Agastache

Agastache: Botanical Identity, Traditional Use, Phytochemistry, and Scientific Evidence

1. Identity and Botanical Classification

Agastache is a genus of aromatic flowering herbaceous perennial plants in the family Lamiaceae. It contains 22 species, mainly native to North America, with one species native to eastern Asia. The common names of the species include a variety of "hyssops" and "mints," and the genus as a whole is known as giant hyssops or hummingbird mints.

The Agastache genus is part of the Lamiaceae family and is native to North America, while one species, Agastache rugosa (A. rugosa), is native to East Asia. Agastache is a small genus comprising 22 species of perennial aromatic medicinal herbs.

The most pharmacologically studied and medicinally significant species are:

• Agastache rugosa (Fisch. & C.A.Mey.) Kuntze — commonly known as Korean mint, purple giant hyssop, wrinkled giant hyssop, or in Chinese as Huo xiang. A. rugosa is commonly known as Korean mint, purple giant hyssop, Indiana mint, and the wrinkled giant hyssop, which belongs to the Lamiaceae family.
• Agastache foeniculum (Pursh) Kuntze — commonly called anise hyssop. The leaves of A. foeniculum have a strong licorice taste, accounting for its English name, anise hyssop.
• Agastache mexicana (Kunth) Lint & Epling — commonly called toronjil or Mexican giant hyssop. Mexico is the center of origin of the species popularly known as toronjil or lemon balm (Agastache mexicana Linton & Epling).

The available scientific data is focused mainly on the description of the chemical composition and bioactivity of A. rugosa, with fewer reports referring to Agastache mexicana (A. mexicana) and Agastache foeniculum (A. foeniculum).

The word "agastache" comes from the Greek aga, meaning abundance, and stachys, meaning ear. Foeniculum is the Latin name for fennel.

Morphological Description

Most species are very upright, 0.5–3 metres tall, with stiff, angular stems clothed in toothed-edged, lance-shaped leaves ranging from 1–15 centimetres long. Upright spikes of tubular, two-lipped flowers develop at the stem tips in summer. The flowers are usually white, pink, mauve, or purple.

Common Dosage Forms and Preparations

Agastache can be prepared alone as a tea, incorporated into a lotion, or prepared as a pill. The leaves are strongly aromatic, but lose this quality with prolonged boiling (over 15 minutes).

The medicinal use of Agastache rugosa primarily involves the flowering tops and the leaves. The flowers are harvested during the blooming season, typically in summer, while the leaves are collected when they are fresh and fully developed. These parts are often dried and used in various preparations. The essential oils extracted from the plant are also a key component in traditional remedies. The roots are occasionally used, though less commonly than the aerial parts.

Both leaves and flowers of A. rugosa are edible. The products of this plant are commercially used in meat marinades, salad dressings, salads, and tea. A. rugosa leaves are used as an ingredient in salads and soups for enhancing the aroma and taste of foods in Korea.

2. Traditional and Historical Use

Traditional Chinese Medicine (A. rugosa)

According to the records, the use of A. rugosa as a medicinal plant can be traced back to the Eastern Han dynasty (25 AD–220 AD) in China. Its first recorded use dates from about 500 AD. It is associated with the lungs, spleen, and stomach and is classified as having a warm nature and an acrid and aromatic taste.

According to Traditional Chinese Medicine (TCM) theory, A. rugosa has been used in folk medicine to treat a variety of diseases, including cholera, vomiting, miasma, and other intestinal disorders. It is classified as an aromatic and damp-dissolving herb and has been widely used as an effective herbal drug to cure diseases of human pathogenic summer-heat and dampness virulence in clinical practice in China.

Agastache rugosa is well-known as a common traditional Chinese medicine with relieving summer-heat, analgesic, and antipyretic effects, and has long been used as a folk remedy in the treatment of several infectious diseases, for its anti-inflammatory properties, and for its antibacterial properties.

