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In the present study, we assessed the antioxidant and antileishmanial potential from fresh leaves of Ballota (B.) hirsuta essential oil (EO). The GC-MS analysis of B. hirsuta EO revealed that spathulenol and germacrene D were the main components accounting for 26.03% and 19.64% of the total EO, respectively. B. hirsuta EO possesses moderate antioxidant activity, both in neutralizing DPPH radicals and in inhibiting β-carotene bleaching. In addition, it exhibits both high antileishmanial activity and selectivity towards the promastigote and amastigote forms. Specifically, B. hirsuta EO showed an IC 50 value of 20.78 µg/mL and 23.62 µg/mL, against the promastigote and amastigote forms of L. infantum, respectively. It also demonstrated an IC 50 value of 22.39 and 25.76 µg/mL, against the promastigote and amastigote forms of L. major, respectively. However, it exhibited moderate cytotoxicity, with a selectivity index below 10. The investigation of the molecular mechanism of action revealed that B. hirsuta EO inhibited only the sterol pathway, including CYP51 gene expression. Additionally, in silico analysis indicated that the main compounds of B. hirsuta EO, germacrene and spathulenol, exhibited excellent affinity energy against Leishmania enzymes trypanothione reductase (TryR) and trypanothione synthase (TryS). This denotes the potential of these compounds as promising agents to control leishmaniasis., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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.

Antibiotic resistance of the Gram-negative bacterium Pseudomonas aeruginosa and its ability to form biofilm through the Quorum Sensing (QS) mechanism are important challenges in the control of infections caused by this pathogen. The extract of Myrtus communis (myrtle) showed strong anti-QS effect on C hromobacterium . violaceum 6267 by inhibiting 80 % of the production of violacein pigment at a sub-MIC concentration of 1/8 (31.25 μg/mL). In addition, the extract exhibited an inhibitory effect on virulence factors of P. aeruginosa PAO1 at half MIC (125 μg/mL), significantly reducing the formation of biofilms (72.02 %), the swarming activity (75 %), and the production of protease (61.83 %) and pyocyanin (97 %). The active fraction also downregulated the expression of selected regulatory genes involved in the biofilm formation and QS in the P. aeruginosa PAO1 strain. These genes included the autoinducer synthase genes ( lasI and rhlI ), the genes involved in the expression of their corresponding receptors ( lasR and rhlR ), and the pqsA genes. The analysis of the active fraction by HPLC/UV/MS and NMR allowed the identification of three phenolic compounds, 3,5-di- O -galloylquinic acid, myricetin 3- O -α-l-rhamnopyranoside (myricitrin), and myricetin 3- O -(2″- O -galloyl)-ß-d-galactopyranoside. In silico studies showed that 3,5-di- O -galloylquinic acid, with an affinity score of -9.20 kcal/mol, had the highest affinity to the active site of the CviR protein (3QP8), a QS receptor from C. violaceum . Additionally, myricetin 3- O -α-l-rhamnopyranoside (myricitrin) and myricetin 3- O -(2″- O -galloyl)-ß-d-galactopyranoside interact to a lesser extent with 3QP8. In conclusion, this study contributed significantly to the discovery of new QS inhibitors from M. communis leaves against resistant Gram-negative pathogens., Competing Interests: 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. Carlos Jiméenez reports financial support was provided by Spanish State Agency for Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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.

Chlorpyrifos (CPF) poisoning is a public health problem for which there is not currently any effective prophylaxis. In this study, we investigated the protective effect of grape seed extract (GSE) against CPF-induced hepatotoxicity. Rats were daily treated either with CPF (2 mg/kg) or CPF and GSE (20 mg/kg) for 1 week, sacrificed, and their livers dissected for biochemical, molecular, and histopathological analyses. CPF generated liver dysfunction by altering carbohydrate, lipid, amino acid, ammonia and urea metabolism, and provoked mitochondrial impairment through disturbing tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and mitochondrial viability. CPF also induced cholinergic excitotoxicity along with oxidative stress and histopathological alterations. Interestingly, treatment with GSE prevented all the detrimental effects of CPF through the regulation of cytochrome P450 (CYP450) gene expression. Molecular docking analysis indicated that GSE-containing polyphenols acted as epigenetic modulators through inhibiting DNA (cytosine-5)-methyltransferase 1 (DNMT1), thus favoring the CYP2C6 detoxification pathway. Thereby, GSE might be a promising strategy in the protection of the liver against CPF toxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aerial parts of cypress ( Cupressus sempervirens L.) of three collect regions (Bizerte, Ben-Arous and Nabeul) were reported for their essential oil (EO) compositions, antioxidant, antimicrobial and insecticidal activities. Results showed that the higher EO yields were observed in Bizerte and Ben Arous (0.56%), followed by Nabeul (0.49%). The EO composition showed the predominance of α-pinene with 36.72% in Bizerte, 30.22% in Nabeul and 30% in Ben-Arous. Cypress EO of Bizerte showed higher antiradical capacity (IC 50  = 55 µg/mL) than Ben-Arous (IC 50  = 97.50 µg/mL) and Nabeul (IC 50  = 155 µg/mL). E. faecalis was the most sensitive strain to cypress EO of Bizerte with the largest inhibition zone (IZ = 65 mm). Regarding the insecticidal activity, cypress EO of Bizerte had the highest mortality of Tribolium castaneum with a lethal concentration of LC 50  = 164.3 µL/L air after 24 h exposure.

The organic solvent extracts (hexane, chloroform, acetone, methanol and water) of coriander fruits were reported for their antioxidant and repellent activities. The methanol and acetone extracts revealed the highest antiradical activity as compared to the other solvent extracts. HPLC analysis revealed that phenolic acids were the major compounds in chloroform and acetone extracts, whereas flavonoids in methanol and water extracts. The methanol extract of coriander fruits exhibited the highest repellent effect against coleopteran insects. Additionally, the hexane extract of coriander fruits also exhibited potent repellent and toxic activities against rice weevil. It appeared that coriander fruit extract obtained with the apolar solvent had more repellent potential against Sitophilus oryzae as compared to Tribolium castaneum . For Lasioderma serricorne , the methanol extract of coriander fruits reduced in a very significant way the adults followed by the chloroform and hexane extracts.