molecules

Review
Bioactive Molecules Derived from Plants in Managing Dengue
Vector Aedes aegypti (Linn.)
Sridhar Shanmuga Priya 1,† , Prabhakaran Vasantha-Srinivasan 2,† , Ammar B. Altemimi 3,4 , Ramji Keerthana 5 ,
Narayanaswamy Radhakrishnan 6 , Sengottayan Senthil-Nathan 7, * , Kandasamy Kalaivani 8 ,
Nainarpandian Chandrasekar 9 , Sengodan Karthi 10 , Raja Ganesan 11 , Zina T. Alkanan 3 , Tarun Pal 12 ,
Om Prakash Verma 13 and Jarosław Proćków 14, *

1 Department of Biotechnology, St. Peter’s Institute of Higher Education Research, Chennai 600077, India
2 Department of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical 17 and Technical
Sciences (SIMATS), Chennai 602105, India
3 Department of Food Science, College of Agriculture, University of Basrah, Basrah 61004, Iraq
4 College of Medicine, University of Warith Al-Anbiyaa, Karbala 56001, Iraq
5 Department of Biotechnology, RV College of Engineering, Bangalore 560059, India
6 Department of Biochemistry, Saveetha Medical College and Hospital, Saveetha Institute of Medical and
Technical Sciences (SIMATS), Chennai 602105, India
7 Division of Bio-Pesticides and Environmental Toxicology, Sri Paramakalyani Centre for 14 Excellence in
Environmental Sciences, Manonmaniam Sundaranar University, Alwarkurichi, 15, Tirunelveli 627412, India
8 Post Graduate and Research Centre, Department of Zoology, Sri Parasakthi College for Women,
Courtrallam 627802, India
9 Centre for Geo–Technology, Manonmaniam Sundaranar University, Tirunelveli 627012, India
10 Department of Entomology, College of Agriculture, Food and Environment, University of Kentucky,
Lexington, KY 40503, USA
11 Institute for Liver and Digestive Diseases, College of Medicine, Hallym University,
Chuncheon 24252, Republic of Korea
12 Department of Biotechnology, Vignan’s Foundation for Science, Technology and Research,
Citation: Priya, S.S.; Vadlamudi, Guntur 522213, India
13 Department of Molecular and Cellular Engineering, Jacob Institute of Biotechnology and Bioengineering,
Vasantha-Srinivasan, P.;
Altemimi, A.B.; Keerthana, R.;
Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj 211007, India
14 Department of Plant Biology, Institute of Environmental Biology, Wrocław University of Environmental and
Radhakrishnan, N.;
Life Sciences, Kożuchowska 5b, 51-631 Wrocław, Poland
Senthil-Nathan, S.; Kalaivani, K.;
* Correspondence: [email protected] (S.S.-N.); [email protected] (J.P.)
Chandrasekar, N.; Karthi, S.; † These authors contributed equally to this work.
Ganesan, R.; et al. Bioactive
Molecules Derived from Plants in Abstract: Mosquitoes are the potential vectors of several viral diseases such as filariasis, malaria,
Managing Dengue Vector Aedes
dengue, yellow fever, Zika fever and encephalitis in humans as well as other species. Dengue, the
aegypti (Linn.). Molecules 2023, 28,
most common mosquito-borne disease in humans caused by the dengue virus is transmitted by the
2386. https://doi.org/10.3390/
vector Ae. aegypti. Fever, chills, nausea and neurological disorders are the frequent symptoms of
molecules28052386
Zika and dengue. Thanks to various anthropogenic activities such as deforestation, industrialized
Academic Editor: Ana Barros farming and poor drainage facilities there has been a significant rise in mosquitoes and vector-borne
Received: 28 January 2023
diseases. Control measures such as the destruction of mosquito breeding places, a reduction in global
Revised: 13 February 2023 warming, as well as the use of natural and chemical repellents, mainly DEET, picaridin, temephos
Accepted: 2 March 2023 and IR-3535 have proven to be effective in many instances. Although potent, these chemicals cause
Published: 5 March 2023 swelling, rashes, and eye irritation in adults and children, and are also toxic to the skin and nervous
system. Due to their shorter protection period and harmful nature towards non-target organisms,
the use of chemical repellents is greatly reduced, and more research and development is taking
place in the field of plant-derived repellents, which are found to be selective, biodegradable and
Copyright: © 2023 by the authors.
harmless to non-target species. Many tribal and rural communities across the world have been using
Licensee MDPI, Basel, Switzerland.
plant-based extracts since ancient times for various traditional and medical purposes, and to ward
This article is an open access article
distributed under the terms and
off mosquitoes and various other insects. In this regard, new species of plants are being identified
conditions of the Creative Commons through ethnobotanical surveys and tested for their repellency against Ae. aegypti. This review aims
Attribution (CC BY) license (https:// to provide insight into many such plant extracts, essential oils and their metabolites, which have been
creativecommons.org/licenses/by/ tested for their mosquitocidal activity against different life cycle forms of Ae. Aegypti, as well as for
4.0/). their efficacy in controlling mosquitoes.

Molecules 2023, 28, 2386. https://doi.org/10.3390/molecules28052386 https://www.mdpi.com/journal/molecules

Molecules 2023, 28, 2386 2 of 28

Keywords: Aedes aegypti; plant crude extracts; metabolites; larvicidal; pupicidal; adulticidal; ovicidal;
oviposition deterrent; non-target toxicity

1. Introduction
Mosquitoes are one of the major vectors that carry harmful viruses that spread fatal and
deadly diseases all over the world [1]. Compared to all the other arthropods, mosquitoes are
responsible for spreading the highest number of mortal diseases like dengue, chikungunya,
elephantiasis, malaria, etc. [2]. They are responsible for spreading vector-borne diseases to
more than 1 billion people every year. Over 1 million people die every year due to these
diseases [3]. The survival and transmission of viral pathogens is entirely dependent on
the vectors carrying the pathogens. Hence, mosquitoes play a major role in the pathology
of diseases [4]. Mosquitoes are considered to be the greatest enemy of the human race
as they greatly affect public health, spread deadly diseases, and are major competitors
in aquatic and terrestrial food chains [5]. There are no significantly specific treatments
for these arboviral diseases and finding eco-friendly ways of eradicating the vector is
a more efficient way to control the disease [4]. With the Zika fever outbreak spreading
across Latin America, many travelers and people in endemic areas are left wondering
how best to protect themselves from mosquitoes. The tropical yellow fever mosquito, Ae.
aegypti, is the primary vector for transmitting dengue. It is a day-feeding mosquito that has
major epidemiological significance, as it is responsible for spreading several other arboviral
diseases like chikungunya and the Zika virus. Other mosquitoes, such as Aedes albopictus,
also called the Asian tiger mosquito, can also act as carriers [6,7].
Of these arboviral diseases, dengue is one of the fastest re-emerging diseases that
greatly affects the economy and health of many countries [8]. Dengue is an acute viral
disease in humans caused by a single-stranded RNA virus that belongs to the Flaviviridae
family. Although the symptoms are clinically in apparent most of the time, they may
lead to severe manifestations like DSS or DHF [9,10]. A cartographic study states that
there are about 390 million dengue infections per year, of which 96 million cases show
significant clinical symptoms [9]. Dengue does not have a particular treatment, but there is a
chimeric tetravalent vaccine that is made of attenuated serotypes of dengue viral strains [11].
Many products claim to deter mosquitoes, but not many have been scientifically proven
effective. Usually, the mosquito larvae are targeted, and their growth is hindered by using
organochlorine, organophosphates, or growth regulators. However, these methods have a
negative impact on the environment [7]. Recent research shows that silver nanoparticles
obtained from plants can effectively act against dengue serotypes DEN-2 and Ae. aegypti [12].
In order to control the vector population, STI combined with auto-dissemination has been
highly efficient and does not have any detrimental effect on the environment [13]. Most
commercially available mosquito repellents contain one or several active ingredients,
including N,N-diethyl-meta-toluamide, commonly known as DEET, IR3535, or picaridin.
A recent study tested commercially available mosquito repellents against both Ae. aegypti
and Ae. albopictus. Those sprays containing DEET were the most effective, repelling both
species with >70% efficacy for at least four hours [14]. Methods like covering open water
containers and introducing fish that feed on mosquito larvae have been found to be efficient
in reducing the population of mosquito vectors [15]. Nevertheless, the use of fish that
feed on mosquito larvae affects the ecosystem and disrupts the food chain by affecting the
native aquatic fauna [16]. The use of insecticides that kill the larval and pupal stages of
mosquitoes is more efficient, but over a period of time, the insects develop resistance to the
insecticide by increasing their metabolism and enzyme activity [17–19]. In addition, the use
of insecticides has a negative impact on the environment and non-target organisms [20].
Later, biorational pesticides were developed based on dose response studies with target and
non-target species, but this method also later proved to affect the non-target organisms [21].
Molecules 2023, 28, 2386 3 of 28

