Excito-repellency and biological safety of β-caryophyllene oxide against Aedes albopictus and Anopheles dirus (Diptera: Culicidae)
Graphical abstract
Introduction
Mosquito-borne diseases represent a key hazard for millions of people worldwide. Mosquitoes serve as vectors of pathogens for devastating human scourge, including malaria, filariasis, yellow fever, dengue, West Nile virus and chikungunya (Benelli and Mehlhorn, 2018). Malaria and dengue are the two most common mosquito-borne diseases that cause high morbidity and mortality (Wiwanitkit, 2011). Millions of humans in the least developed and developing countries are mainly at risk from these diseases. To a lower extent, now developed countries are too at risk of dengue outbreaks due to the invasion of Aedes albopictus (Skuse) into temperate regions and population movement from dengue-endemic areas (Vairo et al., 2018). In 2017, an estimated 219 million cases of malaria occurred worldwide, with an estimated 435,000 deaths from malaria globally (WHO, 2018). Anopheles dirus Peyton & Harrison is the most important malaria vector in Southeast Asia (Tainchum et al., 2015). This species inhabits forest and forest fringes and exhibits mostly exophagic behavior (Baimai et al., 1984; Tananchai et al., 2012, Tananchai et al., 2019). In contrast, dengue and chikungunya are arboviral infections transmitted by two species of Aedes mosquitoes—Aedes aegypti L. and Ae. albopictus. The latter, known as the Asian tiger mosquito, is native from Southeast Asian countries (Smith, 1956). The distribution of Ae. albopictus has been extended recently by invasion into more northerly latitudes as well as into higher altitudes such as the United States of America and Europe (Chouin-Carneiro et al., 2016; Martinet et al., 2019). These two mosquito species have been found highly refractory to common control tools due to their highly exophagic behavior and are regarded as great potential vectors even though they are present in low population densities. Therefore, the prevention and control of most vector-borne diseases remain dependent on various vector control strategies to decrease the transmission risk, which is a major challenge for outdoor-biting mosquitoes such as these two Aedes species.
Among the available vector control tools, chemical method remains the most used and effective in combatting mosquito vectors. A number of chemical compounds can protect humans from blood-feeding pests by one or more of three identified actions: contact irritancy, noncontact spatial repellency, or toxicity (Grieco et al., 2007). The first two properties are potential outcome behavioral responses of mosquitoes after or before they make tarsi contact with treated surfaces (Chareonviriyaphap et al., 1997; Roberts et al., 1997). Most studies have focused primarily on the insecticidal action of chemicals to control mosquitoes, whereas few investigations have payed attention to the non-toxic properties, including irritancy and repellency (Chareonviriyaphap et al., 1997, Chareonviriyaphap et al., 2004, Chareonviriyaphap et al., 2013; Grieco et al., 2007). Moreover, much of the previous work has focused on potent synthetic compounds (Mongkalangoon et al., 2009; Thanispong et al., 2009). The extensive use of these synthetic compounds has raised key concerns over the selection pressure induced by insecticides on resistance gene mechanism (Chareonviriyaphap et al., 2003). For example, the commonly used pyrethroids are applied to control malaria mosquitoes but have become increasingly less effective due to the development of physiological resistance in mosquito populations (Chareonviriyaphap et al., 2000, Chareonviriyaphap et al., 2013). Consequently, alternative plant-based repellents have been used to protect people, particularly children, during outdoor activities. In addition, such alternative repellents cause no harm to various nontarget organisms (with additional benefits as a potential source of bioactive chemicals, fragrances and flavoring agents) and are recommended as an alternative source of materials for insect control (Isman, 2002; Yang et al., 2005).
Personal protection using insect repellents is considered as one of the most efficient measures, which has been widely used to reduce the outdoor transmission of mosquito-borne diseases (Debboun and Strickman, 2013). Commercial mosquito repellents containing N,N-Diethyl-3-methylbenzamide (DEET) have been used by people worldwide. Research has suggested that DEET is not safe when applied to children's skin or if improperly used (Briassoulis et al., 2001). Several side effects have been reported from DEET including rash, skin irritation and eye irritation (Amichai et al., 1994; Patel et al., 2012).
