Plant-Derived Essential Oils; Their Larvicidal Properties and Potential Application for Control of Mosquito-Borne Diseases

Abstract

Mosquito-borne diseases are currently considered as important threats to human health in subtropical and tropical regions. Resistance to synthetic larvicides in different species of mosquitoes, as well as environmental pollution, are the most common adverse effects of excessive use of such agents. Plant-derived essential oils (EOs) with various chemical entities have a lower chance of developing resistance. So far, no proper classification based on lethal concentration at 50% (LC₅₀) has been made for the larvicidal activity of EOs against different species of Aedes, Anopheles and Culex mosquitoes. To better understand the problem, a summary of the most common mosquito-borne diseases have been made. Related articles were gathered, and required information such as scientific name, used part(s) of plant, target species and LC₅₀ values were extracted. 411 LC₅₀ values were found about the larvicidal activity of EOs against different species of mosquitoes. Depending on the obtained results in each species, LC₅₀ values were summarized as follows: 24 EOs with LC₅₀ < 10 µg/mL, 149 EOs with LC₅₀ in range of 10- 50 µg/mL, 143 EOs having LC₅₀ within 50- 100 µg/mL and 95 EOs showing LC₅₀ > 100 µg/mL. EOs of Callitris glaucophylla and Piper betle against Ae. aegypti, Tagetes minuta against An. gambiae, and Cananga odorata against Cx. quinquefasciatus and An. dirus having LC₅₀ of ~ 1 µg/mL were potentially comparable to synthetic larvicides. It appears that these plants could be considered as candidates for botanical larvicides.

Introduction

Arthropod-borne diseases are the cause of more than 17% of all human infectious diseases around the world [1]. Mosquitoes (Diptera: Culicidae) are an important family of Arthropoda phylum which is grouped into 39 genera with a total of over 3000 species [2, 3]. More than half the world’s population lives in areas where mosquito-borne diseases are common. Mosquito-borne diseases represent a critical threat for billions of people worldwide, e.g., more than 3.9 billion people in over 128 countries are at risk of dengue, with 96 million cases estimated per year. Malaria causes more than 400,000 deaths every year globally; the majority of them are children under five years of age [1, 4]. Three genera of mosquito which are very important in the transmission of human diseases include Aedes (Chikungunya, Dengue fever, Lymphatic filariasis, Rift Valley fever, Yellow fever, Zika), Anopheles (Malaria, Lymphatic filariasis) and Culex (Japanese encephalitis, Lymphatic filariasis, West Nile fever) [1, 5]. All mosquitoes have immature aquatic stages. Thus, larviciding could be an efficient method to reduce the population of mosquitos and prevent the transmission of such diseases [6-8]. Larvicides reduce their population in breeding places, where they are concentrated, immobilized and accessible before they emerge into adults [9, 10]. Larviciding is usually performed by applying synthetic larvicides such as organophosphates (e.g., temephos, fenthion, and malathion) or using an insect growth regulator (IGRs) such as methoprene [11, 12]. However, indiscriminate use of these agents affects the population of their natural enemies (such as Gambosia fish) and causes resistance in different species of mosquitoes [10, 13]. Additionally, synthetic insecticides are usually based on a single active ingredient. Thus, resistance against them is more probable compared with botanical insecticides having multiple components [14-16]. Developing resistance against insecticides also has been linked to their tendency to remain in the environment for a long time. During this period, larva starts to produce detoxifying enzymes or change their enzymes’ structure. Thus, resistance against the larvicides may be expected [17, 18]. Moreover, synthetic insecticides leave toxic residues in the environment and make safety concerns [13, 19]. In this regards, identification of active and eco-friendly bio-pesticides is crucial for successful management of mosquito-borne diseases. Essential oils (EOs) have been suggested as alternative sources for control of insects as selective and biodegradable agents with minimal impacts on non-target organisms and environment [13, 20]. EOs are complex mixtures of volatile organic compounds which are produced as secondary metabolites in plants [21]. They are obtained from hydrodistillation or steam distillation of plant entities such as flowers, roots, barks, leaves, seeds, peels, fruits, and woods [22]. EO-based pesticides consist of a combination of molecules which can act concertedly on both behavioral and physiological processes. Thus, there is very little chance of resistance development among the treated mosquitoes [10, 21, 23]. Generally, EOs have different larvicidal activity (LA) against various species of mosquitoes. The most critical factor in developing EO-based larvicides is their potency in terms of their LAs. Currently, there is a single review paper, which has gathered LA of 122 plants against mosquitoes. However, the authors have not separated the LA-based on the mosquito species [24]. In this review we have given an update to the potential of herbal larvicides, gathering data for more than 400 LC₅₀ values of EOs. EOs have been arranged based on their LC₅₀, against each species to provide a better understanding and comprehensive knowledge about their larvicide potential.

Common Mosquito-Borne Diseases

In Table-1, profiles of the most common mosquito-borne diseases (including vectors, pathogenic agent, common hosts in vertebrate and distribution) have been summarized. Malaria, Yellow Fever, Dengue Fever, Zika, Chikungunya, West Nile, and Japanese encephalitis accounted for almost 0.7 million deaths around the world, annually [1].

Table 1. Profiles of the Most Common Mosquito-Borne Diseases.

