Anethole

Life Sci. 2014 Sep 1;112(1-2):74-81.

Effects of the essential oil of Croton zehntneri and its major components, anethole and estragole, on the rat corpora cavernosa.[Pubmed: 25084123]

The effects of the essential oil of Croton zehntneri (EOCz) and its major components Anethole, estragole and methyl eugenol were evaluated in phenylephrine precontracted rat corpora cavernosa (RCC).
METHODS AND RESULTS:
RCC strips were mounted in 5 ml organ baths for isometric recordings of tension, precontracted with 10 μM phenylephrine and exposed to test drugs. All major compounds relaxed RCC. The order of potency was estragole>Anethole>methyl eugenol. The maximal relaxation to EOCz and methyl eugenol was 62.67% (IC50 of 1.67 μM) and 45.8% (IC50 of 1.7 μM), respectively. Estragole relaxed RCC with an IC50 of 0.6 μM (maximal relaxation-76.6%). The maximal relaxation to estragole was significantly reduced by L-NAME (43.46%-IC50 of 1.4 μM), ODQ (53.11%-IC50 of 0.83 μM) and indomethacin (24.41%-IC50 of 1.3 μM). On the other hand, Anethole relaxed RCC by 66.73% (IC50 of 0.96 μM) and this relaxation was blunted by indomethacin (35.65%-IC50 of 1.6 μM). Both estragole and Anethole increased the relaxation achieved upon electrical stimulation. Both compounds increased the levels of cAMP (estragole by 3-fold and Anethole by 2-fold when compared to controls). Estragole also increased the levels of cGMP (0.5-fold).
CONCLUSIONS:
The higher potency of these compounds to relax corpora cavernosa smooth muscle may form the pharmacological basis for the use of such substances as leading compounds in the search of alternative treatments of erectile dysfunction.

Planta Med. 2015 Mar;81(4):292-7.

Essential oil of Croton zehntneri and its main constituent anethole block excitability of rat peripheral nerve.[Pubmed: 25714722]

Croton zehntneri is an aromatic plant native to Northeast Brazil and employed by local people to treat various diseases. The leaves of this plant have a rich content of essential oil. The essential oil of C. zehntneri samples, with Anethole as the major constituent and Anethole itself, have been reported to have several pharmacological activities such as antispasmodic, cardiovascular, and gastroprotective effects and inducing the blockade of neuromuscular transmission and antinociception. Since several works have demonstrated that essential oils and their constituents block cell excitability and in view of the multiple effects of C. zehntneri essential oil and Anethole on biological tissues, we undertook this investigation aiming to characterize and compare the effects of this essential oil and its major constituent on nerve excitability.
METHODS AND RESULTS:
Sciatic nerves of Wistar rats were used. They were mounted in a moist chamber, and evoked compound action potentials were recorded. Nerves were exposed in vitro to the essential oil of C. zehntneri and Anethole (0.1-1 mg/mL) up to 180 min, and alterations in excitability (rheobase and chronaxie) and conductibility (peak-to-peak amplitude and conduction velocity) parameters of the compound action potentials were evaluated. The essential oil of C. zehntneri and Anethole blocked, in a concentration-dependent manner with similar pharmacological potencies (IC50: 0.32 ± 0.07 and 0.22 ± 0.11 mg/mL, respectively), rat sciatic nerve compound action potentials. Strength-duration curves for both agents were shifted upward and to the right compared to the control curve, and the rheobase and chronaxie were increased following essential oil and Anethole exposure. The time courses of the essential oil of C. zehntneri and Anethole effects on peak-to-peak amplitude of compound action potentials followed an exponential decay and reached a steady state. The essential oil of C. zehntneri and Anethole caused a similar reduction in conduction velocities of the compound action potential waves investigated.
CONCLUSIONS:
In conclusion, we demonstrated here that the essential oil of C. zehntneri blocks neuronal excitability and that this effect, which can be predominantly attributable to its major constituent, Anethole, is important since these agents have several pharmacological effects likely related to the alteration of excitability. This finding is relevant due to the use of essential oils in aromatherapy and the low acute toxicity of this agent, which exhibits other effects of potential therapeutic usefulness.

FEBS J. 2014 Feb;281(4):1304-13.

Anethole induces apoptotic cell death accompanied by reactive oxygen species production and DNA fragmentation in Aspergillus fumigatus and Saccharomyces cerevisiae.[Pubmed: 24393541]

trans-Anethole (Anethole), a major component of anise oil, has a broad antimicrobial spectrum, and antimicrobial activity that is weaker than that of other antibiotics on the market.
METHODS AND RESULTS:
When combined with polygodial, nagilactone E, and n-dodecanol, Anethole has been shown to possess significant synergistic antifungal activity against a budding yeast, Saccharomyces cerevisiae, and a human opportunistic pathogenic yeast, Candida albicans. However, the antifungal mechanism of Anethole has not been completely determined. We found that Anethole stimulated cell death of a human opportunistic pathogenic fungus, Aspergillus fumigatus, in addition to S. cerevisiae. The Anethole-induced cell death was accompanied by reactive oxygen species production, metacaspase activation, and DNA fragmentation. Several mutants of S. cerevisiae, in which genes related to the apoptosis-initiating execution signals from mitochondria were deleted, were resistant to Anethole.
CONCLUSIONS:
These results suggest that Anethole-induced cell death could be explained by oxidative stress-dependent apoptosis via typical mitochondrial death cascades in fungi, including A. fumigatus and S. cerevisiae.

