloromethane 2. Methanol 3. Water methanol 4. Alkaloid extracts	IC 50: 1. 8.42 µg/mL 2. 26.43 µg/mL 3. >50 µg/mL 4. 4.35 µg/mL	Alkaloid, triterpens
		Sourabie et al (2018)⁷⁶	Plasmodium berghei ANKA strain	In Vivo	Extract from plant: 1. crude 80% methanolic extract 2. hydromethanolic extract 3. Aqueous extract	% Suppression: 500 mg/kg = 43.1% 500 mg/kg = 40.6% 500 mg/kg = 3.2%	Alkaloids, triterpenes and sterols, anthracenosids, tannins, saponins
59	Vernonia guineensis Benth.	Toyang et al (2013)⁷⁷	Plasmodium falciparum Dd2	In Vitro	1. Crude extract from leaf and root: 1. Dichloromethane 2.Methanol 3. Aqueous 2. Isolated compound: 1.Vernopicrin 2. Vernomelitensin 3. Sucrose ester	IC 50: 1. 1.8 µg/mL (leaf) and 3.1 µg/mL (root) 2. 3.9 µg/mL (leaf) and 29.9 µg/mL (root) 3.11.3 µg/mL (leaf) and 26.1 µg/mL (root) IC 50: 1. 0.8 µg/mL 2. 0.5 µg/mL 3.1.4 µg/mL	Sesquiterpene lactones: - Vernopicrin - Vernomelitensin - Sucrose ester
59	Vernonia guineensis Benth.	Toyang et al (2013)⁷⁷	Plasmodium falciparum Hb3	In Vitro	1. Crude extract from leaf and root: 1. Dichloromethane 2.Methanol 3. Aqueous 2. Isolated compound: 1.Vernopicrin 2. Vernomelitensin 3. Sucrose ester	IC 50: 1. 1.6 µg/mL (leaf) and 3.2 µg/mL (root) 2. 2.0 µg/mL (leaf) and 27.0 µg/mL (root) 3. 9.5 µg/mL (leaf) and 27.2 µg/mL (root) IC 50: 1. 0.6 µg/mL 2. 0.4 µg/mL 3.1.6 µg/mL
60	Vernonia fimbrillifera Less.	Bordignon et al (2018)⁷⁸	Plasmodium falciparum (3D7) strain	In Vitro	Isolated compound from Dichloromethane fraction: 1. s 8-(4’-hydroxymethacrylate)-dehydromelitensin 2. onopordopicrin 3. 8α-[4’-hydroxymethacryloyloxy]-4-epi-sonchucarpolide	IC 50: 1. 2.96 µg/mL 2. 3.37 µg/mL 3. 3.27 µg/mL	Sesquiterpene lactones 1. s 8-(4’-hydroxymethacrylate)-dehydromelitensin 2. onopordopicrin 3. 8α-[4’-hydroxymethacryloyloxy]-4-epi-sonchucarpolide
60	Vernonia fimbrillifera Less.	Ledoux et al (2018)⁶⁵	Plasmodium falciparum 3D7 strain	In Vitro	Leaves & bark-derived: 1. Ethyl acetate	IC 50: 5.9 µg/mL (leaves) >50 µg/mL (bark)	N/A
61	Vernonia colorata	Kraft et al (2003)⁴²	Plasmodium falciparum PoW	In Vitro	1. lipophilic extract (petrol ether/ethyl acetate) from aerial part 2. Isolated compound: 1. vernodalol 2.11β,13-dihydrovernodalin 3. 11β,13-dihydrovernolide	IC 50: 12.1 µg/mL IC 50: 1. 4.0 µg/mL 2. 2.3 µg/mL 3. >50 µg/mL	- vernodalol - 11β,13-dihydrovernodalin
61	Vernonia colorata	Kraft et al (2003)⁴²	Plasmodium falciparum Dd2	In Vitro	1. lipophilic extract (petrol ether/ethyl acetate) from aerial part 2. Isolated compound: 1. vernodalol 2.11β,13-dihydrovernodalin 3. 11β,13-dihydrovernolide	IC 50: 17.8 µg/mL IC 50: 1. 4.8 µg/mL 2. 1.1 µg/mL 3. 37.3 µg/mL	- vernodalol - 11β,13-dihydrovernodalin
62	Xanthium brasilicum Vell	Nour et al (2009)³⁹	Plasmodium falciparum K1 strain	In Vitro	Extract from plant: 1. Hexane extract 2. Dichloromethane extract 3. Ethyl acetate extract isolated compound: 1. 8-Epixanthatin 2. 8-Epixanthatin 1β,5β-epoxide 3. Xanthipungolide 4. Pungiolide A 5. Pungiolide B	IC 50: 4.33 µg/mL 2.41 µg/mL 4.78 µg/mL 1. 1.93 µg/mL 2. 1.71 µg/mL 3. >20 µg/mL 4. 2.52 µg/mL 5. 3.42 µg/mL	Isolated compound: - 8-Epixanthatin - 8-Epixanthatin 1β,5β-epoxide - Pungiolide A - Pungiolide B
63	Zinnia violacea	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Flowers, Leaves, Stem, Pollen-derived: 1. Ethanol extract 2. Aqueous extract	IC 50: µg/mL 112.5 (f); 22.4(l); 111.3(s); 87.8(p) 428.7(f); 197(l); 823.7 (s); 202.8(p)	Flavonoid, Terpenoid, Alkaloid, Tanin, Saponin, Coumarin