Disease	Vectors	Caused by	Vertebrate Hosts	Distribution
Malaria [25]	An. atroparvus, An. labranchiae, An. messeae, An. sacharovi, An. sergentii, An. superpictus Grassi, An. arabiensis , An. funestus, An. gambiae, An. melas, An. merus, An. moucheti, An. nili, An. barbirostris, An. lesteri, An. sinensis, An. aconitus, An. annularis, An. balabacensis, An. culicifacies, An. dirus, An. farauti, An. flavirostris, An. fluviatilis, An. koliensis, An. leucosphyrus, An. maculatus, An. minimus, An. punctulatus, An. stephensi, An. subpictus, An. sundaicus.	Protozoan parasite; Plasmodium	Reptiles, birds, rodents, Primates and humans.	Endemic throughout most of the tropics. Ninety-five countries and territories have ongoing transmission
Yellow Fever [26]	Ae. aegypti, Ae. africanus, Ae. aromeliae, Ae. albopictus, Ae. furcifertaylori, Ae. luteocephalus, Ae. metallicus, Ae. bromeliae, Ae. serratus.	Virus of the family Flaviviridae; genus Flavivirus.	Primates	Ghana, Guinea, Nigeria, Ethiopia, Liberia, Gambia, Mali, Senegal, Sudan, Togo, Uganda, Congo, Chad, Angola, Brazil, Colombia and Peru, Paraguay, Argentina,
Dengue Fever [27]	Ae. aegypti, Ae. albopictus, Ae. polynesiensis, Ae. scutellaris.	Virus of the family Flaviviridae; genus Flavivirus.	Primates	Philippines, Thailand, China, Malaysia, Japan, Pakistan, Taiwan, India, Sri Lanka, Burma, Malay Peninsula, Cambodia, Vietnam, Indonesia, India, Australia, Brazil, Venezuela, Mexico, Bolivia, Argentina, USA
Zika [28, 29]	Ae. africanus, Ae. luteocephalus, Ae. aegypti, Ae. albopictus, Ae. furcifer, Ae. vittatus.	The virus of the family Flaviviridae; genus Flavivirus.	Primates	Brazil, Colombia, Venezuela, Puerto Rico, Martinique, Honduras, Guadeloupe, El Salvador, French Guiana, Guinea Bissau, Angola, Cabo Verde, Thailand, Vietnam, Singapore
Chikungunya [30, 31]	Ae. albopictus, Ae. aegypti, Ae. henselli	Virus of the family Togaviridae; genus Alphavirus	Primates, birds, cattle, and rodents	Benin, Burundi, Cameroon, Central African Republic, Comoros, Congo, Equatorial Guinea, Guinea, Kenya, Madagascar, Malawi, Mauritius, Mayotte, Nigeria, Senegal, South Africa, Sudan, Tanzania, Uganda, Zimbabwe, Cambodia, East Timor, India, Indonesia, Laos, Malaysia, Maldives, Myanmar, Pakistan, Philippines, Réunion, Seychelles, Singapore, Taiwan, Thailand and Vietnam.
West Nile [32]	Ae. aegypti, Cx. pipiens, Cx. quinquefasciatus, Cx. australicus, Cx. globcoxitus, Cx. tarsalis, Cx. univittatus, Cx. annulirostris	Virus of the family Flaviviridae; genus Flavivirus.	Birds, Horses, Other Mammals	Commonly found in Africa, Europe, the Middle East, North America, and West Asia.
Japanese Encephalitis [33]	Cx. tritaeniorhynchus, Cx. annulirostris, Cx. vishnui,  Cx. pseudovishnui,  Cx. gelidus, Cx. sitiens,  Cx. fuscocephela, An. subpictus, An. hyrcanus, Cx. pipiens, Ae. albopictus, Ae. japonicas	Virus of the family Flaviviridae; genus Flavivirus.	Birds, Pigs	Australia, Bangladesh, Burma, Cambodia, China, Guam, India, Indonesia, Japan, Laos, Malaysia, Nepal, North Korea, Pakistan, Papua New Guinea, Phillipines, Russia, Saipan, Singapore, South Korea, Sri Lanka, Taiwan, Thailand, Timor-Leste, Vietnam

Categorizing LA of EOs Against Different Species

Tables-2 to 9 brief 411 LC₅₀ values on LA of different EOs against different species of mosquitoes. Table-2 classifies 152 reports according to LC₅₀ of EOs against Ae. aegypti. The most potent EOs are Callitris glaucophylla and Piper betle with LC₅₀ of 0.69 and 0.72 µg/mL, respectively. Mentioned EOs could be appropriate for preparing potent herbal larvicides, comparable with synthetic ones.From Table-2, LC₅₀ values for 5 EOs are in the range of 1-10 µg/mL: Auxemma glazioviana, Mammea siamensis, Cinnamomum rhyncophyllum, C. microphyllum, and Anacardium occidentale. LC₅₀ of other EOs locate in other 3 groups (i.e. > 10 µg/mL). Table-3 reports the LA of 60 EOs against Ae. albopictus. The most potent EOs (with LC₅₀< 10 µg/mL) were EOs of Echinops grijsii (2.65 µg/mL), C. microphyllum (6.20 µg/mL), C. pubescen (7.90 µg/mL), Tetradium glabrifolium (8.20 µg/mL), C. mollissimum (8.80 µg/mL) and C. impressicostatum (9.30 µg/mL). Seventeen EOs have LC₅₀ between 10-50 µg/mL and remaining have LC₅₀ > 50 µg/mL. Table-4 lists LA of 58 EOs against An. stephensi. From the details, only LC₅₀ of Kelussia odoratissima is under 10 µg/mL (~ 5 µg/mL). LC₅₀ of Artemisia dracunculus (11.36 µg/mL), Platycladus orientalis(11.67 µg/mL), Tagetes patula (12.08 µg/mL), Ferulago carduchorum (12.78 µg/mL), Chloroxylon swietenia (14.90 µg/mL) and Ipomoea cairica (14.90 µg/mL) are between 10-15 µg/mL. LC₅₀ of 19 EOs are in range of 10-50 µg/mL. Table-5 shows reported LA of 16 EOs according to their LC₅₀ against An. subpictus. Among the plant species, EO of Ocimum basilicum with LC₅₀ of 9.75 µg/mL is the first in Table-5. EOs of Eugenia uniflora and Heracleum sprengelianum have similar LC₅₀ values (~ 32 µg/mL). LC₅₀ of other EOs are > 50 µg/mL. Table-6 summarizes information about LA of some EOs against other species of Anopheles such as An. quadrimaculatus, An. gambiae, An. anthropophagus, An. dirus, An. sinensis, An. arabiensis, and An. marajoara. Two EOs show excellent LA (i.e., LC₅₀ ~1µg/mL): T. minuta and Cananga odorata against An. gambiae and An. dirus, respectively. LC₅₀ of two other EOs are also worthy to note: Salvia leucantha (6.20 µg/mL) against An. quadrimaculatus and Echinops grijsii (3.43 µg/mL) against An. sinensis. Among 66 reports on LA of EOs against Cx. quinquefasciatus (Table-7), EO of Cananga odorata demonstrates to be the best result with LC₅₀ of below 1 µg/mL. After that, LC₅₀ of 20 EOs are in the range of 10-50 µg/mL, and LC₅₀ of 20 EOs are between 50- 100 µg/mL. LC₅₀ of 44 EOs are higher than 50 µg/mL. From Table-8, which summarizes LA of some EOs against Cx. pipiens, EOs of K. odoratissima, Echinops grijsii and Pelargonium roseum show to have LC₅₀ at 2.69, 3.43 and 5.49 µg/mL, respectively. They are the most potent EOs against Cx. pipiens. Among other EOs, 8 EOs have LC₅₀ between 10-50 and others have LC₅₀ higher than 50 µg/mL. From Table-9, which briefs the larvicidal activity of different EOs on Cx. tritaeniorhynchus. None of the EOs have LC₅₀ below 10 µg/mL. However, EOs of Ocimum basilicum and Ipomoea cairica with LC₅₀ ~ 14 can be considered as effective against Cx. tritaeniorhynchus. While LC₅₀ of other EOs is in range of 36- 136 µg/mL.