J Econ Entomol. 2009 Feb;102(1):203-9.

Insecticidal activity of basil oil, trans-anethole, estragole, and linalool to adult fruit flies of Ceratitis capitata, Bactrocera dorsalis, and Bactrocera cucurbitae.[Pubmed: 19253638 ]

Basil oil and its three major active constituents (trans-Anethole, estragole, and linalool) obtained from basil (Oscimum basilicum L.) were tested on three tephritid fruit fly species [Ceratitis capitata (Wiedemann), Bactrocera dorsalis (Hendel), and Bactrocera cucurbitae (Coquillett)] for insecticidal activity.
METHODS AND RESULTS:
All test chemicals acted fast and showed a steep dose-response relationship. The lethal times for 90% mortality/knockdown (LT90) of the three fly species to 10% of the test chemicals were between 8 and 38 min. The toxic action of basil oil in C. capitata occurred significantly faster than in B. cucurbitae but slightly faster than in B. dorsalis. Estragole acted faster in B. dorsalis than in C. capitata and B. cucurbitae. Linalool action was faster in B. dorsalis and C. capitata than in B. cucurbitae. trans-Anethole action was similar to all three species. Methyl eugenol acted faster in C. capitata and B. cucurbitae than in B. dorsalis. When linalool was mixed with cuelure (attractant to B. cucurbitae male), its potency to the three fly species decreased as the concentration of cuelure increased. This was due to linalool hydrolysis catalyzed by acetic acid from cuelure degradation, which was confirmed by chemical analysis.
CONCLUSIONS:
When methyl eugenol (B. dorsalis male attractant) was mixed with basil oil, trans-Anethole, estragole, or linalool, it did not affect the toxicity of basil oil and linalool to B. dorsalis, but it did significantly decrease the toxicity of trans-Anethole and estragole. Structural similarity between methyl eugenol and trans-Anethole and estragole suggests that methyl eugenol might act at a site similar to that of trans-Anethole and estragole and serve as an antagonist if an action site exists. Methyl eugenol also may play a physiological role on the toxicity reduction.

Life Sci. 2013 Dec 5;93(24):955-61.

Anti-inflammatory effects of anethole in lipopolysaccharide-induced acute lung injury in mice.[Pubmed: 24404587]

Anethole, the major component of the essential oil of star anise, has been reported to have antioxidant, antibacterial, antifungal, anti-inflammatory, and anesthetic properties. In this study, we investigated the anti-inflammatory effects of Anethole in a mouse model of acute lung injury induced by lipopolysaccharide (LPS).
METHODS AND RESULTS:
BALB/C mice were intraperitoneally administered Anethole (62.5, 125, 250, or 500 mg/kg) 1 h before intratracheal treatment with LPS (1.5 mg/kg) and sacrificed after 4 h. The anti-inflammatory effects of Anethole were assessed by measuring total protein and cell levels and inflammatory mediator production and by histological evaluation and Western blot analysis. LPS significantly increased total protein levels; numbers of total cells, including macrophages and neutrophils; and the production of inflammatory mediators such as matrix metalloproteinase 9 (MMP-9), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in bronchoalveolar lavage fluid. Anethole (250 mg/kg) decreased total protein concentrations; numbers of inflammatory cells, including neutrophils and macrophages; and the inflammatory mediators MMP-9, TNF-α and NO. In addition, pretreatment with Anethole decreased LPS-induced histopathological changes. The anti-inflammatory mechanism of Anethole in LPS-induced acute lung injury was assessed by investigating the effects of Anethole on NF-κB activation. Anethole suppressed the activation of NF-κB by blocking IκB-α degradation.
CONCLUSIONS:
These results, showing that Anethole prevents LPS-induced acute lung inflammation in mice, suggest that Anethole may be therapeutically effective in inflammatory conditions in humans.

Biochem Biophys Res Commun. 2014 May 16;447(4):557-62.

CXCR4 and PTEN are involved in the anti-metastatic regulation of anethole in DU145 prostate cancer cells.[Pubmed: 24525130]

Anethole has been known to have chemopreventive activities as a suppressor of the incidence and multiplicity of both invasive and noninvasive carcinomas. The goal of this study was to understand the anti-metastatic effect of Anethole through C-X-C chemokine receptor type 4 (CXCR4)/tumor suppressor phosphatase and tensin homologue (PTEN) axis in DU145 prostate cancer cells.
METHODS AND RESULTS:
Anethole reduced both of the RNA level and the protein level of CXCR4 in a dose-dependent manner without cytotoxicity. Anethole also reduced the expression of CXCR4 and prolonged the expression of PTEN in DU145 prostate cancers. The phosphorylation of AKT and phosphatidylinositol-3kinase (PI3K) were decreased with Anethole. The inhibition metastatic effect of Anethole was arisen from down-regulating CXCR4 and up-regulating PTEN. Morphologically, Anethole significantly inhibited the invasion of DU145 cell and down-regulated the activities of matrix-metalloproteinase (MMPs) in a dose-dependent manner. However, Anethole didnot decrease the phosphorylation of PI3K and AKT while PTEN was silenced. Furthermore, the CXCR4 inhibition of Anethole was not caused to proteasomal or lysosomal of CXCR4.
CONCLUSIONS:
Taken together, Anethole demonstrated to act as the CXCR4 antagonist and as the PTEN activator which resulted to PI3K/AKT-mediated inhibition of the metastatic prostate cancer progressions.