In Chinese herbalism, A. rugosa is also used to treat summer flu or summer colds with accompanying low fever, feelings of fullness in the chest, and headache. It is also used to treat dark urine and a feeling of heaviness in the arms and legs. A lotion containing A. rugosa is applied externally to treat fungal infections.

In the world's official medicine, species of the genus are not widely used, with the exception of A. rugosa, which is a means of traditional Chinese medicine and is part of several well-known, often prescribed herbal remedies.

Korean Traditional Use

In Korea, A. rugosa has been used as a traditional medicine for the curing of anorexia, anxiety, bacterial infections, cholera, diarrhea, miasma, nausea, and vomiting. As an edible plant, it is used as a herbal medicine for anxiety, nausea, bacterial infections, or gas in folk medicine. A. rugosa is one of the 50 fundamental herbs, known as huò xiāng, and has antifungal, antibacterial, carminative, and antipyretic properties.

Native North American Use (A. foeniculum)

As a plant native to North America, historical sources on the use of anise hyssop come from Native American sources. One review notes that this plant was used by the Cree, Cheyenne, and Ojibwa for fever reduction, to treat respiratory conditions, and as an external application on burns.

Mexican Traditional Medicine (A. mexicana)

Agastache mexicana (Kunth) Lint & Epling (Lamiaceae) is a medicinal plant widely used in the Mexican traditional medicine for the treatment of anxiety, hypertension, and relief of heart disease, insomnia, and diabetes, as well as to reduce stomach ache.

Agastache mexicana subspecies mexicana (Amm) and xolocotziana (Amx) are used in Mexican traditional medicine to relieve cultural affiliation syndromes known as "susto" or "espanto," for "nervous" conditions, and as a sleep aid.

A. mexicana is grown in Mexico and used to treat gastrointestinal upsets, nervous, and cardiovascular ailments.

3. Key Constituents and Active Compounds

Overview of Chemical Classes

Agastache species are characterized by the dominance of flavonoids and phenolic acids, as well as volatile compounds, particularly phenylpropanoids and monoterpenes.

The phytochemical profile of all Agastache species studied to date is generally similar, consisting of two main metabolic classes — phenylpropanoids and terpenoids.

Non-Volatile Phenolic Compounds

Major non-volatile metabolites belong to phenolic compounds, such as caffeic acid derivatives, especially rosmarinic acid, as well as several flavones and flavone glycosides such as acacetin and tilianin.

Six components of A. rugosa are identified as key target components: five flavonoids (acacetin, calycosin, diosmetin, luteolin, and tilianin) and a phenylpropanoid (rosmarinic acid).

Rosmarinic acid (RA), tilianin, acacetin-7-O-(6″-O-malonyl)-β-d-glucopyranoside, isoagastachoside, acacetin-7-O-(2″-O-acetyl-6″-O-malonyl)-β-d-glucopyranoside, and acacetin are the main components in the 70% EtOH extract of A. rugosa.

HPLC analysis has revealed that the full spectrum of phenylpropanoids present in A. rugosa includes rosmarinic acid, tilianin, acacetin, 4-hydroxybenzoic acid, caffeic acid, chlorogenic acid, trans-cinnamic acid, rutin, (–)-epicatechin, quercetin, and kaempferol.

The highest concentrations of rosmarinic acid and its isomers have been reported in the roots of A. rugosa. Another study found that the concentration of rosmarinic acid in A. rugosa varied with plant organ and developmental stage, with flowers having the highest concentration (48.43 μg/g), followed by roots (30.97 μg/g) and leaves (22.14 μg/g).

Seven known compounds have been isolated from the aerial parts of A. rugosa, identified as methyl hexadecanoate, β-sitosterol, acacetin, ursolic acid, apigenin, protocatechuic acid, and tilianin.

Volatile Compounds (Essential Oil)

In the relatively variable essential oils, most populations of different Agastache species contain over 50% of a phenylallyl compound — estragole. Also, other volatile compounds (methyleugenol, pulegone, menthone, isomenthone, and spathulenol) were reported in various proportions.