Table 2. Larvicidal Activity of Essential Oils Against Aedes Aegypti.

No.	Plant species	Used part(s)	LC 50 (µg/mL)	Ref	No.	Plant species	Used part(s)	LC 50 (µg/mL)	Ref
1	Callitris glaucophylla	Unclear	0.69	[34]	80	Piper hostmanianum	Leaf	54.00	[64]
2	Piper betle	Leaf	0.72	[17]	81	Zanthoxylum armatum	Seed	54.00	[74]
3	Auxemma glazioviana	Heartwood	2.98	[35]	82	Croton sonderianus	Aerial parts	54.50	[56]
4	Mammea siamensis	Flower	5.90	[36]	83	Piper aduncum	Aerial parts	54.50	[75]
5	Cinnamomum rhyncophyllum	Leaf	6.00	[37]	84	Carum carvi	Unclear	54.62	[53]
6	Cinnamomum microphyllum	Leaf	6.70	[37]	85	Syzygium lanceolatum	Leaf	55.11	[76]
7	Anacardium occidentale	Seed	9.10	[36]	86	Lippia sidoides	Leaf	56.00	[57]
8	Piper klotzschianum	Root	10.00	[38]	87	Mentha spicata	Leaf	56.08	[77]
9	Cinnamomum mollissimum	Leaf	10.20	[37]	88	Vitex negundo L	Unclear-	56.13	[22]
10	Cananga odorata	Flower	10.40	[39]	89	Salvia officinalis	Seed	56.90	[42]
12	Cinnamomum impressicostatum	Leaf	10.70	[37]	90	Pinus kesiya	Leaf	57.00	[78]
14	Feronia limonia	Leaf	11.59	[40]	91	Lippia pedunculosa	Unclear	58.00	[18]
15	Citrus sinensis	Fruit	11.92	[14]	92	Apium graveolens	Leaf	59.32	[79]
16	Cinnamomum pubescen	Leaf	12.80	[37]	93	Dendropanax morbifera	Flower	62.32	[80]
17	Piper klotzschianum	Seed	13.27	[38]	94	Cordia leucomalloides	Leaf	63.10	[81]
18	Tagetes patula	Whole plant	13.57	[41]	95	Eugenia triquetra	Aerial parts	64.80	[82]
19	Salvia elegans	Aerial parts	14.40	[42]	96	Swinglea glutinosa	Unclear	65.70	[46]
20	Citrus reticulata	Fruit	15.42	[43]	97	Tagetes lucida	Unclear	66.20	[46]
21	Apium graveolens	Seed	16.10	[44]	98	Boswellia ovalifoliolata	Leaf	66.24	[83]
22	Chloroxylon swietenia	Leaf	16.50	[45]	99	Croton nepetaefolius	Aerial parts	66.40	[56]
23	Cymbopogon flexuosus	Unclear	17.10	[46]	100	Origanum scabrum	Leaf	67.13	[84]
24	Hyptis martiusii	Unclear	18.20	[47]	101	Acorus calamus	Root	67.20	[36]
25	Allium monanthum	Stem	19.38	[48]	102	Annona muricata	Seed	69.25	[36]
26	Lippia sidoides	Unclear	19.50	[47]	103	Syzygium aromaticum	Whole plant	77.00	[85]
27	Piper marginatum	Stem	19.90	[49]	104	Eucalyptus citriodora	Unclear	71.20	[46]
28	Piper marginatum	Inflorescence	19.90	[49]	105	Knema globularia	Seed	72.10	[36]
29	Chloroxylon swietenia	Stem	20.20	[50]	106	Capraria biflor	Leaf	73.39	[86]
30	Citrus sinensis	Unclear	20.60	[46]	107	Stemona tuberosa	Root	75.20	[36]
31	Syzigium aromaticum	Unclear	21.40	[47]	108	Samanea saman	Stem bark	79.20	[36]
32	Cinnamomum scortechinii	Leaf	21.50	[37]	109	Croton jacobinenesis	Leaf	79.30	[87]
33	Ipomoea cairica	Unclear	22.30	[51]	110	Tagetes erecta	Leaf Stem	79.78	[88]
34	Piper marginatum	Leaf	23.80	[49]	111	Croton nepetaefolius	Leaf	84.00	[57]
35	Asarum heterotropoides	Root	23.82	[52]	112	Ocimum sanctum	Aerial parts	85.11	[89]
36	Zanthoxylum limonella	Unclear	24.61	[53]	113	Cunninghamia konishii	Wood	85.70	[90]
37	Psidium guajava	Leaf	24.70	[54]	114	Strychnos nux-vomica	Seed	90.00	[36]
37	Plectranthus mollis	Whole plant	25.40	[55]	115	Cunninghamia konishii	Leaf	91.70	[90]
39	Lippia sidoides	Aerial parts	25.50	[56]	116	Syzygium aromaticum	Bud	92.56	[91]
40	Phyllanthus pulcher	Leaf & twig	25.80	[36]	117	Syzygium aromaticum	Bud	93.56	[14]
