Ajuga

Ajuga: A Comprehensive Reference

1. Identity, Taxonomy, and Natural Sources

Ajuga is a genus of flowering herbs belonging to the family Lamiaceae (formerly Labiatae), the large mint family. The plants of genus Ajuga are evergreen, clump-forming rhizomatous perennial or annual herbaceous flowering species, with Ajuga being one of the 266 genera of the family Lamiaceae. According to the World Flora Online, the genus Ajuga in the Lamiaceae family includes approximately 300 species, of which 91 species are recognized as independent taxa, 192 have synonymous names, and 10 species remain undefined.

These plants, growing in Europe, Asia, Africa, Australia, and North America, are used in gardens as ground cover or border for their foliage and beautiful flowers. The Ajuga plant grows to 5–50 cm tall, with opposite leaves that are attractive.

While dozens of species bear ethnomedicinal significance, four are most prominent in the scientific and dietary supplement literature:

• Ajuga reptans L. — Commonly known as bugle, blue bugle, bugleherb, bugleweed, carpetweed, carpet bugleweed, and common bugle, it is an herbaceous flowering plant in the mint family Lamiaceae, native to Europe. It is a sprawling perennial herb with erect flowering stems and grows to a height of about 10 to 35 cm.
• Ajuga turkestanica (Regel) Briq. — A perennial herb native to the mountainous regions of Central Asia, it contains powerful bioactive compounds called ecdysteroids—particularly turkesterone—that have demonstrated remarkable anabolic properties. This plant is especially revered in Uzbekistan and Tajikistan for its benefits on muscle strength and various health conditions.
• Ajuga iva (L.) Schreb. — A medicinal plant commonly used in Africa to treat several diseases such as diabetes, rheumatism, allergy, cancer, renal, metabolic disorders, cardiovascular disorders, digestive, and respiratory disorders.
• Ajuga chamaepitys (L.) Schreb. — Known as yellow bugle or ground pine, this Mediterranean and European species has a distinct phytochemical profile and is noted both for traditional medicinal use and for the presence of potentially hepatotoxic neo-clerodane diterpenoids (discussed further below).

Plants of the genus Ajuga are not officially recognized in main pharmacopeias but are widely used in traditional medicine across many countries.

Common Names and Synonyms

The common name "bugleweed" is shared by multiple unrelated plants, which creates confusion. Ajuga reptans is the true European bugleweed; the name "bugleweed" is also applied to Lycopus virginicus (American bugleweed), a thyroid-active plant from an entirely different genus. Ajuga reptans has also historically been called Carpenter's Herb, a reference to its traditional styptic use. These species have been used as common house plants and are called bugle or bugleweed.

2. Traditional and Historical Use

European Traditions

Ajuga reptans has a particularly well-documented history in European folk medicine. For Ajuga reptans specifically, traditional uses center on topical wound care. Nicholas Culpeper, the well-known 17th-century English herbalist, recommended it highly as an ointment or plaster for wounds, and the old common name Carpenter's herb comes from a reputation for staunching the nicks and cuts that happen on a job site.

Ajuga reptans herb has been used in traditional Austrian medicine internally as a tea for the treatment of disorders related to the respiratory tract.

In Romanian folk medicine, both A. reptans and A. genevensis have been valued. Ajuga genevensis L., known as "Suliman" in Romanian, is traditionally used for sedative, antihemorrhagic, and anti-inflammatory effects, as well as for its wound-healing and epithelization capacity in topical remedies, and is also used for its remarkable property to precipitate the proteins from the digestive tract in the treatment of diarrheal diseases.

North African and Moroccan Traditions

Ajuga iva is used by many North African folk medicine practitioners especially against diabetes and immunological diseases. Ajuga iva has been used as a decoction to treat a variety of conditions, including kidney and digestive disorders, diabetes, hypertension, painful menstruation, rheumatic pain, eye infections, cardiovascular disorders, allergies, cancer, and rheumatism.

