Botanical Pesticides and Their Mode of

Action

Nabil E. El-Wakeil

Gesunde Pflanzen
Pflanzenschutz - Verbraucherschutz -
Umweltschutz

ISSN 0367-4223
Volume 65
Number 4

Gesunde Pflanzen (2013) 65:125-149

DOI 10.1007/s10343-013-0308-3

1 23
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Gesunde Pflanzen (2013) 65:125–149
DOI 10.1007/s10343-013-0308-3
R e v i e w A rt i c l e
Botanical Pesticides and Their Mode of Action
Nabil E. El-Wakeil
Received: 26 August 2013 / Accepted: 1 October 2013 / Published online: 3 November 2013
© Springer-Verlag Berlin Heidelberg 2013
Abstract  Pest management is facing economic and eco-
logical challenge worldwide due to human and environ-
mental hazards caused by majority of the synthetic pesti-
cide chemicals. Identification of novel effective insecticid-
al compounds is essential to combat increasing resistance
rates. Botanical pesticides have long been touted as attrac-
tive alternatives to synthetic chemical pesticides for pest
management because botanicals reputedly pose little threat
to the environment or to human health. The body of scien-
tific literature documenting bioactivity of plant derivatives
to arthropod pests continues to expand, yet only a hand-
ful of botanicals are currently used in agriculture in the
industrialized world, and there are few prospects for com-
mercial development of new botanical products. Pyrethrum
and neem are well established commercially, pesticides
based on plant essential oils have entered the marketplace,
and the use of rotenone appears to be waning. A number
of plant substances have been considered for use as pest
antifeedants, repellents and toxicants, but apart from some
natural mosquito repellents, a little commercial success has
ensued for plant substances that modify arthropod behav-
ior. Several factors appear to limit the success of botani-
cals, most notably regulatory barriers and the availability
of competing products (newer synthetics and fermentation
products) that are cost-effective and relatively safe com-
pared with their predecessors. In the context of agricultural
pest management, botanical pesticides are best suited for
N. E. El-Wakeil ()
Pests and Plant Protection Department,
National Research Centre, Dokki, Cairo, Egypt
e-mail: nabil.el-wakeil@landw.uni-halle.de
N. E. El-Wakeil
Institute of Agricultural and Nutritional Sciences,
Martin Luther-University Halle-Wittenberg, Germany
use in organic food production in industrialized countries
but can play a much greater role in the production and
postharvest protection of food in developing countries.
Botanicals have been in use for a long time for pest con-
trol. The compounds offer many environmental advantag-
es. However, their uses during the 20th century have been
rather marginal compared with other bio-control methods
of pests and pathogens. Improvement in the understanding
of plant allelochemical mechanisms of activity offer new
prospects for using these substances in crop protection. I’m
trying in this article to present different kinds of botanical
pesticides came from different recourses and their mode
of actions as well as I will try to examine the reasons be-
hind their limited use (disadvantages) and the actual crop
protection developments involving biopesticides of plant
origin for organic or traditional agricultures to keep our
environment clean and safer for humankind and animals.
Keywords  Plant-biopesticide · Pyrethrum · Neem ·
Essential oils · Antifeedants · Repellents
Botanische Pestizide und ihre Wirkmechanismen
Zusammenfassung  Die Schädlingsbekämpfung mit che-
misch-synthetischen Pestiziden steht weltweit vor wirt-
schaftlichen und ökologischen Herausforderungen. Die
Identifizierung neuer effektiver insektizider Verbindungen
ist wichtig, um die zunehmend auftretenden Resistenzen zu
bekämpfen. Botanische Pestizide sind seit langem als at-
traktive Alternativen zu chemisch-synthetischen Pestiziden
zur Schädlingsbekämpfung angekündigt worden, weil Pes-
tizide aus pflanzlicher Herkunft weniger Gefahren für die
Umwelt und/oder die menschliche Gesundheit birgen. Die
wissenschaftliche Literatur dokumentiert eine Vielzahl von
13
126
Untersuchungen zur Bioaktivität pflanzlichen Stoffe deren
Derivate geeignet sind, gegen Arthropoden als Schädlinge
eingesetzt zu werden. Aktuell werden aber nur eine Hand-
voll pflanzlicher Stoffe in der Landwirtschaft in den Indus-
trieländern verwendet. Es gibt nur wenige Hinweise auf
eine wirtschaftliche Entwicklung der neuen botanischen
Produkte. Zum Beispiel sind die Wirkstoffe Pyrethrum und
Neem kommerziell gut etabliert und auch Pestizide auf Ba-
sis pflanzlicher ätherischer Ölen sind am Markt zu finden.
Der Einsatz von Rotenon scheint aufgrund von Nebenwir-
kungen zu schwinden. Eine Reihe von pflanzlichen Subs-
tanzen sind interessant für den Einsatz als Fraßhemmer,
und als Repellents, aber abgesehen von einigen natürlichen
Insektenschutzmitteln gibt es kaum kommerziellen Einsatz
für die pflanzlichen Substanzen. Mehrere Faktoren begren-
zen den Erfolg von pflanzlichen Stoffen, hier sind zum
Beispiel regulatorische Barrieren zu nennen.
Im Zusammenhang mit der landwirtschaftlichen Schäd-
lingsbekämpfung, sind botanische Pestizide bestens für den
Einsatz in der ökologischen Bio-Produktion in den Indust-
rieländern geeignet, sie können aber auch eine größere Rol-
le bei der Begrenzung von Nachernte- und Lagerverlusten
spielen. Die Verbindungen bieten viele Vorteile für die Um-
welt. Allerdings sind ihre Anwendungen im 20. Jahrhundert
eher marginal im Vergleich zu anderen Verfahren zur Kont-
rolle von Schädlingen und Krankheitserregern. Die Verbes-
serungen bei der Aufklärung der Mechanismen der Pflanzen
mit allelochemischer Aktivität bieten neue Perspektiven für
die Verwendung dieser Stoffe als Pflanzenschutzmitteln. In
dem vorliegenden Artikel werden verschiedene Wirkme-
chanismen von Bio-Pestiziden vorgestellt und Gründe für
den derzeit begrenzten Einsatz genannt.
Schlusswörter  Biopestizide · Pyrethrum · Neem ·
Ätherische Öle · Repellents
Introduction
Pesticides are the cornerstones upon which the pest man-
agement practices are based, and are likely to remain so as
long as effective and inexpensive chemicals are available
(Haynes 1988). The practice of using plant derivatives, or
botanical pesticides as we now know them, in agriculture
dates back at least two millennia in ancient Egypt, China,
Greece, and India (Ware 1983; Thacker 2002). Even in
Europe and North America, the documented use of botani-
cals extends back more than 150 years, dramatically predat-
ing discoveries of the major classes of synthetic chemical
pesticides (e. g. organochlorines, organophosphates, carba-
mates, and pyrethroids) in the mid-1930s to 1950s which
had caused many environmental problems as insect resis-
tances Fig.  1. Synthetic pesticides effectively relegated
13
N. E. El-Wakeil
Fig. 1  Pest resistance increases with repeated exposure products from
the same chemical family (cited from Gilkeson and Adams 2000)
botanicals from an important role in agriculture to an essen-
tially trivial position in the marketplace among crop protec-
tants. However, history also shows that overzealous use of
synthetic pesticides led to numerous problems unforeseen at
the time of their introduction: acute and chronic poisoning
of applicators, farmworkers, and even consumers; destruc-
tion of fish, birds, and other wildlife; disruption of natural
biological control and pollination; extensive groundwater
contamination, potentially threatening human and environ-
mental health; and the evolution of resistance to pesticides
in pest populations (Casida 1973; McLaughlin 1973; Marco
et al. 1987; Forget et al. 1993; Perry et al. 1998).
Authorities responded to these problems with regulatory
action, replacing chemicals of concern with those demon-
strated to pose fewer or lesser risks to human health and
the environment. In the United States, these policies are
reflected by the definition of “reduced risk” pesticides by
the Environmental Protection Agency in the early 1990s
with their favored regulatory status, and by the Food Qual-
ity Protection Act in USA, which, in reappraising safe lev-
els of pesticide residues in foods, is having the net effect
of removing most synthetic pesticides developed before
1980 from use in agriculture. These changes in the regu-
latory “environment” appeared to heighten the impetus for
the discovery and development of alternative pest manage-
ment products—those with reduced health and environ-
mental impacts—including pesticides derived from plants.
Indeed, the scientific literature of the past 25 years describes
hundreds of isolated plant secondary metabolites that show
feeding deterrent or toxic effects to insects in laboratory
bioassays, and botanical pesticides have been the subject
of several recent volumes (Dev and Koul 1997; Hedin
et al. 1997; Prakash and Rao 1997; Koul and Dhaliwal
2001; Regnault-Roger et al. 2005) and also it takes several
steps to get a commercial product as shown in Fig. 2. There
are many factors determining using the botanical pesticides
for pest control as reported by Deng et al. (2009).
Botanical pesticides are also used in organic garden-
ers, in some cases, over synthetic organic materials. In
general, they act quickly, degrade rapidly and have, with
Botanical Pesticides and Their Mode of Action
Fig. 2  Steps and interactions
between stages from discovery of
a biocide to approved field appli-
cation (cited from Brown 2005)
a few exceptions, low mammalian toxicity. Products con-
taining ingredients derived from plants (Table 1) are consid-
ered pesticides. However, products containing these active
ingredients must be registered for use by the Environmen-
tal Protection Agency (EPA) in USA as well by Ministry of
Agricultural and Land Reclamation in Egypt.
127
Certain essential plant oils, widely used as fragrances and
flavors in the perfume and food industries, have long been
reputed to repel insects. The investigations in several coun-
tries confirm that some plant essential oils not only repel
insects, but have contact and fumigant pesticidal actions
against specific pests, and fungicidal actions against some
13
128 N. E. El-Wakeil