41	Croton zehntneri	Aerial parts	26.20	[56]	118	Abutilon indicum	Root	94.20	[36]
42	Anethum graveolens	Leaf	27.40	[36]	119	Croton argyrophylloides	Aerial parts	94.60	[56]
43	Croton zenhtneri	Leaf	28.00	[57]	120	Eucalyptus urophylla	Leaf	95.50	[59]
44	Cryptomeria japonica	Leaf	28.40	[58]	121	Cordia curassavica	Leaf	97.70	[81]
45	Salvia leucantha	Aerial parts	29.50	[42]	122	Costus speciosus	Root	98.50	[36]
46	Citrus hystrix	Fruit	30.07	[43]	123	Guarea scabra	Leaf	98.60	[72]
47	Kaempferia galanga	Root	30.70	[36]	124	Nigella sativa L	Seed	99.90	[92]
48	Eucalyptus camaldulensis	Leaf	31.00	[59]	125	Pinus sylvestris	Needles	100.39	[91]
49	Curcuma zedoaria	Unclear	31.87	[53]	126	Croton argyrophyloides	Leaf	102.00	[57]
51	Eucalyptus grandis	Leaf	32.40	[60]	127	Croton sonderianus	Leaf	104.00	[57]
52	Youngia japonica	Aerial parts	32.45	[61]	128	Kadsura heteroclita	Leaf	111.79	[93]
53	Chenopodium ambrosioides	Aerial parts	35.00	[62]	129	Lantana montevidensis	Leaf	117.00	[68]
54	Murraya exotica	Leaf	35.80	[63]	130	Guarea silvatica	Leaf	117.80	[72]
55	Piper permucronatum	Leaf	36.00	[64]	131	Piper gaudichaudianum	Leaf	121.00	[64]
56	Curcuma aromatica	Rhizome	36.30	[65]	132	Croton rhamnifolioides	Leaf	122.35	[94]
57	Clausena excavata	Leaf	37.10	[66]	133	Cymbopogon citratus	Unclear	123.30	[46]
58	Chamaecyparis formosensis	Heartwood	38.60	[67]	134	Syzygium aromaticum	Flower	124.69	[43]
59	Spondias purpurea	Leaf	39.70	[54]	135	Echinophora lamondiana	Leaf	138.30	[95]
60	Clausena excavata	Twig	40.10	[66]	136	Sphaeranthus indicus Linn	Leaf	140.00	[6]
61	Cinnamomum sintoc	Leaf	41.10	[37]	137	Guarea convergens	Branch	145.10	[72]
62	Apium graveolens	Unclear	42.07	[53]	138	Croton tetradenius	Leaf	152.00	[96]
63	Lippia alba	Unclear	42.20	[46]	139	Piper humaytanum	Leaf	156.00	[64]
64	Lantana camara	Leaf	42.30	[68]	140	Cinnamomum cordatum	Leaf	183.60	[37]
65	Cinnamomum porrectum	Wood	43.50	[36]	141	Myrcia ovata	Leaf	192.10	[54]
66	Zingiber nimmonii	Rhizome	44.46	[12]	142	Eugenia piauhiensis	Leaf	230.00	[97]
67	Blumea eriantha	Leaf	44.82	[69]	143	Siparuna camporum	Leaf	251.00	[97]
68	Zingiber cernuum	Rhizome	44.88	[21]	144	Guarea silvatica	Branch	273.60	[72]
69	Mentha x villosa	Leaf	45.00	[70]	145	Lippia gracilis	Unclear	282.00	[97]
70	Artemisia absinthium	Leaf	46.33	[71]	146	Piper aduncum	Leaf	289.9	[98]
71	Lavandula gibsoni	Whole plant	48.30	[55]	147	Psidium myrsinites	Leaf	292.00	[97]
72	Guarea humaitensis	Branch	48.60	[72]	148	Croton argyrophyllus	Leaf	310.00	[99]
73	Zingiber zerumbet	Rhizome	48.88	[43]	149	Mentha piperita L	Leaf	367.60	[100]
74	Foeniculum vulgare	Unclear	49.32	[53]	150	Echinophora lamondiana	Flower	>125	[95]
75	Plectranthus amboinicus	Leaf	51.80	[54]	151	Echinophora lamondiana	Stem	>125	[95]
76	Eucalyptus nitens	Leaf	52.83	[73]	152	Salvia apiana	Seed	>125	[42]
77	Cananga odorata	Unclear	52.90	[46]	153	Myrcia erythroxylon	Leaf	>1000	[97]
78	Lippia origanoides	Unclear	53.30	[46]	154	Xylopia frutescens	Unclear	>1000	[18]
79	Kaempferia galanga	Rhizome	53.64	[43]	155	Xylopia laevigata	Unclear	>1000	[18]

Table 3. Larvicidal Activity of Essential Oils Against Aedes albopictus .

