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Inhalation Administration of the Bicyclic Ethers 1,8- and 1,4-cineole Prevent Anxiety and Depressive-Like Behaviours in Mice.

ABSTRACT: The anxiolytic and antidepressant-like activities of the naturally occurring monoterpene 1,8-cineole and its structural isomer 1,4-cineole were evaluated in mice via inhalation administration at doses ranging from 4 × 10-6 to 4 × 10-1 mg per 400 ?L of triethyl citrate. Mice were tested for anxiety-like behaviours by using the light-dark box test (LDB) and marble-burying test (MBT) and for depression-like symptoms by using the forced swimming test (FST) and tail suspension test (TST). Diazepam and fluoxetine were used as standard drugs for anxiolytic and antidepressant tests, respectively. The results showed that 1,8-cineole at 4 × 10-4 mg, and 1,4-cineole at 4 × 10-4 and 4 × 10-3 mg significantly increased the amount of time spent in the light box and the number of entries in the light box in the LDB as well as reduced the number of marbles buried in the MBT relative to those in the control, suggesting an anxiolytic effect. Similarly, 1,8-cineole at 4 × 10-4 and 4 × 10-2 mg and 1,4-cineole at doses of 4 × 10-4 to 4 × 10-2 mg significantly reduced immobility times in the FST and TST relative to those of the control, suggesting an antidepressant activity. The role of the GABAA/benzodiazepine receptor system in the anxiolytic effects of 1,8- and 1,4-cineole was investigated through co-administration of flumazenil, a GABAergic system antagonist. Flumazenil reversed the effects of diazepam and 1,8-cineole, suggesting that 1,8-cineole affects the GABAA/benzodiazepine receptors. Collectively, the results suggest that inhaled 1,8- and 1,4-cineole prevented anxiety and depressive-like symptoms in classic mice models.

SUBMITTER: Dougnon G

PROVIDER: S-EPMC7221571 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Inhalation Administration of the Bicyclic Ethers 1,8- and 1,4-cineole Prevent Anxiety and Depressive-Like Behaviours in Mice.

Dougnon Godfried G Ito Michiho M

Molecules (Basel, Switzerland) 20200418 8

The anxiolytic and antidepressant-like activities of the naturally occurring monoterpene 1,8-cineole and its structural isomer 1,4-cineole were evaluated in mice via inhalation administration at doses ranging from 4 × 10<sup>-6</sup> to 4 × 10<sup>-1</sup> mg per 400 μL of triethyl citrate. Mice were tested for anxiety-like behaviours by using the light-dark box test (LDB) and marble-burying test (MBT) and for depression-like symptoms by using the forced swimming test (FST) and tail suspension t ...[more]

PMID: 32325759

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Project description:We report the isolation and characterization of three new cytochrome P450 monooxygenases: CYP101J2, CYP101J3, and CYP101J4. These P450s were derived from Sphingobium yanoikuyae B2, a strain that was isolated from activated sludge based on its ability to fully mineralize 1,8-cineole. Genome sequencing of this strain in combination with purification of native 1,8-cineole-binding proteins enabled identification of 1,8-cineole-binding P450s. The P450 enzymes were cloned, heterologously expressed (N-terminally His6 tagged) in Escherichia coli BL21(DE3), purified, and spectroscopically characterized. Recombinant whole-cell biotransformation in E. coli demonstrated that all three P450s hydroxylate 1,8-cineole using electron transport partners from E. coli to yield a product putatively identified as (1S)-2α-hydroxy-1,8-cineole or (1R)-6α-hydroxy-1,8-cineole. The new P450s belong to the CYP101 family and share 47% and 44% identity with other 1,8-cineole-hydroxylating members found in Novosphingobium aromaticivorans and Pseudomonas putida Compared to P450cin (CYP176A1), a 1,8-cineole-hydroxylating P450 from Citrobacter braakii, these enzymes share less than 30% amino acid sequence identity and hydroxylate 1,8-cineole in a different orientation. Expansion of the enzyme toolbox for modification of 1,8-cineole creates a starting point for use of hydroxylated derivatives in a range of industrial applications.ImportanceCYP101J2, CYP101J3, and CYP101J4 are cytochrome P450 monooxygenases from S. yanoikuyae B2 that hydroxylate the monoterpenoid 1,8-cineole. These enzymes not only play an important role in microbial degradation of this plant-based chemical but also provide an interesting route to synthesize oxygenated 1,8-cineole derivatives for applications as natural flavor and fragrance precursors or incorporation into polymers. The P450 cytochromes also provide an interesting basis from which to compare other enzymes with a similar function and expand the CYP101 family. This could eventually provide enough bacterial parental enzymes with similar amino acid sequences to enable in vitro evolution via DNA shuffling.

Project description:Chlorhexidine belongs to a group of medicines called antiseptic antibacterial agents. Chlorhexidine is commonly used for the care and clean off the skin, hands, and wounds. In recent years, medicinal and aromatic plants have been used for prevention of disease, maintaining health, and improving disease in traditional and modern medicine as a medicament. According to recent research, cineole is the isolated active agent of eucalyptus oil and possesses antimicrobial activity. It was demonstrated that cineole could enhance the antimicrobial effects of the other antiseptics.The aim of this study was to investigate the efficacy of 1,8-cineole on the antimicrobial effect of chlorhexidine against some microorganisms.The effect of 1,8-cineole on antimicrobial activity of chlorhexidine gluconate (CHG) was tested using seven different microorganisms. In this study, CHG (128-0.125 mg/l) and cineole (512-2 g/l) were analyzed together and separately using checkerboard assay. Interactions between CHG and 1,8-cineole have been identified as synergistic, indifferent, or antagonistic.Synergistic activity was demonstrated between CHG and 1,8-cineole against Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and Candida albicans. Indifferent interactions for these compounds were demonstrated against Pseudomonas aeruginosa.CHG antiseptic properties were found to be increased when CHG was used in combination with 1,8-cineole. In this way, CHG will reveal stronger effect against microorganisms.Cineole has increased the antimicrobial activity of chlorhexidine gluconate against all microorganisms except Pseudomonas aeruginosaIn topical application, using cineole in combination with chlorhexidine may be easier, eradicate certain resistant bacteria by increasing the antimicrobial efficacy. Abbreviation Used: CHG: Chlorhexidine gluconate, MRSA: Methicillin-resistant S. aureus, MHB: Mueller Hinton broth, SDB: Sabouraud dextrose broth, CFU: Colonyforming unit, FIC: Fractional inhibitory concentration, FICI: FIC index, EO: Eucalyptus oil.

Dataset Information

Inhalation Administration of the Bicyclic Ethers 1,8- and 1,4-cineole Prevent Anxiety and Depressive-Like Behaviours in Mice.

Publications

Inhalation Administration of the Bicyclic Ethers 1,8- and 1,4-cineole Prevent Anxiety and Depressive-Like Behaviours in Mice.

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