trans-Anethole

30679204

Transient receptor potential (TRP) cation channels are molecular targets of various natural products. TRPA1, a member of TRP channel family, is specifically activated by natural products such as allyl isothiocyanate (mustard oil), cinnamaldehyde (cinnamon), and allicin (garlic). In this study, we demonstrated that TRPA1 is also a target of trans-anethole in fennel oil (FO) and fennel seed extract. Similar to FO, trans-anethole selectively elicited calcium influx in TRPA1-expressing mouse sensory neurons of the dorsal root and trigeminal ganglia. These FO- and anethole-induced calcium responses were blocked by a selective TRPA1 channel antagonist, HC-030031. Moreover, both FO and trans-anethole induced calcium influx and transmembrane currents in HEK293 cells stably overexpressing human TRPA1 channels, but not in regular HEK293 cells. Mutation of the amino acids S873 and T874 binding site of human TRPA1 significantly attenuated channel activation by trans-anethole, whereas pretreating with glutathione, a nucleophile, did not. Conversely, activation of TRPA1 by the electrophile allyl isothiocyanate was abolished by glutathione, but was ostensibly unaffected by mutation of the ST binding site. Finally, it was found that trans-anethole was capable of desensitizing TRPA1, and unlike allyl isothiocyanate, it failed to induce nocifensive behaviors in mice. We conclude that trans-anethole is a selective, nonelectrophilic, and seemingly less-irritating agonist of TRPA1.
Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.

Hypertension; Nicotine; Restraint; Stress; Trans-anethole.

trans-Anethole of Fennel Oil Is a Selective and Nonelectrophilic Agonist of the TRPA1 Ion Channel

Tosifa Memon 1 , Oleg Yarishkin 2 , Christopher A Reilly 2 , David Križaj 2 , Baldomero M Olivera 2 , Russell W Teichert 2

2019 Apr

28006746

The hepatotoxicity induced by APAP is caused by the excessive production of N-acetyl-para-benzoquinone imine (NAPQI), which, when reacting with hepatic proteins proved to cause irreversible lesions. Associated with this process, an intense inflammatory process is also evidenced, characterized by the increased cell influx and production/release of inflammatory mediators. Trans anethole, an aromatic compounds has been showed anti-inflammatory efficacy by inhibit the cellular recruitment and synthesis/releases of many proinflammatory mediators such as prostaglandin (PGE2), cytokines (TNF, IL-1) and nitrico oxide (NO). The aim of this study is to investigate the effect of trans anethole on some inflammatory parameters that are involved in hepatotoxicity induced by high doses of acetaminophen. Our results demonstrate that treatment with AN at doses 125 and 250mg/kg once a day for seven days prevented the changes caused by the APAP overdose, showing less intensity in the histological changes (necrosis, size of hepatocyte area and inflammatory infiltration), and corroborating the findings of serum activities of transaminases and phosphatases and the activity of the enzyme myeloperoxidase. In addition, the treatment prevented the up-regulation of proinflammatory mediators such as NO, TNF, IL-1α, MIP-1α and MCP-1 and induced the up-regulation of anti-inflammatory cytokines (IL-4 and IL-10). Thus, our results demonstrate a possible protective effect of trans anethole on the hepatotoxicity induced by APAP.

Acetaminophen; Hepatoprotection; Trans anethole.

Acetaminophen-induced Hepatotoxicity: Preventive Effect of Trans Anethole

Bruno Ambrosio da Rocha 1 , Alessandra M Versuti Ritter 2 , Franciele Queiroz Ames 3 , Odinei Hess Goncalves 4 , Fernanda Vitoria Leimann 5 , Livia Bracht 6 , Maria Raquel Marcal Natali 7 , Roberto Kenji Nakamura Cuman 8 , Ciomar Ap Bersani-Amado 9

2017 Feb