No.	Plant species	Used part(s)	LC 50 (µg/mL)	Ref	No.	Plant species	Used part(s)	LC50 (µg/mL)	Ref
1	Echinops grijsii	Root	2.65	[13]	32	Artemisia absinthium	Leaf	57.57	[71]
2	Cinnamomum microphyllum	Leaf	6.20	[37]	33	Cupressus arizonica	Leaf	64.80	[107]
3	Cinnamomum pubescen	Leaf	7.90	[37]	34	Syzygium lanceolatum	Leaf	66.71	[76]
4	Tetradium glabrifolium	Fruit	8.20	[101]	35	Pinus brutia	Aerial parts	67.04	[110]
5	Cinnamomum mollissimum	Leaf	8.80	[37]	36	Coleus aromaticu	Leaf	67.98	[111]
6	Cinnamomum impressicostatum	Leaf	9.30	[37]	37	Toddalia asiatica	Root	69.09	[112]
7	Cinnamomum rhyncophyllum	Leaf	11.80	[37]	38	Pinus halepensis	Aerial parts	70.21	[110]
8	Ocimum basilicum	Leaf	11.97	[102]	39	Tetraclinis articulata	Leaf	70.60	[107]
9	Saussurea lappa	Root	12.41	[103]	40	Allium macrostemon	Bulb	72.86	[113]
10	Cinnamomum scortechinii	Leaf	16.70	[37]	41	Pinus stankewiczii	Aerial parts	81.66	[110]
11	Allium tuberosum	Root	18.00	[104]	42	Plectranthus barbatus	Leaf	87.25	[11]
12	Ocimum gratissimum	Leaf	26.10	[10]	43	Boswellia ovalifoliolata	Leaf	89.80	[83]
13	Eucalyptus nitens	Leaf	28.19	[73]	44	Syzygium zeylanicum	Leaf	90.45	[114]
14	Ruta chalepensis	Leaf	33.18	[105]	45	Pinus strobus	Aerial parts	127.98	[110]
15	Eugenia uniflora	Leaf	33.50	[106]	46	Foeniculum vulgare	Leaf	142.90	[115]
16	Chamaecyparis formosensis	Heartwood	34.90	[67]	47	Pinus nigra	Aerial parts	152.65	[110]
17	Cinnamomum sintoc	Leaf	36.50	[37]	48	Cinnamomum cordatum	Leaf	160.80	[37]
18	Cupressus benthamii	Leaf	37.50	[107]	49	Helichrysum italicum	Leaf	178.10	[115]
19	Heracleum sprengelianum	Leaf	37.50	[108]	50	Cunninghamia konishii	Wood	189.50	[90]
20	Cinnamomum osmophloeum	Leaf	40.80	[109]	51	Cunninghamia konishii	Leaf	194.40	[90]
21	Clausena excavata	Twig	41.10	[66]	52	Achillea millefolium	Leaf	211.30	[115]
22	Clausena excavata	Leaf	41.20	[66]	53	Hyptis suaveolens	Leaf	240.30	[116]
23	Chamaecyparis lawsoniana	Leaf	47.90	[107]	54	Eucalyptus urophylla	Leaf	285.80	[59]
24	Cryptomeria japonica	Leaf	51.20	[58]	55	Coriandrum sativum	Fruit	421.00	[117]
25	Cupressus macrocarpa	Leaf	54.60	[107]	56	Pinus canariensis	Aerial parts	>>200	[110]
26	Cupressus sempervirens	Leaf	54.70	[107]	57	Pinus pinaster	Aerial parts	>>200	[110]
27	Eucalyptus camaldulensis	Leaf	55.30	[59]	58	Lavandula angustifolia	Leaf	>250	[115]
28	Juniperus phoenicea	Leaf	55.50	[107]	59	Myrtus communis	Leaf	>250	[115]
29	Zingiber cernuum	Rhizome	55.84	[21]	60	Rosmarinus officinalis	Leaf	>250	[115]
30	Blumea eriantha	Leaf	56.33	[69]	61	Artemisia absinthium	Leaf	57.57	[71]
31	Cupressus torulosa	Leaf	57.10	[107]	62	Cupressus arizonica	Leaf	64.80	[107]

Table 4. Larvicidal Activity of Essential Oils Against Anopheles stephensi.