Persian/Iranian Traditions

The genus Ajuga (called Kamaphytus in Persian) is used traditionally for the management of jaundice, joint pain, gout, amenorrhea, sciatica, and wound-healing in traditional Persian medicine.

Central Asian Traditions

Ajuga turkestanica was traditionally used in Central Asian folk medicine for various ailments and has recently gained attention in Western fitness communities for its potential to enhance muscle growth, increase strength, and improve recovery.

Chinese and Himalayan Traditions

The whole herb or root of Ajuga forrestii, a related species, has been traditionally used in China to cure dysentery, nephritis, sore throat, lung heat cough, and vasculitis, with topical application of smashed fresh leaves also noted.

Broad Cross-Cultural Summary

Many of these plants have been used in traditional medicine as a remedy for fever, toothache, dysentery, malaria, high blood pressure, diabetes, gastrointestinal disorders, as anthelmintic, diuretic and antifungal, anti-inflammatory, and antimycobacterial agents. The extensive literature survey revealed Ajuga L. species to be a group of important medicinal plants used for the ethnomedical treatment of rheumatism, fever, gout, sclerosis, analgesia, inflammation, hypertension, hyperglycemia, joint pain, palsy, and amenorrhea, although only a few reports address the clinical use and toxicity of these plants.

3. Phytochemistry: Key Constituents and Active Compounds

The genus Ajuga is one of the most chemically diverse in the Lamiaceae family. Currently, more than 280 chemical constituents have been isolated and characterized from these plants. Among these constituents, neo-clerodane diterpenes and diterpenoids, phytoecdysteroids, flavonoids, and iridoids are the major bioactive compounds, possessing wide-reaching biological activities both in vivo and in vitro.

3.1 Phytoecdysteroids

Phytoecdysteroids are structurally analogous to insect molting hormones and represent arguably the most pharmacologically studied class of compounds within Ajuga. These compounds, called phytoecdysteroids, are a class of substances structurally similar to the hormones that govern the molting process in insects. In plants, these compounds act as a defense mechanism against insect herbivores by disrupting their development.

The primary phytoecdysteroids found across Ajuga species include:

• 20-Hydroxyecdysone (20E, ecdysterone) — A naturally occurring ecdysteroid hormone which controls the ecdysis (moulting) and metamorphosis of arthropods, and therefore one of the most common moulting hormones in insects and crabs. A phytoecdysteroid produced by and extracted from various plants including Cyanotis vaga, Ajuga turkestanica, and Rhaponticum carthamoides, it is thought to be a plant defense against herbivory that disrupts the reproduction of insect pests.
• Turkesterone — A particularly active ecdysteroid found in high concentration in Ajuga turkestanica, possessing efficient anabolic activity. What makes turkesterone unique is its structural variation at the 11-alpha hydroxyl group, which is believed to enhance its anabolic potential while minimizing androgenic effects. Ajuga turkestanica ecdysteroids are characterized by the abundance of 11α-hydroxylated compounds and by the simultaneous presence of 24C, 27C, 28C, and 29C ecdysteroids.
• Minor ecdysteroids — From a semi-purified turkesterone fraction of A. turkestanica, fourteen ecdysteroids (including turkesterone and 20-hydroxyecdysone) were isolated, seven of which, all bearing an 11α-hydroxy group, were previously unreported.

In Ajuga iva, chemical characterization using GC-MS, HPLC, and NMR revealed the presence of many chemical compounds such as 20-hydroxyecdysone, cyasterone, ajugasterone, apigenin dihexoside, apigenin, carvacrol, ecdysterone, and palmitic acid.

In Ajuga turkestanica, a recent metabolic profiling study found a total of 51 compounds belonging to various phytochemical classes, including 11 flavonoids, 10 ecdysteroids, 9 diterpenes, 6 fatty acids, 5 iridoids, 3 phenylpropanoids, 3 sugars, 2 phenolics, 1 coumarin, and 1 triterpene. The results showed that 8-O-acetylharpagide, 20-hydroxyecdysone (ecdysterone), and ajugachin B were the most abundant constituents in this species.

