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Mosquitoes and mosquito-borne diseases represent an increasing global challenge. Plant extract and/or oils could serve as alternatives to synthetic insecticides. The larvicidal effects of 32 oils (1000 ppm) were screened against the early 4th larvae of Culex pipiens and the best oils were evaluated against adults and analyzed by gas chromatography-mass spectrometry (GC mass) and HPLC. All oils had larvicidal activity (60.0–100%, 48 h Post-treatment, and their Lethal time 50 (LT 50 ) values ranged from 9.67 ( Thymus vulgaris ) to 37.64 h ( Sesamum indicum ). Oils were classified as a highly effective group (95–100% mortalities), including Allium sativum, Anethum graveolens, Camellia sinensis, Foeniculum vulgare, Nigella sativa, Salvia officinalis, T. vulgaris, and Viola odorata. The moderately effective group (81–92% mortalities) included Boswellia serrata, Cuminum cyminum, Curcuma aromatic, Allium sativum, Melaleuca alternifolia, Piper nigrum, and Simmondsia chinensis . The least effective ones were C. sativus and S. indicum. Viola odorata, Anethum graveolens, T. vulgaris, and N. sativa provide 100% adult mortalities PT with 10, 25, 20, and 25%. The mortality percentages of the adults subjected to 10% of oils (H group) were 48.89%, 88.39%, 63.94%, 51.54%, 92.96%, 44.44%, 72.22%, and 100% for A. sativum, An. graveolens, C. sinensis, F. vulgare, N. sativa, S. officinalis, T. vulgaris, and V. odorata, respectively. Camellia sinensis and F. vulgare were the most potent larvicides whereas V. odorata, T. vulgaris, An. graveolens and N. sativa were the best adulticides and they could be used for integrated mosquito control.

Background. This investigation was designed to evaluate the insecticidal, antiplasmodial, anti-leishmanial, and cytotoxic effects of Capparis spinosa essential oil (CSEO) and its main components, methyl isothiocyanate, hexadecanoic acid, and limonene. Methods. Insecticidal activity of CSEO and its main components, methyl isothiocyanate, hexadecanoic acid, and limonene, was determined against Aedes aegypti 4th-instar larvae at 25 ± 2°C. Antiplasmodial and anti-leishmanial effects of CSEO and its main components were carried out against chloroquine-resistant Plasmodium falciparum K1 strain and Leishmania major amastigotes based on the Malstat method and the macrophage model, respectively. We also performed the cytotoxic activity of CZEO and its main components against J774A1 macrophage cells using the colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. In addition, the plasma membrane permeability and caspase-3-like activity CSEO and its main components were evaluated against L. major. Results. CSEO and its main components showed considerable (p<0.001) larvicidal activity against Ae. aegypti larva. The 50% lethal concentration values for CSEO, methyl isothiocyanate, hexadecanoic acid, and limonene were 21.6, 30.9, 41.6, and 35.3 μg/mL, respectively. By antiplasmodial effects, the 50% inhibitory concentration (IC50) values for CSEO, methyl isothiocyanate, hexadecanoic acid, and limonene were 7.4, 14.5, 19.6, and 21.3 μg/mL, respectively, while these values for their anti-leishmanial effects were 9.1, 20.7, 23.3, and 18.6 μg/mL, respectively. The 50% cytotoxic concentration values for CSEO, methyl isothiocyanate, hexadecanoic acid, and limonene were 93.7, 216.2, 199.4, and 221.3 μg/mL, respectively. Different concentrations of CSEO and its main components significantly (p<0.05) increased the plasma membrane permeability and caspase-3-like activity against L. major promastigote level as dose-dependent response. Conclusion. Based on the obtained results, C. spinosa essential oil and its main components, methyl isothiocyanate, hexadecanoic acid, and limonene, displayed insecticidal, antiplasmodial, and anti-leishmanial activity against healthy 4th-instar larvae of A. aegypti, chloroquine-resistant P. falciparum K1 strain, and L. major amastigotes, respectively. However, further surveys are required to display the mechanisms of action mode of tested drugs and their efficacy in animal model and clinical settings.