While DEET is an active ingredient in many repellents, several reports linking DEET
use to negative health effects have resulted in health changes, external pubic disorders and
chemophobia [22]. However, research shows that with an estimated 200 million applications
of DEET occurring every year, there have been only 14 reported incidents of adverse effects,
and most were the result of overuse [23]. Concerns about the negative effects of DEET have
contributed to the popularity of repellents composed of plant-based compounds.
The traditional mosquito control strategy focused on killing the mosquitoes using
different types of insecticides. An eco-friendly approach, through declining or eliminating
the breeding sites of mosquito, has often been used along with microbiological larvicides,
ovicides and pupicides [8]. Traditionally, insect repellents work by providing a vapor
barrier deterring mosquitoes from meeting the skin surface. Over the past thousand years,
insect repellents have been utilized to stop arthropods from biting. Several species of
primates were experimentally daubing their pelage by rubbing it with plants, including
Piper marginatum, Citrus spp. and Clematis dioica, native to south Asian and American coun-
tries [7]. Naturally derived repellents from plants belong to the Asteraceae, Cupressaceae,
Lamiaceae, Lauraceae, Labiatae, Myrtaceae, Meliaceae, Poaceae, Piperaceae, Umbelliferae,
Rutaceae and Zingiberaceae families [8]. They have been evaluated for repellency against
different mosquito vectors, but few compounds have been found to be commercially avail-
able. The public deliberates herbal-based repellents as harmless and the right alternative to
chemical pesticides; most of them are manufactured and distributed through local herbal
harvesters and suppliers and have been seen on the market for a minimal period. Despite
having many botanical based pieces of research, almost all registered plant-based com-
mercial repellents and their active compounds deliver a limited time of protection and
require recurrent reapplication [5]. Increased curiosity in plant-based arthropod repellents
was generated after the United States Environmental Protection Agency (USEPA) added a
rule to the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) in 1986. Formula-
tions containing essential oils are frequently found in the active ingredients of mosquito
repellents marketed as “organic” or “natural”. Despite their newfound popularity, these
alternatives are largely ineffective when compared to DEET. However, research by [14]
found that DEET-free formulations did not perform as well as those containing DEET,
products containing only essential oils from lemongrass, citronella, soybean, rosemary and
cinnamon provided brief repellency immediately upon application. However, within four
hours after application, the sprays were no longer repellent or had substantially reduced
repellency. Plant-based products can provide effective protection, but their effect is usually
temporary compared to solutions containing synthetic chemicals, which tend to breakdown
less easily. The different herbal extraction methods of essential oil for repellents has been
displayed (Supplementary Figure S1).
Humans have been using plants for medicinal purposes since the birth of civilization.
The oldest documentation of this dates back to around 5000 years ago in Nagpur, India. A
piece of Sumerian clay has been found, upon which 12 different recipes for the preparation
of drugs are mentioned, which refer to over 250 plants. Among them are poppy, henbane
and mandrake [24]. It is likely that medicinal plants have been used for a great deal longer,
and there are documented cases of apes and monkeys using different plants for medicinal
purposes. In Costa Rica, plants of the pepper genus are seen being rubbed on the fur
to repel parasites. This is something that is also being used by the human population,
especially Piper auritum [25]. Following the discovery of the Sumerian clay piece in Nagpur,
many other recordings have followed up to the present day. As a result, medicinal plants
have had and continue to have a significant impact on health care, paralleling the synthetic
pharmaceutical industry around the world. The Lao PDR is very interesting with regard to
ethnobotany. Laos is a multi-ethnic country with a long tradition of using medicinal plants
that is very much alive even today [26]. The country is relatively unharmed by deforestation
and has therefore conserved a large portion of its biodiversity. In 2010, Dr. Hugo de Boer
and his colleagues conducted interviews in 66 villages in Laos and established the use of
92 different plant species for repelling a variety of hematophagous parasites [27].
Molecules 2023, 28, 2386 4 of 28

Herbal-based extracts or essential oils have been involved in a significant part of

managing vector-borne diseases with the discovery of unique phytocompounds from indi-
vidual bio-active extracts or essential oils. Among the different natural extracts or bio-active
compounds, flavonoids have lately been given substantial attention by herbal researchers
due to their favorable chemo-protective abilities in different treatments including for cardio-
vascular diseases, neurodegenerative disorders, inflammatory disorders, diabetes, malaria,
dengue and other deadly microbial infections [27]. Since then, we have conducted further
interviews in northwestern Laos, acknowledging further species. Together with further
extensive study of the existing literature, a selection of plant candidates for repelling Ae.
aegypti emerged.

2. Virus Vector
It has long been known that parasitic arthropods may act as vectors for transmitting
certain viruses. The Ae. aegypti mosquito is a recognised vector for DENV, CHIKV and
YFV [28]. These diseases account for 454–900 million cases annually worldwide [3]. Yellow
fever is not present in the Lao People’s Democratic Republic (Laos) and will therefore not
be in focus within this report. The Ae. aegypti is a small, day-active, black mosquito with
white stripes on its joints. As with all mosquitoes, it is only the female mosquitoes that
show hematophagy behaviour.

2.1. Life Cycle of Aedes aegypti

Adult Aedes mosquitoes are different from other types of mosquitoes due to the fact
that they have narrow black bodies that absorb all radiation falling on them. Unique
alternating patterns of light and dark scales are predominantly seen on their abdomen,
thorax and legs. The females possess tapering abdomen and maxillary palps (shorter than
the proboscis), which distinguish them from their male counterparts [29].
Ae. aegypti have four life stages namely (Figure 1):
• Eggs: About 100 black-coloured eggs are laid by adult female mosquitoes on a
wet/moist surface very near the waterline, especially in places such as marshes,
plant axils, tree holes and even water containers [29]. Man-made objects such as
clay pots, bowls, cups, fountains, barrels, vases and tires are excellent sites for egg
laying [30]. The eggs are very hardy and become glued to the wet surface. Due to
their ability to endure long periods of drying, they can survive extreme cold and other
adverse climatic conditions;
• Larvae: The emergence of larvae from the eggs takes place only after they get fully
immersed in water. The process might take days to weeks and some of the eggs require
multiple soakings before they hatch. The larvae are aquatic. They hang upside down
at an angle from the water surface [29]. They feed on the microorganisms found in
water [30]. Siphon is their short respiratory structure, through which they take up
oxygen from the air above the water [30]. After undergoing the process of moulting
thrice, a larva becomes a pupa.
• Pupa: It takes a larva five days to become a pupa. The pupa continues to develop until
the body of the adult mosquito emerges from the pupal skin and exits the water [30];
• Adult: After around 2–3 days, the adult emerges from the pupa [30]. Within two
days of emerging, adult mosquitoes mate. Male mosquitoes feed on nectar found
in flowers, whereas female mosquitoes consume their blood meal. Though they
feed during daytime, their activity peaks at dawn and dusk [29]. After feeding, the
mosquitoes look for water surfaces to lay their eggs [30]. They usually prefer to live in
close association with humans [29], especially inside homes and buildings where the
windows and doors are kept open [30].
 • Adult: After around 2–3 days, the adult emerges from the pupa [30]. Within two days
of emerging, adult mosquitoes mate. Male mosquitoes feed on nectar found in flow-
ers, whereas female mosquitoes consume their blood meal. Though they feed during
daytime, their activity peaks at dawn and dusk [29]. After feeding, the mosquitoes
look for water surfaces to lay their eggs [30]. They usually prefer to live in close as-
Molecules 2023, 28, 2386 5 of 28
sociation with humans [29], especially inside homes and buildings where the win-
dows and doors are kept open [30].

Figure
Figure 1.
1. Life
Life Cycle
Cycle of
of Aedes
Aedes aegypti.
aegypti.

2.2. Role in Transmission of Diseases

A number of diseases are transmitted by Ae. aegypti. The major ones are:

2.2.1. Dengue
2.2.1. Dengue Fever
Fever
It is
It is estimated
estimated that
thatthere
thereare
areabout
about100,000
100,000cases
casesofof
dengue
dengue fever in in
fever Laos
Laosalone, annually.
alone, annu-
The total costs for these episodes every year is believed to be more than USD
ally. The total costs for these episodes every year is believed to be more than USD 5 million5 million [31].
In a low-income country, such as Laos, this amount to a substantial sum
[31]. In a low-income country, such as Laos, this amount to a substantial sum of money, of money, which
could have
which couldbeen
haveutilized in a developmental
been utilized manner.
in a developmental DENV
manner. comes
DENV in four
comes serotypes:
in four 1, 2,
serotypes:
3 and 4, which are very closely related, thus serological tests suggest cross-reactivity.
1, 2, 3 and 4, which are very closely related, thus serological tests suggest cross-reactivity. Yet,
cross-protective
Yet, immunity
cross-protective does does
immunity not seem to occur
not seem [32]. After
to occur a mosquito
[32]. After carrying
a mosquito the virus
carrying the
bites a person, the subject undergoes a 3–14 day incubation period. Directly following is the
virus bites a person, the subject undergoes a 3–14 day incubation period. Directly following
acute onset of fever accompanied by a variety of common influenza symptoms, depending
is the acute onset of fever accompanied by a variety of common influenza symptoms, de-
on the serotype. These may include headache, retro-orbital pain, joint pains, weakness,
pending on the serotype. These may include headache, retro-orbital pain, joint pains, weak-
nausea and vomiting. The febrile period may last 2–10 days, while the virus circulates in
ness, nausea and vomiting. The febrile period may last 2–10 days, while the virus circulates
the subject’s blood. This is usually followed by a brief period of relative recovery before
in the subject’s blood. This is usually followed by a brief period of relative recovery before
the recurrence of symptoms, such as nosebleeds, circulatory failure and a distinctive rash
the recurrence of symptoms, such as nosebleeds, circulatory failure and a distinctive rash
that begins peripherally and spreads to the thorax and back [32,33].
that begins peripherally and spreads to the thorax and back [32,33].
2.2.2. Chikungunya
2.2.2. Chikungunya
As the name implies Chikungunya fever is an acute febrile illness, caused by the virus
CHIKV. The emergence of CHIKV seems to be cyclical [34,35]. It re-emerged in Kenya
in 2004 and has subsequently, spread to novel areas such as Europe, maybe due to an
increasingly warmer climate. It has since caused millions of disease cases throughout the
globe [34]. Symptoms include high fever and arthralgia or severe joint pain that occurs in
almost all patients.
Most infections are resolved within a few weeks but there are reports of cases lasting
for many months with recurring episodes of symptoms [36]. The risk of death is about 0.2%.
Metz et al. from TI Pharma claimed in 2013 that they had developed a working vaccine
Molecules 2023, 28, 2386 6 of 28

against the virus. Refining and distributing such a product is costly and takes time, thus,
Chikungunya fever may still be regarded as a health issue that may be eluded by botanical
repellents [8].

