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Helenalin

Helenalin is a sesquiterpene lactone, a secondary metabolite primarily isolated from the flowers of Arnica montana and other species in the Asteraceae family, such as Helenium plants.^[1]^[2] With the molecular formula C₁₅H₁₈O₄ (molar mass 262.30 g/mol; CAS 6754-13-8), it features reactive exomethylene and α,β-unsaturated carbonyl groups that enable its biological interactions.^[2] Known for its potent anti-inflammatory effects, helenalin has been used in traditional folk medicine for centuries to treat minor injuries and inflammation, though its therapeutic potential is constrained by toxicity.^[1] The compound's primary mechanism of action involves selective inhibition of the transcription factor NF-κB, achieved by direct alkylation of the p65 subunit through Michael-type addition to its cysteine sulfhydryl groups.^[3] This modification prevents NF-κB from binding to DNA without affecting IκB degradation or nuclear translocation, leading to downregulation of proinflammatory cytokines like IL-1, IL-6, and TNF-α.^[3]^[2] In addition to anti-inflammatory properties, helenalin demonstrates in vitro antineoplastic activity by inducing apoptosis and inhibiting telomerase, as well as antitrypanosomal effects with IC₅₀ values as low as 0.05 μM against Trypanosoma species.^[1]^[4]^[2] The total sesquiterpene lactone content in Arnica montana flowers, including helenalin and its derivatives, typically ranges from 0.4% to 0.6%, as standardized by the European Pharmacopoeia, and helenalin concentrations up to 3% dry weight in Helenium species.^[2] However, its bitterness and toxicity—responsible for the poisonous nature of Arnica—limit safe use, with oral LD₅₀ values of 85–150 mg/kg in mammals and potential for allergic reactions in humans.^[2]^[5]^[1] Ongoing research, including 2023 studies on its anti-cancer potential in breast cancer cell lines, explores synthetic analogs to harness its benefits while mitigating these risks for applications in anti-inflammatory and anticancer therapies.^[1]^[6]

Chemical Properties

Structure

Helenalin is a pseudoguaianolide sesquiterpene lactone characterized by a fused bicyclic ring system consisting of a seven-membered azulene ring and a five-membered furan ring, along with an α-methylene-γ-lactone moiety and a cyclopentenone functional group.^[7] Its molecular formula is C_{15}H_{18}O_4, with a molar mass of 262.305 g·mol^{-1}.^[8] The IUPAC name for helenalin is (3aS,4S,4aR,7aR,8R,9aR)-4-hydroxy-4a,8-dimethyl-3-methylidene-3,3a,4,4a,7a,8,9,9a-octahydroazuleno[6,5-b]furan-2,5-dione, reflecting its specific stereochemistry at six chiral centers (positions 3a, 4, 4a, 7a, 8, and 9a).^[9] Helenalin exists in polymorphic forms that differ primarily in their hydrogen-bonding patterns and molecular packing arrangements within the crystal lattice.^[10]

Reactivity

Helenalin exhibits significant chemical reactivity primarily due to its electrophilic functional groups, which enable interactions with biological nucleophiles. The molecule contains an α-methylene-γ-butyrolactone moiety and an α,β-unsaturated cyclopentenone group, both serving as Michael acceptors that facilitate conjugate additions.^[11]^[12] The reactivity of helenalin is dominated by the Michael addition mechanism, wherein these electrophilic sites undergo 1,4-addition with thiol-containing nucleophiles, such as cysteine residues in proteins or glutathione (GSH). This process forms stable covalent adducts, with the addition to the α-methylene-γ-butyrolactone being irreversible, while the cyclopentenone addition is reversible under physiological conditions.^[11]^[12]^[13] The general reaction for this Michael addition can be represented as:

\text{Helenalin} + \text{R-SH} \rightarrow \text{Helenalin-S-R (adduct)}

where the exocyclic methylene of the lactone or the β-carbon of the enone accepts the thiol nucleophile in a 1,4-fashion, leading to saturation of the double bond and thioether formation.^[12]^[14] Helenalin's lipophilicity, modulated by its rigid molecular conformation and lack of polar substituents, enhances its ability to permeate cell membranes, thereby facilitating access to intracellular targets for these reactive interactions.^[15]^[16]

Derivatives

Helenalin derivatives include both naturally occurring and semi-synthetic compounds that modify its core pseudoguaianolide structure, primarily through saturation of double bonds or conjugation with other molecules.^[17]^[18] A key natural derivative is dihydrohelenalin (also known as 11α,13-dihydrohelenalin), which features saturation of the exocyclic methylene group at positions C-11 and C-13 compared to the parent helenalin, reducing reactivity at that site while retaining the overall sesquiterpene lactone framework.^[17] This compound occurs alongside helenalin in Arnica montana flowers, often as ester forms such as dihydrohelenalin acetate.^[17] Semi-synthetic derivatives encompass glutathione conjugates like 2β-(S-glutathionyl)-2,3-dihydrohelenalin, formed via Michael-type addition of glutathione's thiol group to the α,β-unsaturated carbonyl in the dihydrohelenalin structure, resulting in a more polar adduct at the 2β position.^[18] Additionally, helenalin esters, such as the acetate, involve acylation at the hydroxyl group at C-4, with chain lengths varying from short (acetate) to longer (tiglate or isovalerate).^[17] Structural modifications like esterification at hydroxyl sites generally increase lipophilicity, enhancing membrane permeability, while hydrogenation of double bonds, as in dihydrohelenalin, decreases electrophilic reactivity.^[17] Regarding toxicity, shorter ester chains (e.g., acetate and isobutyrate) exhibit higher cytotoxicity than helenalin itself in cell lines like L1210 leukemia cells, whereas longer chains (e.g., tiglate) reduce toxicity, likely due to steric hindrance and altered lipophilicity.^[17] However, comprehensive toxicity data remain limited for many derivatives, particularly regarding long-term in vivo effects and specific organ impacts beyond sensitization potential.

Biological Sources and Biosynthesis

Natural Occurrence

Helenalin, a sesquiterpene lactone, occurs naturally primarily in species of the genus Arnica and Helenium within the Asteraceae family, with significant concentrations found in Arnica montana (European arnica), Arnica chamissonis (meadow arnica), and various Helenium species such as H. autumnale.^[19]^[20]^[2] These plants are perennial herbs native to temperate regions, where A. montana inhabits nutrient-poor, acidic grasslands and meadows in mountainous areas of Europe, often at elevations between 600 and 2,500 meters, while A. chamissonis grows in similar open, moist meadows across North America. Helenium species are native to North America, with helenalin content reaching 0.5–3% dry weight in flowers.^[21]^[22]^[23]^[24] Within these plants, helenalin concentrations are highest in the flower heads, ranging from 0.2% to 1% of dry weight for helenalin and its derivatives in Arnica, whereas rhizomes and roots contain only trace amounts or none at all. In Helenium, levels are higher, up to 3% dry weight.^[25]^[26]^[2] The compound's levels vary significantly by plant part and are influenced by ecological parameters, including soil composition (e.g., siliceous versus calcareous substrates), altitude, temperature, and precipitation.^[27]^[28] For example, studies have shown a positive correlation between higher altitudes and elevated helenalin content in A. montana, likely due to stress responses in harsher environments.^[29]^[30] Helenalin is typically isolated from the flowers of Arnica and Helenium species using solvent extraction methods, such as with ethanol or other organic solvents, to yield the bioactive compound for further analysis or use.^[20]^[31] As a sesquiterpene lactone, it contributes to the plant's chemical defense against herbivores and pathogens.

