Immortelle (Helichrysum italicum): A Comprehensive Reference
1. Identity and Botanical Classification
Immortelle is the common name for Helichrysum italicum (Roth) G. Don fil., a species of flowering plant in the family Asteraceae. It is sometimes called the curry plant because of the strong fragrance of its leaves, and other common names include Italian strawflower and immortelle. The name Immortelle or Everlasting comes about because the plant retains its yellow color even when dried.
The genus name derives from the Greek words helios (sun) and chryos (gold), referring to the typical bright yellow inflorescences. The genus Helichrysum numbers more than 600 species, which are widespread throughout the world. Immortelle has three principal subspecies — microphyllum, serotinum, and italicum — with almost 25 autochthonous species thriving in the Mediterranean area, of which H. italicum is the most widespread.
Immortelle is an aromatic shrub, 50 to 70 cm tall. The plant is a xerophyte that thrives over a wide range of altitudes, from sea level to 2200 m, and is widespread from the lower Meso-Mediterranean to lower subhumid bioclimatic environments, growing on calcareous, sandy, or clay, well-drained soils. This plant is a small, perennial shrub characterized by its narrow, silver-hairy leaves and clusters of tiny, golden-yellow, daisy-like blossoms. It is native to the Mediterranean region, thriving in the dry, rocky, and sandy soils of countries like France, Italy, Corsica, and the Balkan Peninsula.
Cultivation is currently widely spread in Corsica, Italy, Hungary, Bosnia and Herzegovina, and Croatia. Although there are a number of subspecies of H. italicum, some suppliers and many research papers do not specify the subspecies. The chemical composition of H. italicum essential oil varies as a function of geographic origin and the vegetation cycle.
Common Forms and Preparations
Immortelle is commercialized and used in several distinct forms:
- Essential oil: Steam-distilled from the Helichrysum italicum plant native to the Mediterranean region.
- Absolute: Immortelle is also the source of Immortelle Absolute — an important fragrance material in natural perfumery.
- Hydrosol (hydrolate): A water-based byproduct of steam distillation, studied for its wound-healing and skin-regenerative properties.
- Dried flowers and herbal preparations: The flowers are often dried for use in herbal teas or medicinal applications, but can also be used fresh.
- Extracts: A large variety of extracts of Helichrysum italicum can be prepared, and the resulting products differ in their chemical composition. These include ethanolic, methanolic, hydroalcoholic, and supercritical CO₂ extracts.
- Topical formulations: Creams, emollients, serums, and ointments containing the essential oil or standardized extracts are widely available in the cosmetic and dermatological sectors.
2. Traditional and Historical Use
Known formally as Helichrysum italicum (Roth) G. Don fil. (family Asteraceae), the plant has been used for its medicinal properties for a long time and, even today, continues to play an important role in the traditional medicine of Mediterranean countries. In the Greek-Roman system of medicine, H. italicum was used as an anti-inflammatory and anti-infective plant.
Helichrysum is native to the Mediterranean region, where it has been used for its medicinal properties for thousands of years, especially in countries like Italy, Spain, Turkey, Portugal, and Bosnia and Herzegovina. Helichrysum has been used since the civilization of Ancient Greece, where it was commonly used after battles. Some sources report that helichrysum flowers were dried and offered to the Greek gods.
According to studies on the traditional use of Helichrysum italicum in European countries, particularly Italy, Spain, Portugal, and Bosnia and Herzegovina, its flowers and leaves are the most used parts in the treatment of health disorders such as allergies, colds, cough, skin, liver and gallbladder disorders, inflammation, infections, and sleeplessness.
Dried flowers of Helichrysum italicum had a great reputation in traditional medicine as choleretic, diuretic, and expectorant. Other traditional therapeutic applications include the healing of wounds, treating gall and bladder disorders, and analgesic uses. Historically, the plant has also been used to promote wound healing, reduce the appearance of scars and stretch marks, relieve muscle pain and spasms, and ease the symptoms of respiratory illnesses.