Natural products and their derivatives as an inexpensive, accessible, and useful alternative medicine are broadly applied for the treatment of a wide range of diseases and infectious ones. The present study was designed to evaluate the insecticidal, antimalarial, antileishmanial, and cytotoxic effects of royal jelly and its three main fatty acids (trans-10-hydroxy-2-decenoic acid (10-H2DA), 10-hydroxydecanoic acid (10-HDAA), sebacic acid (1,10-decanedioic acid)). Insecticidal activity of RJ and 10-H2DA, 10-HDAA, and sebacic acid was performed against healthy 4th instar larvae at 25 ± 2°C. Antiplasmodial and antileishmanial effects of RJ and 10-H2DA, 10-HDAA, and sebacic acid were also performed against chloroquine-resistant Plasmodium falciparum K1-strain and Leishmania major amastigotes according to the Malstat method and macrophage model, respectively. In addition, the level of nitric oxide (NO) production in J774-A1 macrophages cells, plasma membrane permeability, and caspase-3-like activity and cytotoxicity effects of RJ and 10-H2DA, 10-HDAA, and sebacic acid against human embryonic kidney 293 (HEK239T cells) were evaluated. Considering the insecticidal activity, the results showed that the lethal concentration 50% value for RJ, 10-H2DA, 10-HDAA, and sebacic acid was 24.6, 31.4, 37.8, and 44.7 μg/mL μg/mL, respectively. RJ, 10-H2DA, 10-HDAA, and sebacic acid showed potent (P<0.0001) antileishmanial effects with IC50 values ranging from 2.4 to 8.4 μg/mL. Various concentrations of RJ, 10-H2DA, 10-HDAA, and sebacic acid significantly (P<0.05) increased the production of NO, plasma membrane permeability, and caspase-3-like activity level as a dose-dependent response. Considering the cytotoxicity, SIs > 10 of these compounds exhibited their specificity to parasites and safety against human HEK239T normal cells. The results of the present investigation revealed the promising insecticidal, antimalarial, and antileishmanial effects of RJ and its three main fatty acids (10-H2DA, 10-HDAA, and sebacic acid). However, more studies are required to confirm the mechanisms of action mode of these compounds as well as their efficacy in animal models and clinical settings.

Mosquitoes are one of the deadliest and most hazardous animals on Earth, where they transmit several diseases that kill millions of people annually. There is an ongoing search almost everywhere in the world for more effective and contemporary ways to control mosquitoes other than pesticides. Phytochemicals are affordable, biodegradable biological agents that specialize in eliminating pests that represent a risk to public health. The effectiveness of Acacia nilotica methanol and aqueous leaf extracts against 4th instar larvae was evaluated. The results revealed that the methanol extract of A. nilotica had a noticeable influence on the mortality rate of mosquito larvae, especially at high concentrations. Not only did the mortality rate rise significantly, but the hatching of the mosquito eggs was potentially suppressed.Terpenes, fatty acids, esters, glycosides, pyrrolidine alkane, piperazine, and phenols were the most prevalent components in the methanol extract, while the aqueous extract of A. nilotica exclusively showed the presence of fatty acids. The insecticidal susceptibility tests of both aqueous and alcoholic extract of A. nilotica confirmed that the Acacia plant could serves as a secure and efficient substitute for chemical pesticides because of its promising effect on killing larvae and egg hatching delaying addition to their safety as one of the natural pesticides. Molecular docking study was performed using one of the crucial and life-controlling protein targets, fatty acid binding protein (FABP) and the most active ingredients as testing ligands to describe their binding ability. Most of the structurally related compounds to the co-crystallized ligand, OLA, like hexadecanoic acid furnished high binding affinity to the target protein with very strong and stable intermolecular hydrogen bonding and this is quite similar to OLA itself. Some other structural non-related compounds revealed extraordinarily strong binding abilities like Methoxy phenyl piperazine. Most of the binding reactivities of the majortested structures are due to high structure similarity between the positive control, OLA, and tested compounds. Such structure similarity reinforced with the binding abilities of some detected compounds in the A. nilotica extract could present a reasonable interpretation for its insecticidal activity via deactivating the FABP protein. The FABP4 enzyme inhibition activity was assessed for of both methanolic and aqueous of acacia plant extract and the inhibition results of methanol extract depicted noticeable potency if compared to orlistat, with half-maximal inhibitory concentration (IC 50 ) of 0.681, and 0.535 µg/ml, respectively.