Biosynthesis

Helenalin, a pseudoguaianolide sesquiterpene lactone, is biosynthesized in plants such as Arnica montana from farnesyl pyrophosphate (FPP), which is produced via the mevalonate (MVA) pathway in the cytosol or the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway in plastids. FPP is formed by the condensation of dimethylallyl pyrophosphate (DMAPP) and isopentenyl diphosphate (IPP) catalyzed by farnesyl diphosphate synthase (FDS). This precursor undergoes cyclization by sesquiterpene synthases (STPSs), such as germacrene A synthase (GAS), to form a germacrane precursor, which serves as the foundational skeleton for pseudoguaianolides like helenalin. Subsequent rearrangements lead to the characteristic pseudoguaianolide framework.^[32] Key biosynthetic steps include the initial cyclization of FPP to germacrene A, followed by oxidation via germacrene A oxidase (GAO, a cytochrome P450 enzyme from the CYP71A2-8 family) to introduce hydroxyl groups and facilitate ring modifications. Further oxidations and hydroxylations by cytochrome P450 enzymes from the CYP71BL subfamily form the α-methylene-γ-lactone ring, while additional modifications by alcohol dehydrogenases, reductases, and acyltransferases introduce the exocyclic methylene and ester functionalities typical of helenalin derivatives. The introduction of the exocyclic methylene occurs through oxidative processes that activate the lactone for biological activity. Although partial involvement of germacrene synthase has been identified, the full enzymatic sequence for helenalin biosynthesis remains unelucidated.^[33]^[32]^[34] Biosynthesis is localized primarily in the flower heads of Arnica species, with high concentrations in glandular trichomes of the corolla, pappus calyx, and ovary, where sesquiterpene lactones colocalize with inulin storage vacuoles. Content increases progressively from flower buds to full maturity, reflecting developmental regulation.^[32] Regulation of helenalin production is elicited by biotic and abiotic factors, including jasmonic acid (JA) at concentrations of 0.25–1 mg/L, which boosts sesquiterpene lactone yields by up to 66% in tissue cultures via JAZ-MYC signaling pathways; chitosan at 50–100 mg/L, increasing levels fivefold and favoring helenalin esters; and red light at 30–150 µmol m⁻² s⁻¹, enhancing accumulation by 60–300%. Recent studies from 2020–2025 demonstrate that these elicitors and stress conditions, such as low light or pathogen exposure, upregulate helenalin derivatives, promoting protective responses in young tissues and shifting metabolic profiles toward pseudoguaianolides under environmental stress.^[33]

Pharmacological Effects

Anti-inflammatory Effects

Helenalin demonstrates potent anti-inflammatory activity primarily through targeted inhibition of key signaling pathways in inflammatory cells. A primary mechanism involves the covalent alkylation of the NF-κB transcription factor, which orchestrates the expression of numerous pro-inflammatory genes. Helenalin alkylates cysteine residues, potentially including Cys38, on the p65 (RelA) subunit via Michael-type addition, thereby preventing NF-κB's DNA binding and subsequent activation of cytokine production, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β).^[3]^[35] This NF-κB inhibition occurs downstream of IκB degradation and nuclear translocation, effectively blocking NF-κB-driven transcription in response to diverse stimuli such as TNF-α or phorbol esters. In vitro studies across cell models, including T-cells, B-cells, epithelial cells, and macrophages, show reduced inflammatory responses, with IC₅₀ values for p65 DNA binding inhibition ranging from 2.5 to 5 μM in electromobility shift and surface plasmon resonance assays.^[20]^[36]^[37] Helenalin also suppresses the 5-lipoxygenase (5-LOX) pathway by alkylating thiol groups on enzymes involved in leukotriene biosynthesis. In human polymorphonuclear granulocytes and platelets, it inhibits 5-LOX activity (IC₅₀ ≈ 9 μM after 60-minute preincubation) and leukotriene C₄ synthase (IC₅₀ ≈ 12 μM), thereby curtailing the production of pro-inflammatory leukotrienes that contribute to conditions like edema and allergic responses.^[38] This dual action on NF-κB and 5-LOX pathways underscores helenalin's broad potential to dampen acute inflammation at multiple levels. Although helenalin's thiol reactivity underpins these effects, as detailed in its chemical properties, in vivo and clinical evidence remains limited, with studies confined largely to in vitro models. Preliminary indications suggest potential for topical application in arthritis models, where localized delivery could exploit its anti-inflammatory potency while minimizing systemic toxicity.^[38]