No.	Plant species	Used part(s)	LC 50 (µg/mL)	Ref	No.	Plant species	Used part(s)	LC 50 (µg/mL)	Ref
1	Kelussia odoratissima	Aerial parts	4.77	[118]	30	Murraya exotica	Leaf	56.30	[63]
2	Kelussia odoratissima	Aerial parts	4.88	[119]	31	Syzigium aromaticum	Unclear	57.49	[129]
3	Artemisia dracunculus	Aerial parts	11.36	[8]	32	Zanthoxylum armatum	Seed	58.00	[74]
4	Platycladus orientalis	Leaf	11.67	[120]	33	Zhumeria majdae	Leaf	61.34	[130]
5	Tagetes patula	Foliage	12.08	[41]	34	Origanum scabrum	Leaf	61.65	[84]
6	Ferulago carduchorum	Aerial parts	12.78	[121]	35	Boswellia ovalifoliolata	Leaf	61.84	[83]
7	Chloroxylon swietenia	Leaf	14.90	[50]	36	Lavandula gibsoni	Aerial parts	62.80	[55]
8	Ipomoea cairica	Unclear	14.90	[51]	37	Origanum vulgare	Leaf	67.00	[4]
9	Feronia limonia	Leaf	15.03	[40]	38	Lawsonia inermis	Leaf	69.40	[131]
10	Chloroxylon swietenia	Stem	19.00	[50]	39	Cionura erecta	Root	77.30	[132]
11	Foeniculum vulgare	Seed	20.10	[122]	40	Cupressus arizonica	Leaf	79.30	[133]
12	Satureja bachtiarica	Aerial parts	24.27	[123]	41	Trachyspermum ammi	Seed	80.77	[134]
13	Bunium persicum	Seed	27.72	[2]	42	Eucalyptus camaldulensis	Leaf	89.85	[135]
14	Plectranthus amboinicus	Leaf	28.37	[124]	43	Coccinia indica	Leaf	95.30	[136]
15	Citrus aurantium	Fruit	31.20	[125]	44	Kadsura heteroclita	Leaf	102.86	[93]
16	Plectranthus mollis	Aerial parts	33.50	[55]	45	Stachys byzantina	Leaf	103.29	[131]
17	Achillea kellalensis	Flower	35.42	[126]	46	Heracleum persicum	Seed	104.80	[122]
18	Citrus paradisi	Fruit	35.71	[125]	47	Ajuga chamaecistus tomentella	Aerial parts	117.72	[137]
19	Anethum graveolens	Aerial parts	38.80	[127]	48	Coriandrum sativum	Seed	120.95	[122]
20	Achillea wilhelmsii	Leaf	39.04	[128]	49	Cedrus deodara	Leaf	128.04	[131]
21	Zingiber nimmonii	Rhizome	41.19	[12]	50	Stachys setifera	Leaf	181.62	[131]
22	Zingiber cernuum	Rhizome	41.34	[21]	51	Thymus vulgaris	Leaf	191.33	[131]
23	Blumea eriantha	Leaf	41.61	[69]	52	Stachys inflata	Leaf	195.84	[131]

Table 5. Larvicidal Activity of Essential Oils Against Anopheles subpictus.

No	Plant species	Used part(s)	LC 50 (µg/mL)	Ref
1	Ocimum basilicum	Leaf	9.75	[102]
2	Eugenia uniflora	Leaf	31.08	[106]
3	Heracleum sprengelianum	Leaf	33.40	[108]
4	Blumea eriantha	Leaf	51.21	[69]
5	Zingiber cernuum	Rhizome	51.42	[21]
6	Artemisia absinthium	Leaf	52.02	[71]
7	Zingiber officinale	Rhizome	57.98	[140]
8	Coleus aromaticus	Leaf	60.31	[111]
9	Zhumeria majdae	Leaf	61.34	[130]
10	Rosmarinus officinalis	Shoot	64.50	[140]
11	Cinnamomum zeylanicum	Leaf	71.96	[140]
12	Origanum vulgare	Leaf	74.14	[4]
13	Cymbopogan citrates	Leaf	77.24	[140]
14	Boswellia ovalifoliolata	Leaf	82.26	[83]
15	Syzygium zeylanicum	Leaf	83.11	[114]
16	Plectranthus barbatus	Leaf	84.20	[11]

Table 6. Larvicidal Activity of Essential Oils Against Other Species of Anopheles.

Plant species	Used part(s)	Target	LC 50 (µg/mL)	Ref
Salvia leucantha	Aerial parts	An. quadrimaculatus	6.20	[42]
Salvia elegans	Aerial parts	An. quadrimaculatus	10.90	[42]
Salvia officinalis	Seed	An. quadrimaculatus	14.10	[42]
Ruta chalepensis	Aerial parts	An. quadrimaculatus	14.90	[141]
Echinophora lamondiana	Leaf	An. quadrimaculatus	26.20	[95]
Echinophora lamondiana	Flower	An. quadrimaculatus	46.90	[95]
Echinophora lamondiana	Stem	An. quadrimaculatus	65.60	[95]
Salvia apiana	Seed	An. quadrimaculatus	>125	[42]
Tagetes minuta	Unclear	An. gambiae	<1.50	[142]
Piper capense	Unclear	An. gambiae	34.90	[143]
Cinnamomum osmophloeum	Leaf	An. gambiae	35.36	[144]
Plectranthus amboinicus	Leaf	An. gambiae	55.20	[145]
Blumea martiniana	Aerial parts	An. anthropophagus	46.86	[146]
Artemisia gilvescens	Unclear	An. anthropophagus	49.95	[147]
Cananga odorata	Flower	An. dirus	<1	[39]
Echinops grijsii	Root	An. sinensis	3.43	[13]
Juniperus procera	Unclear	An. arabiensis	14.42	[148]
Piper aduncum	Aerial parts	An. marajoara	50.90	[75]

Table 7. Larvicidal Activity of Essential Oils Against Culex quinquefasciatus.