The compound tested in this study is β-caryophyllene oxide, generally found in essential oils of various plant species such as Artemisia anomala S. Moore, Salvia miltiorrhiza Bunge, Chloroxylon swietenia DC., Psidium guajava L., Origanum vulgare L., Cinnamomum spp., Syzygium aromaticum (L.) Merr. & L.M. Perry, Piper nigrum L. and Serjania yucatanensis Standl. (Garneau et al., 2013; Gertsch et al., 2008; Jun et al., 2011; Liang et al., 2009; Polanco-Hernández et al., 2012; Shell, 1997; Telang et al., 2003; Zhao et al., 2013). The interest of β-caryophyllene oxide is that it has been reported to repel mosquitoes. Suleiman et al. (2014) reported that leaves of Artabotrys hexapetalus (L. f.) Bhandari contained large amounts of β-caryophyllene oxide with high mosquito repellent activity against Anopheles gambiae s.s. in Africa. A more recent study reported that Ae. aegypti and Anopheles minimus exhibited high avoidance response rates at 0.5% and 1% concentrations of β-caryophyllene oxide compared to DEET (Nararak et al., 2019), showing the high repellent potential of this molecule.
In recent years, the food and cosmetic industries and both national and international health and food safety authorities have extensively debated the safety of novel plants and plant-derived ingredients for their use in foods. These discussions consistently produced a consensus that adequate specifications of plant identity and composition are key issues in the safety assessment of plant-derived ingredients (Antignac et al., 2011). Although β-caryophyllene oxide is beneficial as a mosquito repellent, this compound may produce toxic and adverse effects on humans or animals or both. Consequently, potential cytotoxic effects of hazardous substances must be assessed prior to product development. Little scientific data is available on the possible adverse effects or the biological safety of β-caryophyllene oxide in experimental administration to animals. What has been reported is that based on a biomembrane model, β-caryophyllene oxide could pass through the cell membrane without inducing genotoxic effects at the gene or chromosomal level (Di Sotto et al., 2013).
In the current study, following the repellent study already done on Ae. aegypti and An. minimus (Nararak et al., 2019), we investigated the active excito-repellent properties of β-caryophyllene oxide against Ae. albopictus and An. dirus, using an excito-repellency (ER) test system. The ER test system is the gold standard to quantitatively determine the two distinct forms of behavioral responses in mosquito population in response to test chemicals (Sathantriphop et al., 2006). A test chamber system and protocol that can easily differentiate these two types of behavioral responses has been described (Chareonviriyaphap et al., 1997; Roberts et al., 1997). Moreover, in the current study, we evaluated the safety of β-caryophyllene oxide using an in vitro phototoxicity test and an in vitro micronucleus assay.
Section snippets
Mosquitoes used
Samples of Ae. albopictus were originally captured in 1996 in Chanthaburi province, eastern Thailand by staff from the Ministry of Public Health, Thailand. Representatives of this population have been maintained in the entomological laboratory at Kasetsart University since 2013 and females only were used in the current study. Samples of An. dirus were based on individuals originally collected in 1981 in Khao Mai Kaeo sub-district, Bang Lamung District, Chonburi Province, eastern Thailand. These
Results
Excito-repellency responses of Ae. albopictus and An. dirus exposed to 0.1, 0.25, 0.5, 1.0% v/v of DEET and β-caryophyllene oxide were evaluated for contact irritancy and noncontact repellency responses using an excito-repellency system. DEET was used as a standard repellent for comparison purposes. The results showed that Ae. albopictus (3.51-56.36%) had a much higher escape response to β-caryophyllene oxide than An. dirus (0-32.73%) in both the contact and noncontact trials (Table 1).
The
Discussion
Several plant-based essential oils have been evaluated for mosquito repellent activity as protection against mosquitoes and other arthropod pests in Thailand. These have included Ocimum americanum L. (Hairy basil), Cymbopogon nardus (L.) Rendle (Citronella), Vetiveria zizanioides (L.) Nash (Vetiver), Citrus hystrix DC. (Kaffir lime), Cinnamomum verum J. Presl (Cinnamon leaf), Syzygium aromaticum (L.) Merr. & L.M. Perry (Clove flower), and Zingiber officinale Roscoe (Ginger) (Boonyuan et al.,
Author Contributions
TC conceived and designed the experiments. JN, CS and CG performed the experiments. JN, CS and CG analyzed the data. JN, CS and CG wrote the manuscript. SM, VML, EO and TC consulted and edited the manuscript. All authors read and approved the manuscript.