Table 1  Toxicity of certain botanical pesticides (mg/kg) with potential for future commercialization, suggest why so
Generic name Oral LD50 Dermal LD50 Signal word few botanicals reach the marketplace, and finally suggest in
Nicotine 50–60 50 Danger what contexts botanicals could prove effective in the years
Rotenone 60–1.500a 940–3.000 Caution to come and their distribution on many countries over the
Sabadilla 4.000 – Caution world as appeared in Table 2.
Ryania 750–1.200 4.000 Caution
Pyrethrins 1.200–1.500 > 1.800 Caution
d-Limonene > 5.000 – Caution Definitions
Linalool 2.440–3.180 3.578–8.374 Caution
Neem 13.000 – Caution
Definition of Pesticides
a
Toxicity varies greatly depending on type of solvent used as carrier

Chemical substance designed to kill or retard the growth

Table 2  Botanical insecticides approved for use in specific countries of pests that damage or interfere with the growth of crops,
(Resource (Pesticide Action Network 2004) Pesticide registration by
country) shrubs, trees, timber and other vegetation desired by
Country Pyrethrum Rotenone Nicotine Neema Others humans. Practically all chemical pesticides, however, are
Australia X X – – Citrus oils poisons and pose long-term danger to the environment and
New X X – X humans through their persistence in nature or body tissue.
Zealand Most of the pesticides are non-specific and may kill life
India X X X X Ryania forms that are harmless or useful.
Philippines X – – –
Hungary X – – – Quassia Definition of Botanical Pesticides
Denmark X X – – Lemongrass,
clove, eucalyp-
tus oils Botanical pesticides are naturally occurring chemicals
Egypt X – – X Essential oils, extracted from plants. Natural pesticidal products are avail-
Lemongrass able as an alternative to synthetic chemical formulations but
Germany X – – X they are not necessarily less toxic to humans. Some of the
Nether- X – – – most deadly, fast acting toxins and potent carcinogens occur
lands
naturally (Regnault-Roger et al. 2005; Regnault-Roger and
United X X X –
Kingdom Philogène 2008).
South X – – –
Africa Definition of Mode of Action
Brazil X X – X Garlic
United X X X X Essential oils, Mode of action refers to the specific biochemical interac-
States ryania, sabadilla tion through which a pesticide produces its effect. Usually,
Canada X X X – Specified
the mode of action includes the specific enzyme, protein,
essential oils,
Mexico X X – X Garlic, capsicum or biological step affected. While most other classifica-
X Be present, – Be not present tions are the pests controlled, physical characteristics, or
a
Includes insecticides listing azadirachtin as the active ingredient chemical composition, mode of action specifically refers to
which biological process the pesticide interrupts (Khambay
et al. 2003; Bloomquist et al. 2008).
important plant pathogens (Isman 1999, 2000). As part of an
effort aimed at the development of reduced-risk pesticides Why Mode of Action is Important?
based on plant essential oils, toxic and sublethal effects of
some essential oil terpenes and phenols have been investi- Knowing the mode of action is integral for scientists to
gated using the tobacco cutworm (Spodoptera litura) and improve the quality and sustainability of a product. To
the green peach aphid (Myzus persicae) as model pest spe- understand how pesticides work (their mode of action), it
cies (Weinzierl 2000; Isman 2000, 2006). is necessary to understand how the pests’ targeted systems
So far in spite of the large scale of the research projects, normally function. It is also helpful to understand how
only a handful of botanical pesticides are in commercial use human systems function in order to know similarities and
on vegetable and fruit crops today, with significant com- differences between humans and the pests we try to control.
mercial development of only two new sources of botani- Another reason, it is important to understand the modes of
cals in the past 25 years. In this review, current botanicals action of the pesticides we use is to prevent development
and their trends in use, discuss the few botanical materials of pesticide resistance in the target pest(s). Using pesticides

13
Botanical Pesticides and Their Mode of Action
with the same mode of action contributes to this problem
by killing the susceptible pests and leaving only those with
resistance to the entire class of pesticides that work through
similar mechanisms (Brown 2005).
Historical Background
Having observed that some plants protect themselves better
than others, humans developed the use of plants as pesticides.
Historically, botanicals were used before other kinds of pes-
ticides. They are mentioned in Hieroglyph, Chinese, Greek,
and Roman antiquity and also in India where the use of the
neem tree (Azadirachta indica Juss.; Meliaceae) was reported
in the Veda, a body of manuscripts written in archaic Sanskrit
dated at least 4,000 years ago (Philogène et al. 2005). It is
thus difficult to assess exactly where and when plants or plant
extracts were systematically used in plant protection or, more
generally, in agriculture. In the 18th century, some publica-
tions dealt with plant-based formulations to control insect
pests (Shepard 1951). At the end of the 19th century, methods
including the use of toxic plants or minerals, oils, tars, sul-
focalcic sprays, boiling water, and so forth, were commonly
put into practice (Whittaker and Feeny 1971; Philogène
et al. 1984). Integration of empirical and scientific observa-
tions led to the development of plant extracts.
The first botanicals and allelochemicals to be used as pes-
ticides came from easily available products. Pest insects were
targeted more than pathogens because they could be easily
identified. Several recent books and chapters have reviewed
biopesticides of plant origin (Copping 2001; Koul and Dhali-
wal 2001; Thacker 2002; Regnault-Roger et al. 2005).
The development of botanicals used as pesticides resulted
from two parallel methods: (i) The observation of the tradi-
tional uses of plants and extracts for cattle and crop protec-
tion, followed by checking the efficiency of these practices
and identification of the active molecules. The activity of
nicotine extracted from tobacco, Nicotiana tabacum and
rotenone from Leguminosae Lonchocarpus nicou and Der-
ris elliptica fall in this category. (ii) A systematic screening
of families of plants collected during prospecting campaigns
followed by biological tests in order to discover the active
molecules. Ryanodine, an alkaloid extracted from Ryania
sp., and marketed in the USA in 1945, is the result of such
prospectings carried out with collaboration between Rutgers
University and Merck in 1940s (Copping 2001).
Before the Second World War, four main groups of com-
pounds were in fact commonly used: nicotine and alkaloids,
rotenone and rotenoids, pyrethrum and pyrethrins, and veg-
etable oils. The use of these substances, because of their
toxicity to nontargeted species (nicotine) or the instability
of molecules (pyrethrum), decreased with the commercial-
ization of chemically synthesized insecticides developed
during the Second World War (organochlorides, organo-
129
phosphates, and carbamates). They were easier to handle
and less expensive. This situation continued until the 1960s
(Alburo and Olofson 1987).
But as a result of the many demonstrations of negative
effects on non-target species and environmental risks result-
ing from the massive use of chemical pesticides, there was
renewed interest for botanicals. Even if there were substan-
tially more efforts devoted to the search and the development
of new synthesized pesticides, research on biopesticides of
plant origin was actively pursued throughout the second half
of the 20th century in order to improve their stability or to
discover new molecules and new sources of molecules. This
is well illustrated by the development of pyrethrinoids, syn-
thesized molecules derived from pyrethrum, and of neem
(Meliaceae), during the entire 20th century.
Factors Affecting Use of Botanical Pesticides
1. Raw material availability
2. Standardization of botanical extracts containing a com-
plex mixture of active constituents
3. Solvent types, plant species and part of plant
4. Rapid degradation
5. State registration
6. Market opportunities for botanical pesticides
7. Weather conditions
There are other factors affecting on synthetic botanical pesti-
cide uses, such as the formulation of the pesticide, the active
ingredient, the time of exposure, the direct or indirect con-
tact, the quantity used the pesticides mixtures, the climate
and season of the year when it’s applied, and the person’s
age, amongst others (Henn et al. 1991; Dosemeci et al. 2002).
There are environmental indicators, health indicators,
and other elements that help determine the exposure risk,
such as the person residence and occupational history, the
clinical history, as well as the presence of the pesticides
studied in drinking water, in the ground, in the atmosphere,
and in the fresh or processed foods in the region where the
studied populations inhabit. The exposure can be increased
with the daily time dedicated to the activity, as well as the
years of work, the exposure form, the use of protective gear,
and/or the physical proximity of the housing to agricultural
fields (Arcury et al. 2006).
Resources of Botanical Pesticides
At present there are four major types of botanical products
used for insect control (pyrethrum, rotenone, neem, and
essential oils), along with three others in limited use (ryania,
nicotine, and sabadilla). Additional plant extracts and oils
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130
Table 3  Egyptian medicinal and
aromatic plants, which can be
used as botanical pesticides
(e. g. garlic oil, Capsicum oleoresin) see limited (low vol-
ume) regional use in various countries, but these are not
considered here, as shown in the following Tables 3 and 4.
Functional and Biological Active Plant Ingredients of
Some Botanical Pesticides
Functional of botanical pesticides varied from product to
another and from sources to others as appeared in Table 5.
Commercial development of pesticides based on plant has been
greatly facilitated by exemption from registration for certain
products commonly used in processed foods (Quarles 1996).
This opportunity has spurred the development of botanical
insecticides, acracides, fungicides, bactericides, nematicides
and herbicides for agricultural and industrial applications and
for the consumer market as described by Thibout et al. (1986);
Thibout and Auger (1997); Auger and Thibout (2002).
Current Botanicals in Use and Their Mode of Action
The botanical pesticides could be divided into two gen-
erations: The 1st generation included Nicotine, Rotenone,
13
N. E. El-Wakeil
Sabadilla, Ryania, Pyrethrum, Plant essential oils; while the
2nd generation included Synthetic Pyrethroids and Azadi-
rachtin, as well Potential New Botanicals as stated by Reg-
nault-Roger et al. (2005) in the book: Biopesticides of plant
origin.
The first Generation of Botanical Pesticides
Nicotine
An alkaloid obtained from the foliage of tobacco plants
(Nicotiana tabacum) and related species, has a long history
as an insecticide. Nicotine (Fig. 3) and two closely related
alkaloids, nornicotine and anabasine, are synaptic poisons
that mimic the neurotransmitter acetylcholine. As such,
they cause symptoms of poisoning similar to those seen
with organophosphate and carbamate insecticides (Hayes
1982; Regnault-Roger and Philogène 2008). Owing to the
extreme toxicity of pure nicotine to mammals (rat oral LD50
is 50 mg kg−1) and its rapid dermal absorption in humans,
nicotine has seen declining use, primarily as a fumigant
in greenhouses against soft-bodied pests. However, there
remains some interest in preparing stable nicotine fatty acid
Botanical Pesticides and Their Mode of Action 131

