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

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
A rthropod-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][7][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][15][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 LC 50 values of EOs. EOs have been arranged based on their LC 50 , 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].

Categorizing LA of EOs Against Different Species
Tables-2 to 9 brief 411 LC 50 values on LA of different EOs against different species of mos-quitoes. Continue of Table 3. Larvicidal Activity of Essential Oils Against Aedes albopictus  Continue of Table 7. Larvicidal Activity of Essential Oils Against Culex quinquefasciatus

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][166][167][168]. Furthermore, many reports may be found about the impacts of the larvicides against non-target species. For instance, dichlorvos and tetrae-thyl 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][173][174][175][176][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 GMJ.2019;8:e1532 www.gmj.ir Ae. aegypti 6.00 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][15][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 (LC 50 ) of EOs of Syzygium aromaticum and K. odoratissima (57.49 and 4.77 µg/mL, respectively) signifi-cantly 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

Conflict of Interest
There is no conflict of interest to the authors.