The interest in Helichrysum italicum has been motivated especially by its traditional therapeutic applications in inflammatory and allergy conditions, such as asthma and skin inflammatory conditions. The use of Helichrysum italicum essential oils has also been reported traditionally in aromatherapy applications, wound healing, and skin conditions such as hematoma and sunburn.
The first scientific studies on the medicinal properties of Helichrysum italicum are attributed to Leonardo Santini, whose clinical research in patients with psoriasis was conducted in the 1940s and 1950s.
3. Key Constituents and Active Compounds
3.1 Essential Oil Constituents
The main chemical compounds present in Helichrysum italicum essential oils can be divided into monoterpenes (C10) and sesquiterpenes (C15). The monoterpenes are formed from the coupling of two isoprene units and are the most representative terpenes, constituting up to 90% of essential oils.
The major identified monoterpene and sesquiterpene hydrocarbons include α-pinene (10.2–20.6%), α-cedrene (9.6–20.5%), aromadendrene (4.4–9.4%), β-caryophyllene (4.2–8.9%), limonene (3.8–8.1%), and ar-curcumene (2.3–4.9%). The most abundant oxygenated compounds include neryl acetate (11.5–23.2%) and 2-methylcyclohexylpentanoate (8.3–12.9%).
The essential oil has two chemotypes, rich in either neryl acetate or alpha-pinene, and it also contains gamma-curcumene — a spicy constituent that is sometimes confused with curcumin (they are not the same).
Italidiones are among the most distinctive features of the species. Italidiones are constituents that are not found in any other essential oil, nor in other species of helichrysum, and are considered to be mainly responsible for the plant's therapeutic properties. Helichrysum essential oil is the only commercially available essential oil that contains several diketones known as italidiones. Italidiones make up only a small percentage of the total composition of the essential oil, but they are said to be largely responsible for the anti-inflammatory action.
3.2 Non-Volatile Polyphenolic Constituents (Extracts)
Helichrysum italicum extracts contain mainly non-volatile polyphenolic compounds that possess various beneficial biological effects, namely antioxidative, anti-inflammatory, antimicrobial, and anticarcinogenic effects, with cytoprotective activity towards normal cells and cytotoxic effects against cancer cells.
The quality of Helichrysum italicum extracts is correlated mainly with the content of flavonoids (e.g., gnaphaliin and tiliroside), and a prenylated α-pyrone–phloroglucinol heterodimer arzanol, as well as polyphenolic acids (e.g., chlorogenic acid), acetophenones (e.g., 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone), and triterpenes (e.g., ursolic acid).
A comprehensive phytochemical inventory of the plant includes:
- Phenolic acids: caffeic, p-coumaric, ferulic, and chlorogenic acids
- Flavonoids: apigenin, luteolin, gnaphaliin, naringenin, kaempferol, quercetin, and their glycosides
- Chalcones and pyrones
- α-Pyrones: arzanol (a prenylated heterodimeric phloroglucinyl α-pyrone) and helipyrone
- Triterpenes: β-sitosterol, ursolic acid, α-amyrin, uvaol
- Acetophenone glucosides, benzofurans, coumarins, and benzo-γ-pyrone glucosides
Arzanol merits special attention as the most intensively studied single compound. Arzanol, a prenylated phloroglucinyl α-pyrone heterodimer, was identified as the major anti-inflammatory compound in acetone extracts of aerial parts of Helichrysum italicum subsp. microphyllum, representing 0.32% of extraction yield. In phytochemical profiling studies, arzanol was found to be the predominant metabolite at 7.33% of all identified compounds, while dicaffeoylquinic acid derivatives were also found in high quantities.
4. Mechanisms of Action
4.1 Anti-Inflammatory Mechanisms
The anti-inflammatory and antioxidant activities of the aerial part of Helichrysum italicum extracts have been established in various in-vivo and in-vitro experimental models. The anti-inflammatory activity of Helichrysum italicum can be explained by multiple effects, including inflammatory enzyme inhibition, free-radical scavenging activity, and corticoid-like effects.
