Open access peer-reviewed chapter - ONLINE FIRST
Abstract
Global warming fuels pest infestations, causing massive crop losses and economic damage. Chemical insecticides, though initially effective, come with a heavy toll: environmental harm, health risks, and resistance development. Their overuse creates a vicious cycle, leading to even more pesticide use and devastating consequences for beneficial insects, soil, water, and human health making our current agricultural practices unsustainable. Phyto-insecticides derived from plants are safer and more sustainable alternatives that boast a long history of use and diverse modes of action, making it harder for pests to develop resistance. They pose lower risks to human health and the environment and can be produced sustainably from renewable plant sources. While promising, phyto-insecticides face hurdles. Limited plant biomass, variable effectiveness, and unstable formulations hinder their commercialization. However, innovative solutions are emerging: (1) callus culture: this technique offers a sustainable way to mass-produce valuable secondary metabolites like Azadirachtin and Pyrethrin; (2) understanding insect interactions: Deciphering how these compounds interact with insects paves the way for effective utilization and formulation design; (3) nanotechnology: nanoparticles enhance stability, bioavailability, and targeted delivery, boosting efficacy and reducing environmental impact. Excitingly, trace amounts of phyto-insecticide residues may offer additional benefits. Some compounds, like Azadirachtin, Piperine etc., possess potential nutraceutical properties, promoting bone health, managing diabetes, and even fighting cancer. This opens the door to “nutraresidiceuticals,” where food treated with phyto-insecticides might enhance consumer health. Phyto-insecticides hold immense potential as a sustainable and effective pest management strategy. By addressing challenges related to biomass, formulation, and understanding their modes of action, we can unlock their full potential for a healthier and more sustainable future. Additionally, exploring the potential “nutraresidiceutical” benefits opens up exciting new avenues for research and development.
Keywords
- phyto-insecticides
- sustainable agriculture
- callus culture
- nanotechnology
- nutraceuticals
- nutraresidiceuticals
1. Introduction
Agriculture, the bedrock of human civilisation, faces a constant challenge: the relentless onslaught of pests. This battle for food security intensified as global warming resulted in insect pests’ increased geographic distribution, survival, and invasion, altered interspecific interaction, and converted diverse ecosystems into fertile breeding grounds for these destructive insects [1]. While estimates suggest that less than 0.5% of insects are classified as pests, their impact on crops, livestock, and human health cannot be understated. Studies reveal a staggering 20–40% crop loss due to pest damage, translating to an alarming 70 billion USD annually [2, 3].
As soaring populations and catastrophes caused by world wars necessitated increased food production, Agriculture was compelled to take more intense pest control tactics during the late 1940s and 1950s. The initial success of synthetic chemical insecticides though fuelled the Green Revolution through high-yielding crop varieties, had unleashed a cascade of unforeseen consequences and had become one of the most controversial issues [4, 5].
The widespread and often indiscriminate use of these potent chemicals has wrought havoc on natural ecosystems and disrupted ecological balance. Pesticides, designed to eliminate specific insects, inadvertently select resistant individuals, leading to the rise of “superbugs” immune to their effects [6]. This phenomenon creates a vicious cycle of escalating pesticide use and ultimately exacerbates the problem. Furthermore, these chemicals wreak havoc on natural enemies and beneficial insects, leaving the door open for secondary pest outbreaks and further ecological damage [7, 8, 9, 10]. The long-term consequences of this disruption are far-reaching, impacting soil health, biodiversity, and overall sustainability. The human cost of pesticide use is simply unacceptable, particularly for vulnerable populations in developing countries. Chemical residues on food crops pose a significant threat to consumers, with studies linking pesticide exposure to various health issues, including cancer, birth defects, and neurological disorders [11]. Finally, the environmental impact of chemical pesticides cannot be ignored. These toxic substances pollute water sources and contaminate air and soil [12, 13].
Several hundred pesticides of different chemical nature are currently used in agriculture all over the world [14]. The burgeoning global insecticide market, valued at 19.5 billion USD in 2022 and projected to reach 28.5 billion USD by 2027, highlights the increasing reliance on pest control measures, even now [15].
