From Insecticidal Plants to Reliable Bioproducts: A Scoping Review of Discovery, Standardization, Formulation, and Regulatory Translation

INTRODUCTION

Plants remain a major source of structurally and functionally diverse compounds with potential value in insect management, yet the developmental significance of a positive bioassay is easily overstated. Candidate extracts may vary with taxonomy, plant part, provenance, harvest conditions, extraction procedure, storage, and test system, while laboratory exposure can bear little resemblance to application in crops or stored commodities. The central development problem is not discovering plant activity but converting variable laboratory findings into reproducible products that function under farming conditions [1]. This translation problem requires a chain of evidence that connects the tested botanical material to an intended use, measurable chemical attributes, reproducible biological performance, feasible delivery, and decision-relevant safety.

Source discovery is often informed by traditional use, farmer practice, local availability, or ecological observation. Such knowledge can improve the relevance and efficiency of candidate selection, especially where locally available pesticidal plants are already embedded in pest-management practice. Ethnobotanical use can improve source prioritization, but customary preparation alone does not establish composition, dose, safety or product reproducibility [2]. The same plant name can conceal distinct chemotypes and processing histories, and a locally effective preparation may not be transferable across seasons, locations, pest stages, or production systems. Use history should therefore be treated as contextual evidence for prioritization rather than as validation of a standardized intervention.

Commercial precedents demonstrate that botanical origin is compatible with durable crop-protection products, but they also show that success depends on coordinated development rather than on biological activity alone. The persistence of pyrethrum- and neem-based products shows that botanical insecticides can succeed, but only when chemistry, formulation, efficacy, safety and regulation are aligned [3]. These requirements are cumulative: an extract can be biologically active yet chemically unstable; a defined constituent can have a plausible target yet lack an acceptable delivery profile; and a formulation can be technically feasible while remaining unsuitable for regulatory submission, economical manufacturing, or farmer use. Formulation feasibility is therefore not equivalent to regulatory or commercial readiness.

The available literature does not distribute evidence evenly across this pathway. Discovery studies and short-duration laboratory assays are common, whereas longitudinal batch characterization, stability-linked potency testing, realistic exposure assessment, and documentation of failed translation are comparatively limited. The evidence base is vulnerable to publication bias, heterogeneous methods and overrepresentation of laboratory mortality endpoints, which limits translation-oriented inference [4]. This scoping review consequently asks what recent evidence establishes, leaves uncertain, or contradicts across discovery, chemical characterization, mechanistic verification, standardization, formulation, storage stability, non-target safety, and regulatory translation. Its central argument is that plant-to-product development should be evaluated as a sequence of connected but non-equivalent evidence transitions, with claims bounded by the material tested, organism and life stage, exposure context, analytical method, and development stage.

Scoping review questions and evidence boundaries

The review was structured to map concepts, evidence classes, translation stages, and unresolved gaps rather than to calculate a pooled estimate of insecticidal effectiveness. It asked how botanical sources were selected; how crude materials, fractions, essential oils, purified constituents, and formulated products were defined; what evidence linked chemistry to phenotype or target; how standardization and stability were evaluated; how non-target effects were tested; and which barriers separated laboratory discovery from product registration and adoption. The review will report its questions, eligibility boundaries, information sources, selection logic and charting procedures in accordance with scoping-review reporting guidance [5]. These reporting elements improve transparency, but they do not replace source-level assessment of material identity, exposure realism, controls, endpoint relevance, and inferential limits.

A scoping design is appropriate because the objective is to map evidence classes, translation stages and gaps rather than estimate a pooled treatment effect [6]. Eligible evidence comprised peer-reviewed laboratory, field, chemical, mechanistic, formulation, ecotoxicological, and translation-oriented journal articles, together with rigorous reviews, perspectives, and meta-research that supported a specific analytical claim. The biological boundary covered plant-derived materials intended for agricultural or stored-product insect control and relevant beneficial arthropods. Human pharmacology, antimicrobial-only studies, undefined plant preparations, and sources lacking insect-control relevance were excluded. Crude extracts, fractions, essential oils, purified compounds, and finished formulations were charted as distinct interventions; mortality, behavioural effects, mechanism, chemical reproducibility, stability, non-target effects, and translation outcomes were likewise treated as separate outcome constructs.