Anti-neoplastic Effects

Helenalin exhibits anti-neoplastic effects primarily through inhibition of telomerase and induction of apoptosis in cancer cells. It alkylates the catalytic subunit of telomerase, thereby reducing human telomerase reverse transcriptase (hTERT) activity and expression, which limits the proliferative capacity of tumor cells. For instance, in the T47D breast cancer cell line, helenalin significantly downregulated hTERT gene expression in a dose-dependent manner, with significant inhibition observed at 5 μM after 48 hours of treatment.^[6] This mechanism has also been demonstrated in hematopoietic cancer cells, where helenalin potently suppressed telomerase activity by directly interacting with the enzyme's cysteine residues.^[39] In addition to telomerase inhibition, helenalin promotes apoptosis in various cancer cell types via blockade of NF-κB signaling—sharing this pathway with its anti-inflammatory actions—and by generating reactive oxygen species (ROS). The NF-κB inhibition disrupts prosurvival pathways, sensitizing cells to death signals even in cases of Bcl-2 overexpression, as seen in human leukemic Jurkat cells.^[40] Concurrently, helenalin elevates intracellular ROS levels, which trigger mitochondrial dysfunction and caspase activation; ROS scavengers like N-acetylcysteine attenuated this apoptosis in Jurkat cells, confirming the dependency.^[41] In prostate cancer cells (DU145 and PC-3 lines), helenalin further targeted thioredoxin reductase 1 (TrxR1), amplifying ROS-mediated apoptosis and cell cycle arrest at G2/M phase, with effects prominent at 5-10 μM concentrations.^[42] Helenalin demonstrates in vitro cytotoxicity against multiple cancer cell lines, including those from leukemia (e.g., HL-60, Tmolt3), breast (e.g., T47D), and prostate (e.g., DU145), with IC₅₀ values typically ranging from 0.5 to 10 μM. This potency arises from its ability to selectively target rapidly dividing cancer cells over normal ones, potentially extending to cancer stem cells due to its disruption of key survival pathways common in these populations.^[43]^[44] Derivatives such as helenalin acetate exhibit enhanced potency and improved solubility compared to the parent compound, facilitating better cellular uptake and stronger inhibition of transcription factors like C/EBPβ in tumor cells.^[45] As of 2025, helenalin's anti-neoplastic effects remain confined to preclinical studies, with no ongoing or completed clinical trials reported for cancer treatment.^[46]

Other Effects

Helenalin exhibits anti-trypanosomal activity by inhibiting key parasite enzymes through its reactivity with thiol groups, with in vitro IC₅₀ values below 10 μM against Trypanosoma species; specifically, it shows an IC₅₀ of 0.051 μM against T. brucei rhodesiense and 0.695 μM against T. cruzi.^[4] Similarly, helenalin demonstrates anti-malarial effects against the asexual blood stages of Plasmodium falciparum, with helenalin and related pseudoguaianolide sesquiterpene lactones displaying potent in vitro activity.^[47] Regarding antimicrobial properties, helenalin reduces Staphylococcus aureus growth in vitro within bovine mammary epithelial cells and limits bacterial proliferation in vivo in mouse models of mammary gland infection, leading to significantly fewer recoverable bacteria without causing host cell apoptosis.^[48] Helenalin also possesses immunosuppressive effects, suppressing essential functions of activated CD4⁺ T cells, including cytokine production and proliferation, positioning it as a candidate for treating T cell-mediated immune disorders.^[49] In terms of enzyme inhibition, helenalin partially inhibits human cytochrome P450 enzymes, particularly CYP3A4 and CYP3A5, during its metabolism in liver microsomes, with inhibitory effects observed at micromolar concentrations.^[50]