No.	Plant species	Used part(s)	LC 50 (µg/mL)	Ref	No.	Plant species	Used part(s)	LC 50 (µg/mL)	Ref
1	Cananga odorata	Flower	<1	[39]	34	Boswellia ovalifoliolata	Leaf	72.47	[83]
2	Mentha longifolia	Unclear	17.00	[149]	35	Pimenta dioica	Fruit & berry	77.20	[153]
3	Mentha suaveolens	Unclear	17.00	[149]	36	Origanum vulgare	Leaf	80.35	[4]
4	Achillea kellalensis	Flower	21.79	[126]	37	Peumus boldus	Leaf	82.14	[157]
5	Tagetes patula	Foliage	22.33	[41]	38	Zhumeria majdae	Leaf	88.51	[130]
6	Feronia limonia	Leaf	22.49	[40]	39	Mentha spicata	Unclear	92.00	[149]
7	Satureja montana	Aerial parts	25.60	[150]	40	Pelargonium graveolens)	Aerial parts	98.40	[150]
8	Pimpinella anisum	Fruit	26.10	[151]	41	Hyssopus officinalis	Aerial parts	99.50	[150]
9	Tanacetum persicum	Aerial parts	28.53	[126]	42	Ravensara aromatica	Leaf	101.40	[153]
10	Plectranthus mollis	Whole plant	29.50	[55]	43	Anthemis nobilis	Flower	108.70	[153]
11	Rosmarinus officinalis	Stem & Leaf	30.60	[152]	44	Rosmarinus officinali	Flowering herb	111.10	[153]
12	Thymus vulgare	Flowering top	32.90	[153]	45	Nepeta cataria	Flowering top	112.40	[153]
13	Satureja hortensis	Flowering top	36.10	[153]	46	Mentha aquatica	Unclear	118.00	[149]
14	Murraya exotica	Leaf	43.20	[63]	47	Lavandula angustifolia	Flower	121.60	[153]
15	Thymus satureoides Boiss	Herb	43.60	[153]	48	Kadsura heteroclita	Leaf	121.97	[93]
16	Satureja bachtiarica	Aerial parts	44.96	[123]	49	Syzygium aromaticum	Buds	124.42	[91]
17	Zingiber nimmonii	Rhizome	48.26	[12]	50	Cannabis sativa	Herb	127.30	[153]
18	Zingiber cernuum	Rhizome	48.44	[21]	51	Salvia sclarea	Flower	127.50	[153]
19	Blumea eriantha	Leaf	48.92	[69]	52	Pinus sylvestris	Needles	128.00	[91]
20	Zanthoxylum armatum	Seed	49.00	[74]	53	Sphaeranthus indicus	Leaf	130.00	[6]
21	Pinus nigra	Twig	49.80	[150]	54	Pelargonium roseum	Leaf	130.30	[153]
22	Artemisia absinthium	Unclear	50.57	[71]	55	Nigella sativa	Seed	141.70	[92]
23	Zingiber officinalis	Rhizome	50.78	[154]	56	Erigeron canadensis	Herb	141.90	[153]
24	Lavandula gibsoni	Whole plant	54.70	[55]	57	Juniperus communis	Berry & twig	164.30	[153]
25	Ipomoea cairica	Unclear	58.90	[51]	58	Laurus nobilis	Leaf	167.90	[153]
26	Syzygium lanceolatum	Leaf	60.01	[76]	59	Amyris balsamifera	Wood	170.70	[153]
27	Pinus kesiya	Leaf	62.00	[78]	60	Ocimum basilicum	Leaf	171.60	[153]
28	Mentha spicata	Leaf	62.62	[77]	61	Citrus aurantium	Flower	179.80	[153]
29	Psoralea corylifolia	Seed	63.38	[155]	62	Tanacetum vulgare	Flowering top	186.60	[153]
30	Pulegium vulgare	Unclear	64.00	[149]	63	Zingiber cassumunar Roxb	Root	202.30	[153]
31	Aloysia citrodora	Leaf	65.60	[150]	64	Melaleuca alternifolia	Leaf	204.10	[153]
32	Blumea mollis	Leaf	71.71	[156]	65	Santalum album	Heartwood	225.30	[153]
33	Origanum scabrum	Leaf	72.45	[84]	66	Polygonum hydropiper	Leaf	243.00	[139]

Table 8. Larvicidal Activity of Essential Oils Against Culex pipiens.

Plant species	Used part(s)	LC 50 (µg/mL)	Ref
Kelussia odoratissima	Aerial parts	2.69	[119]
Echinops grijsii	Root	3.43	[13]
Pelargonium roseum	Leaf	5.49	[158]
Platycladus orientalis	Leaf	18.60	[2]
Bunium persicum	Seed	20.61	[2]
Asarum heterotropoides	Root	21.07	[52]
Thymus teucrioides	Aerial parts	23.17	[159]
Citrus limon	Lemon	30.14	[160]
Thymus leucospermus	Aerial parts	34.26	[159]
Citrus aurantium	Bitter orange	39.81	[160]
Oenanthe pimpinelloides	Aerial parts	40.26	[161]
Citrus sinensis	Sweet orange	51.50	[160]
Geranium maculatum	Unclear	57.28	[162]
Bupleurum fruticosum	Aerial parts	64.68	[161]
Conopodium capillifolium	Aerial parts	68.50	[161]
Heracleum sphondylium	Aerial parts	77.41	[161]
Citrus bergamia	Unclear	81.45	[162]
Seseli montanum	Aerial parts	86.60	[161]
Eleoselinum asclepium	Aerial parts	96.96	[161]
Hypericum tomentosum from Tbarka	Aerial parts	102.82	[163]
Hypericum tomentosum from Fernana	Aerial parts	125.26	[163]
Hypericum humifusum	Aerial parts	156.80	[163]
Hypericum perforatum	Aerial parts	194.70	[163]

Table 9. Larvicidal Activity of Essential Oils Against Culex tritaeniorhynchus.

Plant species	Used part (s)	LC 50 (µg/mL)	Ref
Ocimum basilicum	Leaf	14.01	[102]
Ipomoea cairica	Unclear	14.80	[51]
Eugenia uniflora	Leaf	36.35	[106]
Heracleum sprengelianum	Leaf	40.90	[108]
Zingiber cernuum	Rhizome	60.20	[21]
Blumea eriantha	Leaf	61.33	[69]
Artemisia absinthium	Unclear	62.16	[71]
Syzygium lanceolatum	Leaf	72.24	[76]
Coleus aromaticus	Leaf	72.70	[111]
Origanum scabrum	Leaf	78.87	[84]
Origanum vulgare	Leaf	84.93	[4]
Plectranthus barbatus	Unclear	94.34	[11]
Boswellia ovalifoliolata	Leaf	97.95	[83]
Syzygium zeylanicum	Leaf	97.96	[114]
Zingiber officinale	Rhizome	98.83	[140]
Rosmarinus officinalis	Shoot	115.38	[140]
Cinnamomum zeylanicum	Bark	124.70	[140]
Cymbopogan citrates	Leaf	136.58	[140]

