Tanacetum species: Bridging empirical knowledge, phytochemistry, nutritional value, health benefits and clinical evidence

This systematic review addresses the ethnopharmacology, phytochemistry, biological activities, toxicity, and clinical evidence of Tanacetum spp. The genus includes 160 accepted species widely distributed across temperate regions and has extensive traditional uses in medicine, food, cosmetics, and agriculture. The purpose is to collate fragmented information accumulated since the last comprehensive review in 2002, validate traditional claims with pharmacological data, map phytochemical diversity, identify knowledge gaps, and propose directions for future research and conservation, including taxa with critical IUCN status.

Prior reviews (e.g., 2002) summarized chemical and pharmacological aspects of Tanacetum but predate substantial advances in metabolite discovery, modern analytical profiling (HPLC/LC-MS/GC-MS), and clinical/ethnopharmacological reporting. Taxonomic complexity and reclassifications within Anthemideae have influenced species circumscription. Ethnobotanical records are available for only about 10% (16 taxa) of the genus, indicating major documentation gaps. The present review integrates recent phytochemical identifications (241 metabolites), expanded bioactivity screens, and clinical evidence on T. parthenium (feverfew) for migraine prophylaxis.

Data were systematically retrieved from PubMed, Web of Science, Scopus, SciFinder, Wiley Online, ScienceDirect, and the Cochrane Central Register of Controlled Trials. Search terms included Tanacetum, ethnobotany, ethnoveterinary, geographical distribution, morphology, phytochemistry, biological activities, toxicity, and clinical trials. Botanical names were validated via World Flora Online. Studies covering traditional uses, chemical composition, in vitro/in vivo pharmacology, toxicity, and clinical trials were included. Methods across studies encompassed standard phytochemical isolation/identification (HPLC, LC/GC-MS, NMR), biological assays (antimicrobial MIC/MBC, antioxidant DPPH/FRAP, enzyme inhibition, cytotoxicity MTT, anti-inflammatory models, anthelmintic assays), and clinical RCTs/observational studies.

- Chemistry: 241 metabolites isolated from ~20 Tanacetum species; predominant classes: monoterpenes (19%), sesquiterpenes (18%), flavonoids (15%), phenolic acids (12%), fatty acids/alkanes (9%). Unique markers: tanacetamides A–D (T. artemisioides), pyrethrins (T. cinerariifolium), diverse sesquiterpene lactones (e.g., parthenolide in T. parthenium). - Essential oils: Yields 0.04–1.09% (v/w); major constituents include thujones, camphor, carvone, 1,8-cineole; broad antimicrobial and antioxidant activities reported. - Validated ethnomedicinal uses: Evidence supports uses for oral/dental hygiene (inhibition of cariogenic Streptococcus spp.), festering wounds/skin ulcers/UTIs (antimicrobial aldehydes, EOs), gastrointestinal issues and spasms (antispasmodic activity of carvone/EOs), antiparasitic/anthelmintic (schistosomicidal effects of T. vulgare; parthenolide active against S. mansoni), insecticidal/repellent (pyrethrins; EO fumigant toxicity), antioxidant/hepatoprotective (improved liver enzymes, lipid profiles; activation of Nrf2 by sesquiterpene lactones), antidiabetic (α-amylase/α-glucosidase/PTP-1B inhibition; glucose-lowering in STZ rats for T. nubigenum), cytotoxic/anticancer (eudesmanolides active in vitro; EO minor constituents show cytotoxicity). - Clinical evidence: 36 documents, mostly on T. parthenium (feverfew) in migraine. RCTs and observational studies show reduced headache frequency/severity (e.g., MIG-99 CO2 extract 6.25 mg t.i.d. lowered monthly attacks from 4.8 to 2.9 vs 4.8 to 3.5 with placebo; pediatric nutraceutical (riboflavin, Mg, CoQ10, T. parthenium) decreased TTH frequency by ~50%). Sample sizes small (n≈17–218); GI adverse effects reported in a minority. - Nutrition/food: Presence of fat-soluble vitamins (A, D, E, K) in T. densum; use as food additive/flavoring; active packaging with T. balsamita EO extended sausage shelf life by ~50 days. - Conservation: Only 8 species evaluated by IUCN; T. ptarmiciflorum, T. oxystegium, and T. oshanahanii are critically endangered, emphasizing the need for conservation.

The review links traditional uses of Tanacetum species with bioactive secondary metabolites and primary constituents, providing mechanistic plausibility for several folk applications. Antimicrobial, antiparasitic, anti-inflammatory, antispasmodic, antioxidant, hepatoprotective, antidiabetic, and insecticidal activities substantiate many ethnomedicinal claims, with specific compounds (e.g., parthenolide, ceramides, pyrethrins, phenolic acids) implicated. Nonetheless, much of the evidence remains in vitro or preliminary in vivo, limiting clinical translation. Methodological issues in antimicrobial testing (prevalence of disc diffusion), limited in vivo validation for antidiabetic and anticancer activities, and small-sample clinical studies constrain generalizability. Findings underscore research priorities: rigorous in vivo pharmacology with dose optimization and controls; isolation/characterization of actives underlying observed extract-level effects; standardized antimicrobial MIC methodologies; expanded clinical trials with adequate power; and integration of chemotaxonomic markers (e.g., pyrethrins, tanacetamides) with DNA barcoding to resolve taxonomy and ensure quality control. Conservation of threatened taxa is critical to sustain biodiversity and medicinal potential.

This systematic review consolidates two decades of ethnobotanical, phytochemical, pharmacological, toxicological, and clinical data on Tanacetum spp., identifying 241 metabolites and validating multiple traditional uses (e.g., antimicrobial, anthelmintic, antidiabetic, hepatoprotective, insecticidal). Feverfew (T. parthenium) shows the strongest clinical signal for migraine prophylaxis, though larger, long-term RCTs are needed. Key research needs include: (i) ethnobotanical documentation for the majority of unsurveyed taxa, (ii) in vivo confirmation of in vitro activities with mechanistic elucidation, pharmacokinetics, and safety profiling, (iii) improved antimicrobial testing standards and bioassay-guided isolation, (iv) expanded clinical trials of prioritized species/compounds, and (v) conservation actions for IUCN-listed Tanacetum species. Chemotaxonomic markers (tanacetamides, pyrethrins, sesquiterpene lactones) alongside DNA barcoding may aid taxonomy and quality control.

- Evidence base heavily weighted toward in vitro assays; limited in vivo validation for many activities (especially antidiabetic and anticancer). - Clinical studies on feverfew are relatively small and short-term, risking overestimation and bias; heterogeneous formulations/dosing. - Antimicrobial studies frequently used disc diffusion rather than MIC-based methods; polarity-dependent diffusion limits comparability. - Some in vivo studies used high doses that may not translate safely to humans; limited comprehensive toxicity data for extracts/isolates (notably sesquiterpene lactones). - Ethnobotanical data exist for only ~10% of species; substantial knowledge gaps remain. - Taxonomic complexity and reclassifications may affect comparability across studies; few species have IUCN assessments, and some are critically endangered, complicating access and sustainability.