2. Exploring a sustainable alternative: botanical insecticides
2.1 A return to plant-based pest control: a long history and renewed interest
The long-term consequences for the planet are dire, jeopardizing the very foundations of our food security and environmental well-being. In the face of these challenges, the need for a paradigm shift in pest management is undeniable. Moving away from this unsustainable reliance on chemical solutions and embracing a more holistic approach that prioritizes environmental sustainability and human health is a must.
Further, as the concept of pest management was radically revised towards advocating the suppression of pest populations below levels capable of causing economic injury rather than total eradication, insecticides of plant origin which exerted coherent management over insect pests for many centuries got re-attention.
Secondary metabolites have been exploited longer for managing pests [16, 17]. Botanical insecticides have a long history; their use in India, China, and Egypt since thousands of years ago highlighted their efficiency in pest management. The availability of wider choices, a broader spectrum of action, and relative safety made them attractive alternatives for synthetic insecticides [18].
As most of the botanicals are relatively non-toxic to humans, animals, and natural enemies they readily fit into IPM protocol [19, 20]. They help in reducing pesticide usage, environmental contamination, and human and animal health hazards [21].
In recent years, attempts have been made to identify plants, including herbs and weeds and their novel phytochemicals, for their insecticidal property. Different types of plant preparations such as crude extracts, solvent extracts, and powders have been reported for their insecticidal activity. Numerous plant species have been identified as possessing pesticidal properties [22, 23]. They possess secondary metabolites like alkaloids, non-protein amino acids, steroids, phenols, flavonoids, glycosides, glucosinolates, quinones, tannins, and terpenoids, etc., which are responsible for the protective action against the insect pests [24].
Their diverse modes of action, repellence, feeding deterrence, insecticidal, and insect growth regulatory activities, could act additively or synergistically, making resistance development more difficult and a high degree of biodegradation makes them a preferred choice [25, 26].
2.2 Challenges hindering wider adoption: addressing the gaps
Although there is a rich source of plants that could be harnessed as insecticides, commercialization of botanicals has not gained ground. The market share of botanicals along with other biopesticides is a mere 2% [27]. While a few botanicals were commercially exploited like neem, rotenone, pyrethrum, and some essential oils [28], the non-availability of biomass and formulations, lack of standardization and quality control measures hinder their commercialization.
Furthermore, their sensitivity to environmental conditions like light, temperature, humidity, substrate pH, etc. make them more unstable necessitating the need to formulate them as stable phyto-insecticide formulations. Improving phyto-insecticide formulations through new approaches like encapsulation, emulsification, or complexation, aiming to increase shelf life and enhance efficacy by optimizing their delivery and uptake by target insects, results in novel product development [25, 29, 30, 31].
Hence, research efforts are focused towards novel approaches like the use of nanotechnology to encapsulate active ingredients as nanoparticles for improved stability, control-release, and targeted delivery and utilizing biodegradable polymers to create environmentally friendly formulations with improved release profiles.
While formulation plays a crucial role, other aspects also contribute to the limited utilization of botanical insecticides. These include:
Seasonal and ecotype variability: the efficacy of phyto-insecticides can vary significantly depending on the season, and plant source. This makes it challenging to develop standardized and widely applicable products [32].
Synthesis difficulties: isolating and purifying specific active compounds from plants can be complex and expensive, hindering their commercialization.
3. Overcoming barriers to phyto-insecticide commercialization: tackling biomass, formulation, and standardization issues
3.1 Harnessing the power of callus culture: a promising solution
Hence, the synthesis of active ingredients to overcome the non-availability of biomass is not a reliable and economical alternative. However, it could be overcome through plant tissue culture-based
The use of in vitro callus culture for synthesizing various secondary metabolites, including Azadirachtin, Pyrethrin, and others and the bioefficacy of these metabolites against insects highlights their prospective role in solving biomass, ecotype and seasonal variability-related issues.
The following examples of Successful Callus Culture for the development of Insecticidal Compounds highlight its scope.
3.1.1 Azadirachtin
Callus culture offers a consistent and controlled environment for the production of Azadirachtin content. Studies have shown that increased Azadirachtin production was achieved with bioreactors and cell retention techniques [34]. Some authors demonstrated increased extracellular Azadirachtin with specific nitrate: ammonium ratios [35]. A literature reported higher Azadirachtin in zygotic embryo cultures compared to leaf and ovary cultures [36].