Metabolism and Toxicity

Metabolism

Helenalin undergoes phase I metabolism primarily through cytochrome P450 enzymes in hepatic microsomes, with CYP3A4 and CYP3A5 identified as the main isoforms responsible in humans, alongside CYP2B6 and extrahepatic CYP2A13.^[51] This process yields oxidative metabolites such as 14-hydroxyhelenalin in human liver microsomes and 9-hydroxyhelenalin in rat microsomes, along with reduced metabolites in cytosolic fractions.^[51] Notably, helenalin acts as a mechanism-based inhibitor of these enzymes, particularly CYP3A4 (IC₅₀ = 18.7 µM) and CYP3A5 (IC₅₀ = 62.6 µM), which may impair the detoxification of co-administered xenobiotics.^[51] In phase II metabolism, helenalin readily undergoes conjugation with glutathione (GSH) via glutathione S-transferase (GST) enzymes, forming adducts such as the 2β-(S-glutathionyl)helenalin through Michael addition at the α-methylene-γ-lactone moiety. This reaction, which can occur spontaneously or enzymatically (as demonstrated with horse liver GST), depletes intracellular GSH levels and contributes to the compound's electrophilic reactivity in biological systems. Although GST catalysis does not significantly accelerate the conjugation compared to non-enzymatic pathways, the resulting adducts inhibit GST activity, potentially exacerbating oxidative stress. In vitro studies using rat, pig, and human liver microsomes have elucidated the metabolism of helenalin derivatives like helenalin acetate and 11α,13-dihydrohelenalin acetate, revealing predominant thiolation via GSH and cysteine conjugation (yielding up to four mono- and di-GSH adducts for helenalin acetate), alongside phase I hydroxylations but no detectable ester hydrolysis.^[17] These pathways highlight species-specific differences, with rat microsomes showing higher metabolic efficiency than human ones.^[17] Additionally, acute exposure in rodents elevates liver enzymes such as ALT, indicating rapid hepatic impact during metabolism.^[52] Extensive liver conjugation suggests potential biliary and renal excretion routes, consistent with glutathione-mediated metabolism observed in related sesquiterpene lactones.^[53]

Toxicity

Helenalin exhibits significant acute toxicity via oral administration, with an LD₅₀ ranging from 85 to 105 mg/kg in rodents such as mice and rats.^[5] This exposure leads to symptoms including gastroenteritis characterized by vomiting and diarrhea, progressive paralysis, and damage to hepatic and renal tissues, as evidenced by elevated serum markers like alanine aminotransferase and blood urea nitrogen.^[54]^[55] Topical application of helenalin can induce contact dermatitis in sensitive individuals at concentrations exceeding 10%, manifesting as redness, itching, and eczematous reactions.^[56] However, formulations at or below 10% in gels are generally considered safe for external use, with low incidence of adverse skin effects when applied to intact skin.^[57] Chronic exposure to helenalin results in damage to lymphatic tissues, including reduced thymus and spleen weights, alongside immunosuppression that increases susceptibility to infections due to decreased lymphocyte counts.^[55] The primary mechanisms underlying this toxicity involve depletion of glutathione (GSH) through conjugation, leading to protein alkylation via Michael addition to cysteine residues and subsequent oxidative stress.^[58]^[59] This GSH depletion is exacerbated by metabolic conjugation processes.^[58] Human cases of helenalin toxicity are rare and typically arise from misuse of Arnica-containing products, such as internal ingestion, resulting in gastrointestinal distress and dermatitis.^[60] No fatalities have been reported from helenalin exposure after 2000, reflecting improved awareness and restricted use.^[56] Regulatory bodies have imposed strict limits on helenalin due to its toxicity profile; it is not approved by the FDA for internal use, classified as unsafe for ingestion.^[61] The European Medicines Agency (EMA) permits its presence in herbal products only for external application, with defined limits on sesquiterpene lactone content to minimize risks.^[56]