Mosquitoes, one of the deadliest animals on the planet, cause millions of fatalities each year by transmitting several human illnesses. Synthetic pesticides were previously used to prevent the spread of diseases by mosquitoes, which was effective in protecting humans but caused serious human health problems, environmental damage, and developed mosquito pesticide resistance. This research focuses on exploring new, more effective, safer, and environmentally friendly compounds to improve mosquito vector management. Phytochemicals are possible biological agents for controlling pests and many are target-specific, rapidly biodegradable, and eco-friendly. The potential of extracts of Lantana camara, Melia azedarach, Nerium oleander, Ricinus communis, and Withania somnifera against 3rd instar Culex pipiens (Common house mosquito) larvae was evaluated. Methanol extracts had more toxic effects against Cx. pipiens larvae (95–100%, 24 h post-treatment) than aqueous extracts (63–91%, 24 h post-treatment). The methanol extracts of Nerium oleander (LC 50  = 158.92 ppm) and Ricinus communis (LC 50  = 175.04 ppm) were very effective at killing mosquito larvae, 24 h after treatment. N. oleander (LC 50  = 373.29 ppm) showed high efficacy in aqueous plant extracts. Among the different extracts of the five plants screened, the methanol extract of R. communis recorded the highest ovicidal activity of 5% at 800 ppm concentration. Total developmental duration and growth index were highly affected by R. communis and M. azedarach methanol extracts. In field tests it was clear that plant extracts decreased mosquito larval density, especially when mixed with mosquito Bti briquette, with stability up to seven days for N. oleander . GC–MS results showed that the methanol extract had a higher number of chemical compounds, particularly with more terpene compounds. A high-performance liquid chromatography (HPLC) technique was used to detect the existence of non-volatile polyphenols and flavonoids. All five methanol extracts showed high concentrations of active ingredients such as gallic acid, chlorogenic acid (more than 100 μg/ml) and the rosmarinic acid was also found in all the five extracts in addition to 17 active polyphenols and flavonoids presented at moderate to low concentrations. Molecular modeling of 18 active ingredients detected by the HPLC were performed to the vicinity of one of the fatty acid binding proteins of lm -FABP (PDB code: 2FLJ ). Rutin, Caffeic acid, coumaric acid and rosmarinic acid which presented densely in R. communis and N. oleander showed multiple and stable intermolecular hydrogen bonding and π–π stacking interactions. The inhibition ability of the fatty acid binding protein, FABP4, was evaluated with remarkable receptor inhibition evident, especially with R. communis and N. oleander having inhibitory concentrations of IC 50  = 0.425 and 0.599 µg/mL, respectively. The active phytochemical compounds in the plants suggest promising larvicidal and ovicidal activity, and have potential as a safe and effective alternative to synthetic insecticides.

