Synthesis, Biological, and Computational Evaluations of Conformationally Restricted NAD-Mimics as Discriminant Inhibitors of Human NMN-Adenylyltransferase Isozymes.

Nicotinamide adenine dinucleotide (NAD) cofactor metabolism plays a significant role in cancer development. Tumor cells have an increased demand for NAD and ATP to support rapid growth and proliferation. Limiting the amount of available NAD by targeting critical NAD biosynthesis enzymes has emerged as a promising anticancer therapeutic approach. In mammals, the enzyme nicotinamide/nicotinic acid adenylyltransferase (NMNAT) catalyzes a crucial downstream reaction for all known NAD synthesis routes. Novel nicotinamide/nicotinic acid adenine dinucleotide (NAD/NaAD) analogues 1-4, containing a methyl group at the ribose 2'-C and 3'-C-position of the adenosine moiety, were synthesized as inhibitors of the three isoforms of human NMN-adenylyltransferase, named hNMNAT-1, hNMNAT-2, and hNMNAT-3. An NMR-based conformational analysis suggests that individual NAD-analogues (1-4) have distinct conformational preferences. Biological evaluation of dinucleotides 1-4 as inhibitors of hNMNAT isoforms revealed structural relationships between different conformations (North-anti and South-syn) and enzyme-inhibitory activity. Among the new series of NAD analogues synthesized and tested, the 2'-C-methyl-NAD analogue 1 (Ki = 15 and 21 µM towards NMN and ATP, respectively) emerged as the most potent and selective inhibitor of hNMNAT-2 reported so far. Finally, we rationalized the in vitro bioactivity and selectivity of methylated NAD analogues with in silico studies, helping to lay the groundwork for rational scaffold optimization.

Exploring the Efficacy of Four Apiaceae Essential Oils against Nine Stored-Product Pests in Wheat Protection.

The Apiaceae family, known for aromatic plants producing bioactive essential oils (EOs), holds significance across sectors, including agrochemicals. This study evaluated the insecticidal potential of four Apiaceae EOs from Crithmum maritimum L., Trachyspermum ammi (L.) Sprague ex Turrill, Smyrnium olusatrum L., and Elwendia persica (Boiss.) Pimenov and Kljuykov against various significant storage pests (Sitophilus oryzae (L.), Trogoderma granarium Everts, Rhyzopertha dominica (F.), Tribolium castaneum (Herbst), T. confusum Jacquelin du Val, Oryzaephilus surinamensis (L.), Alphitobius diaperinus (Panzer), Acarus siro L., and Tenebrio molitor L.) on wheat. Insect mortality rates were monitored at intervals of 1, 2, 3, 4, 5, 6, and 7 days. Smyrnium olusatrum EO exhibited the highest efficacy, followed by T. ammi, C. maritimum, and E. persica EOs, although efficacy varied by species, developmental stage, and concentration. Notably, complete mortality occurred for several pests at 1000 ppm of S. olusatrum and T. ammi EOs. Gas chromatography-mass spectrometry (GC-MS) analysis revealed key compounds in these EOs, including myrcene, germacrone, and curzerene in S. olusatrum EO, and thymol, γ-terpinene, and p-cymene in T. ammi EO. These findings emphasize their potential as botanical insecticides. Smyrnium olusatrum and T. ammi EOs emerge as promising eco-friendly pest management options due to their efficacy, highlighted compound composition, and availability of biomass from both wild and cultivated sources.

Microwave-assisted hydrodiffusion and gravity extraction: An efficient method to produce pomegranate juice.

Green technologies based on microwaves have been developed by the food industry to produce organoleptically acceptable fruit juices without preliminary processing. Microwave irradiation coupled with hydrodiffusion and gravity (MHG) combines microwave heating with the earth's gravity, allowing the collection of hydrophilic substances released from the irradiated matrix. To the best of our knowledge, MHG extraction has never been experimented to produce pomegranate juice. In this work, we have evaluated it as a potential alternative to the conventional squeezing. A central composite design study (CCD) allowed the selection of the best extractive conditions (irradiation power and extraction time) to obtain a pomegranate juice with higher yield, polyphenol (e.g., catechin and delphinidin-3,5-glucoside) content, and related bioactivities (antioxidant and antidiabetic) than the one obtained by squeezing while maintaining the chemical-physical properties. Thus, this technique appears to be a functional alternative to producing high value pomegranate juice.