3.1.2 Pyrethrin
Production of pyrethrin an insecticidal compound naturally found in Chrysanthemums, have been enhanced through callus culture. Few authors opined higher Pyrethrin concentrations in callus extracts compared to intact plant extracts and observed positive effects of auxin, cytokinin, and other hormones on Pyrethrin production [37, 38].
3.1.3 Other secondary metabolites
Callus culture has been used to produce various other valuable compounds:
Podophyllotoxin was extracted from callus and plant root cultures of
3.1.4 Bioefficacy of callus extracts
Several studies reported strong antifeedant and insecticidal activity of Azadirachtin extracted from callus cultures against various insects [44, 45, 46, 47, 48]. A knockdown effect was demonstrated against
These studies highlight the potential of
3.2 Understanding and optimizing the impact: deciphering the complex modes of action for effective utilization
Further, instead of mere screening for bio-efficacy isolation, identification and evaluation of the active components of the plant products will lead to commercialization of the product if found effective. This may also lead to the synthesis of the components for commercial use if active components are economically and biologically very effective.
Botanicals generally possess dose-dependent varieties of action starting from repellency and leading even to the death of insects. However, large-scale utilization of botanicals in pest management is obstructed by non-availability of formulations. This constraint may be surrounded by conducting detailed studies on the active constituents of the effective plant fractions and their influence on various physiological systems. In support of the above-mentioned point, the availability of plant-based insecticidal formulations derived from neem oil and pyrethrum, whose physiological influences are well studied is available worldwide [52].
Among all present-day living forms, insects are one of the most ancient creatures. These insects with a long evolutionary history and remarkable adaptability roamed the world for almost 350 million years, the reason behind being on top of the evolutionary ladder [53]. Needless to explain one can understand their capacity to adapt. Such superior adaptability is mainly the product of complex and adaptable physiological systems [54].
Hence, the strategic application of control strategies aiming at disrupting the adaptive capacity of the insects is thought over. Consequently, the use of plants, an organism that co-evolved along with insects with a diverse array of bioactive compounds with anti-herbivore properties is to be re-considered [55]. These natural products may be effective in reducing the capacity for adaptation of insects. Their interaction with dynamic physiological processes, if studied will necessarily throw light on the best possible use for efficient control of insect pests.
The interaction between secondary metabolites and insect physiology, and the specific physiological processes targeted, define the “mode of action” of these natural insecticides. Understanding the mode of action is crucial for effective pest management as it reveals essential information about speed of action, target spectrum, and environmental safety. Furthermore, such studies guide formulation design and provide leads for developing novel insecticides.
However, the intricate nature of secondary metabolites, encompassing both their structure and function, presents a significant challenge compared to synthetic insecticides. Specifically, the dose-dependent effects observed (e.g., Azadirachtin inducing diverse morphogenetic defects and mortality based on applied concentration) complicate the determination of the precise mode of action. This challenge is further compounded by the lack of standardized experimental protocols for validation.
The diverse modes of action employed by secondary metabolites against insects can be broadly categorized into:
Neurotoxic
Cytotoxic
Enzyme inhibitory
Metabolic disrupters
Interactions with biomolecules
Intriguingly, individual secondary metabolites can exhibit multiple modes of action depending on the dose and target site. This multifaceted nature, combined with the vast diversity of secondary metabolites, presents a significant challenge for deciphering their precise modes of action. The complexity is further amplified in plant extracts, where synergistic or antagonistic interactions between multiple compounds occur. Therefore, to effectively elucidate the mode of action of a plant extract’s anti-insect activity, it is crucial to isolate and purify the key bioactive molecules, and investigate the individual and combined actions of these purified compounds on relevant targets using appropriate biochemical and physiological assays.
By adopting this stepwise approach, researchers can gain a deeper understanding of the complex mechanisms employed by secondary metabolites in their defense against insects. This knowledge can then be harnessed to develop more targeted and effective pest management strategies.
3.3 Developing stable and effective nanoformulations: key to unlocking potential
The term “nano” is derived from the Greek word meaning dwarf, representing sizes ranging from 1 to 100 nm. Nanotechnology, as termed by Norio Taniguchi, involves the manipulation of matter at the nanoscale to produce materials with unique properties. According to the International Organization for Standardization and the Organization for Economic Cooperation and Development, nanomaterials are defined as materials having external dimensions or internal structures at the nanoscale.