The compound arzanol has been the most mechanistically characterised. Based on its capacity to inhibit in vitro HIV-1 replication in T cells and the release of proinflammatory cytokines in monocytes, the prenylated heterodimeric phloroglucinyl α-pyrone arzanol was identified as the major anti-inflammatory and antiviral constituent from Helichrysum italicum.
Arzanol inhibited 5-lipoxygenase (5-LO) activity and related leukotriene formation in neutrophils, as well as the activity of cyclooxygenase (COX)-1 and the formation of COX-2-derived prostaglandin E₂ in vitro (IC₅₀ = 2.3–9 μM). Detailed studies revealed that arzanol primarily inhibits microsomal PGE₂ synthase (mPGES)-1 (IC₅₀ = 0.4 μM) rather than COX-2 itself.
Arzanol has been reported to inhibit inflammatory transcription factor NF-κB activation, HIV replication in T cells, releases of IL-1β, IL-6, IL-8, and TNF-α, and biosynthesis of PGE₂ by potentially inhibiting the mPGES-1 enzyme.
Arzanol could block COX-2/mPGES-1-mediated PGE₂ biosynthesis in lipopolysaccharide-stimulated human monocytes and human whole blood, but not the concomitant COX-2-derived biosynthesis of thromboxane B₂ or 6-keto PGF₁α, and the expression of COX-2 or mPGES-1 protein was not affected. Arzanol potently suppressed the inflammatory response in carrageenan-induced pleurisy in rats (3.6 mg/kg, i.p.), with significantly reduced levels of PGE₂ in the pleural exudates.
Studies on acute oedemas induced by TPA, ethyl phenylpropiolate, serotonin, and phospholipase A2, as well as on chronic inflammation and delayed-type hypersensitivity, suggest that the anti-inflammatory activity is due to compounds acting via a corticoid-like mechanism.
4.2 Antioxidant Mechanisms
The antioxidant activity of H. italicum extracts is implicated in its anti-inflammatory activity, as the antioxidant fraction inhibits enzymatic and non-enzymatic lipid peroxidation and has free-radical scavenger properties.
4.3 Wound Healing Mechanisms
An in-vitro study investigated the molecular basis of the wound-healing and skin-protective features of Helichrysum italicum, treating a dermal fibroblast cell line with HI hydro-alcoholic extract to detect gene expression levels of FGF-2, HAS-2, and MMP-9. HI extract caused statistically significant upregulation of FGF-2 (P=0.0473) and HAS-2 (P=0.0335) gene expressions compared to untreated control cells, suggesting anabolic effects on the extracellular matrix of the skin.
The significant increases in FGF-2 and HAS-2 gene expressions suggest that H. italicum has some anabolic effects on the extracellular matrix of the skin, mainly due to the angiogenesis-inducing and granulation-tissue-enhancing effects of FGF-2, and the fibroblast-protecting activities of HAS-2 against UV-B mediated stress.
4.4 Antimicrobial Mechanisms
Helichrysum species represent an abundant source of secondary metabolites — including flavonoids, chalcones, phenolic acids, phthalides, coumarins, pyrones, and terpenes — that confer antimicrobial properties. Its flavonoids and terpenes were effective against bacteria (e.g., Staphylococcus aureus), and its acetophenones, phloroglucinols, and terpenoids displayed antifungal action against Candida albicans.
5. Scientific Evidence by Area of Use
5.1 Inflammation and Pain
The anti-inflammatory evidence for H. italicum spans multiple experimental levels. At the preclinical level, studies in animal models and cell-based assays consistently show inhibition of key mediators of inflammation. The anti-inflammatory and antioxidant activities of the aerial part of Helichrysum italicum extracts have been established in various in-vivo and in-vitro experimental models, including results on acute oedemas induced by TPA and ethyl phenylpropiolate.
