Zdeněk Dvořák, Jiří Hrubý
Carvone is a naturally occurring monoterpene and the principal volatile constituent of spearmint (Mentha spicata) and caraway (Carum carvi), plants long used as carminative, digestive, antimicrobial, and flavoring agents. The compound exists as two enantiomers-S-(+)-carvone (predominantly associated with caraway) and R-(-)-carvone (predominantly associated with spearmint)-widely used in food, fragrance, and herbal preparations. Although carvone is a naturally occurring compound, the material used in experimental studies may be synthetically produced, isolated from plant essential oils, or used as a racemic or stereochemically enriched preparation. This review synthesizes evidence from 108 literature sources, complemented by PubChem (1535 records, accessed on 14 July 2026) and ChEMBL (136 records, accessed on 14 July 2026) bioassay data, to compile carvone's molecular targets and biological activities and align the pharmacological evidence with traditional uses. We identified 45 molecular targets and 99 documented biological activities across 38 classes, spanning evidence tiers from comprehensively characterized (Tier A/B) to screening-level observations (Tier C/D), each assigned a four-tier evidence grade (A/B/C/D). Tier A targets comprise the aryl hydrocarbon receptor (AhR) and the GABA-A receptor. Negative results are reported to prevent publication bias, including NCI-60 inactivity across 55 cancer cell lines and a comprehensive counterscreen of steroid/nuclear receptors, human protein kinases, phosphatases, and HSP90-all inactive. The aryl hydrocarbon receptor emerges as the most robustly characterized target by the evidence-tiering criteria: both enantiomers act as noncompetitive allosteric antagonists, validated in vivo in mouse skin. This designation reflects the breadth and quality of evidence for AhR antagonism specifically, not a claim that AhR mediates all of carvone's traditional or pharmacological effects. By mapping mechanistic evidence onto carvone's traditional carminative, antimicrobial, and topical applications, this work provides a plausible mechanistic basis for several of the empirical uses documented in the ethnopharmacological literature.