Table 4  List of plants and their parts used for evaluation of pesticide activities in Thailand (cited from Bussaman et al. 2012a, b)
Scientific name Family Common name Parts
Boesenbergia pandurata Schltr. Zingiberaceae Fingerroot Rhizome
Kaempferia parviflora Wall. Zingiberaceae Belamcanda chinensis Rhizome
Kaempferia pulchra (Ridl.) Ridl Zingiberaceae Peacock ginger, resurrection lily Rhizome
Zingiber zerumbet (L.) Smith. Zingiberaceae Wild ginger, Martinique ginger Rhizome
Zingiber officinale Roscoe. Zingiberaceae Ginger Rhizome
Zingiber montanum (Koenig) Link Zingiberaceae Phlai, cassumunar Rhizome
Alpinia galanga (L.) Swartz. Zingiberaceae Kha, galingale, galangal Rhizome
Curcuma longa Linn. Zingiberaceae Turmeric Rhizome
Curcuma xanthorrhiza Roxb. Zingiberaceae Curcuma Rhizome
Cymbopogon citratus Stapf. Gramineae Takhrai, lemongrass Leaf
Citrus hystrix DC. Rutaceae Leech lime Leaf
Ocimum basilicum Linn. Labiatae Ho-ra-pa, sweet-basil, basil Leaf
Ocimum canum Linn. Labiatae Hairy basil Leaf
Ocimum sanctum Linn. Malvaceae Holy basil, sacred basil Leaf
Moringa oleifera Lam. Moringaceae Horse radish tree Leaf
Annona squamosa Linn. Annonaceae Sugar apple Leaf
Psidium guajava Linn. Myrtaceae Guava Leaf
Eucalyptus camaldulensis Dehnh. Myrtaceae Red river gum, Murray red gum Leaf
Artocarpus heterophyllus Lam. Moraceae Jackfruit tree Leaf
Piper sarmentosum Roxb. Piperaceae Cha-plu Leaf
Murraya paniculata (L.) Jack. Rutaceae Orange jessamine, satin-wood Leaf
Melissa officinalis L. Lamiaceae Kitchen mint, marsh mint Leaf
Cassia siamea (Lam.) Fabaceae Kassod tree, siamese senna Leaf

Table 5  Examples of functional and/or biologically active plant ingredients (Bakkali et al. 2008)
Ingredient type/function Examples
Antioxidants Lycopene, resveratrol, α-carotene, β-carotene, catechins, vitamin C, vitamin E, green tea, soy
isoflavones, curcumin, pomegranate extracts (anthocyanins, delphinidin, cyaniding, pelargonidin),
grape seed extracts, polyphenols, essential oils, kojic acid
Anticarcinogens Resveratrol, lycopene, green tea, genistein, pycnogenol, curcumin, lycopene, pomegranate seed
oils, polypodium extracts, vitamin E, silymarin
Antiinflammatory/anti-irritant Vitamin C, pycnogenol, oatmeal, curcumin, avenanthramides, salicylic acid, polyphenols
Natural colorants Henna, lawsone, indigo, camomille, lycopene, crocin, carmine, anthocyanidins, carotenoids
Fragrances Essential oils terpenes, terpenoides, aldehydes, alcohols, esters, ketones, phenols, methoxyphenols
Preservatives, antiseptics Saponins, essential oils, benzoic/salicylic acids and derivatives, organic acids and esters, phenols,
usnic acid, thymol, bacteriocins
Hydration/moisturizing Silymarin, lipids, sterols, omega-3 fatty acids
Surfactants Saponins, phospholipids
Thickening agents Carrageenan, starches, carbohydrates
Skin whitening Kojic acid, arbutin, soy proteins, aloesin, vitamin C
Anti-ageing/free radical scavenging Lycopene, genistein, vitamin C, vitamin E, pomegranate extracts, grape seed extract, silymarin, soy
proteins, anthocyanins, green tea extracts, Polypodium leucotomos extract, polyphenols, resveratrol,
curcumin, pomegranate seed oils, soy isoflavones
Photo-protection Pomegranate seed oils, genistein, green tea extracts, Polypodium leucotomos extract, polyphenols,
avenanthramides

soaps, presumably with reduced bioavailability and toxicity
to humans (Casanova et al. 2002). Furthermore, alkaloids of
Haloxylon salicornicum and Stemona japonica are known
be strong agonists at nicotinic acetylcholine receptors (El-
Shazly et al. 2005).
Mode of Action In both insects and mammals, nicotine
is an extremely fast-acting nerve toxin. It competes with
acetylcholine, the major neurotransmitter, by bonding
to acetylcholine receptors at nerve synapses and caus-
ing uncontrolled nerve firing. This disruption of normal
nerve impulse activity results in rapid failure of those body
systems that depend on nervous input for proper function-
ing. In insects, the action of nicotine is fairly selective, and
only certain types of insects are affected.