At the clinical level, the evidence is limited and indirect. A search of Cochrane Library revealed six eligible clinical trials with H. italicum, examining indications including pain management, cough, and mental exhaustion. The indications studied were pain (chronic prostatitis and post-surgical pain), cough, and mental exhaustion. Although the efficacy of H. italicum has been demonstrated both in in vitro tests and in humans, it is difficult to attribute results from clinical trials to H. italicum alone, as it has usually not been tested as the sole component.
Evidence strength: Preclinical (in vitro and animal) evidence for anti-inflammatory activity via identified mechanisms is substantial. Clinical human evidence is sparse, indirect, and methodologically limited due to the use of combination products.
5.2 Wound Healing and Skin Regeneration
Helichrysum essential oil has been used in traditional Mediterranean medicine for centuries to heal wounds and reduce inflammation. Scientific investigation has begun to establish mechanistic underpinnings. An in vitro study published in 2024 examined the effect of the Helichrysum italicum hydrolate (HH) on wound repair. The study analysed the regenerative properties of a hydrolate derived from Helichrysum italicum on scratch-tested skin cell populations seeded on a fluidic culture system, recreating skin physiology with a bioreactor that mimics skin stem cell and fibroblast communication as in in vivo skin layers. The extract stimulated cell proliferation specifically in the presence of damage, which is considered important, as inappropriate stimulation at any time could lead to uncontrolled cell proliferation and tumorigenic mechanisms.
The HI extract has been considered to have anabolic effects on the extracellular matrix of the skin, and may therefore have a promising future in anti-aging studies and cosmetic dermatology, potentially explaining improvements in wound healing and protection against UV exposure.
Evidence strength: Predominantly in vitro and cell culture data. No large-scale controlled human clinical trials specifically on wound healing have been identified. Evidence is early-stage and mechanistically suggestive, but not yet clinically confirmed.
5.3 Antioxidant Activity
A 2023 study evaluating the antioxidant activity of a methanol–aqueous extract from Helichrysum italicum ssp. italicum aerial parts found significant radical scavenging activity (110.33 ± 3.47 and 234.70 ± 5.21 mg TE/g for DPPH and ABTS assays) and significant reducing power (354.23 ± 17.51 and 210.24 ± 8.68 mg TE/g for CUPRAC and FRAP assays).
Evidence strength: In vitro antioxidant activity is well-established and consistently replicated across multiple assay types. Translation to in vivo human antioxidant effects has not been clinically demonstrated.
5.4 Antimicrobial and Antifungal Activity
Studies have subjected the aerial parts of H. italicum to hydrodistillation to obtain essential oils, which were then tested for antimicrobial activity against 12 bacteria, two yeasts, and four fungi by agar diffusion method. The essential oil yielded 0.44% (v/w) with 67 compounds accounting for 99.24% of the oil, with high content of oxygenated sesquiterpenes (61.42%). Extracts and essential oils of H. italicum have exhibited antimicrobial and antifungal, antioxidant, wound healing and anti-inflammatory, anti-proliferative, anti-hyperglycaemic, acetylcholinesterase inhibition, anticancer, anti-HIV, anti-collagenase, and anti-elastase activities.
Flavonoids and phloroglucinols inhibited HSV (herpes simplex virus) and HIV, respectively.
Evidence strength: Antimicrobial activity is primarily demonstrated in vitro. No controlled human clinical trials specifically addressing antimicrobial applications have been identified. The in vitro data are robust and consistent across geographic variants of the plant.
5.5 Anti-HIV Activity
An acetone extract of Helichrysum italicum ssp. microphyllum afforded the phloroglucinol α-pyrone arzanol as a potent NF-κB inhibitor. Crude acetonic extracts of the aerial parts of H. italicum ssp. microphyllum, as well as extracted/purified arzanol, were able to inhibit TNFR-induced HIV-1-LTR transactivation in human T-lymphocytes, also exhibiting relevant antiviral properties.