Methyl chavicol (= estragole) is the predominant headspace volatile compound in the flowers with nectar, flower spikes, and leaves, with a total of 97.16%, 96.74%, and 94.35%, respectively.

The major component in the essential oil of A. rugosa was estragole (89.49%), followed by D-limonene (3.40%), menthone (1.80%), and pulegone (1.86%).

Korean A. rugosa plants are grouped into five chemotypes: methyl chavicol (= estragole), methyl eugenol, methyl eugenol plus limonene, menthone, and menthone plus pulegone.

Bioavailability

UPLC-MS/MS analysis showed the dominant components in Korean mint extract are rosmarinic acid (RA), acacetin (AC), and acacetin 7-glucoside (tilianin, TA). Following Korean mint extract consumption, the absorption curve of RA, TA, and AC changed over 6 hours: RA and TA were most abundant 2–3 hours post-initial ingestion with a gradual decrease afterward, while AC appeared in serum delayed to 2 hours but continuously increased until 6 hours post-ingestion.

Consistent results were obtained for AC and TA in Caco-2 cell monolayer studies, but no transport was found for RA in a highly tight cell monolayer, indicating transport through the intercellular space for RA and transepithelial transport for AC and TA.

4. Mechanisms of Action

Anti-Inflammatory Mechanisms

The main components of A. rugosa identified for anti-inflammatory activity are acacetin and luteolin, and the identified core target genes include AKT serine/threonine kinase 1 (AKT1), nuclear factor kappa B inhibitor alpha (NFKBIA), and mitogen-activated protein kinase-3 (MAPK3).

The components of Agastache rugosa are known to have many pharmacological activities. A preincubation with A. rugosa leaf extract (ELAR) significantly and concentration-dependently reduced the expression of iNOS protein in ROS 17/2.8 cells activated with a cytokine mixture (TNF-alpha and IL-1beta). Consequently, the NO production was also significantly reduced by ELAR with an IC₅₀ of 0.75 mg/mL.

Anti-Atherogenic Mechanisms (Tilianin)

Tilianin, a major component of A. rugosa, inhibits the TNF-α-induced expression of VCAM-1 by 74% in cultured human umbilical vein endothelial cells (HUVECs). Also, tilianin (100 μM) reduced TNF-α-induced activation of nuclear factor-κB in HUVECs.

Tilianin has anti-atherogenic properties: mice fed with a high-cholesterol diet supplemented with tilianin had considerably smaller lesions and lower cytokine levels when compared to controls. In another study, TNF-α and IL-1β mRNA levels in primary cultured peritoneal macrophages from Ldlr−/− mice in response to LPS treatment were ameliorated by co-treatment with tilianin. Electrophoretic mobility shift and NF-κB promoter experiments revealed that tilianin suppressed NF-κB activation. Tilianin prevented IκB kinase activation and the subsequent phosphorylation and degradation of IκBα protein upstream of NF-κB activation.

The liver transcriptome revealed that tilianin regulated the transcription of lipid metabolism-related genes. Both in vitro and in vivo analyses revealed the potent effect of tilianin to enhance hepatic LDLR expression and its mediated LDL-C uptake. Further studies confirmed a critical role of SREBP2 in hepatic LDLR up-regulation by tilianin via increasing precursor and thus mature nuclear SREBP2 level. This demonstrated the lipid-lowering effect of tilianin through SREBP2-mediated transcriptional activation of LDLR.

Cardioprotective (Acacetin)

The natural compound acacetin has been reported to be an atrium-selective agent that prolonged the atrial effective refractory period without prolonging the corrected QT interval, and effectively prevented atrial fibrillation (AF) in anesthetized dogs after intraduodenal administration.