13
132
Fig. 3  Chemical structure of nicotine and nicotian plants
Rotenone
As a pesticide, rotenone has been in use for more than 150
years, but its use as a fish poison dates back even further
(Shepard 1951). Rotenone is one of several isoflavonoids
produced in the roots or rhizomes of the tropical legumes
Derris, Lonchocarpus, and Tephrosia. Most rotenone used
at present comes from Lonchocarpus grown in Venezuela
and Peru and is often called cubè root. Extraction of the root
with organic solvents yields resins containing as much as
45 % total rotenoids; studies indicate that the major con-
stituents are rotenone (44 %) (Fig.  4) and deguelin (22 %)
(Fang and Casida 1998; Cabizza et al. 2004). Rotenone is
commonly sold as a dust containing 1 to 5 % active ingredi-
ents for home and garden use, but liquid formulations used
in organic agriculture can contain as much as 8 % rotenone
and 15 % total rotenoids. Rotenone is a mitochondrial poi-
son, which blocks the electron transport chain and prevents
energy production (Hollingworth et al. 1994). As a pesti-
cide it is considered a stomach poison because it must be
ingested to be effective. Pure rotenone is comparable to
DDT and other synthetic pesticides in terms of its acute tox-
icity to mammals (rat oral LD50 is 132 mg kg−1), although it
is much less toxic at the levels seen in formulated products.
Safety of rotenone has recently been called into question
because of (a) controversial reports that acute exposure in
rats produces brain lesions consistent with those observed
in humans and animals with Parkinson’s disease (Betarbet
et al. 2000), and (b) the persistence of rotenone on food
crops after treatment. A study of rotenone residues on olives
conducted in Italy determined that the halflife of rotenone
13
N. E. El-Wakeil
Fig. 4  Chemical structure of rotenone and Derris and Lonchocarpus
plants
is 4 days, and at harvest residue levels were above the tol-
erance limit (Cabras et al. 2002). Moreover, residues were
concentrated in oil obtained from the olives. As an agricul-
tural pesticide, use of rotenone is limited to organic food
production. In California, about 200kg are used annually,
mostly on lettuce and tomato crops (Isman 2006).
Mode of Action  Rotenone is a powerful inhibitor of cellular
respiration, the process that converts nutrient compounds
into energy at the cellular level. In insects rotenone exerts
its toxic effects primarily on nerve and muscle cells, causing
rapid cessation of feeding. Death occurs several hours to a
few days after exposure. Rotenone is extremely toxic to fish,
and is often used as a fish poison (piscicide) in water man-
agement programs. It is effectively synergized by piperonyl
butoxide (PBO) or MGK 264.
Sabadilla
Sabadilla is a botanical pesticide obtained from the seeds of
the South American lily Schoenocaulon officinale. In purity,
the active principles, cevadine-type alkaloids, are extremely
toxic to mammals (rat oral LD50 is ca. 13 mg kg−1), but com-
mercial preparations typically contain less than 1 % active
ingredient, providing a margin of safety (Fig. 5). These alka-
loids are remarkably similar to that of the pyrethrins, despite
their lack of structural similarity. Sabadilla is used primarily
by organic growers; in California about 100 kg is used annu-
ally, primarily on citrus crops and avocado (Isman 2006).
Botanical Pesticides and Their Mode of Action
Fig. 5  Cevadine-type alkaloids and Schoenocaulon officinale plant
Mode of Action  In insects, sabadilla’s toxic alkaloids affect
nerve cell membrane action, causing loss of nerve cell mem-
brane action, causing loss of nerve function, paralysis and
death. Sabadilla kills insects of some species immediately,
while others may survive in a state of paralysis for several
days before dying. Sabadilla is effectively synergized by
PBO or MGK 264.
Ryania
Another botanical in declining use is ryania, obtained by
grinding the wood of the Caribbean shrub Ryania speciosa
(Flacourtiaceae). The powdered wood contains < 1 % ryano-
dine (Fig. 6), an alkaloid that interferes with calcium release
in muscle tissue (National Research Council 2000). It is
used to a limited extent by organic apple growers for con-
trol of the codling moth, Cydia pomonella. More informa-
tion on sabadilla and ryania can be found in the two reviews
(Weinzierl 2000; Isman 2006).
Mode of Action Ryania is a slow-acting stomach poison.
Although it does not produce rapid knockdown paralysis,
Fig. 6  Chemical structure of ryanodine and Ryania speciosa plant
133
it does cause insects to stop feeding soon after ingesting
it. Little has been published concerning its exact mode of
action in insect systems. Ryania is effectively synergized by
PBO and is reported to be most effective in hot weather.
Pyrethrum
Pyrethrum is the powdered, dried flower head of the pyre-
thrum is daisy, Chrysanthemum cinerariaefolium (Astera-
ceae). Most of the world’s pyrethrum crop is grown in
Kenya. The term “pyrethrum” is the name for the crude
flower dust itself, and the term “pyrethrins” refers to the
six related insecticidal compounds that occur naturally in
the crude material, the pyrethrum flowers. The flowers are
ground to a powder and then extracted with hexane or a
similar nonpolar solvent; removal of the solvent yields an
orange-colored liquid that contains the active principles
(Casida and Quistad 1995; Glynne-Jones 2001). These are
three esters of chrysanthemic acid and three esters of pyre-
thric acid. Among the six esters, those incorporating the
alcohol pyrethrolone, namely pyrethrins I and II, are the
most abundant and account for most of the pesticidal activ-
ity (Fig.  7). Technical grade pyrethrum, the resin used in
formulating commercial pesticides, typically contains from
20 to 25 % pyrethrins (Casida and Quistad 1995; Isman
2006).
The insecticidal action of the pyrethrins is character-
ized by a rapid knockdown effect, particularly in flying
insects, and hyperactivity and convulsions in most insects.
These symptoms are a result of the neurotoxic action of
the pyrethrins, which block voltage-gated sodium channels
in nerve axons. As such, the mechanism of action of pyre-
thrins is qualitatively similar to that of DDT and many syn-
thetic organochlorine pesticides. In purity, pyrethrins are
moderately toxic to mammals (rat oral acute LD50 values
range from 350 to 500 mg kg−1), but technical grade pyre-
thrum is considerably less toxic (ca. 1,500 mg kg−1) (Casida
and Quistad 1995). Pyrethrins are especially labile in the
presence of the UV component of sunlight, a fact that has
greatly limited their use outdoors. A recent study indicated
that the half-lives of pyrethrins on field-grown tomato and
bell pepper fruits were 2 h or less (Antonious 2004). This
problem created the impetus for the development of syn-
thetic derivatives (“pyrethroids”) that are more stable in
sunlight. The modern pyrethroids, developed in the 1970s
and 1980s, have been highly successful and represent one
of the rare examples of synthetic pesticide chemistry based
on a natural product model. However, note that the modern
pyrethroids bear little structural resemblance to the natural
pyrethrins, and their molecular mechanism of action differs
as well. Pyrethrum use data from California (CDPR 2005)
in 2003 clearly demonstrate the dominance of this material
13
134
Fig. 7  Chemical structure of
different pyrethrum products and
Chrysanthemum flowers
among botanicals: Pyrethrum accounted for 74 % of all
botanicals used that year, but only 27 % of that amount
was used in agriculture (ca. 800 kg). Major uses of pyre-
thrum in California are for structural pest control, in public
health, and for treatment of animal premises. Pyrethrum
is the predominant botanical in use, perhaps accounting
for 80 % of the global botanical insecticide market (Isman
2005, 2006).
As I reported above, by 1860, the natural pesticides
were used in Europe and the United States (Casida 1973;
McLaughlin 1973). The organic solvent extract of the flow-
ers was tenned pyrethrum, and it possessed many favorable
properties. Its safety for mammals and rapid photo degrada-
tion led to many ses in situations that required low mamma-
lian toxicity and no residue problems (dairies, vegetables).
This combination of desirable characteristics fueled numer-
ous attempts to develop synthetic analogues that would be
more widely available and perhaps more potent; the syn-
thetic pyrethroids will be presented in the second genera-
tion products of the botanical pesticides.
Mode of Action  Pyrethrins exert their toxic effects by dis-
rupting the sodium and potassium ion exchange process in
insect nerve fibers and interrupting the normal transmission
of nerve impulses. Pyrethrins insecticides are extremely
fast acting and cause an immediate “knockdown” paralysis
in insects. Despite their rapid toxic action, however, many
insects are able to metabolize (break down) pyrethrins
quickly. After a brief period of paralysis, these insects may
recover rather than die. To prevent insects from metabo-
lizing pyrethrins and recovering from poisoning, most
products containing pyrethrins also contain the synergist,
piperonyl butoxide (PBO) (Rattan 2010).
13
N. E. El-Wakeil
Plant Essential Oils
Steam distillation of aromatic plants yields essential oils,
long used as fragrances and flavorings in the perfume and
food industries, respectively, and more recently for aro-
matherapy and as herbal medicines (Salama et al. 1970;
Sharaby 1988; Coppen 1995; Abd El-Aziz and Sharaby
1997; Abd El-Aziz and El-Hawary 1997; Buckle 2003).
Plant essential oils are produced commercially from several
botanical sources, many of which are members of the mint
family (Lamiaceae). The oils are generally composed of
complex mixtures of monoterpenes, biogenetically related
phenols, and sesquiterpenes. Examples include 1,8-cineole,
the major constituent of oils from rosemary (Rosmarinus
officinale) and eucalyptus (Eucalyptus globus); eugenol
from clove oil (Syzygium aromaticum); thymol from garden
thyme (Thymus vulgaris); and menthol from various species
of mint (Mentha species) (Isman 1999) (Fig. 8). A number
of the source plants have been traditionally used for pro-
tection of stored commodities, especially in the Mediterra-
nean region and in southern Asia, but interest in the oils was
renewed with emerging demonstration of their fumigant
and contact insecticidal activities to a wide range of pests
(Abdallah et al. 2004). The rapid action against some pests
is indicative of a neurotoxic mode of action, and there is evi-
dence for interference with the neuromodulator octopamine
(Enan 2001; Kostyukovsky et al. 2002) by some oils and
with GABA-gated chloride channels by others (Priestley
et al. 2003; El-Hosary 2011).
Some of the purified terpenoid constituents of essential
oils are moderately toxic to mammals, but, with few excep-
tions, other oils had molluscicidal effects for snails (Hussein
2005; Abdelgaleil 2010). The oils themselves or products
Botanical Pesticides and Their Mode of Action
Fig. 8  The chemical structures
of monoterpenes and Rosmarinus
and Thymus plants
based on oils are mostly nontoxic to mammals, birds, and
fish (Stroh et al. 1998; Isman 2000, 2006). However, as
broad-spectrum pesticides, both pollinators and natural
enemies are vulnerable to poisoning by products based
on essential oils. Owing to their volatility, essential oils
have limited persistence under field conditions; therefore,
although natural enemies are susceptible via direct contact,
predators and parasitoids reinvading a treated crop one or
more days after treatment are unlikely to be poisoned by
residue contact with pesticides (Dimetry et al. 1993; Ismail
et al. 2004; El-Sebai et al. 2005).
In the United States, commercial development of pesti-
cides based on plant essential oils has been greatly facilitated
by exemption from registration for certain oils commonly
used in processed foods and beverages (Quarles 1996).
This opportunity has spurred the development of essential
oil-based insecticides, fungicides, and herbicides for agri-
cultural and industrial applications and for the consumer
market, using rosemary oil, clove oil, and thyme oil as
active ingredients. Interest in these products has been con-
siderable, particularly for control of greenhouse pests and
diseases and for control of domestic and veterinary pests,
with several private companies (e. g. EcoSMART Technolo-
gies, Inc., United States) moving toward or into the market-
place (Khater 2012). Another factor favoring development
of botanical pesticides based on plant essential oils is the
relatively low cost of the active ingredients, a result of their
135
extensive worldwide use as fragrances and flavorings. In
contrast, pyrethrum and neem are used primarily for pesti-
cide production (Khater 2012). On the other hand, plant oils
have harmless effects on the predacious mites as reported
by Amer and Momen (2002, 2005), who studied effects of
some essential oils on Amblyseius swirskii.
Mode of Action  Contact and fumigant insecticidal actions
of plant essential oils have been well demonstrated against
stored product pests (Acanthoscelides obtectus) (Regnault-
Roger et al. 1993). Knockdown activity and lethal toxicity
via contact has been demonstrated in the American cock-
roach (Periplaneta americana) (Ngoh et al. 1998), the
German cockroach (Blattella germanica) and the housefly
(Musca domestica) (Coats et al. 1991; Rice and Coats 1994).
These studies latter pointed to an obvious neurotoxic site-
of-action. Certain essential oil monoterpenes are competi-
tive inhibitors of acetylcholinesterase in vitro (Grundy and
Still 1985; Miyazawa et al. 1997), but this action may not be
correlated with toxicity to insects in vivo. However, system-
atic investigation of the antifungal activities of essential oils
and their constituents predate those of the pesticidal proper-
ties (Kurita et al. 1981).
El-Hawary and Sammour (2006) studied the bioactiv-
ity and mechanism of action of some wild plant extracts on
Aphis craccivora. As well Adel et al. (2010) have several
studies on physiological, biochemical and histopathological
13
136 N. E. El-Wakeil