Agrochemical formulations incorporated as nanoparticles (NPs) or in nanoscale materials with diverse coatings offer a promising avenue for improving the solubility and permeability of active ingredients (AIs). This, in turn, can result in enhanced bioavailability, allowing for a reduction in the AI dosage. Moreover, these formulations enable controlled release and targeted biodistribution of AIs, contributing to more efficient and environmentally friendly agricultural practices [56]. They also offer other advantages such as improved dispersion and wettability, biodegradability in both soil and the environment, non-toxic nature, and photogenerative properties [57, 58].
Various nanocarriers, such as nanocapsules, nanospheres, micelles, nano gels, nanoemulsions, nanodispersions, and inorganic materials, alter the properties of phyto-insecticide’s active ingredients and offer unique advantages like controlled release kinetics, improved solubility, lower dose-requirement, enhanced stability, and prolonged efficiency in pest control. Techniques like coacervation, nanoprecipitation, and microemulsion are commonly used for encapsulating phytochemicals within nanoformulations. These methods help achieve uniform particle size distribution and enhance the overall efficacy.
3.3.1 Nano-formulations for sustainable development
Nano formulations offer multiple advantages. These include active ingredient degradation prevention and improved activity due to smaller particle size and larger surface area [59]. Notably, it is anticipated that the mechanism of action against target pests will be enhanced compared to bulk equivalents, given the increased interaction with target pests resulting from the small size of nanoparticles [60]. Additionally, nanoparticles have demonstrated consistent leaf cover and plant penetration, supporting their potential in pest control and agriculture [61]. These findings indicated reduced insecticide usage that led to sustainable plant protection protocols.
3.3.2 Key aspects related to nanoformulations of phytochemicals
Improved bioavailability: nanoformulations can enhance the bioavailability of phytochemicals, ensuring that a greater proportion of the compound reaches its target site. This is particularly important for phytochemicals with low solubility or poor absorption.
Increased stability: phytochemicals are often sensitive to environmental factors, such as light, heat, and oxygen, which can lead to degradation. Nanoformulations provide a protective environment, increasing the stability of phytochemicals and prolonging their shelf life.
Targeted delivery: nanoformulations enable targeted delivery of phytochemicals to specific cells or tissues. This targeted approach can enhance efficacy while minimizing potential side effects on non-targeted cells.
Controlled release: controlled release is a key feature of nanoformulations. This allows for a sustained and controlled delivery of phytochemicals over time, ensuring a more consistent effect.
3.3.3 Challenges and safety considerations of nanoformulation
Nanoformulations, which involve manipulating materials at the nanoscale, hold great promise in various fields such as medicine, agriculture, and electronics due to their unique properties. However, as with any new technology, some challenges need to be addressed to ensure their successful implementation.
Production scale-up: transitioning from small-scale laboratory production to large-scale manufacturing can be complex. Processes that work well in the lab may not be easily scalable or cost-effective when producing nanoformulations on a commercial scale. Engineers and scientists must develop efficient and reproducible manufacturing processes to meet the demands of mass production.
Regulatory considerations: nanoformulations may fall under specific regulatory frameworks that govern the production, distribution, and use of nanomaterials. Regulatory agencies require comprehensive data on the safety, efficacy, and environmental impact of these formulations before approving them for commercial use. Meeting regulatory requirements often involves extensive testing and documentation, which can be time-consuming and expensive.
Safety evaluations: nanoformulations raise concerns about potential health and environmental risks associated with exposure to nanomaterials. Before these formulations can be widely used, thorough safety evaluations are essential to understand their potential hazards and mitigate any associated risks. This includes assessing their toxicity, biodistribution, biodegradability, and long-term effects on living organisms and ecosystems.
Given the complexity and novelty of nanoformulations, ensuring their safety is crucial to gaining public acceptance and regulatory approval. By addressing these challenges and conducting rigorous safety evaluations, researchers and industries can harness the potential benefits of nanoformulations while minimizing potential risks to human health and the environment.