3.2 Neo-Clerodane Diterpenoids

Among the compounds isolated from Ajuga, neo-clerodane diterpenoids are the characteristic and dominant constituents of Ajuga species. Some biological activities of neo-clerodane diterpenes reported include moderate neuroprotective, antifeedant, antiproliferative, anti-inflammatory, antinociceptive, and vasorelaxant effects. Also, inhibitory activities on LPS-induced NO production and RANKL-induced osteoclastogenesis have been shown.

These compounds have a dual identity: they confer some pharmacological benefits but are also associated with hepatotoxicity concerns. These plants have been widely employed in the past in traditional medicine, but the use has now stopped in some cases due to the presence of toxic secondary metabolites known as neo-clerodane diterpenoids which have clearly been shown to cause hepatotoxicity.

3.3 Iridoid Glycosides

Iridoids are a group of secondary metabolites with a wide range of biological activities present in the genus Ajuga L. Among these compounds, 8-acetylharpagide has been reported to show a strong antitumor-promoting activity. Iridoids such as ajugol and ajugoside are chemotaxonomic markers of the genus Ajuga. The main compounds identified in A. reptans aerial parts extracts were 8-O-acetylharpagide, isoquercitrin, and β-sitosterol, whilst in A. genevensis were 8-O-acetylharpagide, luteolin, and campesterol.

Ajuga reptans L. is used due to the anti-inflammatory effects of its polyphenols, its wound-healing properties, and antidiarrhea, antiulcerogenic, and hepatoprotective effects due to the presence of iridoids.

3.4 Flavonoids and Polyphenols

Using TLC and high-performance liquid chromatography (HPLC), 20 phenolic compounds and quinic acid were identified and quantified in extracts of A. reptans herb. Among phenolic compounds, there were three phenol carboxylic acids, five hydroxycinnamic acids, eight flavonoids, and four tannin metabolites. Among the identified hydroxycinnamic compounds, the dominant ones were p-coumaric and caffeic acids.

Screening for antioxidant potential using different methods (DPPH, TEAC, EPR) showed a good activity in accordance with the polyphenol content (18–26 mg GAE/g dw).

3.5 Withanolides, Sterols, and Essential Oils

A large number of compounds have been isolated from the Ajuga plants, including phytoecdysteroids, neo-clerodane-diterpenes and diterpenoids, triterpenes, sterols, anthocyanidin-glucosides and iridoid glycosides, withanolides, flavonoids, triglycerides, and essential oils. The major constituents across different Ajuga species include phenolic compounds such as phenylethanoid glycosides, neo-clerodane-type diterpenes, iridoids, anthocyanin glycosides, and phytoecdysteroids.

4. Mechanisms of Action

4.1 Anabolic / Protein Synthesis Pathways

The primary mechanism through which ecdysteroids from Ajuga are proposed to exert anabolic effects involves the PI3K–Akt signaling cascade and, potentially, estrogen receptor beta (ERβ) binding. Stimulating effects on protein synthesis in muscles are observed in rats in vivo and on C2C12 murine myotubes in vitro. This is an effect at the level of translation, which involves the phosphorylation of the p70S6K ribosomal protein, at the end of a cascade involving the Akt/PkB protein kinase, a pathway also used by IGF-1 to stimulate protein synthesis.

Recent studies suggest that the anabolic effect of ecdysterone, a naturally occurring steroid hormone claimed to enhance physical performance, is mediated by estrogen receptor (ER) binding. In comparison with prohibited anabolic agents (e.g., metandienone and others), ecdysterone revealed to be even more effective in a recent study performed in rats.

An Ajuga turkestanica extract enriched with phytoecdysones (20-hydroxyecdysone and turkesterone) inhibits the transcription of myostatin and of caspase 3, a protein involved in apoptosis processes.