Search logic combined botanical-material terms with insect targets and terms for discovery, screening, characterization, mechanism, standardization, formulation, stability, ecotoxicology, regulation, or commercialization. A core PubMed search was supplemented by article-level DOI, journal, and claim verification. Title and abstract relevance was followed by full-text or full-metadata assessment, and a source was retained only when its design, context, limitation, and exact manuscript use could be charted. Evidence was classified as observation, mechanistic evidence, model-based inference, contextual support, proposed synthesis, or decision implication; no pooled risk-of-bias score was assigned. Instead, limitations were recorded for each source and synthesized across domains, with particular attention to publication bias, laboratory dominance, material ambiguity, unrealistic exposure, and surrogate-outcome inflation. The review questions, eligibility boundaries, search and screening logic, evidence-classification rules, and bias controls are specified in Table 1.

Table 1. Scoping Review Questions and Evidence Boundaries: Review Questions, Eligibility Boundaries, Search Logic, Screening Rules, Evidence Classification, and Bias Controls

Botanical source selection and bioactivity discovery

Botanical source selection is most informative when it is tied to an intended pest-management use rather than driven only by taxonomic novelty or ease of access. Ethnobotanical records, farmer practice, ecological signals, and local supply can identify plausible candidates, but reproducible discovery additionally requires authenticated species, defined plant part, provenance, harvest context, processing, and a defensible comparator. Field experiments show that selected pesticidal-plant extracts can suppress crop pests under realistic management, although preparation variability prevents treating those extracts as standardized products [7]. Such evidence strengthens use relevance because it moves beyond isolated laboratory exposure, yet its transferability remains conditional on crop, pest complex, season, preparation, and local practice. Field performance of a farmer-prepared extract is therefore evidence for a bounded intervention, not proof that all preparations from the same species are chemically or biologically equivalent.

Bioactivity-guided discovery should progressively reduce uncertainty about both the tested material and the origin of its effects. Initial assays can compare crude extracts or oils under controlled exposure, after which chemical profiling and fraction or constituent testing can investigate whether activity tracks a reproducible chemical feature. Coupling essential-oil profiling with bioassays narrows candidate chemistry, but activity of a characterized mixture is not equivalent to identification of a causal active principle [8]. A chromatographic profile defines the material more precisely than a plant name alone, but correlations between abundant peaks and mortality may reflect co-variation, minor constituents, synergy, antagonism, or matrix effects. Chemical fingerprints should consequently be interpreted as reproducibility tools and hypothesis generators unless activity is retained through fractionation, depletion, recombination, or direct testing of authenticated compounds.

Component-level assays provide a stronger bridge from phenotype to chemical attribution, although they still operate within species-, life-stage-, dose-, and exposure-specific boundaries. Testing major constituents separately can distinguish broad mixture activity from component-associated effects, while also showing that potency may vary among pest species [9]. Conversely, accessible screening of aqueous or otherwise farmer-compatible preparations can identify candidates relevant to local management even when their chemistry remains incompletely resolved. Bioactivity-guided screening of farmer-accessible plants can prioritize candidates against fall armyworm, but crude-extract activity remains preparation- and context-bound [10]. The strongest discovery programmes therefore combine practical relevance with analytical traceability: they retain information on mixture effects, use controls that distinguish solvent and handling artefacts, and predefine the evidence needed before a candidate advances from promising source to chemically specified development material.