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Table 4.

Result for Antiplasmodial and Insecticidal from Ageratum conyzoides

No.	Authors (Year)	Target Species	Study Design	Sample Used	Result	Phytochemical Active	Additional Information
1	Ukwe et al (2010)²²	Plasmodium berghei (NK65 strain)	In Vivo	Leaves-derived: 1. Aqueous extract 2. n-Hexane fraction 3. Chloroform fraction 4. Methanol fraction	LD 50: >5000 mg/kg %Inhibition: 100 mg/kg = 70.46% 100 mg/kg = 52.17% 400 mg/kg = 52.61% 200 mg/kg = 56.52%	Flavonoid, Alkaloid	N/A
2	Owuor et al (2012)³⁵	Plasmodium falciparum (D6) strain	In Vitro	Dichloromethane extract from whole plant	IC 50: 2.1 µg/mL	N/A	N/A
2	Owuor et al (2012)³⁵	Plasmodium falciparum (W2) strain	In Vitro	Dichloromethane extract from whole plant	IC 50: 3.4 µg/mL	N/A	N/A
3	Ifijen et al (2019)⁷⁹	Plasmodium berghei strain ANKA (PbANKA)	In Vivo	Methanol extract from leaves	LD 50: >1000 mg/kg %Inhibition: 100 mg/kg = 61%	Terpenoids, Flavonoids, Alkaloids, Steroids and Chromene.	The extract shows no toxicity
4	Abdullah et al (2011)⁸⁰	Plasmodium falciparum strain FCB	In Vitro	Plant-derived: 1. Dichloromethane extract 2. Methanol extract	IC 50: 9.95 g/mL 25.48 g/mL	N/A	N/A
5	Ukwe et al (2010)²²	Plasmodium berghei (NK65 Strain)	In Vivo	Aqueous extract from leaves	%Suppression: 100 mg/kg = 98.80%	N/A	The first research is a combination with conventional malaria drugs, but toxicity tests and the mechanism of the compounds need to be carried out to see their efficacy and safety
6	Muema et al (2016)⁸¹	Anopheles gambiae s.s larvae instar III	In Vivo	Methanol extract from leaves	LC 50: 232 ppm %Mortality: 250 ppm = 64%	Alkaloids, Aglycone Flavonoids, Triterpenoids, Tannins and Coumarins	The mechanism of the extract on larval development is described
6	Muema et al (2016)⁸¹	Anopheles arabiensis larvae instar III	In Vivo	Methanol extract from leaves	LC 50: 406 ppm %Mortality: 500 ppm = 60%
7	Chaniad et al (2022)¹⁹	Plasmodium falciparum (K1) strain	In Vitro	Leaves & stem-derived: 1. Aqueous extract 2. Ethanol extract	IC 50: 78.4 µg/mL (L); 196.7 µg/mL (S) 31.4 µg/mL (L); 99.7 µg/mL (S)	Flavonoid, Terpenoid, Alkaloid	N/A
8	do Ce´u de Madureira et al (2002)⁸²	Plasmodium falciparum (3D7) strain & Plasmodium falciparum (Dd2) strain	In Vitro	Aerial part-derived: 1. Ethanol extract 2. Petroleum fraction 3. Dichloromethane fraction 4. Ethyl acetate fraction	IC 50: 150 µg/mL 110 µg/mL 55 µg/mL 220 µg/mL	N/A	The first extraction experiment of Ageratum for its antiplasmodial properties
8	do Ce´u de Madureira et al (2002)⁸²	Plasmodium berghei ANKA strain (PbANKA)	In Vivo	Ethanol extract	IC 50: 130 µg/mL	N/A
9	Joshi et al (2016)⁸³	Plasmodium falciparum (K1 strain)	In Vitro	Ethanol extract from whole plant	IC 50: 72.4 µg/mL	Chromenes, benzofurans, flavonoids, farnesene, derivatives daucanolides, triterpenoids, sterols	N/A
10	Jonville et al (2011)⁸⁴	Plasmodium falciparum (3D7) strain	In Vitro	Aerial part-derived: 1. Methanol extract 2. Dichloromethane extract	IC 50: >50 µg/mL >50 µg/mL	N/A	N/A
11	Arya et al (2011)⁸⁵	Anopheles stephensi larvae instar II	In Vivo	Crude extract from plant	%Mortality: 300 ppm = 62% LC 50: 238 ppm	N/A	N/A
11	Arya et al (2011)⁸⁵	Anopheles stephensi larvae instar IV	In Vivo	Crude extract from plant	%Mortality: 300 ppm = 65% LC 50: 228,5 ppm	N/A	N/A
12	Adelaja et al (2022)²⁵	Anopheles gambiae s.s. Kisumu Susceptible Strain (KSS)	In Vivo	Extract plant oil from leaves	%Mortality: 0.1 mg/mL = 77% 0.3 mg/mL = 100%	D-limonene terpene	The active compound has been isolated and has a very good effect
13	Nour et al (2010)²⁴	Plasmodium falciparum (K1) strain	In vitro	Aerial parts-derived: 1. n-Hexane extract 2. Dichloromethane extract 3. Ethyl acetate extract Isolated compound: 1. 5,6,7,8,5-pentamethoxy-3,4-methylenedioxyflavone (eupalestine) 2. 5,6,7,5-tetramethoxy3,4-methylenedioxyflavone 3. - 5,6,7,8,3’,4’,5’-heptamethoxyflavone (5’-methoxynobiletine,) 4. 5,6,7,3,4,5-hexamethoxyflavone 5. 4-hydroxy-5,6,7,3,5-pentamethoxyflavone (ageconyflavone C) 6. encecalol methyl ether	IC 50: 1. 7.1 µg/mL 2. 7.9 µg/mL 3. 15.6 µg/mL IC 50: 1. 4.57 µg/mL 2. 4.26 µg/mL 3. >5 µg/mL 4. 2.99 µg/mL 5. 3.59 µg/mL 6. >5 µg/mL	− 5,6,7,8,5-pentamethoxy-3,4-methylenedioxyflavone (eupalestine) - 5,6,7,5-tetramethoxy3,4-methylenedioxyflavone - 5,6,7,8,3’,4’,5’-heptamethoxyflavone (5’-methoxynobiletine,) - 5,6,7,3,4,5-hexamethoxyflavone - 4-hydroxy-5,6,7,3,5-pentamethoxyflavone (ageconyflavone C) - encecalol methyl ether	The active compound has been isolated and has a very good effect
14	Nour et al (2009)³⁹	Plasmodium falciparum (K1) strain	In vitro	Dichloromethane extract from plant	IC 50: 7.95 µg/mL	N/A	N/A
15	Ramasamy et al (2021)⁸⁶	Anopheles stephensi larvae 4th instar	In vitro	Petroleum ether extract from leave	LC50: 108 ppm % Mortality: 200 ppm = 93%	N/A	N/A