2.2.3. Zika
India is at risk of Zika virus transmission due to the high prevalence of its vector, Ae.
aegypti. Rajasthan, a state in the northwest region of India, also has a high prevalence of the
Aedes mosquito. An explosive Zika epidemic was reported in Brazil in 2015. Though the
WHO declared that ZVD ceased to be a Public Health Emergency of International Concern
after November 2016, GOI continued to be on high alert due to an abundance of the vector
Ae. aegypti and high international travel from endemic countries. The ICMR initiated
ZIKV surveillance through its network of VRDL, with the NIV as the apex laboratory
from 2016. As evident from the present cases, Zika may not be a recent introduction in
India. In 1954, the NIV, Pune (then the Virus Research Centre), had tested samples from the
Bharuch district, which showed ZIKV antibody detection in 16.8 percent of the samples
(Emergencies Preparedness, Response. Zika Virus Infection India) [37].

3. Protection
Currently, there are no effective vaccines against DENV, nor are there any successful
treatments when infected except for the relief of symptoms [3]. Preventive measures are the
most effective way to combat DENV and CHIKV today. Using repellents that are effective
against Ae. aegypti is a successful approach to avoiding bites, which would otherwise
lead to infection risk. According to the World Bank, in 2008, 27.6% of the population in
Laos lived below the poverty line, meaning one must sustain life on USD 1.25 or less per
day. This generally means that synthetic insect repellents are not prioritised. Synthetic
repellents in Laos today are almost exclusively imported from Thailand and are based on
DEET. A recent study by Corbel and colleagues showed the inhibition of cholinesterase and
possibly another neurotoxicity in both insect and mammalian nervous systems by DEET.
This further supports the idea of utilising an innovative, safe and plant-based solution. A
Molecules 2023, 28, 2386 7 of 28
schematic view of the mode of action of a plant metabolite in the mosquito gut is displayed
(Figure 2).

Figure 2. Mode of action of plant metabolites on mosquito gut cells.

Figure 2. Mode of action of plant metabolites on mosquito gut cells.

4. Chemical Repellents Currently in Use against Aedes aegypti

Ranging from spraying aerosols, applying lotions, using coils, curtains, and clothes
treated with active insecticidal compounds, mass fogging, and use in breeding places,
chemical insecticides play a major role in the control of mosquitoes and have been very
Molecules 2023, 28, 2386 7 of 28

4. Chemical Repellents Currently in Use against Aedes aegypti

Ranging from spraying aerosols, applying lotions, using coils, curtains, and clothes
treated with active insecticidal compounds, mass fogging, and use in breeding places,
chemical insecticides play a major role in the control of mosquitoes and have been very
effective [38]. These insecticides potentially target all the life cycle forms of Ae. aegypti and
are divided into larvicidal, adulticidal and pupicidal categories, based on their activity
against the larval, adult and pupal stages of Ae. aegypti.
The four classes of insecticides recommended by the WHO for indoor residual spray-
ing are pyrethroids (permethrin, sumithrin and deltamethrin), carbamates (carbosulfan
and carbaryl), organophosphates (malathion, naled and temephos) and organochlorines
(DDT, DDD, dicofol, aldrin, dieldrin, and chlorobenzoate). Owing to their high efficacy,
low mammalian toxicity and short residual action, pyrethroids are the only insecticides
approved for use on long-duration insecticidal nets against mosquito vectors [39]. Some of
the most common insect repellents currently in use include DEET, IR-3535 and picaridin.
These repellents can be used on clothes, as well as on the skin.

5. Necessity of Natural Mosquito Repellents

Repeated use of the active ingredients in the repellents causes the mosquitos to de-
velop resistance against them. Such resistance development has been reported in several
countries, such as Colombia, Brazil, Grand Cayman, Thailand, India, Malaysia, Mexico
and China [38]. The two main reasons for resistance development are (i) knockdown of
the gene that encodes for the target binding site of the insecticides (kdr mutation sodium
channel resistance) and (ii) upregulation of the mosquito detoxifying enzymes [39]. Most of
these repellents cause allergic reactions such as swelling, rashes and eye irritation in adults
and children, and offer protection only for 2 to 4 h [40]. Though DEET has good efficacy
and offers better protection, it is found to be toxic to the skin and nervous system, as it
inhibits ion channels and human acetylcholinesterase and is involved in the modulation of
G-protein-coupled receptors [41]. Apart from causing pollution in the environment, these
repellents bioaccumulate and are sometimes toxic to non-target species.
Plant-based insecticides (biopesticides) are found to be selective, biodegradable, sus-
tainable and cause little or no harm to non-target organisms [42]. Due to its agro-climatic
conditions, India has the greatest resource of medicinal plants and is therefore considered
to be the botanical backyard of the world [43]. Plant-based repellents have been exploited
by men for thousands of years. The hanging of leaves of certain plants in front of the house,
using dried, burnt leaves to ward off mosquitoes, and applying oils or formulations to the
skin and clothes are still being practised in many countries, and have also been recorded in
the writings of Indian, Greek and Roman scholars [44]. Many rural and tribal communities
in India and several other tropical countries rely on plant-based repellents as the only
means of protection against mosquito bites owing to their poverty [44].

6. Identifying and Screening New Plants for Repellency

On the basis of knowledge of ethnobotany, new plant-based repellents could be
discovered. Ethnobotanical surveys involve the targeted search for medicinal plants by
conducting structured interviews with informants well-versed in folklore and traditional
medicine, in combination with the collection of plant voucher specimens [44]. Indigenous
ethnic groups are questioned on topics related to plant sources, usage and abundance.
This method is easier and more direct when compared to a general screening of all plants
in a particular area [44]. Bioprospecting is another method wherein there is a systematic
screening of plants based on their mode of action. This process is labour intensive and
expensive. PMD, an effective insecticide, was discovered in the 1960s through the process of
mass screening of plants [44]. However, in recent times, with the support of bioinformatics
tools, such as NCBI and many other databases, the search for new repellent plants has
proven to be effortless, cost effective and less time consuming.
Molecules 2023, 28, 2386 8 of 28

7. Plants Tested for Larvicidal Activity against Aedes aegypti

The crude extracts of leaves, flowers, fruits, rhizomes and endosperms of plants
exhibited significant larvicidal activity against Ae. aegypti, which was measured by lethal
concentration (LC) and larval mortality. A few examples of such crude extracts and their
efficacies are given (Table 1).

Table 1. Plants and metabolites that displayed significant larvicidal potency against Ae. aegypti.

Species/Plant Part of Plant Extract Metabolites Detected LC50 LC90 Time of Reference
Family Exposure to
Larvae (hours)
Illicium verum Fruit Essential oil Trans-anethole 2.4 to 3.4 % - 6 [45]
(Schisandraceae)
Zanthoxylum Fruit Essential oil Limonene 2.5 to 2.7% - 6 [45]
limonella
(Rutaceae)
Origanum vulgare Aerial parts Essential oil EO containing 37.5 µg/mL - 48 [46]
(Lamiaceae) terpinen-4-ol, carvacrol,
thymol
Thymus vulgaris Aerial parts Essential oil EO containing thymol, 38.9 µg/mL - 48 [46]
(Lamiaceae) p-cymene, γ-terpinene
Annona mucosa Seed Ethanolic Extract Rolliniatstatin 1, rollinicin Rolliniastatin - 24 [47]
(Annonaceae) 1 = 0.43 µg/mL
Rollinicin =
0.78 µg/mL
Cymbopogon Leaves Essential oil EO containing citral, 120.6 ppm - 24 [48]
citratus (Poaceae) geranial, geraniol,
β-myrcene
Cymbopogon Leaves Essential oil EO containing citronellal, 38.8 ppm - 24 [48]
winteratus citronellol, geraniol,
(Poaceae) elemol
Eucalyptus Leaves Essential oil EO containing citronellal, 104.4 ppm - 24 [48]
citriodora citronellol, isopulegol
(Myrtaceae)
Eucalyptus Leaves Essential oil EO containing 1,8-cineole, 33.7 ppm - 24 [48]
camaldulensis α-pinene, citronellyl
(Myrtaceae) acetate
Achillea Aerial parts Essential oil EO containing EO = - 24 [49]
bieberstenii α-terpinene, p-cymene 23.6 µL/L
(Asteraceae) α-terpinene =
70.1 µL/L
Juniperus procera Aerial parts Essential oil EO containing eugenol, EO = - 24 [49]
(Cupressaceae) β-caryophyllene 12.2 µL/L
Eugenol =
38.3 µL/L
Annona glabra Leaves Extract Silver nanoparticles 5.945 mg/L - 24, 48 [50]
(Annonaceae) (An-AgNPs) for 24 h
3.5485 mg/L
for 48 h
Brassica napus Leaves Essential oil Lipids and fatty acid Fatty acid - 24 [51]
(Brassicaceae) methyl esters methyl esters
= 342.8 ppm
Pavetta tomentosa Fresh Leaves Extract 2,6,10,14,18,22-tetracosane Crude extract Crude extract 24 [52]
(Rubiaceae) hexane; 2,6,10,15,19,23- = 5.96 µg/mL = 7.49 µg/mL
hexamethyltetracosane
Tarenna asiatica Fresh Leaves Extract Tetracontane Crude extract Crude extract 24 [52]
(Rubiaceae) = 1.28 µg/mL = 1.99 µg/mL
Ambrosia Leaves Extract Silver nanoparticles 0.28 ppm 0.43 ppm 24 [53]
arborescens
(Asteraceae)
Pinus sylvestris Needles Essential oil 3-cyclohexane-1-methanol, EO = - 24 [54]
(Pinaceae) alpha, alpha.4-trimethyl 100.39 mg/L
Syzygium Buds Essential oil Eugenol, eugenyl acetate EO = - 24 [54]
aromaticum 92.56 mg/L
(Myrtaceae)
Mentha villosa Leaves Essential oil EO containing EO = 45 ppm - 24 [55]
(Lamiaceae) rotundifolone Rotundifolone
= 62.5 ppm
Molecules 2023, 28, 2386 9 of 28

Table 1. Cont.