Monoamine Oxidase Inhibition

Acacetin, purified from A. rugosa leaves, and its derivative acacetin 7-O-(6-O-malonylglucoside) inhibit monoamine oxidase A and B, suggesting their potential as lead compounds for inhibitor development.

Muscle Atrophy (PI3K/Akt Pathway)

A. rugosa extract (ARE) and tilianin promoted the phosphatidylinositol 3-kinase/protein kinase B pathway, thereby activating mammalian target of rapamycin (a protein anabolism-related factor) in C2C12 myotube models of muscle atrophy. Moreover, A. rugosa contains tilianin, a prominent flavonoid compound that exerts anti-inflammatory, antioxidant, antidiabetic, and antihypertensive effects.

5. Scientific Evidence by Area of Use

Note on evidence strength: As stated by the comprehensive 2023 PMC review, as a result of increasing interest in ethnic and traditional phytotherapeutics, many new studies have been undertaken to examine the pharmacological properties of Agastache species. So far, only a few species of the genus have been fairly represented in the phytochemical and pharmacological literature. Even so, the available data sufficiently support the prospect of increasing use of Agastache spp. and their constituents in herbal therapy. The overwhelming majority of evidence to date comes from in vitro and animal studies, not from human clinical trials.

5.1 Antimicrobial Activity

Evidence level: In vitro / preclinical only

A. rugosa contains many phenolic compounds that exhibit pharmacological and physiological activities, including antioxidant, anticancer, antiviral, antifungal, and antibacterial activities.

Twenty-five bacterial strains, including multidrug-resistant bacteria and one pathogenic yeast strain, were used for antimicrobial screening of A. rugosa hairy roots. The hairy root extracts displayed antibacterial activity against Micrococcus luteus (KCTC 3063) and Bacillus cereus (KCTC 3624).

Regarding the antibacterial activity, A. rugosa essential oil was most active against E. coli (8.91 ± 3.27 μL/mL) and S. aureus (10.80 ± 0.00 μL/mL).

No human clinical trials evaluating Agastache specifically for antimicrobial indications have been identified in the peer-reviewed literature.

5.2 Antifungal Activity

Evidence level: In vitro / preclinical only

The antifungal activities of the essential oil from Agastache rugosa and its main component, estragole, combined with ketoconazole, were evaluated against five Trichophyton species. The fractional inhibitory concentration indices (FICI) of ketoconazole combined with estragole or A. rugosa essential oil, against the tested Trichophyton species, were between 0.05 and 0.27, indicating synergistic effects. These drug combinations exhibited the most significant synergism against T. mentagrophytes, with FICIs of 0.05 and 0.09 for estragole and the essential oil fraction from A. rugosa, respectively.

The antifungal activity of mono-floral Agastache honey and commercially available honeys were tested against dermatophytes (T. mentagrophytes and T. rubrum) and C. albicans by agar well diffusion and micro-dilution. Agastache honey was effective at 40% concentration against dermatophytes (zone diameter, 19.5–20 mm) and C. albicans, with the same MIC and MFC values indicating fungicidal activity. This work was conducted in vitro; no clinical trials in humans exist.

5.3 Cardiovascular and Anti-Atherosclerotic Effects

Evidence level: In vitro and animal models; no human clinical trials identified

Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) play an important role during the early stages of atherogenesis. Agastache rugosa has an anti-atherogenic effect in low density lipoprotein receptor −/− mice. Moreover, A. rugosa reduced macrophage infiltration and VCAM-1 expression localized in aortic endothelium that overlies early foam cell lesions.

A series of pharmacological effects, including antioxidant, cytotoxic, antimicrobial, anti-atherosclerotic, and cardioprotective properties, have been reported for species from the Agastache genus. All such reports to date originate from cell culture or animal experiments.