Declaration of Competing Interest
The authors declare no conflict of interest.
Acknowledgments
We acknowledge the financial support provided for this study by the Thailand Research Fund through the International Research Network (Grant No. IRN58W0003-IRN5803PHDW04). This study was also funded by the French Ministry of Foreign Affairs (MEAE) through the Bio-Asie programme (BioVectrol project) and the PHC Siam (BioVecThai project, Campus France No 33765NG). The first author (JN) was also granted an Erasmus Mundus fellowship for 6 months.
References (62)
- et al.
Safety of botanical ingredients in personal care products/cosmetics
Food Chem. Toxicol.
(2011) - et al.
Genotoxicity assessment of β-caryophyllene oxide
Regul. Toxicol. Pharmacol.
(2013) - et al.
Vinblastine and diethylstilboestrol tested in the in vitro mammalian cell micronucleus test (MNvit) at Swansea University UK in support of OECD draft Test Guideline 487
Mutat. Res. Genet. Toxicol. Environ. Mutagen.
(2010) - et al.
Essential oil composition of Salvia miltiorrhiza flower
Food Chem. Toxicol.
(2009) - et al.
Excito-repellent activity of β-caryophyllene oxide against Aedes aegypti and Anopheles minimus
Acta Trop.
(2019) - et al.
Repellency of essential oils of some plants from the Kenyan coast against Anopheles gambiae
Acta Trop.
(2005) - et al.
Essential oils of green and red Perilla frutescens as potential sources of compounds for mosquito management
Ind. Crop. Prod.
(2015) - et al.
Anopheles species diversity and distribution of the malaria vectors of Thailand
Trends Parasitol.
(2015) - et al.
Diversity and biting patterns of Anopheles species in a malaria endemic area, Umphang Valley, Tak Province, western Thailand
Acta Trop.
(2019) - et al.
Plants traditionally used as mosquito repellents and the implication for their use in vector control
Acta Trop.
(2016)
Concurrent malaria and dengue infection: a brief summary and comment
Asian Pac. J. Trop. Biomed.
Ovicidal and adulticidal activities of Cinnamomum zeylanicum bark essential oil compounds and related compounds against Pediculus humanus capitis (Anoplura: Pediculicidae)
Int. J. Parasitol.
A method of computing the effectiveness of an insecticide. 1925
J. Am. Mosq. Control Assoc.
Contact dermatitis from diethyltoluamide
Dermatitis
Cytogenetic studies of some species complexes of Anopheles in Thailand and Southeast Asia
Southeast Asian J. Trop. Med. Public Health
Mosquito-borne Diseases: Implications for Public Health
Excito-repellency of essential oils against an Aedes aegypti (L.) field population in Thailand
J. Vector Ecol.
Toxic encephalopathy associated with use of DEET insect repellents: a case analysis of its toxicity in children
Hum. Exp. Toxicol.
Larval habitats and distribution patterns of Aedes aegypti (Linnaeus) and Aedes albopictus (Skuse), in Thailand. Southeast Asian
J. Trop. Med. Public Health
Status of malaria in Thailand
Southeast Asian J. Trop. Med. Public Health
Review of insecticide resistance and behavioral avoidance of vectors of human diseases in Thailand
Parasites Vectors
Excito-repellency of deltamethrin on the malaria vectors, Anopheles minimus, Anopheles dirus, Anopheles swadiwongporni, and Anopheles maculatus, in Thailand
J. Am. Mosq. Control Assoc.
An improved excito-repellency test chamber for mosquito behavioral tests
J. Vector Ecol.
Pesticide avoidance behavior in Anopheles albimanus, a malaria vector in the Americas
J. Am. Mosq. Control Assoc.
Differential susceptibilities of Aedes aegypti and Aedes albopictus from the Americas to Zika virus
PLoS Negl. Trop. Dis.
Insect repellents and associated personal protection for a reduction in human disease
Bull. Entomol. Res.
Residual transmission of malaria: An Old issue for new approaches
β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties
Cancer Med.
Essential oils from Bolivia. XII. Asteraceae: Ophryosporus piquerioides (DC) Benth. ex Baker
J. Essent. Oil Res.
Beta-caryophyllene is a dietary cannabinoid
Proc. Natl. Acad. Sci.
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