Species/Plant Part of Plant Extract Metabolites Detected LC50 LC90 Time of Reference
Family Exposure to
Larvae (hours)
Carum carvi Voucher Essential oil Carvone, limonene, EO = - 24 [56]
(Apiaceae) specimen γ-terpenene 54.62 ppm
Apium graveolens Voucher Essential oil D-limonene, phthalides EO = - 24 [56]
(Apiaceae) specimen 42.07 ppm
Foeniculum Voucher Essential oil Trans-anethole, EO = - 24 [56]
vulgare specimen D-limonene, estragole 49.32 ppm
(Apiaceae)
Zanthoxylum Voucher Essential oil D-limonene, terpinen-4-ol, EO = - 24 [56]
limonella specimen sabinene 24.61 ppm
(Rutaceae)
Curcuma zedoaria Voucher Essential oil 1,8-cineole, p-cymene, EO = - 24 [56]
(Zingiberaceae) specimen α-phellandrene 31.87 ppm
Limonia Leaves Extract Niloticin 0.44 ppm 1.17 ppm 24 [57]
acidissima
(Rutaceae)
Mentha arvensis Fresh Leaves Essential oil (Corn mint oil) containing 78.1 ppm 125.7 ppm 24 [58]
(Lamiaceae) menthol, methyl acetate,
menthone and limonene

The ethanolic seed extract of Annona mucosa (Annonaceae) produced an LC50 value
of 2.6 mg/mL when exposed to Ae. aegypti larvae for 24 h [47]. At a concentration of
500 mg/mL, the dichloromethane extract of the leaves of Ateleia glazioviana (Fabaceae)
produced high larvicidal activity [59]. The LC50 values of the aqueous extract of another
plant of the family Annonaceae, Annona glabra, when exposed to Ae. aegypti larvae for 24
and 48 h were 2.43 mg/L and 1.17 mg/L, respectively [50]. The petroleum ether extracts of
leaves of three plants, namely Hyptis suaveolens (Lamiaceae), Lantana camara (Verbenaceae)
and Tecoma stans (Bignoniaceae), had LC50 values of 64.49, 74.93, and 84.09, respectively,
and were found to be toxic against Ae. aegypti larvae [60]. The blend of these four extracts
had an LC50 of 7.19 mg/L and a predator safety factor (for Gambusia affinis) of 12.55. Hence,
these extracts and their blend were safe for non-targets [60].
The methanolic extracts of petals, leaves and roots of Ipomoea cairica (Convolvulaceae)
showed potential larval mortalities, with LC50 values of 12.7, 13.6, and 31.9 mg/L, re-
spectively, against Ae. aegypti [61]. The methanolic extracts of Persea americana (avocado)
(Lauraceae) unripe fruit peel [62], Nerium oleander (Apocynaceae) leaves [60], Rubia cordifolia
(Rubiaceae) roots [63], Argemone mexicana (Papaveraceae) seed [64] and Sida acuta (Mal-
vaceae) leaves [65], displayed good larval toxicity with LC50 values (after 24 and 48 h of
exposure) of 7.12ppm, 84.09 mg/L,102.23 mg/L, 80 mg/mL and 42.08 mg/L respectively.
The plant extracts of Argemone mexicana, when screened, were found to be abundant in
metabolites, such as alkaloids, flavonoids, coumarins, saponins, tannins, cardiotonics,
glycosides, sterols and terpenes [64].
Significant larval mortalities were observed in the methanolic extracts of Anacardium
occidentale (Anacardiaceae), Dianella longifolia (Liliaceae), Litsea leefeana (Lauraceae), Trenica
grandifolia (Ulmaceae), Canthium gueinzii (Rubiaceae), Kigelia pinnata (Bignoniaceae), Rumex
obtusifolius (Polygonaceae) and Ruta chalepensis (Rutaceae), at a concentration of 400 ppm
when exposed to Ae. aegypti larvae for 24 h [66].
An increase in the concentration of ethanolic extract from the leaves of Momordica
charantia (Cucurbitaceae) enhanced the larval mortality of Ae. aegypti [51]. In terms of
the mortality rate, different extracts of the leaves of Pavetta tomentosa and Tarenna asiatica,
both belonging to the family Rubiaceae, produced dissimilar effects, with the highest
toxicity exhibited by the ethyl acetate extract and the lowest toxicity exhibited by the chlo-
roform extract against Ae. aegypti [52]. Similarly, the crude extracts of Ambrosia arborescens
(Asteraceae) leaves [53], Scilla peruvina (Asparagaceae) roots [63], Anamirta cocculus (Menis-
permaceae) endosperms [67], Acorus calamus (Acoraceae) fresh rhizome [68] and Limonia
acidissima (Rutaceae) leaves [57], showed remarkable larval toxicity, with LC50 values of
1844.61 ppm, 114.13 mg/L, 56.73 mg/L, 57.32 mg/L and 4.11 ppm, respectively, after
 Molecules 2023, 28, 2386 10 of 28

24 h exposure to the larvae. The acetone, petroleum ether and ethanol extracts of Tribulus
terrestris (Zygophyllaceae) leaves after just a 4 h exposure to the larvae produced LC50
values of 173.2, 64.6 and 376.4 ppm, respectively, and thus, all three extracts proved to be
effective [69].
The ethanolic extracts and metabolites of Annona mucosa (Annonaceae) were found
to be non-toxic when tested against a non-target organism, such as zebrafish, and hence,
could be further developed as potential mosquito repellents with a good safety factor [47].
Not only the crude extracts but also some of the essential oils extracted from the leaves
and other parts of plants, such as those from Croton nepetaefolius (Euphorbiaceae) and
Syzygium aromaticum (Myrtaceae), were larvicidal in nature, as they produced 50% larval
mortalities at concentrations of 32.7 and 81.7 ppm, respectively [51]. The essential oil
derived from Anethum graveolens (Zingiberaceae) fruit, at 10% concentration, offered 100%
larval mortality with a LC50 of −0.3% after a 72 h exposure period [70].
Three plants from the family Canellaceae, namely Cinnamosma fragrans, Cinnamosma
madagascariensis and Warburgia ugandensis, were examined by [71] for their larvicidal ac-
tivity against Ae. aegypti. Their bark, roots and leaves were used for extraction, and many
metabolites were detected such as CDIAL, UGAN, CPCD, and POLYG from C. fragrans;
CMOS, Cinnafragrin A, and CML from C. madagascariensis; and WARB (a sesquiterpene
dialdehyde) from W. ugandensis. The larvicidal activity was proportional to the amount of
CDIAL and POLYG present, and in the case of C. fragrans, 60% CDIAL was found in the
bark, 30% CDIAL in the root extracts and no detectable CDIAL in the leaf extract. In C. mada-
gascariensis, the bark and root extracts showed almost 75% larvicidal activities, while the
leaf extract had approximately 0.9% efficacy. Of all the metabolites identified, WARB and
CDIAL exhibited the strongest toxicity against Ae. aegypti larvae, with POLYG being mod-
Molecules 2023, 28, 2386 erately toxic and CML and CMOS being nominally toxic [71]. The major phytocompounds11 of 28
that display larvicidal activity are displayed (Figure 3).

Figure 3. Cont.
Molecules 2023, 28, 2386 11 of 28

Figure 3. Chemical structures of major metabolites detected in larvicidal plants [72–78]. (A) trans-
anethole, (B) limonene, (C) terpinen-4-ol, (D) carvacrol, (E) thymol, (F) p-cymene, (G) γ-terpinene,
(H) rolliniastatin-1, (I) rollinicin, (J) α-terpinene, (K) citral, (L) citronellal, (M) citronellyl ac-
etate, (N) eugenol, (P) geraniol, (Q) isopulegol, (Q’) CDIAL, (R) CML, (S) CMOS, (T) CFRAG,
(a) 2,6,10,14,18,22-tetracosane hexane, (b) 2,6,10,15,19,23-hexamethyltetracosane, (c) 3-cyclohexene-1-
methanol,.alpha., .alpha.4-trimethyl, (d) α-phellandrene, (e) carvone, (f) d-limonene, (g) estragole,
(h) eugenyl acetate, (i) niloticin, (j) rotundifolone, (k) sabinene, (m) tetracontane, (n) 1,8-cineole,
(o) α-pinene, (p) β-myrcene, (q) CPCD, (r) citronellol, (s) phthalide, (s’) POLYG, (t) elemol, (u) WARB,
(v) UGAN, (w) geranial, (y) neral.

