Nerolidol

Appl Microbiol Biotechnol. 2014 Nov;98(22):9447-57.

Anti-biofilm, anti-hemolysis, and anti-virulence activities of black pepper, cananga, myrrh oils, and nerolidol against Staphylococcus aureus.[Pubmed: 25027570]

The long-term usage of antibiotics has resulted in the evolution of multidrug-resistant bacteria. Unlike antibiotics, anti-virulence approaches target bacterial virulence without affecting cell viability, which may be less prone to develop drug resistance. Staphylococcus aureus is a major human pathogen that produces diverse virulence factors, such as α-toxin, which is hemolytic. Also, biofilm formation of S. aureus is one of the mechanisms of its drug resistance.
METHODS AND RESULTS:
In this study, anti-biofilm screening of 83 essential oils showed that black pepper, cananga, and myrrh oils and their common constituent cis-Nerolidol at 0.01 % markedly inhibited S. aureus biofilm formation. Furthermore, the three essential oils and cis-Nerolidol at below 0.005 % almost abolished the hemolytic activity of S. aureus. Transcriptional analyses showed that black pepper oil down-regulated the expressions of the α-toxin gene (hla), the nuclease genes, and the regulatory genes. In addition, black pepper, cananga, and myrrh oils and cis-Nerolidol attenuated S. aureus virulence in the nematode Caenorhabditis elegans. This study is one of the most extensive on anti-virulence screening using diverse essential oils and provides comprehensive data on the subject.
CONCLUSIONS:
This finding implies other beneficial effects of essential oils and suggests that black pepper, cananga, and myrrh oils have potential use as anti-virulence strategies against persistent S. aureus infections.

Antimicrob Agents Chemother. 2005 May;49(5):1679-87.

Antileishmanial activity of the terpene nerolidol.[Pubmed: 15855481 ]

The activity of Nerolidol, a sesquiterpene used as a food-flavoring agent and currently under testing as a skin penetration enhancer for the transdermal delivery of therapeutic drugs, was evaluated against Leishmania species.
METHODS AND RESULTS:
Nerolidol inhibited the growth of Leishmania amazonensis, L. braziliensis, and L. chagasi promastigotes and L. amazonensis amastigotes with in vitro 50% inhibitory concentrations of 85, 74, 75, and 67 microM, respectively. The treatment of L. amazonensis-infected macrophages with 100 microM Nerolidol resulted in 95% reduction in infection rates. Inhibition of isoprenoid biosynthesis, as shown by reduced incorporation of [2-(14)C]mevalonic acid (MVA) or [1-(14)C]acetic acid precursors into dolichol, ergosterol, and ubiquinone, was observed in Nerolidol-treated promastigotes. This drug effect can be attributed to the blockage of an early step in the mevalonate pathway, since incorporation of the precursor [1(n)-(3)H]farnesyl pyrophosphate in polyisoprenoids is not inhibited by Nerolidol. L. amazonensis-infected BALB/c mice were treated with intraperitoneal doses of 100 mg/kg/day for 12 days or topically with 5 or 10% ointments for 4 weeks. Significant reduction of lesion sizes in Nerolidol treated mice was observed for both treatment routes. However, long-term follow up indicated that the disease was not cured in this highly susceptible animal model.
CONCLUSIONS:
Nonetheless, the in vitro activity of Nerolidol against these parasites may prove a useful tool for the development of new drugs for the treatment of leishmaniasis. In addition, biosynthesis of dolichols with 11 and 12 isoprene units was identified in Leishmania, as described for other trypanosomatids and Apicomplexa.

J.Chem. Ecol., 1980, 6(4):845-51.

Nerolidol: An antifeeding sesquiterpene alcohol for gypsy moth larvae fromMelaleuca leucadendron[Reference: WebLink]

A systematic procedure is reported for the isolation of a feeding deterrent, (E,S)-Nerolidol (I), fromMelaleuca leucadendron leaves for the gypsy moth larvae. Testing of the related alcohols, farnesol (II) and geraniol (III) showed them to be deterrent, but the simpler isoprene-related compounds, 2-methyl-3-buten-2-ol andt-amyl alcohol were inactive.

Neurochem Res. 2013 Sep;38(9):1861-70.

Antioxidant effects of nerolidol in mice hippocampus after open field test.[Pubmed: 23765368]

The aim of this study was to evaluate the neuroprotective effects of Nerolidol in mice hippocampus against oxidative stress in neuronal cells compared to ascorbic acid (positive control) as well as evaluated the Nerolidol sedative effects by open field test compared to diazepam (positive control).
METHODS AND RESULTS:
Thirty minutes prior to behavioral observation on open field test, mice were intraperitoneally treated with vehicle, Nerolidol (25, 50 and 75 mg/kg), diazepam (1 mg/kg) or ascorbic acid (250 mg/kg). To clarify the action mechanism of of Nerolidol on oxidative stress in animals subjected to the open field test, Western blot analysis of Mn-superoxide dismutase and catalase in mice hippocampus were performed. In Nerolidol group, there was a significant decrease in lipid peroxidation and nitrite levels when compared to negative control (vehicle). However, a significant increase was observed in superoxide dismutase and catalase activities in this group when compared to the other groups. Vehicle, diazepam, ascorbic acid and Nerolidol groups did not affected Mn-superoxide dismutase, catalase mRNA or protein levels.
CONCLUSIONS:
Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus. Nerolidol showed sedative effects in animals subjected to the open field test. Oxidative process plays a crucial role on neuronal pathological consequence, and implies that antioxidant effects could be achieved using this sesquiterpene.

