Sandy everlasting

Sandy Everlasting (Helichrysum arenarium): A Comprehensive Reference

1. Identity and Botanical Classification

Scientific Name and Taxonomy

Sandy everlasting [Helichrysum arenarium (L.) Moench] is a herbaceous perennial plant belonging to the family Asteraceae, native to Europe, Central Asia, and China. The genus name is derived from the Greek words helios, meaning "sun," and chrysos, meaning "gold," referring to the shiny golden color of the inflorescence. It belongs to the section HELICHRYSUM of the genus Helichrysum, along with H. plicatum DC., which has a very similar phenolic profile, and H. italicum (Roth), which is widely used for essential oil extraction.

Common Names

The plant is known by several common names, including "Sandy everlasting," "Dwarf everlasting," "Immortelle," and "Siminoc" in popular Romanian folklore.

Medicinal Part

Sandy everlasting is the common name for the flowers of the plant Helichrysum arenarium (L.) Moench. The HMPC conclusions cover a sandy everlasting preparation obtained by drying and comminuting (reducing into tiny pieces) the flowers. Herbal medicines containing this preparation are usually available as herbal teas to be drunk.

Geographical Distribution

H. arenarium is a herbaceous perennial plant naturally distributed in Central, Eastern, and South-Eastern Europe, North of the Balkans, West Siberia, Central Asia, Mongolia, and China. While it can be found mainly in Poland, Russia, Lithuania, and Latvia, it also occurs in the Mediterranean region of Slovenia and in other regions with similar climatic conditions, such as coastal Croatia, Italy, Spain, and Portugal.

Conservation Status

Natural sources of the plant are rather limited; harvesting from wild habitats is restricted as it can increase the impoverishment or even extermination of populations of the species. For these reasons, H. arenarium is under protection in many European countries. Although H. arenarium is well known in phytotherapy for its potential in the treatment of gallbladder disease, it is classified as an endangered species in a number of European countries. The commercial cultivation of H. arenarium using traditional methods is illegal in Poland, and only plant tissue and cell culture techniques are allowed to obtain clonal material there.

2. Traditional and Historical Use

European Ethnomedicine

Sandy everlasting has a long tradition in European ethnomedicine as a medicinal plant attributed to cholagogue, choleretic, hepatoprotective, and detoxifying activities. Choleretic, cholagogue, hepatoprotective, and detoxifying activity of the inflorescence of H. arenarium has been recognized for a long time in Europe, documented as early as Kroeber (1951), Szadowska (1962), Wagner (1993), and Shikov et al. (2014).

Helichrysum arenarium inflorescences use in Central Europe has been reported for its antiseptic, choleretic, and spasmolytic properties. It is used as a choleretic, hepatoprotective, and detoxifying agent, diuretic, as a mild antimicrobial, and spasmolytic agent.

Russian Traditional Medicine

In Russia, the inflorescence of H. arenarium has been applied in the form of infusions for stimulating gastric secretion, treating gallbladder disorders, as well as cystitis. It is also indicated for indigestion as well as for loss of appetite.

Romanian Traditional Medicine

Helichrysum arenarium (L.) Moench is known in Romanian traditional medicine for its diuretic, choleretic, and anti-inflammatory properties. Both A. dioica and H. arenarium are used for different purposes in Romanian traditional medicine.

Lithuanian Folk Medicine

Helichrysi flos is used in Lithuanian folk medicine for healing gall-bladder and gastric disorders, cystitis, and arthritis.

Traditional Preparations

Use for digestive disorders (including feeling of fullness and bloating) has been approved by the World Health Organization (WHO) and the European Medicines Agency (EMA) for the species Helichrysum arenarium only, using its flowers in the form of an infusion or decoction. Aerial parts of the plant or the whole overground plant were used to prepare infusions, decoctions, essential oils, and extracts with different qualitative content.

Pharmacopoeial and Monograph Recognition

Although Helichrysi arenarii flos has not been included in the European Pharmacopoeia, the State Pharmacopoeia of the USSR, Pharmacopoeia Helvetica, and Polish Pharmacopoeia listed it as an officinal drug for its choleretic and cholagogue activity. Due to its long usage in traditional medicine as well as proven therapeutic properties, it has been included in the monographs of the World Health Organization, German Commission E, Physician's Desk Reference for herbal medicines, and German pharmaceutical codex.