Lethal and sublethal effects of carlina oxide on Tetranychus urticae (Acari: Tetranychidae) and Neoseiulus californicus (Acari: Phytoseiidae).

BACKGROUND: Tetranychus urticae Koch, is a polyphagous and damaging pest, presenting several resistant populations worldwide. Among new and more environmentally friendly control tools, botanical pesticides represent a valuable alternative to synthetic ones within integrated pest management strategies. Accordingly, we investigated the lethal and sublethal effects of carlina oxide isolated from Carlina acaulis (Asteraceae) roots on T. urticae and its natural enemy, the predatory mite, Neoseiulus californicus (McGregor). RESULTS: Carlina oxide (98.7% pure compound) was used for acaricidal tests on eggs, nymphs, and adult females of T. urticae (concentrations of 312.5, 625, 1250, 2500 and 5000 µL L-1 ), and eggs and females of N. californicus (1250 and 5000 µL L-1 on eggs and females, respectively). Behavioral two-choice tests were also conducted on phytoseiid females. Carlina oxide toxicity was higher on T. urticae females than nymphs (median lethal dose 1145 and 1825 µL L-1 , respectively), whereas egg mortality and mean hatching time were significantly affected by all tested concentrations. A decreasing daily oviposition rate for T. urticae was recorded with concentrations ranging from 625 to 5000 µL L-1 , whereas negative effects on the population growth rate were recorded only with the three higher concentrations (1250, 2500 and 5000 µL L-1 ). No toxic effect on N. californicus females was found, but a strong repellent activity lasting for 48 h from application was recorded. CONCLUSION: Carlina oxide reduced longevity and fecundity of T. urticae adults, but not of N. californicus. This selective property allows us to propose it as a novel active ingredient of ecofriendly acaricides for T. urticae management. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Editorial for the Special Issue "Antiprotozoal Activity of Natural Products".

Neglected tropical diseases (NTDs), a diverse group of infectious diseases, represent the leading cause of morbidity and mortality among the world's low-income populations [...].

Analgesic effect of Centaurium erythraea and molecular docking investigation of the major component swertiamarin.

Centaurium erythraea Rafn is employed in Algerian traditional medicine for treating pain. The analgesic activity of the ethanolic extract (EE) from the flowering aerial parts of this plant was examined, and molecular docking of the main bioactive compound was performed. The EE, characterised by the iridoid swertiamarin, was administered to Wistar albino rats in pain models. Peripheral analgesic activity was evaluated using the acetic acid-induced writhing test, and a hot plate test was performed for central antinociceptive activity evaluation. Treatment with EE significantly decreased rats' writhing induced by acetic acid suggesting peripheral analgesic activity. Furthermore, the elevation of mean basal reaction time in the hot plate method indicated central analgesic activity. Molecular docking studies showed good docking energy with acceptable binding interactions of swertiamarin with cyclooxygenase-2 protein. This supports the analgesic activity of C. erythraea EE, justifying the traditional use of the plant as an analgesic herbal remedy.

Plant-Derived Epi-Nutraceuticals as Potential Broad-Spectrum Anti-Viral Agents.

Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to their inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances in which vaccination is not accessible or in individuals with compromised immune systems, drugs can provide additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Moreover, targeting host factors allows us to develop compounds that are effective against different viral variants as well as against newly emerging virus strains. In recent years, the globe has experienced climate change, which may contribute to the emergence and spread of infectious diseases through a variety of factors. Warmer temperatures and changing precipitation patterns can increase the geographic range of disease-carrying vectors, increasing the risk of diseases spreading to new areas. Climate change may also affect vector behavior, leading to a longer breeding season and more breeding sites for disease vectors. Climate change may also disrupt ecosystems, bringing humans closer to wildlife that transmits zoonotic diseases. All the above factors may accelerate the emergence of new viral epidemics. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds, including those with anti-viral activity. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Interest in herbal antiviral products has increased. More than 50% of approved drugs originate from herbal sources. Plant-derived compounds offer diverse structures and bioactive molecules that are candidates for new drug development. Combining these therapies with conventional drugs could improve patient outcomes. Epigenetics modifications in the genome can affect gene expression without altering DNA sequences. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses recruit cellular epitranscriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells' epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we explore the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing their modulation processes and anti-viral effects on DNA and RNA viruses, as well as addressing future research objectives in this rapidly emerging field.