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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.

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

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

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

Natural Compounds Isolated from Asteraceae with Inactive Antimalaria Activity. 1: Eudesmaafgraucolid, 2: 11β,13-dihydrovernolide.⁴²

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

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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PERMALINK

The Potentials of Ageratum conyzoides and Other Plants from Asteraceae as an Antiplasmodial and Insecticidal for Malaria Vector: An Article Review

Irfan Taufik Kusman

Gita Widya Pradini

Ilma Fauziah Ma’ruf

Nisa Fauziah

Afiat Berbudi

Achadiyani Achadiyani

Hesti Lina Wiraswati

Abstract

Background

Purpose

Data Source

Study Selection

Data Extraction

Data Synthesis

Conclusion

Introduction

Materials and Methods

Results and Discussion

Results of Literature Review

Figure 1.

Table 1.

Table 2.

Traditional Use of Asteracea Family as Antimalaria

In vitro and in vivo Assay of Antiplasmodial Potency of Asteraceae Family

Table 3.

Table 4.

Insecticidal Activity from Asteraceae Family

A. conyzoides, a Medicinal Plant with Potential Antimalarial Activity

Antimalaria an Insecticidal Natural Compounds Isolated from Asteraceae

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Conclusion

Acknowledgments

Disclosure

References

ACTIONS

PERMALINK

RESOURCES

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