3. Key Constituents and Active Compounds

Overview of Phytochemical Classes

The flowers of sandy everlasting (H. arenarium) are a rich source of phenolic compounds including flavonoids, chalcones, phenolic acids, phthalides, coumarins, and pyrones. Apart from polyphenols, other compounds such as sterols, lignans, and glycosides of aromatic compounds have also been isolated and identified from H. arenarium.

Flavonoids — The Primary Active Group

Flavonoids are the main characteristic components of H. arenarium, comprising 39 compounds. In general, the inflorescence of H. arenarium contains three types of flavonoids: flavonols, flavones, and flavanones.

Chalcone isosalipurposide and flavanones naringenin and naringenin-5-O-glucoside are the dominant compounds in sandy everlasting. Naringenin and naringenin-5-O-glucoside are two flavanone derivatives; (+)-naringenin-5-D-glucoside is named helichrysin A, and (-)-naringenin-5-D-glucoside is called helichrysin B or salipurposide.

Eight flavonoids have been identified by LC-DAD-MS in H. flos extracts: kaempferol, kaempferol-3-O-glucoside, apigenin, apigenin-7-O-glucoside, naringenin, naringenin-5-O-glucoside, naringenin-4'-O-glucoside, quercetin-3-O-glucoside (isoquercitrin), the chalcone derivative isosalipurposide (2',4,4',6'-tetrahydroxychalcone-6'-O-glucoside), and chlorogenic acid.

The majority of authors confirm that the most important group of compounds responsible for biological activities is flavonoids. Moreover, significant activities of naringenin, one of the main flavonoids of H. arenarium, have been reported.

Additional Phenolic Compounds and Non-Polyphenolic Constituents

The main compounds identified in H. arenarium methanolic extracts by HPLC-DAD-TOF include luteolin-7-O-glucoside, naringenin and its glucoside, apigenin, chlorogenic acid, arenol, and arzanol.

The main biologically active compounds of Helichrysi arenarii inflorescentia are flavonoids, with chalcone isosalipurposide and flavanones salipurposide, prunin, and naringenin as dominant constituents. Other compounds present in remarkable amounts are phthalides, carotenoids, essential oil, and yellow pigments — alpha-pyrone derivatives. Other compounds found include alpha-pyrrole derivatives such as arenol and homoarenol.

Essential Oil

Most of the papers dealing with sandy everlasting flowers' essential oil report a content in an amount of about 0.04–0.09%. The predominant constituents in H. arenarium essential oil from Bulgarian populations were α-pinene (34.64–44.35%) and sabinene (10.63–11.1%), which confirmed the examined population as a new chemical type. In Lithuanian wild plants, palmitic acid (≤23.8%), myristic acid (≤14.9%), lauric acid (6.1%), n-nonanal (10.4%), and trans-β-caryophyllene (≤6.5%) were the major constituents in the essential oils.

Polyphenol Content by Extraction Method

LC-MS analyses were performed on methanolic, ethanolic, and 70% v/v ethanolic extracts, before and after acid hydrolysis, and revealed high amounts of polyphenols. Quercitrin was dominant in H. arenarium (424.28 ± 21.21 mg/100 g d.w.) in 70% v/v ethanolic extracts before hydrolysis.

4. Established and Proposed Mechanisms of Action

Cholagogue and Choleretic Activity

Smirnova and Pervykh (1998) reported that it is the sum of flavonoids that accounts for the cholagogue activity of the everlasting flower extracts. A group of researchers demonstrated in 1998 that flavonoids are responsible for the cholagogue activity of extracts from sandy everlasting flowers. The ability to stimulate bile secretion is the most likely mechanism leading to reduced cholesterol levels observed in studies.

Antioxidant Mechanisms

Antioxidant capacity assays showed an important antioxidant potential, which can be correlated with the determined polyphenolic compounds. Flavonoids such as naringenin and naringenin-5-O-glucoside exert antioxidant properties and inhibit processes mediated by free radicals due to their phenolic structure.

Anti-inflammatory Activity

Anti-inflammatory activity has been reported for H. arenarium. The flowers contain antibacterial constituents and bitter substances, which may also promote gastric and pancreatic secretion.

Antimicrobial Mechanisms

The first investigation of the antibacterial activity of the everlasting flower flavonoid compounds was performed in the former Soviet Union and concluded that preparations at a concentration of 20–40 μg/mL were active against two important Gram-positive species: Staphylococcus sp. and Streptococcus sp. Clinical isolates of Candida albicans and several fungal species were tested, and the minimum inhibitory concentration (MIC) detected was between 10 and 30 μg/mL, while the minimum fungicidal concentration (MFC) ranged from 15 to 60 μg/mL.