effects of Artemisia monosperma against the cotton leaf-

worm, Spodoptera littoralis in Egypt. Sammour et al. (2011)
had comparative studies on the efficacy of neemix and basil
oil formulations on the cowpea aphid Aphis craccivora in
laboratory in Egypt. On the other side, Dimetry and El-
Hawary (1997) conducted some experiments to enhance the
synergistic effects of some additives on the biological activ-
ity and toxicity of Nem-based formulations against cowpea
aphids.
The modes of action of limonene and linalool in insects
are not fully understood. Limonene is thought to cause
an increase in the spontaneous activity of sensory nerves.
This heightened activity sends spurious information to
motor nerves and results in twitching, lack of coordination,
and convulsions. The central nervous system may also be
affected, resulting in additional stimulation of motor nerves.
Massive over stimulation of motor nerves leads to rapid
knockdown paralysis. Adult fleas and other insects may
recover from knockdown, however, unless limonene is syn-
ergized by PBO. Linalool is also synergized by PBO. Little
has been published regarding the mode of action of linalool
in insects (Abdelgaleil and El-Aswad 2005; Abdelgaleil
et al. 2008; Rattan 2010). Fig. 9 Different products of synthetic pyrethroids and their LD50
values
The Second Generation
theses and purifications now can generate the most potent
Synthetic Pyrethroids individual stereoisomers for production.
Although the majority of studies have demonstrated
The earliest synthetic pyrethroids retained most of the ben- favorable selectivity ratios for synthetic pyrethroids, a few
eficial proper ties. Allethrin varied from pyrethrin I only in effects have been reported in mammals. A transitory tin-
the three carbon length of the side chain on the cyclopen- gling of the skin can occur during occupational exposures
tenone ring. Replacement of that photolabile ring with the (Cagen et al. 1984). Permethrin caused increases in tumors
furan ring and the photo stable benzene ring generated pyre- in mice, but they were benign tumors. The EPA does not
throids (e. g. resmethrin) with slightly more residual time fol- consider this chemical to present a significant health hazard
lowing their application (Davies 1985). In the 1970s, great to humans. A metabolite formed from cholesterol and the
strides were made in the United Kingdom and Japan toward chlorophenyl isovaleric acid portion of the R, S-isomer of
enhancing insecticidal potency, increasing photostability, fen valerate reportedly caused a liver granuloma condition
and improving the chemistry to achieve a host of commer- in rats (Okuna et al. 1986).
cially viable synthetic pyrethroid pesticides. The evolution From an environmental perspective, the pyrethroids
of this class of compounds has since yielded a vast array of represent improvements in many ways over the previously
molecules, some with greater lipophilicity, extremely low used classes. The widely used pyrethoids seem to pres-
water solubility, and considerable persistence because of the ent no problem to birds or other wildlife. Bees, important
use of single or multiple halogen atoms (Coats 1990, 1994). non-target arthropods, are only affected if sprayed directly;
Mammalian and avian studies on the toxicity of the syn- otherwise, the pyrethroids effectively repel them from for-
thetic pyrethroids have demonstrated, in general, retention aging in fields that have been sprayed. Aquatic arthropods
of safety for warm blooded species. The LD50 S of many are generally very susceptible to these compounds, but the
of the photostable analogues were more than 100 or even bioavailability of them depends on suspended solids in the
1,000 mg/kg in mammals, and were even greater in birds. water (Coats et al. 1989).
However, some of the most powerful compounds, e.g.
lambda cyhalothrin, deltamethrin, tefluthrin and flucythri- Mode of Action  Synthetic pyrethroids are generally recog-
nate (Bradbury and Coats 1989) as shown in Fig  9, have nized as neurotoxicants that act directly on excitable mem-
different LD50 values in rats and mice. Stereoselective syn- branes. These compounds induce intense repetitive activity
in sense organs and in myelinated nerve fibers. In the lat-

13
Botanical Pesticides and Their Mode of Action
eral-line sense organ this repetitive activity increases with
cooling, a phenomenon that may be related to the negative
temperature coefficient of toxicity of pyrethroids in insects.
Pyrethroids are also known to cause prolongation of the
sodium current together with repetitive activity in nerve
fibers of invertebrates (Henk et al. 1982). It has been sug-
gested that the sodium channel in the nerve membrane is the
major target site of pyrethroids. Other results showed that
these compounds modify sodium channel gating in a strik-
ingly similar way and reduce selectively the rate of closing
of the activation gate (Narahashi 1976).
Neem Products (Azadirachtin)
Two types of botanical pesticides can be obtained from
seeds of the Indian neem tree, Azadirachta indica (Melia-
ceae) (Schmutterer 1990, 2002). Neem oil, obtained by
cold-pressing seeds, can be effective against soft-bodied
insects and mites but is also useful in the management of
phytopathogens. Apart from the physical effects of neem oil
on pests and fungi, disulfides in the oil likely contribute to
the bioactivity of this material (Dimetry et al. 2010; Dim-
etry 2012). More highly valued than neem oil are medium-
polarity extracts of the seed residue after removal of the oil,
as these extracts contain the complex triterpene azadirachtin
(Fig. 10). Neem seeds actually contain more than a dozen
azadirachtin analogs, but the major form is azadirachtin
and the remaining minor analogs likely contribute little to
overall efficacy of the extract. Seed extracts include con-
siderable quantities of other triterpenoids, notably salan-
nin, nimbin, and derivatives thereof. The role of these other
natural substances has been controversial (El-Sayed 1982–
1983a, b), but most evidence points to azadirachtin as the
most important active principle (Isman et al. 1996). Neem
seeds typically contain 0.2–0.6 % azadirachtin by weight, so
solvent partitions or other chemical processes are required
to concentrate this active ingredient to level 10–50 % seen in
the technical grade material used to produce their products
(Sallena 1989; Schmutterer 1990).
Azadirachtin has two profound effects on insects. At
the physiological level, azadirachtin blocks the synthesis
Fig. 10  Active constituents of neem (Azadirachtin) and neem tree
137
and release of molting hormones (ecdysteroids) from the
prothoracic gland, leading to incomplete ecdysis in imma-
ture insects. In adult female insects, a similar mechanism
of action leads to sterility. In addition, azadirachtin is a
potent antifeedant to many insects. The discovery of neem
by western science is attributed to Schmutterer (1990), who
observed that swarming desert locusts in Sudan defoliated
almost all local flora except for some introduced neem trees
(National Research Council 1992). Indeed, azadirachtin was
first isolated based on its exceptional antifeedant activity in
the desert locust, and this substance remains the most potent
locust antifeedant discovered to date. Unlike pyrethrins,
azadirachtin has defied total synthesis to this point. In USA,
Neem rapidly became the modern paradigm for develop-
ment of botanical pesticides (Weinzierl 2000).
Enthusiasm for neem was fostered by several interna-
tional conferences in the 1980s and 1990s, and several vol-
umes dedicated to neem and neem insecticides have been
published (Jacobson 1989; National Research Council
1992; Schmutterer 2002). Unfortunately, neem’s commer-
cial success has fallen well short of the initial hype fueled
by the explosive scientific literature surrounding it. In part
this is due to the relatively high cost of the refined product
(Isman 2004) and the relatively slow action on pest insects.
Nonetheless, several azadirachtin based pesticides are sold
in the United States and at least two such products in the
European Union. In California, azadirachtin-based insecti-
cides constituted about one third of the botanicals used in
agriculture in 2003 (ca. 600  kg). In practice, reliable effi-
cacy is linked to the physiological action of azadirachtin as
an insect growth regulator; the antifeedant effect, which is
spectacular in the desert locust, is highly variable among
pest species, and even those species initially deterred are
often capable of rapid desensitization to azadirachtin (Bom-
ford and Isman 1996). What is clear is that azadirachtin
is considered nontoxic to mammals (rat oral acute LD50 is
> 5,000  mg kg−1), fish (Wan et al. 1996), and pollinators
(Naumann and Isman 1996). The influence of azadirachtin
on natural enemies is highly variable (Lowery and Isman
1995; Spollen and Isman 1996). Like the pyrethrins, aza-
dirachtin is rapidly degraded by sunlight. For example,
on olives growing in Italy, azadirachtin has a half-life of
approximately 20 h (Caboni et al. 2002). Azadirachtin has
systemic action in certain crop plants, greatly enhancing its
efficacy and field persistence (Schmutterer 2002). On the
other hand, El-Wakeil et al. (2006, 2013) mentioned further
that NeemAzal-T/S had reduced the parasitism rates, to 40,
55.4, 77.8 and 81.3 % (at 2, 1, 0.5, 0.25 % cons.), respec-
tively, compared to 93.3 % on control plants.
13
138
Fig. 11 Active constituents of 1-cinnamoyl-3-feruoyl-11-hydro­
- marily as a feeding deterrent but can also serve as a syner-
xy­melia­carpin
Melia Extracts
The remarkable bioactivity of azadirachtin from the Indian
neem tree (Azadirachta indica) led to the search for natural
pesticides in the most closely related genus, Melia. Seeds
from the chinaberry tree, Melia azedarach, contain a num-
ber of triterpenoids, the meliacarpins (Fig. 11), that are simi-
lar but not identical to the azadirachtins, and these also have
insect growth regulating bioactivities (Kraus 2002). But in
spite of the abundance of chinaberry trees in Asia and other
tropical and subtropical areas to which they were introduced,
development of commercial pesticides has not paralleled
that of the neem pesticides. The main reason is the pres-
ence, in chinaberry seeds, of additional triterpenoids, the
meliatoxins, that have demonstrated toxicity to mammals
(Ascher et al. 2002). However the chemistry of chinaberry
varies considerably across its natural and introduced range,
and seeds of M. azedarach growing in Argentina lack melia-
toxins but produce triterpenoids (most notably meliartenin)
that are strong feeding deterrents to insect pests and could
prove useful for pest management (Carpinella et al. 2003).
Similar results have been obtained from South Africa using
aqueous extracts of chinaberry leaves, presumably lacking
meliatoxins but efficacious against the diamondback moth
(Charleston 2004).
In the early 1990s a botanical insecticide produced in
China was based on an extract of bark of Melia toosen-
dan, a tree considered by most taxonomists to be synony-
mous with M. azedarach. The extract contains a number of
triterpenoids based on toosendanin (Fig.  12), a substance
Fig. 12 Active constituents
of some botanical insecticides
(toosendanin)
13
N. E. El-Wakeil
Fig. 13  Active constituents
of some botanical insecticides
(volkensin)
reported to be a stomach poison for chewing insects (Chiu
1988). Later studies suggest that this substance acts pri-
gist for conventional insecticides (Chen et al. 1995; Feng
et al. 1995). Although relatively nontoxic to mammals, it
is unclear whether this material remains in production or
whether it is sufficiently efficacious as a stand-alone crop
protectant.
When M. toosendan came under scientific scrutiny,
investigation of the east African M. volkensii demonstrated
bioactivity in insects from seed extracts of this species. The
active principles in M. volkensii include the triterpenoid
salannin, also a major constituent of neem seed extracts,
and some novel triterpenoids such as volkensin (Fig.  13).
Collectively these function as feeding deterrents and
stomach poisons with moderate efficacy against chewing
insects and as a mosquito larvicide. Although a standard-
ized seed extract has been made in quantities sufficient for
research (Rembold and Mwangi 2002), commercial pro-
duction appears unlikely owing to a lack of infrastructure
for harvesting seeds in addition to regulatory impediments
(Weinzierl 2000; Isman 2006).
Mode of Action Neem products are complex mixtures
of biologically active materials, and they are difficult to
pinpoint the exact modes of action of various extracts or
preparations. In insects, neem is most active as a feeding
deterrent, but in various forms it also serves as a repellent,
growth regulator, oviposition (egg deposition) suppressant,
sterilant, or toxin. As a repellent, neem prevents insects from
initiating feeding. As a feeding deterrent, it causes insects to
stop feeding. As a feeding, either immediately after the first
“taste” (due to the presence of deterrent taste factors) (Sal-
ama and Sharaby 1988), or at some point soon after ingest-
ing the food (due to secondary hormonal or physiological
effects of the deterrent substance). As a growth regulator,
neem is thought to disrupt normal development interfering
with chitin synthesis. Susceptibility to the various effects of
neem differs by species.
Potential new Botanicals
Annonaceous Acetogenins
Botanical pesticides have been traditionally prepared from
the seeds of tropical Annona species, members of the cus-
Botanical Pesticides and Their Mode of Action
Fig. 14  Active constituents of
Annona species (asimicin) and
Annona squamosa plant
tard apple family (Annonaceae). These include the sweetsop
(A. squamosa) and soursop (A. muricata), important sources
of fruit juices in Southeast Asia. Detailed investigations in
the 1980s led to the isolation of a number of long-chain
fatty acid derivatives, termed acetogenins, responsible for
the insecticidal bioactivity. The major acetogenin obtained
from seeds of A. squamosa is annonin I, or squamocin, and
a similar compound, asimicin (Fig. 14), was isolated from
the bark of the American pawpaw tree, Asimina triloba
(McLaughlin et al. 1997; Johnson et al. 2000). Mikolajc-
zak et al. (1988) hold a US patent on insecticides ased on
acetogenins from A. triloba; Bayer AG (Germany) holds a
similar patent based on Annona acetogenins for Moeschler
et al. (1987). These compounds are slow acting stomach
poisons, particularly effective against chewing insects such
as lepidopterans and the Colorado potato beetle (Leptino-
tarsa decemlineata).
Further investigations revealed that the acetogenins have
a mode of action identical to that of rotenone, i. e., they
block energy production in mitochondria in both insects and
mammals (Londershausen et al. 1991). In purity certain ace-
togenins are toxic to mammals (LD50 is < 20 mg kg−1), an
impediment to regulatory approval, even though standard-
ized extracts from Annona seeds and Asimina bark are much
less toxic.
Johnson et al. (2000) have isolated hundreds of aceto-
genins from the Annonaceae, and for many their potential
as anticancer agents exceeds their value as pesticides. In
spite of the patents based on the insecticidal activities of
these materials, no commercial development has proceeded
with the exception of a head lice shampoo that contains a
standardized pawpaw extract among its active ingredients
Fig. 15  Chemical structure of
sucrose esters obtained from
wild tobacco (N. gossei)
139
(Nature’s Sunshine Products, Inc., United States). Annona
seed extracts may prove more useful in tropical countries
where the fruits are commonly consumed or used to pro-
duce fruit juice, in which case the seeds are a waste prod-
uct. For example, Leatemia and Isman (2004a, b) recently
demonstrated that crude ethanolic extracts or even aqueous
extracts of seeds from A. squamosa collected at several sites
in eastern Indonesia are effective against the diamondback
moth (Plutella xylostella) (Isman 2006).
The Insecticidal Mode of Action of Asimicin It reduced
the rate of oxygen consumption by fourth instar Ostrinia
nubilalis as measured with a constant volume manometer.
Further examination of the respiratory effect of asimicin
was carried out on mitochondria isolated from the midguts
of fifth instar O. nubilalis and in which O2 was measured
polarographically. The results of these studies indicate a
significant reduction in state 3 respiration using malate and
pyruvate as substrate, caused by asimicin (concentration
for 50 % inhibition = 0.55  nmol/mg protein) (Lewis et al.
1993).
Sucrose Esters
In the early 1990s scientists at the US Department of Agri-
culture discovered that sugar esters naturally occurring in
the foliage of wild tobacco (Nicotiana gossei) were pesti-
cidal to certain soft-bodied insects and mites. Although pat-
ented (Pittarelli et al. 1993), extraction of these substances
on a commercial scale from plant biomass proved impracti-
cal, leading to the development of sucrose esters manufac-
tured from sugar and fatty acids obtained from vegetable
13
140 N. E. El-Wakeil