5.4 Antioxidant Activity

Evidence level: In vitro; one preliminary human bioavailability study

Total phenolic compounds and total antiradical, nitrite scavenging, superoxide scavenging, antielastase, and antihyaluronidase activities of a hot water extract of A. rugosa Kuntze leaves were spectrophotometrically determined. The extract contained a total phenolic content of 38.9 mg gallic acid equivalent/g extract and exhibited DPPH radical, superoxide radical, and nitrite scavenging activities.

Findings from a preliminary human bioavailability study suggest that Korean mint polyphenols are readily available in circulation, providing a potential direct role in health benefits. This study was described as preliminary and was not a clinical intervention trial targeting a specific health outcome.

5.5 Anti-Inflammatory Effects

Evidence level: In vitro and animal models only

A. rugosa possesses anti-inflammatory, antioxidant, and antiatherosclerosis properties. A previous study demonstrated that A. rugosa exhibits antioxidant activity by reducing ROS and activating antioxidant enzymes, and anti-inflammatory activity by downregulating inflammatory cytokines.

All evidence for anti-inflammatory activity is from cell-based and rodent models. No human clinical trials have been identified.

5.6 Anti-HIV Integrase Activity

Evidence level: In vitro only

One 1999 study done at Seoul National University in Korea showed that in test tube experiments an extract of A. rugosa significantly inhibited the action of certain proteins associated with the reproduction of the HIV virus. Some studies reported that A. rugosa has antioxidant activity and anti-HIV integrase action. This activity has not been evaluated in human trials.

5.7 Gastroprotection and Gastritis

Evidence level: In vitro, network pharmacology modeling; no human trials

A network pharmacology study identified mechanisms by which A. rugosa components may act against gastritis. The main components were acacetin and luteolin, and the identified core genes were AKT1, NFKBIA, and MAPK3. This approach identifies candidate pathways but does not constitute clinical evidence. A. rugosa has been used in traditional Chinese medicine to treat nausea, vomiting, and to dispel damp.

5.8 Skin and Dermatological Effects

Evidence level: In vitro (keratinocyte cell lines); no human clinical trials

Agastache rugosa, a perennial herb grown throughout East Asian countries including Korea, Japan, and China, has been used to treat colds, anorexia, cholera, vomiting, and miasma in traditional folk medicine. Its diversified pharmacological properties such as antimicrobial, antifungal, insecticidal, antiviral, antihypertensive, anti-inflammatory, anticancer, antioxidant, antiatherogenic, and vasorelaxant activities have been recognized.

When A. rugosa extract was subjected to probiotic bacterial fermentation using Lactobacillus rhamnosus HK-9, the fermented extract showed higher antioxidant and anti-inflammatory activities than non-fermented extract in LPS-stimulated HaCaT keratinocytes. Similarly, the fermented extract appeared to contain higher attenuating activity on UV-B-induced ROS, proMMP-2, and -9, and higher augmenting activity on UV-B-reduced total GSH and SOD in HaCaT keratinocytes, compared to the non-fermented extract. These findings suggest that probiotic bacterial fermentation could be used as a tool for improving some therapeutic and cosmetic values of A. rugosa leaves.

5.9 Central Nervous System and Anxiolytic Effects (A. mexicana)

Evidence level: Animal models only; preliminary, conflicting results

The first pharmacological study on the effects of water-soluble A. mexicana extract on the central nervous system showed an anxiogenic-like effect in behavioral experiments at the doses tested in male rats. Chemical and pharmacological studies performed in 2014 to identify the effects of aqueous extracts from both subspecies on the central nervous system found similar chemical profiles but different compound abundances. Low doses of the extracts produced an anxiolytic effect, but higher doses sedated mice. Flavonoid derivatives may be responsible for the observed pharmacological effect.

Additionally, organic extracts of A. mexicana ssp. xolocotziana contain acacetin and ursolic acid and produce anxiolytic, spasmolytic, and antinociceptive effects in in vitro and in vivo experiments in mice.