In arthropods, 20-hydroxyecdysone acts through the ecdysone receptor. Although mammals (including humans) lack this receptor, 20-hydroxyecdysone affects mammalian biological systems. In mammals, it is hypothesized to bind to the estrogen receptor beta (ERβ) protein.

4.2 Anti-Inflammatory Mechanisms

Ethanol extracts of Ajuga reptans and A. genevensis had anti-inflammatory activity through lowering the oxidative stress, phagocytosis, PMN, and total leukocytes. The flavonoids and hydroxycinnamic acid derivatives found in A. reptans are considered to be among the primary contributors to this activity, alongside iridoid glycosides.

4.3 Antioxidant Mechanisms

The polyphenol-rich extracts of Ajuga species demonstrate radical scavenging activity measurable by standard assays. In vitro, the aqueous extract of Ajuga iva possessed a very high antioxidant effect (1 mg/ml was similar to those of trolox 300 mmol/l). In animal studies, plasma thiobarbituric acid reactive substances (TBARS) values were reduced by 41% in A. iva-treated compared with untreated diabetic rats, with TBARS concentrations lower in liver, heart, muscle, and brain in the treated group.

4.4 Antidiabetic Mechanisms

Ajuga iva showed potent antidiabetic activity against key targets involved in the regulation of glucose metabolism and control of diabetogenesis. The ecdysteroids in A. iva, including 20-hydroxyecdysone, have been studied in this context, and their effects may also be mediated via antioxidant pathways reducing oxidative damage to pancreatic beta cells.

5. Scientific Evidence by Area of Use

5.1 Skeletal Muscle, Anabolism, and Physical Performance

This is the area of greatest contemporary scientific interest for Ajuga, driven largely by A. turkestanica and its ecdysteroid content.

In Vitro Evidence

Phytoecdysteroids, in particular 20-hydroxyecdysone (20E), increase protein synthesis in C2C12 skeletal muscle cells. An extract from A. turkestanica decreased myostatin mRNA expression fourfold after treatment in myotubes in vitro. These cell-culture findings support mechanistic plausibility but cannot be directly extrapolated to humans.

Animal Studies

Phytoecdysteroids, in particular 20-hydroxyecdysone (20E), increase muscle strength in young rats. Continuous administration of purified 20E to young adult male C57BL/6J mice for 5 days resulted in significant increases in the mass of the triceps brachii, although longer administration (15 days) showed no effect.

However, in a study specifically designed to test the anti-sarcopenic potential, the objective was to determine whether an extract from Ajuga turkestanica (ATE), enriched in phytoecdysteroids, and 20E affect skeletal muscle mass and fiber size, fiber type, activation of the PI3K–Akt signaling pathway, and the mRNA levels of MAFbx, MuRF-1, and myostatin in sedentary aging mice. Aging male C57BL/6 mice (20 months old) received ATE, 20E, or vehicle once per day for 28 days or a single acute dose. Treatment did not alter body, muscle, or organ mass; fiber cross-sectional area; or fiber type in the triceps brachii or plantaris muscles. This null result in aging mice contrasts with positive results in younger animals, indicating the anabolic response may be age- and context-dependent.

Human Clinical Evidence

The most important human trial to date is the Isenmann et al. (2019) study. The most significant study is by Isenmann et al. (2019, Archives of Toxicology) — a WADA-funded, 10-week intervention study in 46 trained young men. Participants were split into groups receiving 200 mg ecdysterone, 800 mg ecdysterone, or placebo alongside a strength training programme. The result: participants dosed with ecdysterone showed significantly higher increases in muscle mass compared to the placebo group. The results were strong enough that the researchers recommended including ecdysterone on WADA's list of prohibited substances.

Counterbalancing this, a 2006 study concluded that the use of 30 mg per day of 20-hydroxyecdysone administered orally did not significantly affect anabolic or catabolic responses to resistance training, body composition, or training adaptations. Similarly, despite preclinical findings, the evidence in humans is limited, with a study involving resistance-trained males finding no significant changes in muscle mass or strength with ecdysterone supplementation compared to a placebo.