8. Plants Tested for Repellent Activity against Aedes aegypti

The methanolic extracts of Sonnerita alba (Lythraceae), Avicennia marina (Acanthaceae),
Avicennia alba (Acanthaceae), Rhizophora stylosa (Rhizophoraceae) and Rhizophora apiculata
Molecules 2023, 28, 2386 12 of 28

(Rhizophoraceae) showed excellent repellence of 85.8%, 80.5%, 80.5%, 81.3% and 80.3% for
a period of 2 h, 3 h, 1 h, 1 h and 2 h, respectively, when exposed to Ae. aegypti for 6 h [79].
They are mangrove plants, which are rich in compounds such as alkaloids, flavonoids,
saponins, steroids, quinones, phenols, triterpenoids and glycosides [79].
Lotions were prepared from the essential oils of Citrus aurantifolia (Rutaceae) leaves,
Citrus grandis (Rutaceae) fruit peels and Alpinia galanga (Zingiberaceae) rhizomes, through
microencapsulation [80]. At a concentration of 20%, all three lotions offered complete
protection against Ae. aegypti for 2 h. At a concentration >90% the protection was extended
to 4 h. The A. galanga-based formulation exhibited the highest protection of 98.91% for 4 h
post-application [80].
The crude extracts of Clausena anisata (Rutaceae) leaves were examined for three types
of repellency, namely: topical-based repellency, repellent-treated nets and space spraying
assays [81]. The repellency over 3 h was found to be 83% for the acetone crude extract (with
a concentration of 15%) and 54% at 7.5% concentration for the hexane extract. For mosquito
bites, repellency was found to be 93% for the crude extract and 67% for the hexane fraction.
Butanol and chloroform were found to be ineffective at any of the concentrations [81]. As
with treated nets, acetone and hexane extracts of Clausena anisata had a repellency of 46.89%
and 50.13%, respectively, after 3 h. Finally, as nebulisers, the EC50 of these extracts were
78.9 and 71.6 mg/mL, respectively, and they caused mosquito knockdown and, eventually,
death [81]. The essential oils are extracted from the fruits of plants in the Rutaceae family,
specifically Citrus aurantifolia, Citrus aurantium, Citrus hystrix, Citrus maxima, Citrus medica,
Citrus reticulata and Citrus macrocarpa, which have been shown to repel Ae. aegypti [82]. The
order of repellency of their essential oils (EOs) was as follows: C. aurantifolia > C. microcarpa
> C. maxima > C. reticulata > C. hystrix > C. aurantium > C. medica. All the EOs had a longer
protection time than the chemical repellent IR3535 (Johnson’s Baby Cream). C. aurantifolia
had the highest repellency, with a CPT, biting rate and % protection of 65 min, 1.5%, and
98.5% protection, respectively [82].
At a concentration of 5 mg/cm2 , the methanolic extract of the leaves of Sida acuta
(Malvaceae) provided 100% protection for 180 min against Ae. Aegypti. The repellency was
dependent on the concentration of the crude extract [65].
The protection time was found to be directly related to the concentration of the
essential oil in the case of Clausena dentata (Rutaceae) [83]. At a concentration of 2.5%, the
mean protection time was 180 min (the lowest), while at a concentration of 10%, the mean
protection time had increased to 255 min. The essential oil of C. dentata was also found to
be skin friendly, as its mean score for the skin potential test was zero [83].
Generally, repellents may task at a distance (spatial repellents likely pointing the olfac-
tory system) or contact (likely starting gustatory or other sensory systems). Alternatively,
insect repellents may not modify the function of the olfactory neurons directly, but as
an alternative, avert other odours from stimulating olfactory neurons by dipping odour
volatility at the surface of skin [17]. Since most testing for the efficacy of specific plant’s
repellent effect examines only the final step in host seeking (the number of mosquito bites),
these different modes of action are frequently not eminent, which can cause misperception
when trying to assign a single function to an insect repellent. The specific mode of action
and their major sensory receptors, and channels along with sensory appendages have been
displayed (Figure 4).
 Molecules 2023, 28, 2386 13 of 28

bites), these different modes of action are frequently not eminent, which can cause mis-
Molecules 2023, 28, 2386 13 of 28
perception when trying to assign a single function to an insect repellent. The specific mode
of action and their major sensory receptors, and channels along with sensory appendages
have been displayed (Figure 4).

Figure 4. (A) Dengue mosquitoes use chemical cues to find a host and feed. Also, plant repellents
Figure 4. (A) Dengue mosquitoes
with different use chemical
phytocompounds cues to
with different find
modes of a host(B)
action. and feed. Also,
Repellent’s plant
response repellents
to specific
molecular targets including sensory receptors (odorant receptor (OR),
with different phytocompounds with different modes of action. (B) Repellent’s response to gustatory receptor (GR) andspecific
ionotropic receptor (IR)) distributed on various arthropod appendages. Future insect repellents may
molecular targets interact
including sensory
with other receptors
receptor (odorant
families including the receptor (OR),potential
transient receptor gustatory receptor
channel (GR) and
(TRP), pick-
pocket
ionotropic receptor receptor
(IR)) (PPK) andon
distributed G-protein-coupled
various arthropod receptor (GPCR). (C) Sensory
appendages. appendages
Future insectof mos-
repellents
quito vector.
may interact with other receptor families including the transient receptor potential channel (TRP),
pickpocket receptor (PPK) and G-protein-coupled
The combination and blend of essentialreceptor
oils and(GPCR). (C)some
extracts of Sensory
plants appendages
produced of
mosquito vector. better repellency than that produced by individual extracts/oils. A few examples are: com-
binations of basil-peppermint oils displayed protection of 71.11% to 6.67%; nutmeg-pep-
permint oils showed protection of 96.67% to 3.33%; and basil-nutmeg oils showed protec-
The combination and toblend
tion of 87.77% 0% from ofthe
essential oils
1st to the 5th and
hour extracts
when exposed of some
to Ae. plants
aegypti produced
for a total of
better repellency
6 hthan that
[84]. The produced
repellent action ofby individual
major extracts/oils.
plant metabolites A few
against the dengue examples
mosquito vec- are:
combinations oftor have been displayed (Figure
basil-peppermint 5 and Table 2).
oils displayed protection of 71.11% to 6.67%; nutmeg-
peppermint oils showed protection of 96.67% to 3.33%; and basil-nutmeg oils showed
protection of 87.77% to 0% from the 1st to the 5th hour when exposed to Ae. aegypti for
a total of 6 h [84]. The repellent action of major plant metabolites against the dengue
mosquito vector have been displayed (Figure 5 and Table 2).

Table 2. Plants and their metabolites that displayed significant repellency against Ae. aegypti.

Plant Part Metabolites Detected % Repellency % Protec- Complete Time of Ref.

Species/Family of the Plant tion/Duration Protection Exposure to
of Protection Time (CPT) the-
Mosquito
Origanum Aerial parts Terpinen-4-ol, 8.9% to 37.8% - - 24 h [46]
vulgare carvacrol, thymol (Essential oil)
(Lamiaceae)
Thymus Aerial parts Thymol, 4.4% to 68.9% - - 24 h [46]
vulgaris p-cymene, (Essential oil)
(Lamiaceae) γ-terpenes
Ateleia Leaves Flavonoids 84.5% - - 24 h [59]
glazioviana (Dichloroethane
(Fabaceae) extract)
Ocimum Leaves Eucalyptol, linalool, 70.5% - - 24 h [59]
basilicum eugenol (Alcoholic spray
(Lamiaceae) derived from
essential oil)
Myristica Nutmeg oil α-pinene, - 100% protection - 6h [84]
fragrans terpinen-4-ol, for first 2 h, 90
(Myristicaceae) safrole to 23.32% for
the next 4 h
Mentha piperita Peppermint oil Menthol - 96.67% to - 6h [84]
(Lamiaceae) 27.78% for the
first 4 h
Molecules 2023, 28, 2386 14 of 28

Table 2. Cont.

Plant Part Metabolites Detected % Repellency % Protec- Complete Time of Ref.

Species/Family of the Plant tion/Duration Protection Exposure to
of Protection Time (CPT) the-
Mosquito
Ocimum Basil oil Methyl chavicol, - 98.9% to 2.22% - 6h [84]
basilicum geraniol, methyl for 5 h
(Lamiaceae) eugenol
Chenopodium Aerial parts Trans-pinocarveol, 39.7% - - 5 min [85]
ambrosioides cis-carveol, (Essential oil)
(Amaran- trans-pinocarvyl
thaceae) acetate
Conyza Aerial parts Cis-lachnophyllum ester, 51.4% (Essential oil) - - 5 min [85]
sumatrensis limonene,
(Asteraceae) trans-β-ocimene
Erigeron Aerial parts Limonene, matricaria ester 80% (Essential oil) - - 5 min [85]
canadensis
(Asteraceae)
Eucalyptus Fresh leaves Pinocarveol, myrtenol, 13.7% (Essential oil) - - 5 min [85]
camaldulensis β-phellandrene
(Myrtaceae)
Mentha spicata Aerial parts Piperitenone oxide, 100% (Essential oil) - - 5 min [85]
(Lamiaceae) eucalyptol
Parthenium Aerial parts Germacrene-D, 63.9% - - 5 min [85]
hysterophorus β-myrcene, (Essential oil)
(Asteraceae) trans-β-ocimene
Targetes minuta Aerial parts Cis-β-ocimene, 50.2% - - 5 min [85]
(Asteraceae) cis-tagetenone, limonene (Essential oil)
Nepeta cataria CR9, CR3 crude Z, E-nepetalactone and 10% CR9 crude oil - - 24 h [41]
(Lamiaceae) essential oils E, Z nepetalactone isomers showed >95%
repellency for the first
2h
Cymbopogon Leaves Citral, The blend of all
citratus limonene, extracts was
(Poaceae) α-terpineol, used
- - - [40]
citronellol For 1%
w/v-1 h
Lantana Camara Leaves Oleanonic acid, lantadene 2% w/v-2 to 3 h
(Verbenaceae) A&B, lantanilic acid 5% w/v-5 to 6 h
Calotropis Leaves Acetate, citrates, chloride
gigantea
(Apocynaceae)
Ocimum Leaves, flowers, Eugenol, ursolic acid,
sanctum branches rosmarinic acid
(Lamiaceae)
Azadirachta Leaves Nimbolinin, nimbin,
indica quercetin, nimbidiol
(Meliaceae)
Calotropis Leaves Uscharin,
Procera calotoxin,
(Apocynaceae) calotropeol acetate
Angelica sinensis Rhizome and 3-N-butylphthalide, - - 2.5 h Every 3 min [86]
(Apiaceae / root butylidenephthalide, (EO) in a 30 min
Umbelliferae) di-iso-octyl phthalate, 2.5 h (Ethanolic interval
ligustilide extract)
7.5 h
(Hexane extract)
1.75 h (Acetone
extract)
0.5 h
(Methanolic
extract)
Mentha arvensis Fresh leaves Essential oil (corn mint oil) - - 25% EO–45 min - [58]
(Lamiaceae) containing menthol, 90 min
methyl acetate, menthone, (50% EO)
and limonene 165 min (100%
EO)
Note: The essential oil Hierochloe odorata (Poaceae) was extracted from its leaves by and was found to contain
metabolites such as phytol, coumarin, 2-methoxy-4-vinyl alcohol and 6,10,14-trimethyl-2-pentadecanone. The
repellency of this plant’s EO, hexane and ethanol crude extracts were determined using PNB, and their PNB
values were found to be 0.84, 0.48 and 0.44, respectively.
Molecules 2023, 28, 2386 15 of 28
Molecules 2023, 28, 2386 14 of 28

