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Combination therapy at appropriately suitable doses presents a promising alternative to monotherapeutic drugs. In this study, Cinnamomum verum and Syzygium aromaticum essential oils and their major compounds have exhibited substantial leishmaniacidal potential against both promastigote and amastigote forms of Leishmania (L.) major . However, they displayed high cytotoxicity against Raw264.7 macrophage cells. Interestingly, when combined with each other or with amphotericin B, they demonstrated a synergistic effect (FIC<0.5) with low cytotoxicity. These combinations are able to modulate the production of nitric oxide (NO) by macrophages. Notably, the combination of S. aromaticum Essential oil with amphotericin B stimulates macrophage cells by increasing NO production to eliminate leishmanial parasites. Furthermore, investigation of the molecular mechanism of action of these synergistic combinations reveals potent inhibition of the sterol pathway through the inhibition of the CYP51 gene expression. The findings suggest that combination therapy may offer significant therapeutic benefits in both food and pharmaceutical fields.

In cattle, Hyalomma scupense serves as an important vector of several pathogens resulting in diseases, subsequently affecting the agricultural field as well as the economy. Resistance to chemical acaricides has become widespread affirming the need for new drugs to tick control. The goal of this study was to investigate the acaricidal, repellent activities as well as the putative mode of action of two essential oils (EOs) from Melaleuca alternifolia (Tea tree) and Chamaemelum nobile (Roman chamomile) on Hyalomma scupense. The chemical composition of EOs was also evaluated. Different concentrations of EOs were tested in vitro for their acaricidal property on adults and larvae of H. scupense using adult immersion test (AIT) and larval packet test (LPT). Additionally, using Ellman's spectrophotometric method, the anticholinesterase (AChE) inhibition activity of M. alternifolia and C. nobile EOs was assessed in order to understand their putative mode of action. The main compounds of C. nobile were α-Bisabolene (22.20%) and (E)-β-Famesene (20.41%). The major components in the analyzed M. alternifolia were Terpinen-4-ol (36.32%) and γ-Terpinene (13.69%). Adulticidal and larvicidal assays demonstrated a promising efficacy of the essential oils against tick H. scupense. The lethal concentration (LC 50 ) values obtained for M. alternifolia and C. nobile oils were 0.84 and 0.96 mg/mL in the AIT and 0.37 and 0.48 mg/mL in the LPT, respectively. Regarding repellent activity, M. alternifolia achieved 100% repellency at the concentration of 1 mg/mL while C. nobile showed 95.98% repellency activity at concentration of 4 mg/mL. Also, M. alternifolia and C. nobile EOs displayed potent AChE inhibition with IC 50 value of 91.27 and 100.12 μg/mL, respectively. In the present study, M. alternifolia and, to a lesser degree, C. nobile EOs were found to be effective in vitro acaricides, repellents and acetylcholinesterase inhibitor against H. scupense ticks. These plants may represent an economical and sustainable alternative to toxic synthetic acaricides in the management of ectoparasites of veterinary importance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The present study aimed to evaluate the leishmanicidal potential of the essential oil (EO) of Micromeria ( M. ) nervosa and to investigate its molecular mechanism of action by qPCR. Furthermore, in silicointeraction study of the major M. nervosa EO compounds with the enzyme cytochrome P450 sterol 14α-demethylase (CYP51) was also performed. M. nervosa EO was analyzed by gas chromatography-mass spectrometry (GC-MS). Results showed that α-pinene (26.44%), t -cadinol (26.27%), caryophyllene Oxide (7.73 ± 1.04%), and α-Cadinene (3.79 ± 0.12%) are the major compounds of M. nervosa EO. However, limited antioxidant activity was observed, as this EO was ineffective in neutralizing DPPH free radicals and in inhibiting β-carotene bleaching. Interestingly, it displayed effective leishmanicidal potential against promastigote (IC 50 of 6.79 and 5.25 μg/mL) and amastigote (IC 50 of 8.04 and 7.32 μg/mL) forms of leishmania (L.) infantum and L. major , respectively. Molecular mechanism investigation showed that M. nervosa EO displayed potent inhibition on the thiol regulatory pathway. Furthermore, a docking study of the main components of the EO with cytochrome P450 sterol 14α-demethylase (CYP51) enzyme revealed that t -cadinol exhibited the best binding energy values (-7.5 kcal/mol), followed by α-cadinene (-7.3 kcal/mol) and caryophyllene oxide (-7 kcal/mol). These values were notably higher than that of the conventional drug fluconazole showing weaker binding energy (-6.9 kcal/mol). These results suggest that M. nervosa EO could serve as a potent and promising candidate for the development of alternative antileishmanial agent in the treatment of leishmaniasis.