Strength of evidence assessment: The human evidence base for the anabolic effects of ecdysteroids from Ajuga is preliminary and mixed. The 2019 Isenmann trial is the most frequently cited human study and showed a positive dose-responsive effect, but it is a single small trial. The body of human clinical evidence is insufficient to establish firm conclusions, and importantly, much of the research uses isolated 20-hydroxyecdysone from various plant sources, not exclusively Ajuga. Turkesterone specifically has no completed, peer-reviewed human clinical trials published as of the available literature. Much of the current excitement is driven by anecdotal reports, while large-scale human clinical trials are necessary to validate these effects.

5.2 Diabetes and Blood Glucose Regulation

Research here has focused primarily on Ajuga iva. Analysis of previous reports confirmed the scientific evidence of A. iva ethnomedicinal uses, especially the antidiabetic and anti-hypercholesterolemia activity.

In a rodent study with Ajuga iva aqueous extract: the study investigated the possible antioxidant effect of an aqueous extract of Ajuga iva in streptozotocin (STZ)-induced diabetic rats. Twelve diabetic rats were divided into two groups fed a casein diet supplemented or not with Ajuga iva (0.5%), for 4 weeks. The extract improved multiple antioxidant enzyme markers and reduced lipid peroxidation in these animals. In another rodent study, the effect of Ajuga iva extract on blood glucose, lipid profile, hepatic and renal toxicity, and antioxidant enzyme activities in alloxan-induced diabetic rats was investigated. Ajuga iva extract supplementation increased the levels of both enzymatic antioxidants and decreased lipid peroxidation. Besides, Ajuga iva ameliorated diabetes-provoked hepatic and renal toxicity as evidenced by lower levels of total and direct bilirubin, urea, creatinine, triglyceride, cholesterol, and higher HDL-cholesterol.

Strength of evidence assessment: The antidiabetic evidence for A. iva is largely preclinical (animal and in vitro). Analysis confirmed the scientific evidence of A. iva ethnomedicinal uses, especially the antidiabetic and anti-hypercholesterolemia activity. However, there was no clear correlation between previous pharmacological reports on A. iva and its other ethnomedicinal uses in the treatment of rheumatism, allergy, metabolic, digestive, and respiratory disorders. No large-scale randomized human clinical trials have been published. This area remains at the animal and mechanistic study phase.

5.3 Anti-Inflammatory Activity

Many Ajuga species have been used as a traditional medicine for the treatment of inflammation, pain, diabetes, hypertension, or gastrointestinal disorders. Recent studies have demonstrated their efficacy as anti-inflammatory agents, antioxidant, cytotoxic, antimalarial, hypolipidemic, analgesic, anabolic, antibacterial, antifungal, cardiotonic, and hepatoprotective agents.

In a comparative animal study: Ajuga reptans and A. genevensis ethanol extracts had anti-inflammatory activity through lowering oxidative stress, phagocytosis, PMN, and total leukocytes. The best anti-oxidative and anti-inflammatory activity was observed for the Ajuga reptans 100 mg dw/mL extract when compared with diclofenac. These findings provide substantial evidence that both selected Ajuga species have the potential to be valued as sources of phytochemicals in effective anti-inflammatory herbal preparations.

A 2025 PMC-published study found that A. reptans herb extracts are practically non-toxic, exhibit hepatoprotective activity (dose 25 mg/kg) in experimental carbon tetrachloride-induced hepatitis, moderate anti-inflammatory activity (dose 100 mg/kg) in carrageenan-induced edema models, and possess significant local hemostatic (reducing bleeding time by 40.6%) and wound-healing properties (complete wound healing after 9 days).

Strength of evidence assessment: Anti-inflammatory effects are well-supported in preclinical (in vivo and in vitro) models, but no human clinical trials specifically for Ajuga anti-inflammatory applications have been published. The activity is considered biologically plausible and is consistent across multiple species within the genus.