Figure 5. Chemical structures of major metabolites detected in plants showing repellency [74,75,77].
(A) 2-methoxy-4-vinyl alcohol, (B) 6,10,14-trimethyl-2-pentadecanone, (C) α-pinene, (D) α-terpineol,
(E) β-myrcene, (F) β-phellandrene, (G) butylidene phthalide, (H) butylphthalide, (I) calotoxin, (J) car-
vacrol, (K) cis and trans-β-ocimene, (L) cis-carveol, (M) cis-tagetenone, (N) citral, (O) citronellol,
(P) coumarin, (Q) diisooctyl phthalate, (R) E,Z-nepetalactone, (S) eucalyptol, (T) eugenol, (U) γ-
terpinene, (V) geraniol, (W) germacrene D, (X) trans-pinocarveol acetate, (Y) lacnophylum ester,
(Z) lantadene A and B, (a) lantanilic acid, (b) ligustilide, (c) limonene, (d) linalool, (e) matricaria
ester, (f) menthol, (g) methyl carvacrol/estragole, (h) methyl eugenol, (i) nimbidiol, (j) nimbin,
(k) nimbolinin A, (l) Z,E-nepetalactone, (m) oleanonic acid, (n) p-cymene, (o) phytol, (p) pinocarveol,
(q) piperitenone oxide, (r) quercetin, (s) rosmarinic acid, (t) safrole, (u) terpinen-4-ol, (v) thymol,
(w) trans-β-ocimene, (x) trans-pinocarveol, (y) ursolic acid, (z) uscharin.
Molecules 2023, 28, 2386 16 of 28

9. Plants Tested for Adulticidal Activity against Aedes aegypti

The evaluation of the adulticidal activity of the plant extracts and essential oils was
carried out through the determination of the percentage of mortality of adult mosquitoes,
lethal concentrations and lethal times when exposed to these extracts, oils and metabolites
for a predetermined period.
The crude extracts of Anamirta cocculus (Menispermaceae) endosperm [67] displayed
potent adulticidal activities. The PE extract produced LC50 , LC90 and LC99 values of 140.16,
178.28 and 214.71 mg/L, respectively. While the same plant’s aqueous extract produced
an LC50 value of 141.93 mg/L against Ae. aegypti after 24 h exposure [67]. The methanolic
extracts of the leaves and seeds of the plant Pithecellobium dulce (Fabaceae) exhibited good
adulticidal activities against Ae. aegypti when exposed for 24 h [87]. The LC50 and LC90
values for the leaves were 218.64 and 257.99 mg/L, and for the seeds, they were 426.05 and
Molecules 2023, 28, 2386 507.73 mg/L, respectively [87]. The adulticidal action of major plant metabolites 18 against
of 28
the dengue mosquito vector have been displayed (Figure 6 and Table 3).

Figure
Figure 6. Chemicalstructures
6. Chemical structures of major
of major metabolites
metabolites detected
detected in adulticidal
in adulticidal plants [73,75,77,78].
plants [73,75,77,78]. (a)
(a) 2,6,10,14,18,22-tetracosane
2,6,10,14,18,22-tetracosane hexane,
hexane, (a1) p-cymene,
(a1) p-cymene, (b) 2,6,10,15,19,23-hexamethyl
(b) 2,6,10,15,19,23-hexamethyl tetracosane,
tetracosane, (b1)
terpinen-4-ol,
(b1) (c) linalool,
terpinen-4-ol, (c1) thymol,
(c) linalool, (d) eugenol,
(c1) thymol, (e) 𝛽-pinene,
(d) eugenol, (f) d-limonene,
(e) β-pinene, (g) estragole,
(f) d-limonene, (h)
(g) estragole,
carvone,
(h) (i) 𝛼-terpinene,
carvone, (j) citronellal,
(i) α-terpinene, (k) β-caryophyllene,
(j) citronellal, (l) citronellol,
(k) β-caryophyllene, (m) tetracontane,
(l) citronellol, (n) 1,8-
(m) tetracontane,
cineole, (o) 𝛼-pinene, (p) geraniol, (q) carvacrol, (r) 𝛾-terpinene, (s) neral, (t) geranyl acetate, (u)
(n) 1,8-cineole, (o) α-pinene, (p) geraniol, (q) carvacrol, (r) γ-terpinene, (s) neral, (t) geranyl acetate,
methyl benzoate, (v) myrcene, (w) octanol, (x) piperitenone, (y) pulegol, (z) sabinene.
(u) methyl benzoate, (v) myrcene, (w) octanol, (x) piperitenone, (y) pulegol, (z) sabinene.
10. Plants Tested for Pupicidal Activity against Aedes aegypti
The pupicidal activity of the plant extracts/essential oils was deduced depending on
the mortality rates of the Ae. aegypti pupae when exposed to these extracts for a specific
time period, following which lethal concentration and lethal time values were calculated.
The essential oils extracted from four plants, namely Alpinia galanga (Zingiberaceae), An-
ethum graveolens (Apiaceae), Foeniculum vulgare (Apiaceae) and Pimpinella anisum
Molecules 2023, 28, 2386 17 of 28

Table 3. Plants and metabolites that displayed significant adulticidal activity against Ae. aegypti.

Species/Plant Part of Plant Metabolites Detected LC50 LC90 % Mortality Time of Reference
Family Exposure to
the
Mosquito
Origanum vulgare Aerial parts EO containing 14.3 µg/mL - - 90 min [46]
(Lamiaceae) terpinen-4-ol, carvacrol,
thymol
Thymus vulgaris Aerial parts EO containing thymol, 11.7 µg/mL - - 90 min [46]
(Lamiaceae) p-cymene, γ-terpinene
Achillea Aerial parts EO containing 30.2 µL/L (EO) - - 24 h [49]
bieberstenii α-terpinene, p-cymene 66.8 µL/L
(Asteraceae) (α-terpinene)
54.1 µL/L
(p-cymene)
Juniperus procera Aerial parts EO containing eugenol, 10.1 µL/L (EO) - - 24 h [49]
(Cupressaceae) β-caryophyllene 18.3 µL/L
(Eugenol)
46.4 µL/L (β-
caryophyllene)
Pavetta tomentosa Fresh leaves 2,6,10,14,18,22- 32.105 µg/mL 41.001 µg/mL - 60 min [52]
(Rubiaceae) tetracosane hexane; (Crude extract) (Crude extract)
2,6,10,15,19,23-
hexamethyltetracosane
Tarenna asiatica Fresh leaves Tetracontane 9.012 µg/mL 11.854 µg/mL - 60 min [52]
(Rubiaceae) (Crude extract) (Crude extract)
Lippia alba Dry whole plant Limonene, carvone, - - 24% (at 390 ppm 24 h [88]
(Verbenaceae) (voucher piperitenone of EO after 24 h)
specimen)
Lippia origanoides Dry whole plant Carvacrol, p-cymene, - - 68% (at 300 ppm 24 h [88]
(Verbenaceae) (voucher thymol of EO within
specimen) 2 min)
Eucalyptus Dry whole plant Citronellol, pulegol, - - 13% (at 390 ppm 24 h [88]
citriodora (voucher citronellal of EO after 24 h)
(Myrtaceae) specimen)
Cymbopogon Dry whole plant Neral, geraniol, geranyl - - >92% (at 24 h [88]
flexuosus (voucher acetate 1000 ppm of EO
(Poaceae) specimen) after 60 min)
Citrus sinensis Dry whole plant Limonene, myrcene, - - 76% (at 390 ppm 24 h [88]
(Rutaceae) (voucher n-octanol of EO after 24 h)
specimen)
Cananga odorata Dry whole plant Methyl benzoate, - - >92% (at 24 h [88]
(Annonaceae) (voucher linalool 1000 ppm of EO
specimen) after 60 min)
Swinglea Dry whole plant α-pinene, β-pinene, - - >92% (at 24 h [88]
glutinosa (voucher sabinene,1,8- cineole 1000 ppm of EO
(Rutaceae) specimen) after 120 min)
Tagetes lucida Dry whole plant Myrcene, estragole, - - >92% (at 24 h [88]
(Asteraceae) (voucher trans-β-ocimene 1000 ppm of EO
specimen) after 24 h)