Potent EOs in Terms of LA

Reviewing Tables-2 to 9, some EOs demonstrate proper LA against at least two species, thus, may be suggested as attractive candidates for preparing EO-based larvicides (Table-10). For instance, LC₅₀ of Echinops grijsii is ~ 3 µg/mL against three species: Cx. pipiens, An. sinensis and Ae. albopictus. EO of Cananga odorata is another candidate with LC₅₀ ~ 1 µg/mL against Cx. quinquefasciatus and An. dirus and LC₅₀ of 10 µg/mL against Ae. aegypti. EO of K. odoratissima with LC₅₀ of 2 and 4 µg/mL against Cx. pipiens and An. stephensi respectively, could also be considered as a potent larvicide.Besides mentioned EOs, the LA of 4 EOs is comparable with classic larvicide (i.e., ~ 1 µg/mL). LC₅₀ of Callitris glaucophylla and Piper betle against Ae. aegypti are 0.69 and 0.72 µg/mL, respectively. Cananga odorata show LC₅₀ < 1 µg/mL against both of Cx. quinquefasciatus and An. Dirus. EO of T. minuta has excellent LA against An. gambiae (LC₅₀ < 1.5 µg/mL).

Table 10. Potent Essential Oils as Larvicide Against at Least 2 Species of Mosquitoes.

Plant species	Target	LC 50 (µg/mL)	Ref
Ocimum basilicum	Cx. tritaeniorhynchus	14.01	[102]
	An. subpictus	9.75
Kelussia odoratissima	Cx. pipiens	2.69	[118, 119]
	An. stephensi	4.77
	An. stephensi	4.88
Echinops grijsii	Cx. pipiens	3.43	[13]
	An. sinensis	3.43
	Ae. albopictus	2.65
Cananga odorata	Cx. quinquefasciatus	<1	[39]
	An. dirus	<1
	Ae. aegypti	10.40
Cinnamomum microphyllum	Ae. albopictus	6.20	[37]
	Ae. aegypti	10.70
Cinnamomum pubescen	Ae. albopictus	7.90	[37]
	Ae. aegypti	10.20
Cinnamomum impressicostatum	Ae. albopictus	9.30	[37]
	Ae. aegypti	10.70
Cinnamomum rhyncophyllum	Ae. albopictus	11.80	[37]
	Ae. aegypti	6.00

Advantages of EOs as Larvicides

To control mosquito-borne diseases such as malaria, world health organization (WHO) recommends using larvicides; nowadays using in 55 countries around the worlds [164]. Continuous use of synthetic larvicides such as malathion and temephos along with environmental pollution, lead to occurring resistance in a various population of mosquitos such as Ae. aegypti, Cx. pipiens and An. stephensi [165-168].Furthermore, many reports may be found about the impacts of the larvicides against non-target species. For instance, dichlorvos and tetraethyl pyrophosphate (belonging to organophosphates larvicides) and carbofuran (carbamates) have an effect on acetylcholinesterase in some species of fishes including Arapaima gigas, Rachycentron canadum, Oreochromis niloticus, and Electrophorus electricus [169]. In another study, sides effects of 2 other larvicides including Temephos and Novaluron against 10 species of aquatic insect families and copepods have been evaluated. It was revealed that their impact on Veliidae, Odonata, Dytiscidae are significantly higher than that of other [170]. Oudemans (Amblyseius cucumeris) is a crucial predator of mites of tetranychid while two other common pesticides, i.e., Bifenthrin and Malathion posed an extremely effect on this beneficial non-target arthropod [171].EOs are naturally extracted aroma compounds with broad applications such as flavoring additives, medicines, antioxidants, antifungal/bacterial and also larvicides [172-177]. In the past decade, EO based formulation have been suggested as alternative sources for control of mosquitoes to be used as larvicides [8, 127]. They offer advantages such as biodegradability, negligible effects on non-target specious and environment [101, 178]. Besides, resistance against larvicides is observed when a single active agent is used compared with those having multi-components, thus by using EOs, decreases the risk of occurring resistance in mosquito populations [14-16]. EOs are mixtures of many constituents such as flavonoids, alkaloids, and monoterpenes [179, 180]. Modes of action of mentioned constituents are different, for instance, main sites action of alkaloids and monoterpenes are Na-K-ATPase or Na+ and K+ channels [19, 181, 182], while flavonoids target acetylcholinesterase [183]. Synergistic effects of constituents of some EOs are nowadays well-known when they are used as anti-fungal or anti-bacterial agents [184, 185]. Types of synergism also reported in larvicidal studies, e.g., larvicidal activities (LC₅₀) of EOs of Syzygium aromaticum and K. odoratissima (57.49 and 4.77 µg/mL, respectively) significantly better than their major constituents, i.e., Eugenol (86.96 µg/mL) and Z-ligustilide (8.73 µg/mL) against An. stephensi [118, 129].

Conclusion

In this paper, mosquito-borne diseases have been reviewed. Previous studies about LA of EOs against different species of mosquitoes including Aedes, Anopheles, and Culex were investigated. For the first time, 411 LC₅₀ were ranked against each species, separately. LC₅₀ of 4 EOs are ~ 1µg/mL, including Callitris glaucophylla and Piper betle against Ae. aegypti, T. minuta against An. gambiae, and Cananga odorata against Cx. quinquefasciatus and An. dirus. The potency of mentioned EOs is comparable with synthetic larvicides, while simultaneously having some advantages such as reducing the chance of resistance and minimum sides’ effects on non-target species. Thus, it could be considered as candidates for preparing botanical larvicides.

Acknowledgment

This study was supported by Tehran University of Medical Sciences & Health Services (grant No. 95-01-87-31860).

Conflict of Interest

There is no conflict of interest to the authors.