Table 6  Mechanism of action of pesticides of plant origin (modified from Rattan 2010)
System Mechanism of action Compound Plant source References
Cholinergic system Inhibition of acetylecholinestrase Essential oils Azadirachtina indica, Mentha Grundy and Still (1985);
(AChE) spp., Lavendula spp. Ryan and Byrne (1988);
Miyazawa et al. (1997);
Keane and Ryan (1999)
Cholinergic acetylcholine nicotinic Nicotine Nicotiana spp., Haloxylon sali- Richards and Cutkomp
receptor Agonist/antagonist cornicum, Stemona Japonicum (1945); Kukel and Jen-
nings (1994)
GABA system GABA-gated chloride channel Thymol, Thymus vulgaris Ratra and Casida (2001);
Silphinenes Priestley et al. (2003);
Bloomquist et al. (2008)
Mitochondrial Sodium and potassium ion exchange Pyrethrin Crysanthemum cinerariaefolium Casida (1973)
system disruption
Inhibitor of cellular Rotenone Lonchocarpus spp. Yamamoto and Kuroka-
respiration(mitochondrial complex I wa (1970); Ware (1988);
electron transport inhibitor (METI) Khambay et al. (2003)
Affect calcium channels Ryanodine Ryania spp. Copping and Menn
(2000)
Affect nerve cell membrane action Sabadilla Schoenocaulon officinale Bloomquist (1996, 2003)
Octopaminergic Octopaminergic receptors Essential oils Cedrus spp., Pinus spp., Citro- Nathanson et al. (1993);
system nella spp., Eucalyptus spp. Kostyukovsky et al.
(2002); Enan (2005a)
Block octopamine receptors by Thymol Thymus vulgaris Enan (2005a, b)
working through tyramine receptors
cascade
Miscellaneous Hormonal balance disruption Azadirachtin Azadiractina indica Copping and Menn
(2000)

oils. AVA Chemical Ventures (United States) has patented
and registered an insecticide/miticide based on C8 and C10
fatty acid mono-, di-, and triesters of sucrose octanoate and
sucrose dioctanoate (Farone et al. 2002) (Fig. 15). The prod-
uct, first registered in 2002, contains 40 % active ingredient.
The major isomers are composed of an acetyl group (R3)
and three 3-methylvaleryl groups (R1, R2, R4) esterified to
three hydroxyl groups of sucrose. Extensive studies have
shown that the glandular trichomes of wild tobacco contain
complexes of either glucose or sucrose esters (sometimes
both). These leaf surface lipids have biological activity
against insects and microorganisms. Compounds of this
type have been synthesized in a search for a new class of
bioinsecticides (Matsuzaki et al. 1991).
Mode of Action  Functionally, this product appears to dif-
fer little from the pesticidal soaps based on fatty acid salts
developed in the 1980s, particularly potassium oleate. This
product is contact pesticide that kills small insects and mites
through suffocation (by blocking the spiracles) or disrup-
tion of cuticular waxes and membranes in the integument
as recorded by Buta et al. (1993), leading to desiccation
(Isman 2006). Although useful in garden products and in
greenhouse production, the utility of these materials for
agriculture remains to be seen.
Summary of Different Mode of Actions
Botanical pesticides can be grouped according to their mode
of action or the way a pesticide destroys or controls the tar-
get pest. This is also referred to the primary site of action.
For example, one insecticide may affect insect nerves,
while another may affect moulting. There are many mode
of actions for various botanical pesticides shown in Table 6.
Efficiency of Botanical Pesticides on Pests
Antifeedants
The possibility of using nontoxic deterrents and repellents
as crop protectants is intuitively attractive. The concept
of using insect antifeedants (= feeding deterrents) gained
strength in the 1970s and 1980s with the demonstration of
the potent feeding deterrent effect of azadirachtin and neem
seed extracts to a large number of pest species. Indeed, con-
siderable literature, scientific and otherwise, touts neem as
a successful demonstration of the antifeedant concept. In
reality, it is the physiological actions of azadirachtin that
appear most reliably linked to field efficacy of neem pesti-
cides (Immaraju 1998); although purely behavioral effects
cannot be ruled out, there is hardly any irrefutable evidence