Chemical characterization and mechanistic verification

Chemical characterization answers what material was tested; mechanistic verification addresses how that material may produce a biological effect. These tasks are connected but not interchangeable. Reliable characterization should move from authenticated botanical source and processing history to fit-for-purpose fingerprints, quantitative markers, reference-standard confirmation, and batch information. Pyrethrum illustrates that reliable botanical development depends on defining biosynthetic origin, extraction effects, analyte identity and quantitative determination rather than relying on plant name alone [11]. The appropriate analytical depth depends on the claim: a discovery screen may require a reproducible fingerprint, whereas standardization or registration requires quantitative specifications linked to biological performance and degradation. A list of tentatively identified peaks is not a product specification, and chemical consistency alone does not establish biological equivalence.

Mechanistic evidence becomes more causally informative as it moves from broad phenotypes toward direct perturbation of a defined target, while retaining organism-level relevance. Behavioural avoidance, feeding inhibition, developmental disruption, physiological stress, tissue injury, biochemical change, and target-level activity occupy different evidentiary levels. Target-level electrophysiology with purified pyrethrins provides stronger mechanistic evidence than whole-extract mortality because it directly tests modulation of insect sodium channels [12]. Even this direct target evidence remains bounded by the purified compounds, expressed channel, and heterologous assay; it does not reproduce absorption, metabolism, mixture interactions, formulation, or field exposure in a whole insect. Mechanistic verification should therefore be described as a graded chain of evidence rather than a binary designation.

Species and assay context further constrain mechanistic generalization. Mechanistic claims should remain species-specific because even closely related drosophilids can differ in behavioral and physiological responses to the same plant volatiles [13]. Multi-endpoint studies can reduce reliance on a single mortality measure by connecting chemical profiles with deterrence, toxicity, physiology, or tissue effects. Combining oviposition behavior, toxicity and histological observations strengthens mechanistic plausibility, but tissue damage remains associative unless a causal molecular target is independently verified [14]. Accordingly, proposed mechanisms should be labelled by evidential level, computational or histological findings should be presented as hypotheses unless experimentally resolved, and mixture-versus-component uncertainty should remain explicit. Chemical identity supports reproducibility, while target-oriented evidence supports causal explanation; neither alone establishes a standardized, safe, or operationally effective bioproduct.

Standardization, formulation, and storage stability

Standardization begins before formulation because a delivery system cannot compensate for an undefined or unstable active material. Botanical provenance, plant part, harvest conditions, extraction procedure, chemical fingerprint, quantitative markers, impurities, and baseline biological performance should be documented before formulation comparisons are interpreted. Nanoemulsification can enhance delivery of anise essential oil and laboratory activity, but formulation feasibility remains distinct from shelf-life, field effectiveness, and registration evidence [15]. Apparent formulation gains may reflect improved dispersion, altered contact, surfactant effects, or changes in exposure rather than an inherent increase in active-compound potency. Comparative studies should therefore include the unformulated active material, blank carrier, suitable conventional comparator, and a consistent bioassay capable of tracking potency across production batches.

Formulation also changes the unit for which safety and performance must be demonstrated. Encapsulation, nanoemulsification, inclusion complexes, and other delivery systems may alter droplet size, release, persistence, penetration, environmental transport, and organism exposure. Formulation is part of the hazard and exposure profile: pyrethrum nanocarriers require product-specific bee assessment rather than safety inference from botanical origin [16]. A carrier that increases target exposure may also increase exposure among pollinators, predators, aquatic organisms, or handlers. Consequently, formulation characterization should extend beyond particle size or encapsulation efficiency to include release behaviour, carrier controls, active loading, batch reproducibility, and changes in target and non-target effects. Natural origin is not equivalent to non-target safety, and greater delivery efficiency cannot automatically be interpreted as greater sustainability.