Phenotypic and Genotypic Comparison of Antimicrobial-Resistant Variants of Escherichia coli and Salmonella Typhimurium Isolated from Evolution Assays with Antibiotics or Commercial Products Based on Essential Oils.

On account of the widespread development and propagation of antimicrobial-resistant (AMR) bacteria, essential oils (EOs) have emerged as potential alternatives to antibiotics. However, as already observed for antibiotics, recent studies have raised concerns regarding the potential emergence of resistant variants (RVs) to EOs. In this study, we assessed the emergence of RVs in Escherichia coli and Salmonella enterica Typhimurium after evolution assays under extended exposure to subinhibitory doses of two commercial EOs (AEN and COLIFIT) as well as to two antibiotics (amoxicillin and colistin). Phenotypic characterization of RVs from evolution assays with commercial EOs yielded no relevant increases in the minimum inhibitory concentration (MIC) of E. coli and did not even modify MIC values in S. Typhimurium. Conversely, RVs of E. coli and S. Typhimurium isolated from evolution assays with antibiotics showed increased resistance. Genotypic analysis demonstrated that resistance to commercial EOs was associated with enhanced protection against oxidative stress and redirection of cell energy toward efflux activity, while resistance to antibiotics was primarily linked to modifications in the cell binding sites of antibiotics. These findings suggest that AEN and COLIFIT could serve as safe alternatives to antibiotics in combating the emergence and dissemination of antimicrobial resistance within the agrifood system.

Acmella oleracea extracts as green pesticides against eight arthropods attacking stored products.

Developing sustainable control tools for managing noxious pests attacking stored foodstuffs is a timely research challenge. Acmella oleracea (L.) R. K. Jansen is a crop widely cultivated for its multiple usages on an industrial level. In this study, the extracts prepared with A. oleracea aerial parts were applied on wheat kernels for the management of eight important arthropod pests attacking stored products, i.e., Cryptolestes ferrugineus, Tenebrio molitor, Oryzaephilus surinamensis, Trogoderma granarium, Tribolium castaneum, Tribolium confusum, Alphitobius diaperinus (adults/larvae), and Acarus siro (adults/nymphs). Extraction of A. oleracea was optimized on the base of the yield and content of spilanthol and other N-alkylamides which were analysed by HPLC-DAD-MS. Two concentrations of n-hexane or methanol extracts (500 ppm and 1000 ppm), obtained through Soxhlet extraction, were tested to acquire mortality data on the above-mentioned pests after 4, 8, and 16 h and 1 to 7 days of exposure. Both extracts achieved complete mortality (100.0%) of C. ferrugineus adults. In the case of A. diaperinus adults, mortalities were very low at any concentrations of both extracts. In general, the n-hexane extract was more efficient than methanol extract against almost all species and stages. Considering both extracts, the susceptibility order, from most to least susceptible species/stage, was C. ferrugineus adults > A. diaperinus larvae > C. ferrugineus larvae > T. granarium adults > T. molitor larvae > O. surinamensis adults > O. surinamensis larvae > T. confusum larvae > T. castaneum larvae > A. siro adults > T. molitor adults > A. siro nymphs > T. granarium larvae > T. castaneum adults > T. confusum adults > A. diaperinus adults. Our research provides useful knowledge on the efficacy of N-alkylamides-rich A. oleracea extracts as grain protectants, pointing out the importance of targeting the most susceptible species/ developmental stages.

Synthesis of Carlina Oxide Analogues and Evaluation of Their Insecticidal Efficacy and Cytotoxicity.