Results from research on the medicinal effects of A. mexicana ssp. mexicana and ssp. xolocotziana support their use in traditional medicine as an anxiolytic, tranquilizer, and sedative, as well as a remedy to alleviate "nervousness." In most cases these studies are preliminary, and the understanding of the mechanism of action is inconclusive. The need for systematic studies in preclinical and clinical research is evident.

5.10 Muscle Atrophy

Evidence level: In vitro (C2C12 myotubes); no human data

Skeletal muscle atrophy is characterized by diminished muscle mass, strength, and function. Korean mint possesses various biological functions, including anti-inflammatory, antioxidant, anticancer, and antiosteoporosis activities. Moreover, it contains tilianin, which is a glycosylated flavone that exerts antioxidant, anti-inflammatory, antidiabetic, and neuroprotective activities. However, no studies had analyzed the inhibitory activity of A. rugosa extract (ARE) and tilianin on muscle atrophy prior to the referenced study, which investigated their potential in C2C12 myotubes treated with TNF-α.

5.11 Neurological/EEG Effects of Essential Oil Aromatherapy

Evidence level: One small human EEG study

In an EEG study, significant decreases in absolute theta (AT) and relative theta (RT) power spectra were observed during exposure to A. rugosa essential oil compared to no odor exposure, whereas relative alpha (RA), relative slow alpha (RSA), spectral edge frequency 50% (SEF50), and spectral edge frequency 50% of alpha (ASEF) power spectra values significantly increased. These results reveal that the EEG power spectra changes during exposure to the essential oil of A. rugosa may be associated with the enhancement of freshness and concentration states of the human brain. This is a single exploratory study and its results should be considered preliminary.

5.12 Cytotoxic and Anticancer Effects

Evidence level: In vitro only

Investigation of the antiproliferative effect showed that A. rugosa and A. foeniculum essential oils had significant cytotoxic activity on MDA-MB-231 and HepG2 tumour cell lines, with the most promising effect on the MDA-MB-231 breast cancer cell line for A. foeniculum "Aromat de Buzău" EO (IC₅₀ = 203.70 ± 0.24 μg/mL). This is the first report on the cytotoxic effect of Agastache sp. essential oils on MDA-MB-231, HCT116, and HepG2 tumour cell lines. The results provide new and promising information for the subsequent in vivo study of the pharmacological properties of Agastache sp. essential oils. No human studies exist.

6. Body Systems Associated

• Gastrointestinal system: A. rugosa is classified as an aromatic and damp-dissolving herb in TCM and has been widely used as an effective herbal drug to cure diseases of human pathogenic summer-heat and dampness virulence in clinical China.
• Respiratory system: It is associated with the lungs, spleen, and stomach in TCM classification. A. mexicana ssp. mexicana is used in Mexican traditional medicine for the treatment of hypertension, anxiety, and respiratory disorders.
• Cardiovascular system: Ursolic acid, acacetin, and tilianin are the main chemical components in A. rugosa known to have a wide range of biological activities and play a role in triggering cardiovascular activities.
• Central nervous system: A. mexicana exhibits a broad range of pharmacological properties, such as anti-inflammatory, anxiolytic, and antioxidant.
• Integumentary (skin): In vitro evidence supports antioxidant, anti-inflammatory, antielastase, and antihyaluronidase activity in keratinocyte models, as described in Section 5.8.
• Immune system: A. rugosa has been widely used in traditional medicine for aromatic, stomachic, antipyretic, and analgesic applications. Its main bioactive components include essential oils, flavonoids, and phenolic compounds, which have been reported to exhibit various pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, and antiviral effects.
• Musculoskeletal system: Preclinical evidence suggests potential for modulating skeletal muscle atrophy pathways via the PI3K/Akt/FoxO3 pathway, as described in Section 5.10.