10. Plants Tested for Pupicidal Activity against Aedes aegypti

The pupicidal activity of the plant extracts/essential oils was deduced depending on
the mortality rates of the Ae. aegypti pupae when exposed to these extracts for a specific time
period, following which lethal concentration and lethal time values were calculated. The
essential oils extracted from four plants, namely Alpinia galanga (Zingiberaceae), Anethum
graveolens (Apiaceae), Foeniculum vulgare (Apiaceae) and Pimpinella anisum (Apiaceae),
exhibited good toxicity when exposed to Ae. aegypti pupae for a period of 72 h. At 5%
concentrations, the oils of An. graveolens and F. vulgare produced 100 and 94% mortalities
with LT50 values of 10.3 and 14.6 h, respectively [70]. At 10% concentration, An. graveolens
displayed the highest pupicidal activity with 100% mortality and LT50 and LC50 values of
6.7 h and 2.9%, respectively [70]. The essential oils from F. vulgare, P. anisum and Al. galanga
produced 99.7%, 3.5%; 98.3%, 3.84%; and 92%, 6.3% mortalities and LC50 values against the
pupae of Ae. aegypti, respectively [70].
The crude leaf extracts of Tribulus terrestris (Zygophyllaceae) were pupicidal in na-
ture [69]. This plant’s acetone extract, at concentrations of 400, 200, 100 and 50 ppm
 Molecules 2023, 28, 2386 19 of 28

Molecules 2023, 28, 2386 18 of 28

The crude leaf extracts of Tribulus terrestris (Zygophyllaceae) were pupicidal in na-
ture [69]. This plant’s acetone extract, at concentrations of 400, 200, 100 and 50 ppm pro-
duced 57.1%,
produced 57.1%,30.8%,
30.8%,23.8%
23.8%andand7.7%
7.7%pupal
pupal mortalities,
mortalities, respectively [69]. The
respectively [69]. Thepetroleum
petroleum
etherextract
ether extractofof Tribulus
Tribulus terrestris
terrestris alsoalso produced
produced significant
significant pupalpupal mortalities
mortalities of 100%,
of 100%, 100%,
82.3%
100%,and
82.3%54.5% at concentrations
and 54.5% of 200,
at concentrations of 100, 50 and
200, 100, 25 ppm,
50 and respectively
25 ppm, respectively [69].
[69].The
The
pupicidal
pupicidalaction
actionofofmajor
majorplant
plantmetabolites
metabolitesagainst
againstthe
thedengue
denguemosquito
mosquitovector
vectorhave
havebeen
been
displayed
displayed(Figure
(Figure77and
andTable
Table4).4).

Figure 7. Chemical structures of major metabolites detected in pupicidal plants [73,75,77].

Figure 7. Chemical structures of major metabolites detected in pupicidal plants [73,75,77]. (a)
(a) 2,6,10,14,18,22-tetracosanehexane,
2,6,10,14,18,22-tetracosane hexane,(a1)
(a1)trans-anethole,
trans-anethole,(b)
(b)2,6,10,15,19,23-hexamethyl
2,6,10,15,19,23-hexamethyltetracosane,
tetracosane,
(c)
(c)linalool,
linalool,(d)
(d)carvone,
carvone,(e) 𝛽-pinene,(f)
(e)β-pinene, (f)d-limonene,
d-limonene,(g) (g)estragole,
estragole,(h)
(h)niloticin,
niloticin,(i)
(i)carvacrol,
carvacrol,(j)
(j)cit-
ronellal, (k) (k)
citronellal, p-cymene,
p-cymene,(l) (l)
citronellol, (m)
citronellol, (m)tetracontane,
tetracontane,(n)
(n)1,8-cineole,
1,8-cineole,(o) 𝛼-pinene,(p)
(o)α-pinene, (p) geraniol,
geraniol,
(q)thymol,
(q) thymol, (r)
(r) trans-β-ocimene,
trans-𝛽-ocimene, (s) (s) neral,
neral,(t)
(t)geranyl
geranylacetate,
acetate,(u)(u)
methyl benzoate,
methyl benzoate,(v) myrcene, (w)
(v) myrcene,
octanol,
(w) (x) (x)
octanol, piperitenone,
piperitenone,(y)(y)
pulegol, (z)(z)
pulegol, sabinene.
sabinene.
Molecules 2023, 28, 2386 19 of 28

Table 4. Plants and metabolites that displayed significant pupicidal potency against Aedes aegypti.

Plant Part of Plant Metabolites LC50 LC90 % Mortality LT50 Time of Exposure to Reference
Species/Family Detected the Mosquito
Illicium verum Fruit Trans-anethole - - 86.4 to 100% (5% 6.9 to 28.8 h (5% 72 h [45]
(Schisandraceae) trans-anethole) trans-anethole)
1.5 to 5.2 h (2.5% EO
+ 2.5%
trans-anethole)
Zanthoxylum Fruit Limonene - - 89.6 to 94.4% (5% 23.8 to 28.5 h (5% 72 h [45]
limonella (Rutaceae) d-limonene)) d-limonene)
7.9 to 15.3 h (2.5%
EO + 2.5%
d-limonene)
Pavetta tomentosa Fresh leaves 2,6,10,14,18,22- For 24 h, Acetone - - - 24 and 48 h [52]
(Rubiaceae) tetracosane hexane; extract =
2,6,10,15,19,23 - 1.361‘µg/mL;
hexamethyltetracosane Hexane extract =
2.044 µg/mL;
Chloroform extract =
2.512 µg/mL
For 48 h, Acetone
extract =
3.273 µg/mL;
Hexane extract =
1.682 µg/mL;
Chloroform extract =
2.298 µg/mL
Tarenna asiatica Fresh leaves Tetracontane For 24 h, Acetone - - - 24 and 48 h [52]
(Rubiaceae) extract =
1.682 µg/mL;
Hexane extract =
1.990 g/mL;
Chloroform extract =
2.429 µg/mL
For 48 h, Acetone
extract =
4.555 µg/mL;
Hexane extract =
3.008 µg/mL;
Chloroform extract =
3.975 µg/mL
Molecules 2023, 28, 2386 20 of 28

Table 4. Cont.

Plant Part of Plant Metabolites LC50 LC90 % Mortality LT50 Time of Exposure to Reference
Species/Family Detected the Mosquito
Lippia alba Dry whole plant Limonene, carvone, - - 24% and 29% after 24 - 24 and 48 h [88]
(Verbenaceae) (voucher specimen) piperitenone and 48 h (at 390 ppm
of EO)
Lippia origanoides Dry whole plant Carvacrol, p-cymene, - - 67% and 73% after 24 - 24 and 48 h [88]
(Verbenaceae) (voucher specimen) thymol and 48 h (at 250 ppm
of EO)
Eucalyptus citriodora Dry whole plant Citronellol, pulegol, - - 13% and 47% after 24 - 24 and 48 h [88]
(Myrtaceae) (voucher specimen) citronellal and 48 h (at 390 ppm
of EO)
Cymbopogon flexuosus Dry whole plant Neral, geraniol, - - 13% and 47% after 24 - 24 and 48 h [88]
(Poaceae) (voucher specimen) geranyl acetate and 48 h (at 390 ppm
of EO)
Citrus sinensis Dry whole plant Limonene, myrcene, - - 27% and 42% after 24 - 24 and 48 h [88]
(Rutaceae) (voucher specimen) n-octanol and 48 h (at 390 ppm
of EO)
Cananga odorata Dry whole plant Methyl benzoate, - - 27% and 56% after 24 - 24 and 48 h [88]
(Annonaceae) (voucher specimen) linalool and 48 h (at 390 ppm
of EO)
Swinglea glutinosa Dry whole plant α-pinene, β-pinene, - - 38% and 73% after 24 - 24 and 48 h [88]
(Rutaceae) (voucher specimen) sabinene,1,8- cineole and 48 h (at 390 ppm
of EO)
Tagetes lucida Dry whole plant Myrcene, estragole, - - 56% and 67% after 24 - 24 and 48 h [88]
(Asteraceae) (voucher specimen) trans-β-ocimene and 48 h (at 390 ppm
of EO)
Limonia acidissima Leaves Niloticin 0.62 ppm (Niloticin) 1.45 ppm (Niloticin) - - 24 h [57]
(Rutaceae) 4.19 ppm (Hexane 8.10 ppm (Hexane
extract) Extract)
Molecules 2023, 28, 2386 21 of 28

11. Plants Tested for Ovicidal and Oviposition Deterrent Activities against Aedes
aegypti
The ovicidal activity was calculated by exposing the eggs of Ae. aegypti to the plant
extracts for a certain time period, followed by counting the number of hatched/unhatched
eggs (mortality) in comparison to the number of eggs laid. In the case of oviposition
deterrence, the extracts were exposed to the adult Ae. aegypti and % repellency was
measured based on the number of eggs laid by the mosquitoes.
The hexane leaf extract of Limonia acidissima (Rutaceae) displayed a formidable ovicidal
activity of 60% at 500 ppm against the eggs of Ae. aegypti, while at the same concentration,
the hexane extract of Aegle marmelos (Rutaceae) was moderately ovicidal with an activity
of 48.8% [57]. The ethyl acetate extract of Chromolaena odorata (Asteraceae) also produced
13.6% activity against the mosquito eggs at an identical concentration [57]. For all tested
concentrations, L. acidissima hexane extract showed 100% oviposition deterrent activity [57].
At 500 ppm, A. marmelos hexane extract produced 71.79% deterrence, while the ethyl acetate
extract of Sphaeranthus amaranthoides (Asteraceae) produced 20.48% deterrence at the same
concentration [57].
The methanolic extract (500 mg/L) of Rubia cordifolia (Rubiaceae) roots produced high
ovicidal activity of 70–40% against the eggs of Ae. aegypti [63]. The second highest ovicidal
activity was shown by the hexane extract of Scilla peruvina (Asparagaceae) root with 43.2%,
followed by hexane extract of R. cordifolia with 25.6% [63]. The ovicidal and oviposition
deterrent action of the major plant metabolites against the dengue mosquito vector have
been displayed (Figure 8 & Table 5).