3.3.4 Types of nanoformulations
3.3.4.1 Nanoemulsions
Nanoemulsions (NEs) are small droplets of one liquid dispersed in another, stabilized by an amphiphilic surfactant, commonly water in oil (W/O) or oil in water (O/W) [62]. Very small oil/water emulsion nanoscale droplets with diameters less than 100 nm create nanoemulsions. The nanoemulsion is designed to improve pest management by increasing pesticide solubility, bioavailability, stability, and wettability. With sizes around 100 nm, these NEs exhibit advantageous properties such as a large surface area, strong stability, clear appearance, and adjustable rheology [63].
3.3.4.1.1 Nanoemulsion preparation techniques
High-energy techniques like membrane emulsification, high-pressure homogenization, and sonication, as well as low-energy methods based on nonionic surfactant phase transitions or spontaneous emulsification, are employed for NE preparation. NEs possess unique characteristics, including a high elastic modulus, Laplace pressure, surface area to volume ratio, and small droplet size, requiring specialized equipment like ultrasonic generators or high-pressure homogenizers due to the energy-intensive nature of the process. However, low-energy methods, like spontaneous emulsification, offer a simpler approach without the need for expensive equipment.
3.3.4.1.2 Applications
The incorporation of these natural ingredients aims to enhance bioavailability, reduce negative side effects, minimize non-specific absorption, and enable precise targeting to specific cells. Targeting ligands, such as folate, are introduced on the surface of NEs to further improve their performance in specific applications. This targeted technology often involves nanocarrier functionalization, which can be achieved through surface modification [64, 65] and/or ligand grafting [66].
3.3.4.2 Nanoencapsulation
Nanoencapsulation involves enclosing pesticides within nano-sized materials, often polymers, to create nanocapsules that release the pesticide under specific environmental conditions [67]. It is employed in crop protection chemical formulations to achieve enhanced solubility, specificity, and stability at varying environmental conditions
3.3.4.2.1 Nanoencapsulation preparation techniques
Creating efficient polymeric nanocapsules with various synthesis protocols including layer-by-layer deposition, double emulsification, emulsification-coacervation, solvent evaporation, nanoprecipitation, melt dispersion, emulsion polymerization, interfacial polymerization, interfacial deposition methods, solvent displacement technique, and emulsion-evaporation. These methods contribute to the utilization of this formulation technique in the development of chemically varying botanical AIs as phyto-insecticide formulations.
3.3.4.2.2 Applications
Their design enables them to withstand environmental processes such as leaching, evaporation, photolytic hydrolysis, and microbial destruction. Importantly, these formulations feature built-in switches for regulating the release and availability of pesticides over a specific duration, optimizing their efficiency. These facts highlight their utility in phyto-insecticide formulation development as their commercial success entirely depends on these parameters.
3.3.4.3 Nanosuspension
Nanosuspension technology offers significant improvements in the solubility, wettability, and activity of poorly soluble substances, with uniform particle sizes below 100 nm. The key outcomes arise from the increased surface area, rapid dissolving rate, and excellent penetrability. Notably, the nanosuspension approach reduces the required amount of surfactants and eliminates the need for organic solvents, making it an environmentally friendly and efficient method for phyto-insecticide formulation.
3.3.4.3.1 Nanosuspension preparation techniques
In contrast to traditional methods like micronization, which involves milling coarse powders to create suspension concentrations (SC) resulting in particle sizes around 13 μm, nanosuspension technology takes the process from micrometer- to nanometer-sized particles. Phyto-insecticides often have low solubility, and micronization may not achieve sufficient bioavailability. Nanosuspensions, typically in the size range of 200–500 nm, become the next step in enhancing the effectiveness of these poorly soluble AIs.
Two main methods for producing nanosuspensions are bottom-up (controlled precipitation/crystallization) and top-down technologies. In the bottom-up method, the AI is dissolved in an organic solvent and precipitated with an anti-solvent in the presence of a stabilizer, resulting in homogeneous particles with smaller sizes. This method may also generate amorphous nanoparticles with high dissolution rates. On the other hand, the top-down approach involves various methods such as media milling, high-pressure homogenization, and microfluidization to reduce particle size. Combination procedures that integrate pre-treatment with subsequent size-reduction phases are commonly used for producing more homogeneous nanoparticles. Overall, nanosuspension technology presents a versatile and effective means of addressing solubility challenges and enhancing phyto-insecticide formulation performance.