13
Botanical Pesticides and Their Mode of Action
or documentation of field efficacy based on the antifeedant
effects of neem alone. The antifeedant index (AFI) is calcu-
lated from the formula:
AFI = [ (C − T) (C + T)] × 100 (in %)
Where:
C Consumption of control,
T Consumption of treated disks (Pavela et al. 2008)
As an academic exercise, the discovery and demonstration
of plant natural products as insect antifeedants has been
unquestionably successful. In addition to the neem triter-
penoids, extensive work has been performed on clerodane
diterpenes from the Lamiaceae (Klein Gebbinck et al. 2002)
and sesquiterpene lactones from the Asteraceae (Gonzalez-
Coloma et al. 2002). On the other hand, not a single crop
protection product based unequivocally on feeding or ovi-
position deterrence has been commercialized. Two main
problems face the use of antifeedants in agriculture (Isman
2002). The first is interspecific variation in response even
closely related species can differ dramatically in behavioral
responses to a substance limiting the range of pests affected
by a particular antifeedant (Isman 1993). Some substances
that deter feeding by one pest can even serve as attractants
or stimulants for other pests. The second is the behavioral
plasticity in insects pests can rapidly habituate to feeding
deterrents, rendering them ineffective in a matter of hours.
This has been recently demonstrated not only for pure sub-
stances like azadirachtin (Bomford and Isman 1996), but
also for complex mixtures (plant extracts) (Akhtar et al.
2003). Whereas a highly mobile insect may leave a plant
upon first encountering an antifeedant, a less mobile one
(larva) may remain on the plant long enough for the deter-
rent response to wane. Such behavioral changes are impor-
tant in light of the observation that some plant substances
are initially feeding deterrents but lack toxicity if ingested.
Azadirachtin is an exception to this rule, as ingestion leads
to deleterious physiological consequences, but other com-
pounds with demonstrated antifeedant effects lack toxicity
when administered topically (Bernays 1990, 1991).
Repellents
For many chemists, an effective alternative to DEET (N,
N-diethyl-m-toluamide) for personal protection against
mosquitoes and biting flies is the holy grail. In spite of five
decades of research, no chemical has been found that pro-
vides the degree of protection against biting mosquitoes or
persistence on human skin afforded by DEET (Peterson and
Coats 2001). Concerns with the safety of DEET, especially
to children, have resulted in the introduction of several plant
141
oils as natural alternatives. Some personal repellents in the
US marketplace contain oils of citronella, eucalyptus, or
cedar wood as active ingredients; 2-phenethylpropionate, a
constituent of peanut oil, and p-menthane-3,8-diol (obtained
from a particular species of mint) (Fig. 8) are also used in
consumer products. All of these materials can provide some
protection, but the duration of their effect can be limited
(often < 1 h) (Fradin and Day 2002). In tropical areas where
mosquito-borne disease is a threat (e.g., yellow fever, den-
gue, malaria), DEET probably remains the only reliable
repellent. Oil of citronella or the constituent citronellal
(Fig. 8) is also used in mosquito coils to repel mosquitoes
from outdoor areas. Several veterinary products for flea and
tick control on domestic pets contain d-limonene (from cit-
rus peels; Fig.  8) as the active ingredient. Other uses for
repellents under investigation include perimeter treatments
of buildings to exclude termites and the use of essential
oils to repel cockroaches from kitchens and flies from dairy
barns (Maistrello et al. 2004). Another important use of
plant essential oil constituents is in fumigation of beehives
to manage economically important honey bee parasites, the
Varroa mite (Varroa jacobsoni). In USA, menthol is widely
used for this purpose (Delaplane 1992) and in Europe thy-
mol is most used (Floris et al. 2004). Abdel-Khalek et al.
(2010) studied repellency and toxicity of extract from Fran-
coeria crispa to Eutetranychus orientalis.
Toxicity of Botanical Pesticides
The botanical pesticides are biodegradable and harmless
to the environment. Furthermore, unlike conventional pes-
ticides that are based on a single active ingredient, plant-
derived pesticides comprise an array of chemical compounds
which act concertedly on both behavioral and physiological
processes. One plant species may possess substances with
a wide range of activities; for example, extracts from the
neem tree Azadirachta indica are antifeedant, antioviposi-
tion, repellent and growth-regulating. In contrast, the toxic-
ity of conventional synthetic insecticides is mainly restricted
to neuro-muscular function (Ware 1983). Conventional
synthetic insecticides require special safety procedures and
equipment during production and application because of the
exposure risks for humans, the environment (Schmutterer
1990; Childs et al. 2001).
Summary of Botanicals Used to Control Different
Insect Pests
Summary of different botanical pesticides and their effects
on various insect pests is appeared in Table 7.
13
142 N. E. El-Wakeil

Table 7  Botanical pesticides used to control different insect pests

Botanical pesticides Insect pests References
Nicotine Aphids, thrips, caterpillars Casanova et al. (2002)
Rotenone Bugs, aphids, potato beetles, spider mites, carpenter ants Cabras et al. (2002); Cabizza et al. (2004)
Ryania Codling moths, potato aphids, onion thrips, corn earworms, silkworms Copping and Menn (2000); Isman (2006)
Sabadilla Grasshoppers, codling moths, armyworms, aphids, cabbage loopers, Bloomquist (1996, 2003)
squash bugs
Pyrethrum Caterpillars, aphids, leafhoppers, spider mites, bugs, cabbage worms, Casida (1973); Glynne-Jones (2001)
beetles
Essential oils Caterpillars, cabbage worms, aphids, white flies Land sanils Enan (2005a, b); Abdelgaleil (2010)
Neem products Armyworms, cutworms, stemborers, bollworms, leaf miners, caterpil- Dimetry et al. (1993, 2010)
lars, aphids, whiteflies, leafhoppers, psyllids, scales, mites and thrips
Synthetic pyrethroids Caterpillars, aphids, thrips Coats (1990); Sallam et al. (2009)

Vision and Expectation
Drawbacks and Barriers to Commercialization
Isman (1997) identified three main barriers to commer-
cialization for botanical insecticides: sustainability of the
botanical resource, standardization of chemically complex
extracts, and regulatory approval. For each of these there
are also important cost considerations. Other drawbacks or
limitations are the slow action of many botanicals-growers
must gain confidence in insecticides that do not produce
an immediate “knockdown” effect and the lack of residual
action for most botanicals.
Sustainability
To produce a botanical insecticide on a commercial scale,
the source plant biomass must be obtainable on an agricul-
tural scale and preferably not on a seasonal basis. Unless the
plant in question is extremely abundant in nature, or already
grown for another purpose (e. g., sweetsop, Annona squa-
mosa, grown for its edible fruit; rosemary, Rosmarinus offi-
cinale, as a flavoring), it must be amenable to cultivation.
Pyrethrum and neem meet this criterion; the latter has been
extensively introduced into Africa, Australia, and Latin
America, more so as a shade tree, windbreak, or source of
firewood than for its yield of natural medicines or insecti-
cides. Research aimed at producing azadirachtin from neem
tissue culture provided proof of concept, but economic fea-
sibility has yet to be attained (Allan et al. 2002).
In the not-too-distant future it may be possible to produce
botanical insecticides by “phytopharming,” i. e., through
genetic engineering of an existing field crop to produce
high-value natural products originally isolated from a dif-
ferent botanical source. But as progress in plant biotechnol-
ogy continues at a rapid pace, it may prove just as easy to
modify the plants we wish to protect from pests directly,
such that they produce the natural product protectant consti-
tutively, alleviating the need to obtain the desired botanical
product through extraction, formulate it, and then apply it
to the crop we wish to protect (Isman 2006). These sorts of
technological advancements seem far more likely now than
they did even a decade ago; however, the cost of these tech-
nologies will dictate that the traditional means of obtaining
botanical insecticides, and indeed their minor uses (on small
acreage specialty crops) or uses in developing countries on
lesser value crops will continue for many years to come. For
example, neem seed oil had a long history of use in India for
the production of soaps and low grade industrial oil. When
extraction companies began purchasing neem seeds in bulk
to produce insecticides, the price of seeds increased 10-fold.
In contrast, certain plant essential oils have numerous uses
as fragrances and flavorings, and the massive volumes
required to satisfy these industries maintain low prices that
make their use as insecticides attractive (Weinzierl 2000;
Isman 2006).
Standardization of Botanical Extracts
An often cited drawback to the adoption of botanical insec-
ticides by growers is the variation in performance of a par-
ticular product, even when prepared by the same process.
Natural variation in the chemistry of a plant-based commod-
ity should come as no surprise to anyone who enjoys coffee,
tea, wine, or chocolate. The investigation of seed extracts
from sweetsop (A. squamosa) collected in Indonesia dem-
onstrated both geographical and annual variation in their
insecticidal potency (Leatemia and Isman 2004b). For a
botanical insecticide to provide a reliable level of efficacy to
the user there must be some degree of chemical standardiza-
tion, presumably based on the putative active ingredient(s).
This has certainly been achieved with more refined products
based on pyrethrum, neem, and rotenone, but crude prepara-
tions often contain low concentrations of active ingredients
without adequate quantitation. To achieve standardization,
the producer must have an analytical method and the equip-
ment necessary for analysis and may need to mix or blend
extracts from different sources, which requires storage facil-
ities and is partially dependent on the inherent stability of