The essential oils (EOs) of Coriandrum sativum , Carum carvi and Artemisia herba-alba have been screened for their insecticidal activity against Tribolium castaneum , Sitophilus oryzae and Lasioderma serricorne and for their antimicrobial activity against Gram (+), Gram (-) bacteria and against yeast strain. Artemisia herba-alba EO showed good insecticidal activity with 24-h against L. serricorne (LC 50  = 29.7) and against T. castaneum (66.1 µg/mL) and antibacterial potentials against Staphyloccocus aureus (MIC = 0.125 mg/mL). The antimicrobial activities of C. carvi EO, rich in D-carvone (72.4%) and D-limonene (23.8%) were particularly remarkable, with LC 50 of 27.9 µg/mL against L. serricorne . Similarly, coriander EO, with linalool (64.6%) as the major compound was selected for its antimicrobial activities ( Candida albicans , MIC = 1 mg/mL). These findings demonstrated that the tested EOs could be used as a natural source of insecticidal and antimicrobial activity, which may have a variety of uses in the food and pharmaceutical sectors.

The goal of this work was to assess the in vitro acaricidal effects of Pistacia lentiscus essential oil and its pure active components against red poultry mites Dermanyssus gallinae as an alternative to chemical acaricide (formamidines). Essential oil was obtained using hydrodistillation and then analyzed using GC-MS. The following major components were identified: α-pinene (20.58 %), D-Limonene (18.16 %), β-Myrcène (15.06 %), 4-Terpineol (7.68 %), caryophyllene (5.45 %) and γ-terpinene (5.21 %). The toxicity of essential oil and its six monoterpenes were tested at concentrations ranging from 0.43 to 3.50 mg/cm 2 , using contact and spraying bioassays. Toxicity was expressed as a lethal concentration (LC 50 or LC 90 ). The experiment results revealed that activity was method and concentration dependent, and the spraying method was more effective than the contact bioassay for acaricidal activity. In this bioassay, the highest mortality was observed with 4-Terpineol. The LC 50 was estimated to be 0.184 mg/cm 2 for this substance, followed by α-pinene, the LC 50 of which was estimated to be 0.203 mg/cm 2 . Caryophyllene and γ-terpinene were found less effective in controlling D. gallinae. P. lentiscus oil and its major compounds were also evaluated for anti-acetylcholinesterase (AChE) effects; 4-Terpineol was found to be the most effective AChE inhibitor with IC 50 values reaching 18.73 ± 2.83 µg/mL. This framework pointed out the importance of the traditional use of P. lentiscus as an ecofriendly alternative against ectoparasite of veterinary importance; D. gallinae. In vivo trials should also be conducted to assure the safe use of essential oils or individual compounds and to achieve efficient acaricidal property., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nanoencapsulation is widely considered as a highly effective strategy to enhance essential oils' (EO) stability by protecting them from oxidative deterioration and evaporation. The present study aims to optimize and characterize an efficient technique for encapsulating Cinnamomum (C.) verum essential oil into chitosan nanoparticles using response surface methodology (RSM). Moreover, the optimized C. verum EO nanoparticle was investigated for its antibacterial (against Gram-positive and Gram-negative bacteria), antifungal (against Candida albicans ), and antiparasitic activity (against Leishmania parasites). Five parameters were investigated using a Plackett-Burman and Box-Behnken statistical design: the chitosan molecular weight, TPP concentration, C. verum EO/chitosan ratio, mixing method, and the duration of the reaction. Encapsulation efficiency and anti-candida activity were considered as responses. The antibacterial, anticandidal, and anti-leishmanial activities were also assessed using a standard micro-broth dilution assay and the cytotoxicity assay was assessed against the macrophage cell line RAW 264.7. The optimized nanoparticles were characterized using Fourier transform infrared spectroscopy, Zeta potential, and scanning electron microscopy. The study results indicated that under optimal conditions, the nanoencapsulation of C. verum EO into chitosan nanoparticles resulted in an encapsulation efficiency of 92.58%, with a regular distribution, a nanoparticle size of 480 ± 14.55 nm, and a favorable Zeta potential of 35.64 ± 1.37 mV. The optimized C. verum EO/chitosan nanoparticles showed strong antifungal activity against C. albicans pathogens (CMI = 125 µg mL -1 ), notable antibacterial activity against both Gram-positive and Gram-negative bacteria (ranging from 125 to 250 µg mL -1 ), high leishmanicidal potential against the promastigotes form of L. tropica and L. major (IC50 = 10.47 and 15.09 µg mL -1 , respectively), and a four-fold cytotoxicity reduction compared to non-encapsulated essential oil. These results suggest that C. verum EO-loaded chitosan nanoparticles could be a promising delivery system for the treatment of cutaneous Candida albicans infections.