(1) Background: Mosquito control with essential oils is a growing demand. This work evaluated the novel larvicidal and adulticidal activity of fennel and green tea oils and their Layered double hydroxides (LDHs) nanohybrid against Culex pipiens (Cx. pipiens) in both laboratory and field conditions and evaluated their effect against non-target organisms; (2) Methods: Two types of nanoclays, MgAl-LDH and NiAl-LDH were synthesized and characterized using PXRD, TEM and SEM, whereas their elemental analysis was accomplished by SEM-EDX; (3) Results: Mg and Ni LDHs were synthesized by the co-precipitation method. The adsorption and desorption of active ingredients were conducted using LC MS/MS, with reference to the SEM-EXD analysis. The desorption process of MgAl-LDH intercalated green tea oil was conducted using ethanol, and reveled significant peaks related to polyphenols and flavonoids like Vanillin, Catechin, Daidzein, Ellagic acid, Naringenin, Myricetin and Syringic acid with concentrations of 0.76, 0.73, 0.67, 0.59, 0.52, 0.44 and 0.42 μg/g, respectively. The larvicidal LC50 values of fennel oil, Mg-LDH-F, and Ni-LDH-F were 843.88, 451.95, 550.12 ppm, respectively, whereas the corresponding values of green tea were 938.93, 530.46, and 769.94 ppm. The larval reduction percentage of fennel oil and Mg-LDH-F reached 90.1 and 96.2%, 24 h PT and their persistence reached five and seven days PT, respectively. The reduction percentage of green tea oil and Mg-LDH-GT reached 88.00 and 92.01%, 24 h PT and their persistence reached five and six days PT, respectively. Against adults, Mg-LDH-GT and Ni-LDH-GT were less effective than green tea oil as their LC95 values were 5.45, 25.90, and 35.39%, respectively. The reduction in adult density PT with fennel oil, Mg-LDH-F, green tea oil, and Mg-LDH-GT reached 83.1, 100, 77.0, and 99.0%, respectively, 24 h PT and were effective for three days. Mg-LDH-GT and Mg-LDH-F increased the predation Cybister tripunctatus (71% and 69%), respectively; (4) Conclusions: For the first time, Mg-LDH-GT and Mg-LDH-F was the best system loaded with relatively good desorption release to its active ingredients and significantly affected Cx. pipiens larvae and adults in both laboratory and field circumstances, and it could be included in mosquito control.

(1) Background: A molecular hybridization docking approach was employed to develop and detect a new category of naturally activated compounds against Culex pipiens as acetylcholinesterase inhibitors via designing a one-pot multicomponent nano-delivery system. (2) Methods: A nanostructure lipid carrier (NLC), as a second generation of solid lipid nanoparticles, was used as a carrier to deliver the active components of curcumin (Cur), geraniol (G), and linalool (L) in one nanoformulation after studying their applicability in replacing the co-crystallized ligand imidacloprid. (3) Results: The prepared nanostructure showed spherical-shaped, polydisperse particles ranging in size from 50 nm to 300 nm, as found using a transmission electron microscope. Additionally, dynamic light scattering confirmed an average size of 169 nm and a highly stable dispersed solution, as indicated by the zeta potential (−38 mV). The prepared NLC-Cur-LG displayed competitive, high-malignancy insecticidal activity against fourth instar C. pipiens with an elevated rate of death of 0.649 µg/mL. The treatment, due to the prepared nanostructure, affects oxidative stress enzymes, e.g., hydrogen peroxide (4 ppm), superoxide dismutase (SOD) (0.03 OD/mg), and protein carbonyl (0.08 OD/mg), and there are observable upward and downward fluctuations when using different concentrations of NLC-Cur-LG, suggesting significant problems in its foreseeable insecticidal activity. The acetylcholinesterase activity was assessed by an enzyme inhibition assay, and strengthened inhibition occurred due to the encapsulated NLCs (IC50 = 1.95 µg/mL). An investigation of the gene expression by Western blotting, due to treatment with NLC-Cur-LG, revealed a severe reduction of nearly a quarter of what was seen in the untreated group. As a preliminary safety step, the nanoformulation’s toxicity against normal cell lines was tested, and a reassuring result was obtained of IC50 = 158.1 µg/mL for the normal lung fibroblast cell line. (4) Conclusions: the synthesized nanoformulation, NLC-Cur-LG, is a useful insecticide in field conditions.