5.4 Antimicrobial Activity

A. reptans extracts are capable of inhibiting the growth of microorganisms and showing higher activity against Gram-positive bacteria. Ajuga sp. extracts have antimicrobial activity against C. albicans, C. tropicalis, and C. parapsilosis. The evidence here is purely in vitro.

5.5 Hepatoprotection

Several Ajuga species have been studied for hepatoprotective effects. Hepatoprotective potential of Ajuga bracteosa extracts was demonstrated against paracetamol-induced hepatotoxicity, with both methanolic and aqueous extracts showing hepatoprotective potential evidenced by serum analysis of biomarkers. Hepatotoxic mice pretreated with A. bracteosa plant extract or silymarin exhibited significant decrease in ALP, AST, and ALT enzyme levels while GSH levels were markedly increased, with preservation of the normal liver structural features.

The aqueous-ethanolic soft A. reptans extract (extractant 50% ethanol) demonstrated the most pronounced hepatoprotective and anti-inflammatory effects.

Strength of evidence assessment: All hepatoprotective data are from animal models. Human data are absent.

5.6 Antiproliferative / Anticancer Activity

A. reptans extracts demonstrated antiproliferative potential against prostate and lung cancer cells. In a study using three indigenous Ajuga species: standardized ethanolic extracts of A. genevensis, A. chamaepitys, and A. laxmannii on C26 and B16.F10 murine cancer cell lines were evaluated via ELISA BrdU-colorimetric immunoassay, additionally investigating the potential anti-inflammatory and antioxidant/pro-oxidant activity underlying the observed cancer cell growth inhibition. A. laxmannii exhibited the strongest inhibitory effect with a corresponding IC50 of 176.3 μg/mL on C26 cells and 236.8 μg/mL on B16.F10 cells.

Strength of evidence assessment: All antiproliferative data are in vitro. No clinical trials exist. These findings are hypothesis-generating only.

5.7 Cardiovascular and Vasorelaxant Effects

In Morocco, Ajuga iva was investigated for its in vivo antidiabetic effect, and the aqueous extract of Ajuga iva whole plant was tested for its antidiabetic effect in normal and streptozotocin diabetic rats. Vasorelaxant activity of Ajuga iva aqueous extracts in rat aorta has been reported in pharmacological literature, though this remains at the preclinical level. Neo-clerodane diterpenoids have also been reported to have vasoconstrictor activities in some in vitro models.

6. Body Systems and Health Areas Associated with Ajuga

• Musculoskeletal system: Anabolic and anti-sarcopenic effects (ecdysteroids; predominantly preclinical with limited clinical data)
• Metabolic / endocrine system: Blood glucose regulation, lipid-lowering effects (A. iva; animal data)
• Immune and inflammatory system: Anti-inflammatory activity across multiple species (animal and in vitro)
• Hepatic system: Hepatoprotective effects (A. reptans, A. bracteosa; animal data)
• Hemostatic / wound healing: Traditional and experimentally supported styptic/wound-healing effects (A. reptans)
• Respiratory tract: Traditional Austrian use of A. reptans as a tea for respiratory disorders
• Antimicrobial: In vitro activity against bacteria and fungi
• Antioxidant: Demonstrated in vitro and in animal models

7. Dosage Forms and Reported Dosages

The genus Ajuga is widely used in traditional medicine for its diaphoretic, antiseptic, hemostatic, and anti-inflammatory properties, but scarcely in official preparations. As a result, standardized dosing recommendations are not codified in any major pharmacopeia.