13
Botanical Pesticides and Their Mode of Action
the active principles in the source plant material or extracts
thereof held in storage (Atkinson et al. 2004).
Regulatory Approval
Regulatory approval remains the most formidable barrier
to the commercialization of new botanical insecticides. In
many jurisdictions, no distinction is made between synthetic
pesticides and biopesticides, including botanicals. Simply
put, the market for botanicals in industrialized countries
based mostly on uses in greenhouse production and organic
agriculture is too small to generate sufficient profits to offset
multimillion dollar regulatory costs. Unfortunately, this sit-
uation may prevent many “green” pesticides from reaching
the marketplace in countries where the demand is greatest.
I am not making the case that botanicals should be exempt
from all regulatory scrutiny; as discussed above, nicotine
is as toxic and hazardous as many synthetic pesticides, and
strychnine, still used for rodent and insect control in some
regions, is responsible for some human poisonings (Katz
et al. 1996). Natural products can pose risks, and safety
cannot be assumed (Coats 1994; Trumble 2002). But most
of the botanicals discussed in this review are characterized
by low mammalian toxicity, reduced effects on nontarget
organisms, and minimal environmental persistence.
As noted, several plant essential oils and their constituents
are exempt from registration in the United States, attributed
to their long use history as food and beverage flavorings or
as culinary spices. This exemption has facilitated the rapid
development and commercialization of pesticides based on
these materials as active ingredients (Isman 2000). Although
other jurisdictions have yet to follow the lead of the United
States in this regard, there are proposals in some Asian coun-
tries to exempt some types of pesticides from registration
for specific uses in public health, for example, in head lice
preparations or for cockroach and fly suppression. It seems
that regulatory agencies continue to focus their efforts on
protecting the general public from miniscule traces of pesti-
cides in the food supply rather than focusing on the safety of
applicators and farm workers, for whom, arguably, the more
demonstrable hazards occur (Isman 2006).
Advantages and Disadvantages of Botanical Pesticides
Advantages
1. Plants producing the above mentioned compounds are
known by the farmer because most of the time they
grow in the same general area.
2. Often these plants also have other uses like household in-
sect repellents or are plants with medicinal applications.
143
3. The rapid degradation of the active product may be con-
venient as it reduces the risk of residues on food.
4. Some of these products may be used shortly before
harvesting.
5. Many of these products act very quickly inhibiting in-
sect feeding even though long term they do (will?) not
cause insect death.
6. Since most of these products have a stomach action and
are rapidly decomposed they may be more selective to
insect pests and less aggressive with natural enemies.
7. Most of these compounds are not phytotoxic.
8. Resistance to these compounds is not developed as
quickly as with synthetic pesticides.
Disadvantages
1. Most of these products are not truly pesticides since
many are merely insect deterrents and their effect is
slow.
2. They are rapidly degraded by UV light so that their re-
sidual action is short.
3. Not all plant pesticides are less toxic to other animals
than the synthetic ones.
4. They are not necessarily available season long.
5. Most of them have no established residue tolerances.
6. There are no legal registrations establishing their use.
7. Not all recommendations followed by growers have
been scientifically verified. 
Botanical Pesticides: for Richer and Poorer Countries
The botanical pesticides should prove most beneficial in two
contrasting applications (developed and developing coun-
tries), one for affluent consumers and the other for farmers
in developing countries (Isman 2008). Apart from economic
considerations and potential health benefits, another impor-
tant force driving botanicals into these disparate markets is
the regulatory environment. Regulatory approval in indus-
trial nations has become so costly and time consuming
that only multinational agrochemical companies have the
resources to satisfy regulatory requirements for their pesti-
cides to see widespread agricultural use (Thacker 2002). As
a consequence, botanicals will only see use on food crops
in niche markets such as certified organic production or in
controlled environments. On the other hand, regulation, or
at least enforcement of pesticide regulations, in developing
counties is generally more relaxed, particularly for domes-
tic food production. While it might appear irresponsible to
advocate the use of unregistered crop protectants for which
health hazards have not been rigorously established, there
is reasonable evidence to suggest that, with few exceptions,
crude botanical preparations at worst pose no greater risk to
human health than conventional pesticides and indeed are
13
144
probably of substantially lower risk. Moreover, indigenous
knowledge often extends beyond the potential efficacy of
endemic plants as crop protectants to include their toxicity
to users. This may well represent a case where our highly
technological society can learn that long-established agro-
ecological practices have a role to play in food production
in the twenty-first century.
Role of Botanical Pesticides in the Future
What role can botanical pesticides play in crop protection
and for other uses in the near future? In industrialized coun-
tries it is hard to imagine botanicals playing a greater role
than at present, except in organic food production. Organic
production is estimated to be growing by 8 to 15 % per
annum in Europe and in North America (National Research
Council 2000), and it is in those marketplaces that botani-
cals face the fewest competitors. Even there, however,
microbial insecticides and spinosad have proven efficacious
and cost-effective. Rather than considered as stand-alone
products, botanicals might be better placed as products in
crop protectant rotations, especially in light of the docu-
mented resistance of the diamondback moth to Bacillus
thuringiensis and spinosad due to overuse (Tang et al. 1997;
Zhao et al. 2002). In conventional agriculture, botanicals
face tremendous competition from the newest generation of
“reduced risk” synthetic insecticides such as the neonicoti-
noids. Between 1998 and 2003, use of reduced risk pesti-
cides in California increased more than threefold (from 138
to 483  t), whereas biopesticide use declined (from 652 to
472 t) (CDPR 2005).
Botanicals, constituting less than 1 % of biopesticide use
in California (CDPR 2005), are also in decline. Overall, it
is hard not to conclude that the best role for botanicals in
the wealthier countries is in public health (mosquito, cock-
roach abatement) and for consumer (home and garden) use.
The real benefits of botanical pesticides can be best real-
ized in developing countries, where farmers may not be
able to afford synthetic pesticides and the traditional use of
plants and plant derivatives for protection of stored prod-
ucts is long established. Even where synthetic pesticides are
affordable to growers (e.g., through government subsidies),
limited literacy and a lack of protective equipment result in
thousands of accidental poisonings annually (Forget et al.
1993; Isman 2000, 2006).
More attention has been paid to traditional plants used in
West Africa for postharvest protection against insects (Bel-
main and Stevenson 2001; Boeke et al. 2004a, b). Some of
the more efficacious plants used have well-known active
principles (e. g., rotenoids from Tephrosia, nicotine from
Nicotiana, methyl salicylate from Securidaca, and eugenol
from Ocimum); some of these are volatile and act as natural
fumigants that kill adult pests and their progeny (Jayasekara
13
N. E. El-Wakeil
et al. 2005). At least one study indicates that these materials
are relatively safe in the forms in which they are used (Bel-
main et al. 2001). Some plant products could even be useful
in industrialized countries for the protection of grain from
storage pests (Fields et al. 2001).
Many of the plants discussed in this review are tropical in
distribution and theoretically available to growers in devel-
oping countries. However, efficacy against pests is only one
factor in the adoption of botanicals logistics of production,
preparation, or use of botanicals can mitigate against their
use (Morse et al. 2002). Perhaps it is time to refocus the
attention of the research community toward the develop-
ment and application of known botanicals rather than screen
more plants and isolate further novel bioactive substances
that satisfy our curiosity but are unlikely to be of much
utility.
Conclusions
In summary, the insecticidal activity of extracts may be due
to synergistic effects shown by the phenolic components of
the mixtures in the test system used in this investigation.
These facts are indicative of the potency of the methanol
extracts. Thus, the effect of compounds on reducing insect
growth, increasing development time, and increasing mor-
tality of Spodoptera is similar to that of gedunin and more
potent than the MeOH extract from Cedrela salvadorensis
(Céspedes et al. 2000, 2006).
The sites and mode of action of these compounds and
extracts are being investigated and probably correspond to
a combination of antifeedant action as midgut phenol oxi-
dase, proteinase, AChE, tyrosinase, or other PPOs and cuti-
cle synthesis inhibition, as well as molting, sclerotization,
toxicity, and nerval system inhibition, as has been found for
other phenolics and terpenoids (Miyazawa et al. 1997; Kubo
2000) and extracts (Feng et al. 1995). In addition, the pres-
ence of an orcinol or catechol group seems to be important
for these activities as shown for the most potent compounds
in this article. Furthermore, a great percentage of larvae that
reached pupation decreased with the application of pheno-
lics in comparison to control, which might be due to the
inhibition by tyrosinase as well or to the accumulation of
proteinase inhibitors (Tamayo et al. 2000). The activity of
these plants, their metabolites, and MeOH extracts is com-
parable to the insect growth regulators gedunin and toosen-
danin, which suggests potential for further development of
these materials.
The plant kingdom offers a rich source of a wide range of
structural biodiversity of natural secondary metabolites. One
of the most recent trends in fungal and insect pest control is
to reduce heavy reliance on synthetic pesticides and to move
towards biodegradable substances. Synthetic pesticides of
broad spectrum have been widely used as the main tools
Botanical Pesticides and Their Mode of Action
for controlling weeds, and fungal and insect pest, which
are highly toxic to many living organisms as well as to the
environment. Hence, new biorational and specific trends to
pest control should be developed. In this article, an update
of findings in the field were presented, those approaches
resulting from the studies on inhibition of growth (including
larval growth, pupation, and emergence) and of the enzymes
involved in key processes of insect life, specially modifying
the apolysis during molting, sclerotization, pupation, and
emergence. Since these approaches refer to control of insect
pests, many of them can be extrapolated and also considered
suitable for medicinal chemistry studies, because the mode
of action of these inhibitors is similar to that from human
and other animals (Guerrero and Rosell 2004, 2005).
Therefore, there is an increasing expectation about the
research on enzymes inhibition by those compounds of
botanical origin that could serve as lead compounds for the
development of important substances with agrochemical
and pharmacological properties. Thus, by studying the plant
organisms that protect themselves against the pest attack,
we can learn to control this attack in an ecological way and
in addition can get pesticide active substances.
Acknowledgements  The author is grateful to Prof. Ahmed Sallam for
reviewing this manuscript in the early stage.
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Dr. Nabil E. El-Wakeil, was born
in 1969 in Tanta, Egypt, he com-
pleted his doctorate in 2003 at
Department of Entomology, Crop
Sciences, University of Göttingen,
Germany. The topic of his disser-
tation was “new aspects of bio-
logical control of Helicoverpa
armigera in organic cotton pro-
duction”. He had started working
in national research Center (Pests
and Plant Protection dept.) in
Cairo, Egypt from June 2013 as
professor of Biological Control. Actually Dr. Nabil El-Wakeil works as
Post doc fellow at Martin Luther-Halle University.
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