Table 5. Plants and metabolites that displayed significant ovicidal and oviposition deterrent activities
against Aedes aegypti.

Plant Part of the Plant Metabolite Ovicidal Activity Oviposition Time of Exposure Ref.
Species/Family Detected (% Mortality) Deterrent Activity to the Eggs/Adult
(Number of Eggs Aedes aegypti
Laid)
Limonia acidissima Leaves Niloticin 83.2% (at 2 ppm of - 120 h [57]
(Rutaceae) niloticin)
Cyanthocline Leaves 3-n-decyl acrylic >70% (ethanolic - 48 h [89]
purpurea acid, C16 extract at
(Asteraceae) sphinganine, 0.2 mg/mL)
mytiloxanthin
Blumea lacera Leaves Phytosphingosine, ≈75% (ethanolic - 48 h [89]
(Asteraceae) cosmosiin, valine, extract at
serine, arginine 0.1 mg/mL)
Neanotis lancifolia Leaves Fentanyl, 8-hydroxy 90% (ethanolic - 48 h [89]
(Rubiaceae) mianserin, extract at
1-dodecanoyl-2- 0.1 mg/mL)
octadecanoyl-
glycero-3-phospho-
(10 -sn-glycerol)
Neanotis montholonii Leaves (6RS)-6,19-epidioxy- ≈90% (ethanolic - 48 h [89]
(Rubiaceae) 24,24 extract at
difluoro-25- 0.1 mg/mL)
hydroxy-6,19-
dihydrovitamin
D3/(6RS)-6,19-
epidioxy-24,24-dif,
1-dodecanoyl-2-
octadecanoyl-
glycero-3-phospho-
(10 -sn-glycerol),
fipexide
Piper marginatum Leaves and stem D-elemene, - <50% eggs laid (at 14 h [89]
(Piperaceae) α-Copaene, 50 and 100 ppm of
patchouli alcohol, leaf and stem
(Z)-asarone extracts)
<40% eggs laid
(essential oil)
 octadecanoyl-glycero-3-phos-
pho-(1′-sn-glycerol), fipexide
Piper marginatum (Pipe- Leaves and D-elemene, α-Copaene, patch- - <50% eggs laid (at 14 h [89]
raceae) stem ouli alcohol, (Z)-asarone 50 and 100 ppm of
leaf and stem ex-
tracts)
Molecules 2023, 28, 2386 22 of 28
<40% eggs laid (es-
sential oil)

Figure 8. Chemical structures of major metabolites detected in plants displaying ovicidal and
oviposition deterrence
Figure 8. Chemical activities
structures of [75–77]. (a) (6RS)-6,19-epidioxy-24,24
major metabolites difluoro-25-hydroxy-6,19-
detected in plants displaying ovicidal and ovi-
dihydroxyvitamin
position deterrenceD3activities
(6RS)- 6,19-epidioxy-24,24-dif, (b) niloticin, (c) difluoro-25-hydroxy-6,19-dihy-
[75–77]. (a) (6RS)-6,19-epidioxy-24,24 Z-azarone, (d) 1-dodecanoyl-2-
octadecanoyl-glycero-3-phospho-(1 0 -sn-glycerol), (e) 3-n-decyl-acrylic acid, (f) 8-hydroxy mianserin,
droxyvitamin D3 (6RS)- 6,19-epidioxy-24,24-dif, (b) niloticin, (c) Z-azarone, (d) 1-dodecanoyl-2-oc-
(g) α-copaene, (h) arginine, (i) C16 sphinganine, (j)(e)
tadecanoyl-glycero-3-phospho-(1′-sn-glycerol), cosmosiin, (k) δ-elemene,
3-n-decyl-acrylic (l) fentanyl,
acid, (f) 8-hydroxy (m) fipexide,
mianserin,
(n) 𝛼-copaene, (h) (o)
(g)mytiloxanthin, arginine, (i) C16
patchouli sphinganine,
alcohol, (j) cosmosiin, (k)
(p) phytosphingosine, (q) δ-elemene, (l) fentanyl, (m) fipex-
serine, (r) valine.
ide, (n) mytiloxanthin, (o) patchouli alcohol, (p) phytosphingosine, (q) serine, (r) valine.
12. Conclusions and Future Development
This work presents detailed information on the various kinds of plant species that
have been explored over the years for their mosquitocidal potential against different life
cycle forms of Ae. aegypti.
• About 40 plant families were involved in these studies against Ae. aegypti and they
include Schisandraceae, Rutaceae, Lamiaceae, Annonaceae, Fabaceae, Poaceae, Myr-
taceae, Asteraceae, Cupressaceae, Lauraceae, Euphorbiaceae, Cucurbitaceae, Mal-
vaceae, Linaceae, Brassicaceae, Myristicaceae, Canellaceae, Rubiaceae, Amaranthaceae,
Zingiberaceae, Apiaceae, Verbenaceae, Apocynaceae, Bignoniaceae, Acanthaceae,
Lythraceae, Arecaceae, Amaryllidaceae, Melastomataceae, Rhizophoraceae, Meliaceae,
Asparagaceae, Celastraceae, Papaveraceae, Menispermaceae, Acoraceae, Convolvu-
laceae, Pinaceae, Zygophyllaceae, Anacardiaceae, Ulmaceae and Polygonaceae. All
these plant families enriched with essential oils and their bio-active compounds either
for its fragrance or other benefits, and the repellents that have been found to repel the
dengue vector for a maximum period of 60–180 min.
Molecules 2023, 28, 2386 23 of 28

• Among these, plants belonging to the Rutaceae, Lamiaceae, Asteraceae, Apiaceae,

Myrtaceae, Poaceae and Fabaceae families have been frequently researched in recent
times for their larvicidal, adulticidal, pupicidal and ovicidal activities against Ae.
aegypti and other mosquito vectors.
• When compared to individual plant compounds/extracts, a blend or their combination
was found to be more effective against the mosquitoes and increased the protection
time [90–97].
The selection of insect repellent plants could be tailor-made, specific with the safety
warnings and information about biting mosquitoes for travellers and the public and about
the incidence of illness. The use of advance technologies, including effective nano-based
formulation strategies with increasing repellent time, to enhance the performance of natural
repellents may transform the repellent commercial market and make herbal derivatives
a more feasible option for use in enduring repellents. Through the proper optimisation
of repellent products by endorsing the compound binding ability to mosquitoes’ odorant
receptors on the antennae and dropping their volatility, a rational and consumable pattern
exists for the expansion of new bio-rational repellent formulations that could be installed as
spatial repellents in effective vector control strategies across nations. Moreover, improving
the technologies and cash cropping strategies of repellent herbs meet the expense of a
dynamic source of revenue for agriculturalists and producers and elevate the country’s
economy. Furthermore, in countries where their primary revenue depends on tourism, the
practice and development of novel herbal-based repellents would increase the desire and
security of travellers. As an endnote, faster work needs to be done to discover new and
safe repellents for personal protection from mosquitoes. Hence, more extensive research
needs to be carried out in this regard to determine the type of plant, the type of extract,
the type of metabolite, the concentration and the right combinations at which they can be
infused for more pronounced activity.

Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/molecules28052386/s1, Figure S1: Different extraction processes
for plant repellent substances.
Author Contributions: S.S.P.—Writing—original draft, Conceptualization, Formal analysis;
P.V.-S.—Writing—original draft, Investigation, Methodology; A.B.A.—Resources, Formal analysis,
Software; Funding acquisition; R.K.—Conceptualization, Data curation, Methodology, Validation;
N.R.—Formal analysis, Investigation, Visualization; S.S.-N.—Project administration, Supervision,
Writing—review & editing; K.K.—Data curation, Supervision, Visualization; N.C.—Data curation,
Resources, Visualization; S.K.—Methodology, Resources, Validation; R.G.—Methodology, Resources,
Validation; Z.T.A.—Software, Visualization; T.P.—Software, Visualization; O.P.V.—Resources, Valida-
tion; A.A-M.—Software; Funding acquisition; J.P.—Conceptualization, Software, Formal analysis, Data
curation, Writing-review & editing, Visualization, Project administration, Resources, Supervision and
Funding acquisition. All authors have read and agreed to the published version of the manuscript.
Funding: The APC is financed by Wrocław University of Environmental and Life Sciences. Also, this
research was supported by the Department of Science and Technology (DST-FIST), India under FIST
program (SR/FIST/LS-1/2019/522).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.

Abbreviations
DSS Dengue Shock Syndrome
DHF Dengue Haemorrhagic Fever
DEN-2 Dengue Virus Type-2
Molecules 2023, 28, 2386 24 of 28

STI Sterile Insect Technique

DEET N, N-diethyl-meta-toluamide
Lao PDR Lao People’s Democratic Republic
CDIAL Cinnamodial
CHIKV Chikungunya Virus
CML Cinnamolide
CMOS Cinnamosmolide
CPCD Capsicodendrin
DDD Dichlorodiphenyldichloroethane
DDT Dichlorodiphenyltrichloroethane
DENVEO Dengue Fever VirusEssential Oil
GOI Government of India
ICMR Indian Council of Medical Research
LC Lethal Concentration
NCBI National Center for Biotechnology Information
NIV National Institute of Virology
PMD Para-menthane-3,8-diol
POLYG Polygodial
RNA Ribonucleic Acid
UGAN Ugandensolide
USD United States Dollars
VRDL Virus Research & Diagnostic Labs
WARB Warburganal
WHO World Health Organization
YFV Yellow Fever Virus
ZIKV Zika Virus
ZVD Zika Virus Disease

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