Arzanol also inhibits HIV-1 replication in T cells, hence it has anti-HIV properties in in vitro testing.
Evidence strength: Entirely preclinical (cell culture). No human studies on anti-HIV effects exist. Findings are mechanistically interesting but at a very early stage.
5.6 Photoprotection and Dermatological Applications
The anti-erythematous and photoprotective activities of H. italicum flavonoids have been demonstrated both in animals and humans, along with anti-inflammatory properties exhibited by its flavonoids, acetophenones, and phloroglucinols, as seen in animal models.
Evidence strength: The photoprotective and anti-erythematous effects represent one of the areas with some limited human data, although the published studies (Facino et al., 1988, referenced in the literature) are older and used topical preparations in small-scale settings. This area warrants further controlled study.
5.7 Cognitive Enhancement and Neuroprotection
A 2023 study explored potential cognitive benefits. The extract showed average acetylcholinesterase and low butyrylcholinesterase inhibitory potential. In animal experiments, H. italicum extract (200 mg/kg, per os) administered in combination with galantamine (3 mg/kg, per os) for 12 days significantly improved memory and the learning process compared with galantamine alone in the passive avoidance test, with the effect comparable to that of Ginkgo biloba extract (100 mg/kg, per os).
Evidence strength: Very preliminary. Results are from a small animal study. No human clinical data on cognitive effects exist. This is an emerging area of investigation only.
5.8 Hepatic (Liver and Gallbladder) Applications
Traditional use in several European Mediterranean countries specifically includes flowers and leaves for liver and gallbladder disorders. Dried flowers had a great reputation in traditional medicine as choleretic and diuretic. These traditional indications have not been validated in controlled clinical studies.
Evidence strength: Traditional use only. No controlled clinical trials on hepatobiliary effects have been identified.
5.9 Respiratory Applications
Traditional therapeutic applications in inflammatory and allergy conditions such as asthma are documented in ethnopharmacological surveys. Flowers and leaves have traditionally been used for allergies, colds, and cough. Among the six clinical trials identified in the Cochrane Library, cough was among the indications studied, and the dosage forms used included inhalation preparations.
Evidence strength: Traditional use is documented. There is clinical trial evidence for cough, but H. italicum was used in combination with other botanicals, limiting attribution. Evidence is preliminary.
6. Body Systems and Health Areas of Association
The native Mediterranean plant immortelle has been found to possess numerous phytochemicals with various biological effects, including anti-inflammatory, antimicrobial, antioxidant, antiviral, anti-HIV, antilarvicidal, and repellent activities. The plant is associated with, and has been researched in relation to, the following body systems:
- Integumentary system (skin): Wound healing, hematoma resolution, scar reduction, anti-aging, photoprotection, UV damage mitigation, and eczema/psoriasis
- Immune system: Anti-inflammatory action via NF-κB, COX, 5-LO, and mPGES-1 pathways; modulation of cytokines (IL-1β, IL-6, IL-8, TNF-α)
- Respiratory system: Traditional use in coughs, colds, and asthma; some clinical trial investigation in combination products
- Hepatobiliary system: Traditional choleretic and hepatoprotective use; no validated clinical evidence
- Musculoskeletal system: Analgesic and muscle-relaxant traditional uses; pain studied in clinical trials as part of combination products
- Nervous system: Preliminary preclinical data on acetylcholinesterase inhibition and cognitive enhancement
- Infectious disease context: In vitro antiviral (HSV, HIV-1) and antibacterial/antifungal activities
7. Dosage Forms and Dosages Reported in Studies
Doses and forms described in the scientific literature vary considerably depending on the preparation type and indication:
- Clinical trials identified in the Cochrane Library used diverse dosage forms including granules, syrup, inhalation preparation, and suppositories.
- Animal cognitive study: H. italicum extract at 200 mg/kg per os, administered in combination with galantamine (3 mg/kg, per os) for 12 days.