Compounds isolated from botanical sources represent innovative and promising alternatives to conventional insecticides. Carlina oxide is a compound isolated from Carlina acaulis L. (Asteraceae) essential oil (EO) with great potential as bioinsecticide, being effective on various arthropod vectors and agricultural pests, with moderate toxicity on non-target species. Since the production from the wild source is limited, there is the need of exploring new synthetic routes for obtaining this compound and analogues with improved bioactivity and lower toxicity. Herein, the chemical synthesis of carlina oxide analogues was developed. Their insecticidal activity was assessed on the vectors Musca domestica L. and Culex quinquefasciatus Say, and their cytotoxicity was evaluated on a human keratinocyte cell line (HaCaT). The compounds' activity was compared with that of the natural counterparts EO and carlina oxide. In housefly tests, the analogues were comparably effective to purified carlina oxide. In Cx. quinquefasciatus assays, the meta-chloro analogue provided a significantly higher efficacy (LC50 of 0.71 µg mL-1) than the EO and carlina oxide (LC50 1.21 and 1.31 µg mL-1, respectively) and a better safety profile than carlina oxide on keratinocytes. Overall, this study can open the way to an agrochemical production of carlina oxide analogues employable as nature-inspired insecticides.

Free Amino Group Transfer via α-Amination of Native Carbonyls.

We report herein a straightforward transfer of a free amino group (NH2 ) from a commercially available nitrogen source to unfunctionalized, native carbonyls (amides and ketones) resulting in direct α-amination. Primary α-amino carbonyls are readily produced under mild conditions, further enabling diverse in situ functionalization reactions-including peptide coupling and Pictet-Spengler cyclization-that capitalize on the presence of the unprotected primary amine.

Efficacy of Mentha aquatica L. Essential Oil (Linalool/Linalool Acetate Chemotype) against Insect Vectors and Agricultural Pests.

In recent years, agrochemical industries have been focused on the development of essential oil (EO)-based biopesticides, which can be considered valuable alternatives to traditional chemical products. The genus Mentha (Lamiaceae) comprises 30 species characterized by a wide range of biological activities, and some of their EOs showed good potential as pesticidal agents. In this regard, the aim of this study was to evaluate the insecticidal activity of the EO obtained from a rare linalool/linalool acetate chemotype of Mentha aquatica L. The EO was found to be highly effective against Culex quinquefasciatus (Say) 2nd instar larvae, Metopolophium dirhodum (Walker) adults, Spodoptera littoralis (Boisduval) 2nd instar larvae, and Tetranychus urticae (Koch) adults, showing lethal concentrations (LC50) or doses (LD50) of 31.5 ± 2.2 µL L-1, 4.9 ± 0.8 mL L-1, 18.5 ± 2.1 µg larvae-1, and 3.3 ± 0.5 mL L-1, respectively. On the contrary, Musca domestica L. adults and 3rd instar larvae of C. quinquefasciatus and S. littoralis were moderately affected by the treatment (LC50 or LD50: 71.4 ± 7.2 µg adult-1, 79.4 ± 5.2 µL L-1, 44.2 ± 5.8 µg larvae-1, respectively). The results obtained in this work demonstrated that various insects and pests could be differently sensible to the same EO and may lead to the exploitation of this plant or its major volatile compounds as novel ingredients of botanical insecticides and pesticides.

The Type of Grain Counts: Effectiveness of Three Essential Oil-Based Nanoemulsions against Sitophilus oryzae.

Essential oil (EO)-based nanoemulsions (NEs) are promising grain protectants in the management of stored-product pests. However, the potential impact of the stored-grain species on the green insecticide effectiveness has been poorly studied. In this study, two concentrations of EO-based NEs from Carlina acaulis L., Mentha longifolia (L.) Huds., and Hazomalania voyronii (Jum.) Capuron were evaluated as insecticides against the major stored-product pest Sitophilus oryzae (L.) on barley, oats, and maize kernels. The C. acaulis EO-based NE applied at 1000 ppm on barley achieved the highest mortality, killing 94.4% of S. oryzae adults after a 7-day exposure, followed by 1000 ppm of H. voyronii EO-based NE (83.3%). The lowest mortality (1.1%) was recorded with 500 ppm of M. longifolia EO-based NE on maize after the same interval. All tested NEs exhibited elevated efficacy when applied on barley, while mortalities were lower on oats and maize. Furthermore, C. acaulis EO-based NE was the most effective when applied on all commodities, followed by H. voyronii and M. longifolia EO-based NEs. Overall, our results highlighted the significant impact of the stored cereal on the insecticidal effectiveness of EO-based NE used for stored-product pest control. Sitophilus oryzae adults on barley can be adequately controlled through the application of C. acaulis and H. voyronii EO-based NEs.

