α‐Asarone, β‐asarone, and γ‐asarone: Current status of toxicological evaluation

Abstract

Asarone isomers are naturally occurring in Acorus calamus Linné, Guatteria gaumeri Greenman, and Aniba hostmanniana Nees. These secondary plant metabolites belong to the class of phenylpropenes (phenylpropanoids or alkenylbenzenes). They are further chemically classified into the propenylic trans-and cis-isomers α-asarone and β-asarone and the allylic γ-asarone.Flavoring, as well as potentially pharmacologically useful properties, enables the application of asarone isomers in fragrances, food, and traditional phytomedicine not only since their isolation in the 1950s. However, efficacy and safety in humans are still not known. Preclinical evidence has not been systematically studied, and several pharmacological effects have been reported for extracts of Acorus calamus and propenylic asarone isomers. Toxicological data are rare and not critically evaluated altogether in the 21st century yet. Therefore, within this review, available toxicological data of asarone isomers were assessed in detail. This assessment revealed that cardiotoxicity, hepatotoxicity, reproductive toxicity, and mutagenicity as well as carcinogenicity were described for propenylic asarone isomers with varying levels of reliability. The toxicodynamic profile of γ-asarone is unknown except for mutagenicity.Based on the estimated daily exposure and reported adverse effects, officials restricted or published recommendations for the use of β-asarone and preparations of Acorus calamus. In contrast, α-asarone and γ-asarone were not directly addressed due to a limited data situation.

A Comparative Study on the Larvicidal Effects of Piper sarmentosum (Kaduk) Leaves Extracts against Aedes aegypti

“…β-asarone extracted from the root bark of Cordia alliodora has shown a minimal concentration of 25 µg/mL to kill all tested larvae (Ioset et al, 2000) and at LC 50 value of 26.99 µg/mL from Asarum heterotropoides roots (Perumalsamy et al, 2009). However, asarone isomers have demonstrated mammalian carcinogenic effects (Haupenthal et al, 2017, Uebel et al, 2020. On the other hand, myristicin was found to be one of the major components in P. permucronatum (25.61%) and P. hostmanianum (20.26%) (de Morais et al, 2007).…”

Sesquiterpenoids of diverse types from the rhizomes ofAcorus calamus

“…[24][25][26][27] However, toxicological studies suggested it possess carcinogenicity and genetic toxicity. 28,29 Apparently, in this sense, it's not reasonable to view b-asarone as the representative neuroprotective constituent of A. calamus. Therefore, it is necessary to evaluate the neuroprotective bioactivities of other types of compounds.…”

Strategy for the multi‐component characterization and quality evaluation of volatile organic components in Kaixin San by correlating the analysis by headspace gas chromatography/ion mobility spectrometry and headspace gas chromatography/mass spectrometry

“…According to relevant literature reports and pharmacopoeia's main pharmacological effects and main drug components, we found that the common component is the main substance to exert efficacy. There are 54 common components in ATS and KXS, such as β-asarone, α-asarone, γ-asarone, methyleugenol, linalool, camphor and methyl eugenol are the main effective components in the treatment of amnesia 31.…”

“…Existing studies have shown that isocalamenediol, α-asarone, β-asarone, methyl eugenol, isoeugenol methyl ether, camphor, anethol, 2,4-di-tert-butylphenol, linalool, and asarylaldehyde are the 10 main medicinal components in KXS VOCs which have good medicinal effects. For example, β-asarone and α-asarone have good effects as antidepressants, and in the treatment of anti-senile dementia and memory improvement; methyl eugenol has anesthetic effects 31,37. For the reason that quantitative analysis of the main volatile medicinal substances which provides a basis for the study of the medicinal substance basis of KXS.…”