Traditional Preparations

• Infusion/tea (internal use): aerial parts of A. reptans brewed as a tea for respiratory conditions
• Decoction: whole plant of A. iva decocted for antidiabetic and antihypertensive use in North Africa
• Topical ointment or oil infusion: aerial parts of A. reptans in wound-healing preparations

Dosages Reported in Scientific Studies

• A. iva aqueous extract, oral, chronic (rodent toxicology): In chronic toxicological studies in rats, the AI-extract was administered orally at daily doses of 100, 300, and 600 mg/kg for 3 months. Previously, single oral doses (2–14 g/kg) in mice or daily oral administration of 10 mg/kg in rats for 2 weeks did not result in any adverse effects.
• A. iva aqueous extract, antioxidant study (rodent): Diabetic rats were fed a casein diet supplemented with A. iva at 0.5%, for 4 weeks.
• Ecdysterone (20-hydroxyecdysone), human clinical trial: Participants received 200 mg or 800 mg ecdysterone daily alongside a 10-week strength training programme.
• 20-Hydroxyecdysone, older human study (negative result): A 2006 study used 30 mg per day of 20-hydroxyecdysone administered orally in a resistance training context.
• A. reptans extracts, animal pharmacology: Hepatoprotective activity was assessed at a dose of 25 mg/kg, and moderate anti-inflammatory activity was measured at 100 mg/kg in carrageenan-induced edema models.
• A. bracteosa hepatoprotection (rodent): Methanol extract was tested at 200 mg/kg BW and aqueous extract at 1,000 mg/kg BW, with standard drug silymarin used at 100 mg/kg BW for comparison.

8. Safety Considerations

8.1 General Toxicity Profile of A. reptans and A. iva

The findings from animal studies indicate the absence of hepatotoxicity during the intake of A. reptans extracts. Intragastric administration of A. reptans herb extracts at a dose of 5,000 mg/kg did not result in animal mortality, indicating an absence of toxic effects at this dose and characterizing the extracts as practically non-toxic (toxicity class V, LD50 > 5,000 mg/kg).

For Ajuga iva, no toxicity was observed in mice after single oral doses of as high as 14 g/kg of the AI-extract. In chronic toxicological studies in rats (administered orally at daily doses of 100, 300, and 600 mg/kg for 3 months), did not cause any changes in haematological and biochemical parameters, with the exception of a transient rise in platelet counts and a short-term decrease in serum glucose levels. Histopathological examination of the brain, liver, and kidneys at the end of the study showed normal architecture suggesting no morphological disturbances.

8.2 Hepatotoxicity Concerns: Neo-Clerodane Diterpenoids

The most significant documented safety concern for the Ajuga genus is hepatotoxicity linked to specific constituents. These plants have been widely employed in the past in traditional medicine, but the use has now stopped in some cases due to the presence of toxic secondary metabolites known as neo-clerodane diterpenoids, which have clearly been shown to cause hepatotoxicity. This concern is of particular relevance to species in the closely related genus Teucrium (which shares these diterpenoids) and to certain Ajuga species, most notably A. chamaepitys. The degree to which neo-clerodane diterpenoids vary in concentration across Ajuga species means that safety profiles cannot be generalized across the entire genus without species-specific data.

8.3 Species-Specific Considerations

Notwithstanding the widespread use of Ajuga plants in traditional medicine and despite the fact that many plants exhibit significant toxicity, some as serious as enhancement of mutagenecity, carcinogenicity, or embryotoxicity, no systematic toxicological study has been undertaken in many species of this genus. This gap is important: the relatively reassuring toxicity data for A. reptans and A. iva cannot be assumed to apply to other species such as A. chamaepitys.

8.4 Supplement Adulteration and Identity Concerns

A quality-control issue specific to the dietary supplement market is the potential for mislabeling or substitution between Ajuga species. Many supplements claiming to contain turkesterone or ecdysterone either contain low actual active ingredient, the incorrect plant species (e.g., Ajuga reptans instead of Ajuga turkestanica), or are spiked with actual steroids or SARMs according to some laboratory tests. This raises the practical safety concern that consumers may not be receiving what is labeled, and may be receiving unlisted pharmacologically active substances.