Solid lipid nanoparticles second generation, nanostructure lipid carrier (NLC), is one of the most important biodegradable nanoparticles. Nanostructure Lipid carrier (NLC) was used to encapsulate methylene blue (MB) dye, carvacrol and citronellal and their efficacy as insecticidal against Culex pipiens ( Cx. pipiens ) were distinguished. The prepared nanoformulation revealed very good physicochemical properties, especially the homogeneity of the particle size. Transmission electron microscope showed spherical shaped nanoparticles within range less than 200 nm. The prepared NLC-MB-MT system showed a very competitive insecticidal activity and high virulence against the mosquito larvae with higher mortality rate of LC 50 of 0.141 µl/mL, in addition to high level of Oxidative stress parameters obtained through all the tested enzymes including hydrogen peroxide (4.8 ppm), protein carbonyl amount (0.12 OD/mg protein), ascorbic acid (0.15 mg) and Superoxide dismutase (SOD) showed strong increasing (0.09 OD/mg protein/min) at 6 µg/mL, respectively. Whereas paradoxical results of the oxidative stress enzymes were obtained from different concentration of nanoformulation that introduce a convenient reason for their potential insecticidal effect. The cytotoxic effect of NLC-MB-MT was evaluated using WI38 human lung cell lines, the LC 50 was 6.4 mg/mL. The low cytotoxic reactivity towards the tested cell line makes the NLC-MB-MT nanoformulation has its promising insecticidal efficacy. Molecular docking study for each component were done against acetylcholine esterase protein and accepted binding modes achieved by the three compounds.

Monoterpenes are one of the most common groups belonging to the terpenoid family, with a C10 structure comprising of two isoprene units. Most of monoterpenes are volatile plant compounds, and they act as signaling molecules between plants and the environment, particularly as defensive compounds against herbivores and pathogens. In this study, 1,8-cineole synthase ( SgCINS ) gene was identified and cloned from the leaves of Salvia guaranitica plant. To examine the role of SgCINS in insect resistance, we transformed and expressed this gene into tobacco leaves. The metabolic analysis revealed that the production of various types and amount of terpenoid was increased and decreased in SgCINS overexpression and control lines, respectively, suggesting that overexpressing SgCINS in transgenic tobacco plants lead to an increase in the production of various types of terpenoids and other phytochemical compounds. These results indicated why transgenic tobacco was highly resistant against cotton worm than the highly susceptible control plants. Our results demonstrate that the SgCINS gene can play an important role in plants against cotton worm insect attack, and pave the way for using terpenoids genes for improving resistance to insect attack in higher plants.

Mosquito-borne diseases represent a growing health challenge over time. Nanostructured lipid carriers (NLCs) are the second generation of solid lipid nanoparticles (SLNs), and they continue to attract significant interest as potential diagnostic and therapeutic tools in disease inhibition and insect control. Activated ingredients presented in the Poinciana leaves were extracted and GC–MS data indicated an increased abundance of terpenes, flavonoids, and phenolic substances. Poinciana extract was encapsulated to the vicinity of nanostructure lipid carrier, Po-NLC, and surface modified with magnetic nanoparticles, Po-NLC-MNPs. The synthesized nanoparticles depicted average particle size of 73.2 and 75.55 nm while zeta potential of (− 29.4) and (‒ 4.44 mV) for Po-NLC and Po-NLC-MNPs, respectively. Transmission electron microscope and morphology determination showed regular, irregular spherical and oval shapes with diverse single particle size. X-rays diffraction pattern of the freely synthesized MNPs was compared to the decorated NLC and the results manifested that the NLC was successfully decorated with MNPs. The larvicidal activity of plant extract, Poinciana extract (Po), and their nanoparticle conjugates against 3rd instar larvae of Culex pipiens was evaluated at 50, 100, 200, 500, 1000, and 1500 ppm concentrations. Both high and low concentrations of Po-NLC-MNPs, indicated potential larval mortality than plant extracts (Po extract) itself. The mortality rate reached 100% for 3rd instar larvae. Based on their relative toxicity, (Po-NLC-MNPs) was the best at killing larvae, followed by Po-NLC. The synthesized nps were checked for their cytotoxic effect against wi38 cell line. The in-vitro cytotoxicity results indicated that there was no significant cytotoxicity and the nanocomposite barely caused weak changes in the tested cells. The synthesized nanoparticles have potential to create a new generation of eco-friendly, effective alternatives for controlling mosquito-borne diseases.