Applications

Historical Uses

Helenalin, a sesquiterpene lactone primarily found in plants of the genus Arnica, particularly Arnica montana, has been utilized in traditional medicine through the application of these plants for centuries. In European folk medicine, Arnica montana was employed topically to treat sprains, bruises, and rheumatism, with records dating back to the medieval period and continuing into the 18th century.^[62] Native American communities also incorporated various Arnica species, such as Arnica cordifolia, into their healing practices for similar purposes, including the treatment of trauma, cuts, bruises, and sore throats.^[62] By the 19th century, Arnica preparations gained formal recognition in pharmacopeias across Europe and North America, where diluted tinctures were introduced in homeopathic medicine for pain relief associated with injuries and inflammation.^[63] These homeopathic formulations, often highly diluted to minimize risks, were applied externally or taken orally in low doses to alleviate muscle and joint pain.^[64] Helenalin was first isolated in 1949 from the flowers of Helenium autumnale.^[65] It was subsequently identified in Arnica montana flowers during the mid-20th century, marking a shift toward scientific investigation of its active components.^[56] Initial studies in the 1960s explored its anti-inflammatory potential, building on the empirical uses of Arnica extracts.^[56] However, concerns over toxicity led to the abandonment of oral Arnica use by the mid-20th century, restricting applications to topical forms to avoid adverse effects like gastroenteritis and cardiac issues.^[23]

Modern Applications

In modern applications, helenalin is primarily utilized in topical formulations derived from Arnica montana extracts, such as gels and creams, for the symptomatic relief of muscle and joint pain, bruises, and inflammation associated with blunt injuries. These products typically contain low concentrations of sesquiterpene lactones, including helenalin at levels of 0.3–1.0% in the herbal substance, ensuring external use only to minimize toxicity risks. Homeopathic preparations incorporating helenalin are commonly available in Europe for similar indications, including rheumatic complaints and post-traumatic swelling.^[56] Ongoing preclinical research explores helenalin's potential as an adjunct in cancer therapy, particularly for its anti-neoplastic effects in cell lines like T47D breast cancer, where it inhibits telomerase gene expression and promotes cytotoxicity. As of 2025, no clinical trials investigating helenalin for cancer treatment are registered, limiting its advancement to therapeutic use. To address helenalin's poor aqueous solubility, nanoparticle-based delivery systems, such as nano-encapsulated forms and β-cyclodextrin complexes, have been developed in laboratory settings to enhance bioavailability and targeted efficacy against tumor cells.^[6]^[66]^[67] The European Medicines Agency (EMA) permits low-dose herbal preparations of Arnica montana containing helenalin for traditional topical use under well-established or traditional registration, but systemic administration remains unapproved due to toxicity concerns. Challenges in broader application stem from helenalin's hepatotoxic and allergenic profile, prompting studies on derivatives like esters to potentially reduce toxicity while retaining bioactivity; for instance, certain acyl esters exhibit lower cytotoxicity in vitro compared to the parent compound. Future developments may include helenalin in anti-malarial combinations, given its demonstrated in vitro activity against Plasmodium falciparum blood stages at micromolar concentrations.^[56]^[15]^[47]