7. Dosage Forms and Dosages Reported in Studies

The following dosages and concentrations reflect what has been reported in the scientific literature and do not represent standardized clinical recommendations:

• In vitro anti-inflammatory screening (RAW 264.7 cells): A. rugosa extracts were applied at concentrations of 100 and 200 μg/mL with LPS (1 μg/mL).
• iNOS inhibition (ROS 17/2.8 cells): A. rugosa leaf extract (ELAR) significantly and concentration-dependently reduced iNOS protein expression. NO production was also significantly reduced by ELAR with an IC₅₀ of 0.75 mg/mL.
• Tilianin VCAM-1 inhibition (HUVECs): Tilianin at 100 μM inhibited TNF-alpha-induced expression of VCAM-1 by 74% in HUVECs. Also, tilianin (100 μM) reduced TNF-alpha-induced activation of nuclear factor-kappaB in HUVECs.
• Antifungal (Agastache honey, in vitro): Agastache honey was effective at 40% concentration against dermatophytes and C. albicans.
• Cytotoxic/antiproliferative (cell lines): The IC₅₀ for the cytotoxic effect of A. foeniculum "Aromat de Buzău" essential oil on the MDA-MB-231 breast cancer cell line was 203.70 ± 0.24 μg/mL.
• Hairy root antimicrobial: The best carbon source for A. rugosa hairy root cultures produced rosmarinic acid at 7.656 ± 0.407 mg/g dry weight and a total phenolic content of 12.714 ± 0.202 mg/g gallic acid equivalent.

No published randomized controlled trials in humans have established standardized dosing guidelines for any Agastache species as a supplement or medicine.

8. Safety Considerations

Estragole: Genotoxicity and Carcinogenicity Concerns

Estragole was suspected to be carcinogenic and genotoxic, according to the European Union Committee on Herbal Medicinal Products. Further studies are needed on safe daily intake of Agastache as herbal tea or honey, as well as for topical uses.

Naturally occurring genotoxic and carcinogenic volatile compounds such as estragole are often present in aromatic plants. Several studies have shown the carcinogenicity of estragole in experimental animals after a few reported doses, and after chronic exposure in bacteria and yeast cells.

The EMA (European Medicines Agency) Committee on Herbal Medicinal Products (HMPC) issued a public statement on the use of herbal medicinal products containing estragole, which lists estragole (synonyms: 1-allyl-4-methoxybenzene; 1-methoxy-4-(2-propenyl)-benzene; p-allylanisole; chavicyl methylether; methylchavicol; isoanethole) as present in Agastache rugosa Kuntz and other Agastache spp.

Coagulation Effects

The extract of A. rugosa showed a significant procoagulant activity by shortening the time of prothrombin time (PT) and increasing fibrinogen (FIB) content, as compared with Vitamin K1. In contrast, its major constituents acacetin and tilianin exhibited significant anticoagulant activities by prolonging the times of PT, APTT, TT and reducing FIB content (P < 0.001), as compared with the blank control group. This divergence between the whole extract (procoagulant) and isolated constituents (anticoagulant) represents a potentially significant pharmacological interaction that has not been studied in human subjects and may be relevant for individuals taking anticoagulant or antiplatelet drugs.

Dose-Dependent CNS Effects

Low doses of A. mexicana extracts produced an anxiolytic effect, but higher doses sedated mice. This dose-dependent bidirectional CNS response has been observed only in rodent models.

Lamiaceae Family Cross-Reactivity

Individuals with known allergies to plants in the Lamiaceae family, such as mint or sage, may be at risk of cross-reactivity with Agastache rugosa.

Essential Oil Chemotype Variation

Agastache essential oils can be dominated by potent aromatics — for example, estragole in some A. rugosa oils. Essential oil misuse can cause skin irritation or rash, especially with undiluted use.

General Assessment

Only 7 species of the Agastache genus are known to be used in ethnomedicine. In the world's official medicine, species of the genus are not widely used, with the exception of A. rugosa, which is a component of traditional Chinese medicine. No Agastache species has received a regulatory approval as a standardized medicine in any major Western jurisdiction as of the available literature. The safety profile in human populations has not been systematically investigated through controlled trials.

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