3.3.4.3.2 Applications
3.3.5 Nanoformulation characterization
3.3.5.1 Particle size and its distribution
The characterization of particle size and distribution is pivotal for evaluating the efficacy and stability of nanoformulations. Small and uniform particle sizes contribute to an increased surface area, facilitating improved interactions with biological systems. Dynamic Light Scattering (DLS) is a widely employed technique for determining the size and distribution of nanoformulations. To achieve optimal efficiency, samples are diluted with deionized water before analysis to prevent multiple scattering caused by aggregation via electrostatic interaction. During the measurement process, the polydispersity index (PDI) is a critical parameter, with a value less than 0.5 considered acceptable for agricultural use, indicating good uniformity of particle diameter. Samples with higher PDI, signifying polydispersity, are deemed unsuitable for characterization using DLS [72].
The size of nanoemulsions is influenced by various factors, with surfactant concentration and packing parameters playing a significant role. Surfactant packing parameters, crucial for changes in surfactant curvature and finer nanoemulsion droplet formation, are highly affected by the ratio of hydrophobic and hydrophilic regions. The surfactant arrangement at the oil/water (O/W) boundary with low interfacial tension creates a bicontinuous microemulsion, resulting in smaller particles. Research studies consistently indicate that an increased ratio of surfactant to oil leads to smaller droplet sizes [73]. This scientific understanding contributes to the nuanced design and optimization of nanoemulsions for phyto-insecticide formulation development.
3.3.5.2 Viscosity, zeta and pH measurement
The electrophoretic properties, specifically the zeta potential, of nanoformulations are commonly measured using Zetasizer. The zeta potential, influenced by the surface properties around the particles, is indicative of nanoformulation stability, with pH value playing a crucial role. A negative zeta potential generates repulsive forces that surpass the attractive forces among droplets, preventing coagulation and coalescence in the emulsion. The stability of nanoformulation tends to decrease with an increase in oil concentration in the system [74, 75, 76]. Utilizing an Ostwald viscometer, viscosity values of nanoformulations influenced by the nature of surfactants, organic phase components, and oil viscosity can be measured. Phyto-insecticide nanoformulations typically exhibit low viscosity, given their classification as O/W type with high water loading. However, surfactant concentration can be a variable influencing the viscosity of nanoformulations [77]. This scientific understanding contributes to the meticulous design and optimization of nanoformulations, especially in the context of phyto-insecticide delivery systems.
3.3.5.3 Morphology and stability study
The shape and morphology of nanoformulations are elucidated through advanced imaging techniques such as atomic force microscopy (AFM), transmission electron microscopy (TEM), and cryogenic-field emission scanning electron microscopy (Cryo-FESEM). Commonly observed shapes for nanoformulations include spherical or core-shell structures, attributed to the formation of nano micelle clusters during the preparation process.
To assess stability, rigorous tests involve varying storage time and temperatures, typically spanning 0, 5, 10 days, and even up to 12 months, with temperatures ranging from 4 to 54°C. Stability is determined by monitoring sample appearance and measuring physicochemical properties, such as zeta potential and particle size, at predetermined intervals. Stable systems exhibit no changes like phase separation, creaming, flocculation, coalescence, or sedimentation. The zeta potential and particle size are compared before and after storage, with maintained values indicating stability.
Temperature plays a critical role in stability, with higher temperatures potentially inducing instability through particle movement and emulsifier dissolution into water, leading to particle aggregation. Factors like Ostwald ripening, occurring in the initial 5–10 days, contribute to stability challenges like flocculation and coalescence. The coarsening mechanism in nanoemulsions, influenced by factors like the oil phase fraction, emphasizes the role of appropriate surfactants and small droplet sizes in controlling stability. High curvature of nanoformulations prevents flocculation and coalescence due to Laplace pressure, but Ostwald ripening remains a concern for long-term storage. Strategies to counter Ostwald ripening involve increasing droplet elasticity and adding surfactants to reduce interfacial free energy, forming a protective barrier against coalescence [78, 79, 80].
3.3.5.4 Retention and contact angle measurement
Retention and contact angle measurements are crucial in understanding the interaction between nanoformulation and leaf surfaces. These metrics provide insights into the affinity of the phyto-insecticide liquid towards the leaves, impacting the efficiency of the nanoformulation. Increased adhesion of nanoformulations to leaves can enhance their effectiveness in pest control.