- Animal anti-inflammatory study: Arzanol at 3.6 mg/kg intraperitoneally in carrageenan-induced pleurisy rat model, resulting in significantly reduced PGE₂ levels in pleural exudates.
- In vitro (arzanol, NF-κB inhibition): IC₅₀ value of 5 μM for inhibition of NF-κB activation.
- In vitro (arzanol, eicosanoids): IC₅₀ values of 2.3–9 μM for 5-LO and COX-1 activity, and IC₅₀ of 0.4 μM for mPGES-1 inhibition.
- In vitro cytotoxicity testing: Extracts at the tested concentration of 100 µg/mL after 72 h of exposure had low toxicity, with cell viability values similar or higher than those obtained for green and red bush teas.
- In vitro wound healing (hydrolate): Two concentrations tested — 30% and 20% — applied to skin stem cells and fibroblasts after scratch assay for collagen deposition analysis.
No standardized human clinical dosage for any indication has been established in the peer-reviewed literature as of the most recent reviews.
8. Safety Considerations and Interactions
8.1 General Safety Profile
Clinical trials identified in the literature provide positive information on the safety profile of H. italicum since no adverse effects have been reported in those studies. Researchers concluded that H. italicum is safe to use internally, while new clinical studies with H. italicum as a single component are needed to prove its efficacy.
While Helichrysum italicum does not display significant levels of cytotoxicity or genotoxicity, one of its flavonoids has been found to inhibit some CYP isoforms.
8.2 Contact Dermatitis (Allergic Reaction)
A case report described a case of contact dermatitis in a 69-year-old woman, caused by the hydrophilic and lipophilic fractions of Helichrysum italicum contained in an emollient cream. Her reaction was demonstrated by a patch test and confirmed by isolating the botanical extract; however, additional testing on 10 volunteers yielded negative results. This observed case therefore appears to represent an isolated hypersensitivity reaction.
8.3 CYP Enzyme Inhibition and Drug Interactions
A 2010 study on human cells in the laboratory found that helichrysum may potentially stop some liver enzymes (CYP isoforms) from working properly. This means there is a theoretical possibility it could interact with medications that are metabolized by these liver enzymes. This is an in vitro finding and its clinical significance has not been established in human pharmacokinetic studies.
8.4 Membership in Asteraceae (Compositae) Family
As a member of the Asteraceae family, immortelle shares the potential for cross-reactivity with other Compositae-family plants in individuals with known Asteraceae allergies (e.g., ragweed, chrysanthemums, and chamomile). This is a general class-level consideration applicable to all Asteraceae.
8.5 Diketone Content and Theoretical Neurotoxicity
The ketones found in immortelle essential oil are diones, or diketones, meaning molecules with two ketone groups. Like most essential oils, helichrysum essential oil is not recommended for pregnant women, as essential oils containing ketone functional groups present theoretical neurotoxic and abortifacient risks during pregnancy. However, it should be noted that the italidione diketones in H. italicum appear structurally distinct from the simple monoketone-rich oils (e.g., pennyroyal, thuja) that are most commonly flagged for neurotoxicity; the clinical safety of italidiones specifically has not been investigated in formal toxicological trials.
8.6 Species and Subspecies Identification
Although there are a number of subspecies of H. italicum, some suppliers and many research papers do not specify the subspecies, making it wise to verify the exact species and subspecies with a supplier and to request a GC/MS specification sheet in order to clarify key chemical constituents. This matters for safety as well as efficacy, since phytochemical profiles and bioactive compound concentrations vary significantly by subspecies and geographic origin.
8.7 Summary of Evidence Strength for Safety
Most of the traditionally claimed applications of H. italicum are not yet scientifically proven, and clinical trials are needed to further confirm available data and promote Helichrysum italicum as an important tool in the treatment of several diseases. The overall body of safety data is limited, reflecting the plant's relatively recent entry into mainstream research, with the most significant documented risks being a single case of allergic contact dermatitis and theoretical (in vitro only) drug interaction potential via CYP inhibition.
References
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