The present study evaluated the acaricidal and anthelmintic action of Ocimum basilicum essential oil and its main components against ticks and helminth parasites as well as to relate these activities to acetylcholinesterase inhibition. The in vitro acaricidal activity against Hyalomma scupense was evaluated by Adult Immersion Test (AIT) and Larval Packet Test (LPT), while the in vivo nematocidal potential was assessed in laboratory mice infected with Heligmosomoides polygyrus using fecal egg count reduction (FECR) and total worm count reduction (TWCR). Chemical analyzes were performed by gas chromatography coupled to mass spectrometry (GC-MS). Estragole (80.87%) and linalool (16.12%) were the major compounds detected in O. basilicum essential oil. In the AIT assay for H. scupense tick, LC 50 of estragole, O. basilicum oil and linalool were 0.73, 0.81 and 0.97 mg/mL, respectively. In LPT, estragole, linalool and essential oil showed LC 50 of 0.22, 1.11 and 1.19 mg/mL, respectively. Against He. polygyrus, the highest activity was observed with estragole administered at 100 mg/kg body weight (bwt), which resulted in a FECR of 90.86% and a TWCR of 82.91%. The O. basilicum essential oil, estragole and linalool inhibited the enzyme acetylcholinesterase (AChE) extracted from both parasites species. Estragole was found the most active AChE inhibitor with IC 50 of 0.176 mg/mL for H. scupense and IC 50 of 0.138 mg/mL for He. polygyrus larvae. The results of the present study pointed out the importance of the traditional use of O. basilicum as an eco-friendly alternative against endo and ectoparasites. In vivo trials should also be conducted to confirm the above-mentioned activities and to assure the safe use of natural plants., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The adulticidal, larvicidal, and repellent effects of Cupressus sempervirens, Mentha pulegium, and their combination (C. sempervirens and M. pulegium) against Hyalomma scupense were investigated, as well as their putative mode of action. The evaluation on H. scupense was performed with the adult immersion test at concentrations ranging from 2.5-20 mg/mL and the larval packet test from 0.625 to 20 mg/mlL. The same concentrations were used for combined oils. Essential oils were obtained using hydrodistillation and then analyzed using GC-MS. The following major components were identified: α-pinene (56.89 %) and δ-3-Carene (15.61 %) for C. sempervirens, while pulegone (70.50 %) and cis-Menthone (18.26 %) for M. pulegium. At 20 mg/mL concentration, C. sempervirens had (94.40 %) acaricide action and inhibited the egg from hatching, however at 10 mg/mL, it had 100 % larvicidal activity. Adulticidal and larvicidal activities of M. pulegium oil reached to 87.19 % and 81.02 % respectively, at 20 mg/mL concentration. The highest acaricidal property against H. scupense was exhibited by combination oils with minimum LC 50 values of 1.76 mg/mL on adultes and 0.60 mg/mL on larvae. The repellent activities were 100, 95.80 and 100 %, at the 20 mg/mL concentration used in 6 h, for C. sempervirens, M. pulegium and mixture oil respectively. Our findings revealed that the mixture of C. sempervirens and M. pulegium, at the ratio 1:1 (v: v) of each oil, showed high synergistic effect (SF > 1) and the use of combination oil (C. sempervirens 50 %: M. pulegium 50 %) is more toxic against H.scupense. Furthermore, the volatile oils examined revealed significant inhibition of H.scupense acetylcholinesterase activity AChE. Based on the findings of the present framework, these essential oils have the potential to be applied as substitute for synthetic acaricides in the management of H.scupense bovine ticks., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The current study assayed the toxicity of Laurus nobilis essential oil and crude extracts obtained using solvents of increasing polarity (cyclohexane, acetone and ethanol), on two ectoparasites of veterinary importance, i.e., Hyalomma scupense and Dermanyssus gallinae. The major components detected in bay laurel essential oil were dominated by 1.8-cineole (46.56 %), α-terpinenyl acetate (13.99 %), sabinene (7.69), α-pinene (5.75), linalool (5.50), methyleugenol (5.36 %) and β-pinene (3.97). The highest total phenolic and flavonoids contents were present in the ethalonic extract of L. nobilis leaves at an amount of 152.88 mg gallic acid equivalents per gram of dry weight (GAE/g DW) and 21.77 mg quercetin equivalent per gram of dry weight (QE/g DW), respectively. In vitro acaricidal effects of essensial oil and crude extract of L. nobilis against H. scupense were ascertained by adult immersion test of engorged females (AIT) and larval packet test (LPT) compared with a reference drug amitraz. The essential oil exhibited strong acaricidal activity against tick engorged female and inhibition of hatching eggs. After 24 h of exposure, at the highest tested concentration (100 mg/mL) essential oil induced 90.67 % mortality of H. scupense larvae (LC 50  = 10.69 mg/mL). Otherwise, essential oil exhibited high acaricidal activity compared to extracts, and among the extract, the ethanolic extract revealed the highest acaricidal efficacy (81.27 % female mortality). Results from mite contact toxicity showed that essential oil and extracts from L. nobilis were toxic to D. gallinae. Bay essential oil was both more toxic to mites, and faster in exerting this toxicity than other tested crude extracts. L. nobilis essential oil concentration leaded to enhance mortality of D. gallinae reaching the highest (100 %) mortality at 12 h with a concentration of 320 mg/mL. While, ethanolic extract acheived this rate after 24 h of exposure at same concentration. Cyclohexanic extract showed weak acaricidal activity., (Copyright © 2021. Published by Elsevier B.V.)