8.5 Regulatory and Doping Status

20-Hydroxyecdysone and other ecdysteroids are marketed as ingredients in nutritional supplements for various sports, particularly bodybuilding. The results of the Isenmann et al. (2019) study were strong enough that the researchers recommended including ecdysterone on WADA's list of prohibited substances — though ecdysterone remains fully legal. Competitive athletes should verify the current status of ecdysteroid-containing supplements with their relevant anti-doping authority, as the regulatory landscape may evolve.

8.6 Pregnancy, Lactation, and Drug Interactions

Formal human safety data on Ajuga use during pregnancy and lactation are absent from the peer-reviewed literature. The extensive literature survey on the genus found only a few reports addressing the clinical use and toxicity of these plants. Potential pharmacodynamic interactions are theoretically plausible with antidiabetic drugs (based on the glucose-lowering effects of A. iva), antihypertensive agents, and anticoagulants (given the hemostatic vitamin K1 content of A. reptans), but no formal interaction studies in humans have been published.

References

• Ethnopharmacology of the plants of genus Ajuga — PubMed (2009)
• Ajuga reptans L. Herb Extracts: Phytochemical Composition and Pharmacological Activity Screening — PMC (2025)
• Comparative Phytochemical Profile, Antioxidant, Antimicrobial and In Vivo Anti-Inflammatory Activity of Romanian Ajuga genevensis L. and A. reptans L. — PMC (2019)
• Phytochemical Characterization of Phenolic Compounds by LC-MS/MS and Biological Activities of Ajuga reptans L., Ajuga salicifolia and Ajuga genevensis L. — PMC (2021)
• Comparative metabolic profiling and quantitative analysis of metabolites in different tissues of Ajuga turkestanica — PubMed (2024)
• The minor ecdysteroids from Ajuga turkestanica — PubMed (2015)
• Phytoecdysteroids Do Not Have Anabolic Effects in Skeletal Muscle in Sedentary Aging Mice — MDPI International Journal of Environmental Research and Public Health (2021)
• Phytoecdysteroids Do Not Have Anabolic Effects in Skeletal Muscle in Sedentary Aging Mice — PMC (2021)
• Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans — Archives of Toxicology (2019)
• 20-Hydroxyecdysone — Wikipedia (references Isenmann 2019 and Wilborn 2006 trials)
• Ethnomedicinal use, phytochemistry, pharmacology, and toxicology of Ajuga iva (L.) Schreb — ScienceDirect / Journal of Ethnopharmacology (2020)
• Phytochemical Profile, Antioxidant, Antimicrobial, and Antidiabetic Activities of Ajuga iva (L.) — PMC (2023)
• Therapeutic effect of phytoecdysteroids rich extract from Ajuga iva on alloxan induced diabetic rats — PubMed (2009)
• Antioxidant effect of Ajuga iva aqueous extract in streptozotocin-induced diabetic rats — PubMed (2009)
• Acute and chronic toxicological studies of Ajuga iva in experimental animals — PubMed (2004)
• Biologically Active Ajuga Species Extracts Modulate Supportive Processes for Cancer Cell Development — PMC (2019)
• Medicinal Importance of Ajuga Species in Iran: Ethnobotanical and Traditional Applications — Journal of Jundishapur Natural Pharmaceutical Products (2022)
• Phytochemistry, micromorphology and bioactivities of Ajuga chamaepitys (L.) Schreb. (Lamiaceae, Ajugoideae) — ScienceDirect / Fitoterapia (2016)
• Antifeedant, cytotoxic, and anti-inflammatory neo-clerodane diterpenoids in the peltate glandular trichomes and fresh leaves of Ajuga forrestii — ScienceDirect / Phytochemistry (2021)
• Attenuation of paracetamol-induced hepatotoxicity in Ajuga bracteosa extract treated mice — ScienceDirect / Heliyon (2024)
• Combined Effects of Exercise and Phytoanabolic Extracts in Castrated Male and Female Mice — PMC (2021)
• Ajuga reptans — Wikipedia