Storage stability requires linked chemical and biological measurements because initial activity does not establish retained product performance. Volatile and oxidation-prone constituents may be affected by light, oxygen, temperature, humidity, packaging, and interactions with carriers or co-formulants. Controlled-delivery systems may mitigate volatility, degradation, and poor persistence, but sustainability claims require concurrent evaluation of carrier fate, exposure, and non-target effects [17]. Similarly, cyclodextrin inclusion can improve essential-oil delivery, yet in silico target predictions remain hypotheses until confirmed by biochemical or physiological experiments [18]. Accelerated and real-time storage studies should therefore track marker compounds, degradation products, physical properties, release behaviour, and retained bioactivity under predefined conditions. Initial encapsulation efficiency is not equivalent to storage stability, and formulation feasibility is not equivalent to regulatory or commercial readiness. The evidence dimensions and interpretive boundaries for standardization formulation and storage stability are summarized in Table 2.

Table 2. Standardization, Formulation, and Storage Stability: Chemical Identity, Mechanism, Standardization, Formulation, Safety, Resistance, and Translation Requirements

Non-target safety and regulatory evaluation

Non-target safety is a product- and exposure-specific property rather than an attribute conferred by botanical origin. Relevant assessment begins by distinguishing intrinsic hazard from exposure and by identifying organisms likely to encounter the material through spray, residue, contaminated food, soil, water, drift, or treated commodities. Comparative assays show that pest activity and predator selectivity are separable properties, so efficacy cannot serve as a proxy for ecological safety [19]. Early screening against predators, parasitoids, pollinators, and other beneficial organisms can remove broadly toxic candidates before extensive formulation investment. Nevertheless, a favourable result for one species, life stage, route, or acute endpoint cannot establish community-level safety or exclude chronic, reproductive, behavioural, developmental, or mixture effects.

Field observations can strengthen ecological relevance by integrating pest suppression, crop response, beneficial insects, preparation, and local management, but they remain bounded by site and use pattern. Field evidence can integrate pest suppression, yield, product quality, and beneficial-insect observations, but such outcomes remain conditional on crop, location, preparation, and exposure [20]. Low observed harm may reflect limited exposure, application timing, avoidance, environmental dissipation, or insufficient sensitivity rather than intrinsic selectivity. Conversely, laboratory hazard may overpredict field risk where realistic exposure is low. Interpretation should therefore combine effect and exposure evidence while preserving differences among crude extracts, purified constituents, and finished formulations.

Chemical specificity improves hazard attribution but does not complete regulatory evaluation. Even when insecticidal activity is assigned to named constituents, target-pest toxicity does not establish non-target safety, acceptable exposure, or regulatory suitability [21]. Bee evidence contradicts the assumption that botanical origin guarantees benign non-target effects, particularly when species, formulation, dose, and exposure route differ [22]. Regulatory evaluation consequently requires a defined product identity, manufacturing controls, efficacy evidence, toxicology, ecotoxicology, exposure characterization, storage information, and an intended use pattern appropriate to the jurisdiction. The relevant unit is the marketed formulation, including impurities, carriers, co-formulants, and degradants. A review can identify these evidence requirements and gaps, but it cannot infer registration, approval, acceptable risk, or compliance for an individual product.

Translation bottlenecks from extract to registered product

Plant-to-product translation is a cumulative attrition process rather than a continuous extension of laboratory bioactivity. A candidate may fail because its source cannot be authenticated or supplied consistently, activity cannot be reproduced across batches, causal chemistry remains unresolved, formulation is unstable, non-target effects are unacceptable, manufacturing is impractical, or the intended market cannot support development. Natural-product commercialization is an attrition process in which biological promise can fail at manufacturing, formulation, toxicology, regulation, cost, or market adoption [23]. Because unsuccessful candidates are less visible in published literature, discovery success is systematically easier to observe than developmental failure. Translation-oriented research should therefore define stage-specific advancement criteria and record why candidates are reformulated, redirected, or discontinued.

The pathway should begin with an intended product profile that connects pest, crop or commodity, user, application method, performance requirement, safety context, storage condition, and target jurisdiction. Discovery, characterization, mechanism, standardization, formulation, safety, and regulatory planning then provide distinct decisions rather than interchangeable demonstrations of promise. Botanical substitution is constrained by variable composition, limited persistence, formulation needs, user practices, and regulatory requirements rather than efficacy alone [24]. Figure 1 maps the plant-to-product translation pathway within the analytical logic developed in this section.