Retention is typically measured using methods like dipping and micro-weighing, providing a quantitative assessment of the amount of phyto-insecticide retained on the leaf surface. On the other hand, contact angle measurements involve using precision instruments equipped with a charged-coupled device (CCD) camera to evaluate the angle formed between the pesticide droplet and the leaf surface. A decreasing contact angle with an increasing agrochemical content indicates a lower interfacial tension of the active ingredient, facilitating effective pesticide diffusion on the plant surface [81].
3.4 Beyond pest control: exploring the health benefits of phyto-insecticide treated foods
Azadirachtin A, a compound from the neem tree, shows promising health benefits against bone health, cancer, and inflammation. In calvaria cells, it boosts bone formation (1–5 mg/kg BW) [82]. It also fights cervical cancer cells (135 μM) [83] and reduces tumor growth in buccal cancer (10–100 μg/kg BW) [84]. Additionally, Azadirachtin (120 mg/kg BW) reduces inflammation and pain in mice. This versatile compound holds the potential for diverse therapeutic applications [85].
Piperine, the active compound in black pepper, packs a punch in diverse areas. It inhibits HeLa cancer cell growth (20–100 μg/ml), tackles high blood sugar (20 mg/kg), and even fights obesity (40 mg/kg). Lower doses (1–10 mg/kg) bring down blood pressure and protect the heart. Piperine enhances cognitive and motor function in Parkinson’s (10 mg/kg), combats seizures (10 mg/kg), and improves mobility in Alzheimer’s (2 mg/kg). This spicy wonder holds promise for a range of health benefits [86].
The Pongamia tree, also known as
From fighting microbes (100 μg/ml) to shielding cells from damage (25 mg/kg),
The versatile
Eucalyptus oil, extracted from the leaves, reveals antimicrobial and anti-cancerous potential. At a potent concentration of 20 ml/L, it effectively inhibits the growth of common bacterial pathogens like
Phyto insecticides render various insecticidal properties due to the presence of secondary metabolites such as steroids, tannins, alkaloids, terpenoids, flavonoids, coumarins, phenols etc., [95] also offer medicinal effects [96]. Synthetic insecticides become persistent pollutants (residues) and result in inevitable loss to human health and the environment [97, 98]. A pesticide residue is any specified substance in food, agricultural commodities, or animal feed resulting from the use of a pesticide [99]. In 2021, the European Food Safety Authority reported that 39.8% and 2.1% of food samples contain one or more residues in concentrations below or equal to permitted levels (MRLs) and the latter with residues exceeding the permitted levels [100].
Talukder et al. reported that, unlike conventional pesticides, botanical pesticides leave minimal or no residue, minimizing risks to human health, the environment, and ecosystems [101]. Whereas EPA exempt, botanical oils with a zero re-entry interval, zero pre- and post-harvest interval and maximum residue levels (MRLs) [102] and vulnerable to the degradation process [103].
3.5 Fate of phytoinsecticidal residues and potential for “nutraceuticalization”
What is the effect of residual phytoinsecticidal compounds present in treated produce? Recalling Paracelsus’s principle, “the dose makes the poison,” the
As discussed in Section 3.4, trace amounts of phytoinsecticide
4. Conclusion
Developing effective and stable phyto-insecticide formulations is a multifaceted challenge. By addressing the sensitivity of these natural compounds through innovative formulations and tackling biomass availability and variability difficulty in their synthesis through callus culture, we can unlock their potential for sustainable pest management. However further research is needed to optimize callus culture for various plants and scale production to decipher the intricate modes of action and to validate the potential health benefits of nutraresidueuticals through clinical trials.
The future of phytoinsecticides lies in a confluence of cutting-edge technologies and strategic development approaches. Genomics, transcriptomics, and metabolomics will unlock deeper knowledge of biosynthetic pathways and modes of action, paving the way for targeted optimization. Artificial intelligence and machine learning will accelerate the discovery of novel bioactive compounds through high-throughput screening of plant extracts. Synergistic effects and broader pest control can be achieved by developing combination formulations that integrate botanicals with other biocontrol agents. Exploring the potential of “nutraceuticalization” could offer additional health benefits from trace residues in treated food, opening exciting new research avenues.
By overcoming current challenges and harnessing these powerful tools, phytoinsecticides have the potential to revolutionize pest management, contributing to a more sustainable and healthier food production system for all.
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