Carcinogenesis. 1991 Jan;12(1):151-2.

Inhibition of azoxymethane-induced neoplasia of the large bowel by 3-hydroxy-3,7,11-trimethyl-1,6,10-dodecatriene (nerolidol).[Pubmed: 1988176]

The inhibitory capacities of four terpenes on azoxymethane (AOM)-induced neoplasia of the large bowel and duodenum was studied in male F344 rats.
METHODS AND RESULTS:
A complete course of AOM administrations was given and 3 days later the rats were fed a semipurified diet containing 5 mg/g of the test compounds, i.e. 3-hydroxy-3,7,11-trimethyl-1,6,10-dodecatriene (Nerolidol), beta-citronellol, (+/-)-linalool and (1R,2S,5R)-(-)-menthol or a corresponding control diet. The experiment was terminated 22 weeks after the last dose of AOM. Under these conditions, Nerolidol showed an inhibitory effect on carcinogenesis of the large bowel. The number of rats bearing large bowel neoplasms (adenomas) was reduced from 82% in the controls to 33% in rats fed Nerolidol and the number of tumors/rat from 1.5 in the controls to 0.7 in the Nerolidol group. A reduction in adenocarcinomas of the duodenum was found but the data are not statistically significant.
CONCLUSIONS:
The effects of Nerolidol are of interest in terms of the identification of a new inhibitor of carcinogenesis of the large bowel. The chemical structure of Nerolidol suggests the possibility that the compound might have an impact on protein prenylation or some other aspect of the mevalonate pathway, but this remains to be established.

Z Naturforsch C. 2007 Jul-Aug;62(7-8):537-42.

Nerolidol, an antiulcer constituent from the essential oil of Baccharis dracunculifolia DC (Asteraceae).[Pubmed: 17913068]

In this study, the antiulcerogenic effect of essential oil from Baccharis dracunculifolia was evaluated using the model of acute gastric lesions induced by ethanol.
METHODS AND RESULTS:
The ulcerative lesion index (ULI) was significantly reduced by oral administration of the essential oil of B. dracunculifolia at doses of 50, 250 and 500 mg/kg which reduced the lesions by 42.79, 45.70 and 61.61%, respectively. The analysis of the chemical composition of the essential oil from B. dracunculifolia by GC showed that this was composed mainly of mono- and sesquiterpenes and the majority compound was Nerolidol. Therefore, antiulcerogenic activity of Nerolidol (50, 250 and 500 mg/kg) was investigated using ethanol-, indomethacin- and stress-induced ulcer models in rat. In the stress-induced ulcer model, a significant reduction of the ULI in animals treated with Nerolidol (50, 250 and 500 mg/kg) and cimetidine (100 mg/kg) was observed, compared to the control group (p < 0.05). The percentage of inhibition of ulcer was 41.22, 51.31, 56.57 and 53.50% in groups treated with 50, 250, 500 mg/kg of Nerolidol and 100 mg/kg of cimetidine (positive control), respectively. Regarding ethanol- and indomethacin-induced ulcer models, it was observed that the treatment with Nerolidol (250 and 500 mg/ kg) significantly reduced the ULI in comparison with the control group (p < 0.05). The dose of 50 mg/kg reduced the parameters analyzed but this was not statistically significant. In the ethanol-induced model percentage of inhibition of ulcer was 34.20, 52.63, 87.63 and 50.87% in groups treated with 50, 250, 500 mg/kg of Nerolidol and 30 mg/kg of omeprazol (positive control), respectively. In indomethacin-ulcer the percentage of inhibition of ulcer was 34.69, 40.80, 51.02 and 46.93% in groups treated with 50, 250, 500 mg/kg of Nerolidol and 100 mg/ kg of cimetidine (positive control), respectively.
CONCLUSIONS:
The results of this study show that Nerolidol displays antiulcer activity, as it significantly inhibited the formation of ulcers induced in different animal models. However, further pharmacological and toxicological investigations, to delineate the mechanism(s) of action and the toxic effects, are required to allow the use of Nerolidol for the treatment of gastric ulcer.

Biol Pharm Bull. 2007 Jan;30(1):184-8.

Antifungal effect of eugenol and nerolidol against Microsporum gypseum in a guinea pig model.[Pubmed: 17202684]

Essential oils have been widely used in anti-infectious application. In the present study, we elucidated the antifungal activities of eugenol and Nerolidol isolated from Japanese cypress oil in a guinea pig model infected by Microsporum gypseum (M. gypseum).
METHODS AND RESULTS:
A minimal inhibitory concentration (MIC), skin lesion scoring, hair culture and histopathologic examination of skin tissues were performed to evaluate the antifungal effect of these oils. The MICs of eugenol, Nerolidol and econazole (positive control) were 0.01-0.03% and 0.5-2% and 4-16 microg/ml, respectively. Based on these MICs, eugenol and Nerolidol were adjusted to 10% concentration with a base of Vaseline petroleum jelly and were applied topically to the skin lesion infected with M. gypseum daily for 3 weeks. Both eugenol and Nerolidol were clinically effective at improving the lesion during the first week of application, as determined by skin lesion scoring. Nerolidol improved the skin lesions infected by M. gypseum, but eugenol did not, as determined in the hair culture test. Histopathologic examination revealed that the eugenol- and Nerolidol-treated groups had a lower degree of hyperkeratosis and inflammatory cell infiltration than the positive control.
CONCLUSIONS:
Taken together, these results suggest that eugenol and Nerolidol could apply supplementary antifungal agents.