Microwave-Assisted Hydrodistillation of the Insecticidal Essential Oil from Carlina acaulis: A Fractional Factorial Design Optimization Study.

Recently, microwave-assisted hydrodistillation (MAH) has been reported as an innovative technique leading to increased essential oil (EO) extraction yield, coupled with reduced extraction time and energy costs. The EO of Carlina acaulis L. (Asteraceae), mainly constituted by carlina oxide (>95%) and conventionally obtained through traditional hydrodistillation (HD), has been reported as extremely effective against several arthropod vectors and pests of medical and economic importance with limited impact on non-target species, including mammals. This study aimed to the optimization of the EO extraction through MAH by using a one-step design of experiments (DoE) approach that allowed us to relate the characteristics of the produced EOs with the applied experimental conditions using mathematical models. The preliminary screening allowed us to optimize the protocol only by the extraction time, skipping complex data analysis. Moreover, the comparison of the optimized MAH conditions with traditional HD pointed out the higher efficiency of MAH in terms of EO yield (0.65 and 0.49% for MAH and HD, respectively) and extraction time (210 min for MAH). The results obtained confirmed the promising role that MAH could have in C. acaulis EO extraction, with increased yield and reduced extraction time, water consumption, and energy costs, and being employable on an industrial scale, with special reference to insecticidal and acaricidal formulations.

The Essential Oil from the Resurrection Plant Myrothamnus moschatus Is Effective against Arthropods of Agricultural and Medical Interest.

This work aimed to evaluate the chemical composition, insecticidal and acaricidal potential of the essential oil (EO) obtained from the resurrection plant Myrothamnus moschatus (Baill.) Baill. (Myrothamnaceae) from Madagascar. The EO bioactivity was evaluated against selected arthropod pests and vectors of agricultural and public health relevance. The most abundant volatile compounds were trans-pinocarveol (37.7 ± 4.2%) and pinocarvone (20.8 ± 3.1%), similar to the EO of the chemotype collected from the same region. Lethal concentrations (LC50) or doses (LD50) from acute toxicity tests were estimated for Musca domestica (L.) adults at 22.7 µg adult-1, for Spodoptera littoralis (Boisduval) larvae at 35.6 µg larva-1, for Culex quinquefasciatus (Say) at 43.6 µg mL-1, for adults of Metopolophium dirhodum (Walker) at 2.4 mL L-1, and for adults of Tetranychus urticae (Koch) at 1.2 mL L-1. The good insecticidal and acaricidal activities determined in this work may open a new perspective on the use of this plant as a source of botanical insecticide ingredients. The exploitation of this species could also be important for the African economy, helping local farmers cultivating this plant.

A Review of the Chemistry and Biological Activities of Acmella oleracea ("jambù", Asteraceae), with a View to the Development of Bioinsecticides and Acaricides.

Human pathologies, environmental pollution, and resistance phenomena caused by the intensive use of chemical pesticides have shifted the attention of the agrochemical industries towards eco-friendly insecticides and acaricides. Acmella oleracea (L.) R. K. Jansen (jambù) is a plant native to South America, widely distributed and cultivated in many countries due to its numerous pharmacological properties. This review analyzes literature about the plant, its uses, and current knowledge regarding insecticidal and acaricidal activity. Acmella oleracea has proven to be a potential pesticide candidate against several key arthropod pest and vector species. This property is inherent to its essential oil and plant extract, which contain spilanthol, the main representative of N-alkylamides. As a result, there is a scientific basis for the industrial exploitation of jambù in the preparation of green insecticides. However, studies related to its toxicity towards non-target species and those aimed at formulating and developing marketable products are lacking.

Insecticidal Activity of Four Essential Oils Extracted from Chilean Patagonian Plants as Potential Organic Pesticides.