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Helenalin reduces Staphylococcus aureus infection in vitro and in vivo
Helenalin reduces Staphylococcus aureus infection in vitro and in vivo. Vet ... Helenalin is a sesquiterpene lactone with potent anti-inflammatory properties.
[46]
Antimicrobial Activity of Lactones - PMC - PubMed Central - NIH
Sep 29, 2022 · Helenalin—A ... Inhibition of Quorum Sensing-Controlled Biofilm Formation in Pseudomonas Aeruginosa by Quorum-Sensing Inhibitors.
[47]
Helenalin suppresses essential immune functions of activated CD4+ ...
Helenalin is a naturally occuring sesquiterpene lactone extracted from Arnica montana and Arnica chamissonis ssp. foliosa. Helenalin and its derivatives are ...Missing: biosynthesis | Show results with:biosynthesis
[48]
In vitro metabolism of helenalin and its inhibitory effect on human ...
Jan 6, 2022 · The overall oxidation of helenalin was several times more efficient in rat than in human liver microsomes. In humans, CYP3A4 and CYP3A5 followed ...<|control11|><|separator|>
[49]
https://pubmed.ncbi.nlm.nih.gov/19656571/
[50]
Acute Toxicity of Helenalin in BDF1 Mice - ResearchGate
Aug 7, 2025 · Cholesterol synthesis was also inhibited, resulting in lower serum cholesterol levels in tumor-bearing animals. Data obtained in vitro ...
[51]
Mammalian toxicity of helenalin, the toxic principle of Helenium ...
The oral median lethal dose of helenalin for 5 mammalian species was between 85 and 105 mg/kg. MeSH terms. Animals; Cricetinae; Lactones / toxicity*; Mice ...
[52]
Range Plants of Temperate North America - Toxicology
Anorexia, severe gastroenteritis, salivation, diarrhea, paralysis, photosensitization, hemoglobinuria. Unknown toxic principle in B incana causes rapid ...
[53]
[PDF] Assessment report on Arnica montana L., flos
May 6, 2014 · Topical 20% Arnica ointment may be able to reduce bruising more than low-concentration vitamin K formulations. 4 patients reported redness and ...<|control11|><|separator|>
[54]
Treatment of viral infections and virally associated lesions with ...
... 2β-(S-glutathionyl)-2,3-dihydrohelenalin. In general, most derivatives are more toxic than H. tox itself. Among these, derivatives with the shortest ester ...
[55]
Role of glutathione in the toxicity of the sesquiterpene lactones ...
These studies suggest that the in vivo and in vitro toxicity of hymenoxon and helenalin is strongly dependent on hepatic glutathione levels, which hymenoxon and ...Missing: GSH protein
[56]
https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-arnica-montana-l-flos_en.pdf
[57]
Final Report on the Safety Assessment of Arnica Montana Extract ...
Ingestion of A. montana–containing products has induced severe gastroenteritis, nervousness, accelerated heart rate, muscular weakness, and death. Absent any ...
[58]
Arnica Uses, Benefits & Dosage - Drugs.com
May 8, 2025 · Arnica irritates mucous membranes and causes stomach pain, diarrhea, and vomiting. Allergy and contact dermatitis have been reported. Toxicology.
[59]
Arnica | Herbs - Herbal Reality
Feb 1, 2025 · Arnica is largely used to treat bruises and sprains for this rubefacient (counter-irritant) action, bringing warmth to an area via the increased blood flow.
[60]
[PDF] Arnica - A.Vogel
Vogel Rheumatism Gel possesses anti-inflammatory, antiseptic, antiphlogistic and blood-flow promoting properties. The anti-inflammatory action is based mainly.
[61]
Arnica for Pain: Clinical Trials, Mechanisms & Effects
Oct 9, 2021 · In clinical trials, adverse dermatologic effects were commonly reported with topical therapies. Contact dermatitis can develop, resulting in a ...
[62]
Helenalin. I. Isolation and Properties - ACS Publications
Untersuchungen über die Inhaltsstoffe von Arnica‐Arten, 9. Mitt. Zwei Sesquiterpenlactone aus den Blüten von Arnica longifolia. Archiv der Pharmazie 1976 ...
[63]
A comparison of the inhibitory effect of nano-encapsulated helenalin ...
A recent study used the PLGA-PEG-helenalin complex, and free helenalin, to inhibit the expression of telomerase in the breast cancer cell line. The purpose of ...
[64]
Inhibitory effects of β-cyclodextrin-helenalin complexes on H-TERT ...
Helenalin, with a hydrophobic structure obtained from flowers of Arnica chamissonis and Arnica Montana, has anti-cancer and anti-inflammatory activity but low ...