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A structured conceptual diagram that maps the plant-to-product translation pathway, with labelled components, directional relations, contextual modifiers, uncertainty points, and a clear boundary between observed evidence and proposed synthesis.

Translation does not require every candidate to remain an unchanged crude extract. A promising natural molecule may reach crop protection through optimization or synthetic inspiration rather than direct commercialization of the original extract [25]. Translation requires simultaneous optimization of potency, selectivity, physicochemical properties, manufacturability, and use pattern, which explains why discovery success alone is an insufficient predictor [26]. Extract-based, purified-active, semisynthetic, and nature-inspired routes should therefore be compared according to the intended use rather than ranked by perceived naturalness. Major attrition points arise where evidence fails to connect across stages: activity without chemical identity, identity without scalable supply, mechanism without realistic performance, formulation without stability, efficacy without safety, and technical feasibility without regulatory or economic viability. Figure 2 illustrates the major attrition points between laboratory discovery and commercial adoption within the analytical logic developed in this section.

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A structured conceptual diagram that illustrates the major attrition points between laboratory discovery and commercial adoption, with labelled components, directional relations, contextual modifiers, uncertainty points, and a clear boundary between observed evidence and proposed synthesis.

Scoping synthesis and development priorities

The strongest convergent finding is that botanical materials can generate biologically credible insect-control candidates, but translation depends on solving use-specific delivery and persistence problems. For aphid control, essential oils remain promising, but development priorities must address volatility, persistence, delivery, crop compatibility, and realistic field testing [27]. This boundary applies more widely: laboratory activity establishes a candidate response under defined conditions, not operational effectiveness across crops, environments, application methods, or pest stages. Development studies should therefore use suitable comparators, report the tested material precisely, and link laboratory endpoints to the intended use without treating mortality as a universal measure of product value.

Botanical identity must also be resolved at a level capable of explaining chemical and biological variability. Mentha-based evidence shows why botanical identity must include species, chemotype, plant part, harvest, and extraction conditions rather than a genus label alone [28]. Similar names can encompass chemically distinct materials, while processing and storage may create additional divergence. Source selection should consequently combine ethnobotanical relevance with voucher identification, provenance, supply feasibility, and fit-for-purpose chemical profiling. Where activity depends on mixtures, standardization may require several markers or a validated biological assay rather than reliance on one abundant compound.

Formulation research provides important tools for improving solubility, dispersion, protection, release, and persistence, but novelty of the carrier is not the relevant endpoint. Across essential-oil research, innovations in delivery are meaningful only when they improve reproducibility, realistic efficacy, storage behaviour, and safety together [29]. Comparative formulation studies should include the active material, blank carrier, appropriate benchmark, realistic exposure, stability-linked potency, and product-specific non-target assessment. Mechanistic claims based on modelling should be experimentally tested, while lifecycle questions concerning carrier fate, manufacturing, packaging, and disposal should be integrated before sustainability conclusions are made.

The most consequential gap is the mismatch between a large discovery literature and a comparatively thin body of interoperable translation evidence. The literature remains concentrated in selected phytochemical classes, pest taxa, and laboratory endpoints, producing a large discovery record but a thinner translation evidence base [30]. Priorities should therefore include preregistered or prospectively specified comparisons, negative-result reporting, batch-linked chemistry and potency, depletion or recombination tests for mixture attribution, real-time stability studies, relevant non-target species, and stage-gated development decisions. Stored-grain applications demonstrate that development priorities must be use-case specific, incorporating commodity quality, persistence, residue, scale-up, and storage conditions [31]. The convergent findings, context-dependent results, methodological limitations, and remaining uncertainties are synthesized in Table 3.

Table 3. Scoping Synthesis and Development Priorities: Convergent Findings, Context Dependence, Methodological Limitations, Evidence Confidence, and Residual Uncertainty