Patagonia is a geographical area characterized by a wide plant biodiversity. Several native plant species are traditionally used in medicine by the local population and demonstrated to be sources of biologically active compounds. Due to the massive need for green and sustainable pesticides, this study was conducted to evaluate the insecticidal activity of essential oils (EOs) from understudied plants growing in this propitious area. Ciprés (Pilgerodendron uviferum), tepa (Laureliopsis philippiana), canelo (Drimys winteri), and paramela (Adesmia boronioides) EOs were extracted through steam distillation, and their compositions were analyzed through GC−MS analysis. EO contact toxicity against Musca domestica L., Spodoptera littoralis (Boisd.), and Culex quinquefasciatus Say was then evaluated. As a general trend, EOs performed better on housefly males over females. Ciprés EO showed the highest insecticidal efficacy. The LD50(90) values were 68.6 (183.7) and 11.3 (75.1) µg adult−1 on housefly females and males, respectively. All EOs were effective against S. littoralis larvae; LD50 values were 33.2−66.7 µg larva−1, and tepa EO was the most effective in terms of LD90 (i.e., <100 µg larva−1). Canelo, tepa, and paramela EOs were highly effective on C. quinquefasciatus larvae, with LC50 values < 100 µL L−1. Again, tepa EO achieved LD90 < 100 µL L−1. This EO was characterized by safrole (43.1%), linalool (27.9%), and methyl eugenol (6.9%) as major constituents. Overall, Patagonian native plant EOs can represent a valid resource for local stakeholders, to develop effective insecticides for pest and vector management, pending a proper focus on their formulation and nontarget effects.

Carlina acaulis essential oil nanoemulsion as a new grain protectant against different developmental stages of three stored-product beetles.

BACKGROUND: Plant essential oils (EOs) represent eco-friendly alternatives to conventional insecticides for managing pest populations. Carlina acaulis root EO showed a wide insecticidal spectrum, being highly effective against insect pests and vectors, coupled with low mammal toxicity. To boost the chemico-physical properties of this EO and its main active ingredient, carlina oxide, C. acaulis EO was encapsulated in a nanoemulsion [NE, 6% EO (w/w)], and its insecticidal properties evaluated against larvae and adults of Tribolium castaneum, Tribolium confusum and Tenebrio molitor. Two NE concentrations (500 and 1000 ppm) were applied on stored wheat. Mortality was determined after 4, 8 and 16 h and 1, 2, 3, 4, 5, 6 and 7 days. RESULTS: The NE was toxic to larvae of T. castaneum and T. confusum, killing 93.9% and 98.9% at 1000 ppm after 7 days of exposure, respectively. Tenebrio molitor larvae were tolerant: only 18.9% were dead after 7 days of exposure on stored wheat treated with 1000 ppm NE. However, the NE exhibited high adulticidal activity leading to 85.2% mortality at 1000 ppm, 7 days post-exposure. The mortalities of T. confusum and T. castaneum adults were low (21.4% and 23.3% respectively) at 1000 ppm, 7 days post-exposure. CONCLUSIONS: A NE based on C. acaulis EO could be regarded as an efficacious green adulticide or larvicide, depending on the target insect species and its life stage, advancing and specifying the pest management strategies of the tested species in an eco-friendly way. © 2022 Society of Chemical Industry.

Lethal and behavioural effects of a green insecticide against an invasive polyphagous fruit fly pest and its safety to mammals.

Plant essential oil-based insecticides, with special reference to those that may be obtained from largely available biomasses, represent a valuable tool for Integrated Pest Management. However, the sublethal effects and the potential effects on aggressive insect traits of these green insecticides are understudied. Herein, the lethal and sub-lethal effects of the carlina oxide, constituting more than 97% of the whole Carlina acaulis (Asteraceae) root essential oil (EO), were determined against an invasive polyphagous tephritid pest, Ceratitis capitata (medfly). The carlina oxide was formulated in a mucilaginous solution containing carboxymethylcellulose sodium salt, sucrose, and hydrolysed proteins, showing high ingestion toxicity on medfly adults. The behavioural effects of carlina oxide at LC10 and LC30 were evaluated on the medfly aggressive traits, which are crucial for securing reproductive success in both sexes. Insecticide exposure affected the directionality of aggressive actions, but not the aggression escalation intensity and duration. The EO safety to mammals was investigated by studying its acute toxicity on the stomach, liver, and kidney of rats after oral administration. Only the highest dose (1000 mg/kg) of the EO caused modest neurological signs and moderate effects on the stomach, liver, and kidney. The other doses, which are closer to the practical use of the EO when formulated in protein baits, did not cause side effects. Overall, C. acaulis-based products are effective and safe to non-target mammals, deserving further consideration for eco-friendly pesticide formulations.