5. Scientific Evidence by Area of Use

5.1 Digestive and Hepatobiliary System

Regulatory Status

According to the WHO (2015), the only use of Helichrysi arenarii flos described in pharmacopeias and well-established documents is the treatment of dyspeptic disorders. The HMPC concluded that, on the basis of its long-standing use, the sandy everlasting preparation can be used for digestive disorders with a feeling of fullness and bloating. An assessment report of the European Medicines Agency (EMA) Committee on Herbal Medicinal Products (HMPC) supports its stimulatory role in bile flow and in the release of cholesterol into the bile.

Animal/Preclinical Evidence

Szadowska (1962) reported a mild choleretic and spasmolytic effect of this drug observed on rats. In this research, intravenous administration of three flavonoids from sandy everlasting (kaempferol-3-glycoside, naringenin-5-glycoside, and apigenin) was applied at a dose of 4 mg/100 g versus a positive control (Decholin, deoxycholic acid) as well as a negative control (isotonic NaCl). Increases of bile secretion were 180%, 185%, and 160%, respectively, in comparison to baseline (100%) after 15 minutes. An increase of 135% was also obtained with the ether extract of sandy everlasting applied at a dose of 5 mg/100 g, with a maximum after 30 minutes.

Absence of Clinical Trials

There are no clinical data about testing the extracts or preparations based on H. arenarium specifically for hepatobiliary indications. The European Medicines Agency (EMA) advises using Helichrysi flos in the form of tea blends made in pharmacies because there are currently no clinical data on the therapy with preparations. The evidence supporting gallbladder and hepatic use therefore rests on long-standing traditional use, pharmacopoeial recognition, and preclinical (animal) studies rather than controlled human trials.

5.2 Metabolic Syndrome and Lipid Profile

Clinical Evidence

A randomised double-blind comparative study was conducted in which participants with at least two traits of metabolic syndrome consumed an infusion of either Helichrysum italicum subsp. italicum (HI, n = 14) or Helichrysum arenarium (HA, n = 13) daily for 28 days. Anthropometric and biochemical parameters were measured at baseline, at the end of the intervention, and after a 2-week washout period.

In the HA group, there was a greater reduction in serum glucose levels and an improvement in the lipid profile. Only in the HA group did levels of glucose and triacylglycerols also drop in the follow-up period. Previously, an HA methanol extract was shown to diminish the glucose rise after sucrose ingestion, while a reduction of triacylglycerols was only demonstrated in investigations of separate compounds, such as naringenin.

Regular consumption of Helichrysum arenarium ameliorates lipid profile, and therefore holds great potential for the management of metabolic syndrome.

Gut Microbiota Study

To investigate whether effects on metabolic syndrome are mediated by the gut microbiota, researchers analyzed the effects of daily consumption of HA infusion on the composition of gut microbiota, inflammatory status, and zonulin, a marker of gut barrier permeability. The study was a randomized, double-blind comparative trial in which thirty participants were randomly assigned and received either HA or HI tea filter bags, each containing 1 g of dried plant material, for daily consumption lasting 4 weeks. The results showed that consumption of both infusions resulted in a reduction of some genera belonging to Firmicutes and a slight but significant reduction in Shannon diversity index.

Strength of Evidence

The available clinical evidence for metabolic syndrome is preliminary. The double-blind trials cited involved small participant numbers (13–14 per arm) and a short intervention period (28 days). Results are promising but require replication in larger, placebo-controlled studies before conclusions can be drawn.

5.3 Antioxidant Activity

H. arenarium has also been used in chronic liver inflammatory disease and as a scavenger of free radicals. Antioxidant capacity assays showed an important antioxidant potential, which can be correlated with the determined polyphenolic compounds, with the 70% v/v ethanolic extracts of the two species showing notable activity. The connection between the phenolic content of this species and its antioxidant, anti-inflammatory, and antimicrobial activities has been studied by different authors. Evidence for antioxidant activity is derived from in vitro studies only; no controlled human trials specifically testing antioxidant outcomes for H. arenarium have been published.

5.4 Antimicrobial and Antifungal Activity

The antimicrobial activity of essential oils of H. arenarium has been investigated on different test microorganisms, clinical isolates, and food contamination microbes. Rančić et al. (2005) tested the antibacterial activity of 1–5 μL of everlasting flower essential oil against Escherichia coli, Micrococcus luteus, Pseudomonas tolaasii, Salmonella enteritidis, S. typhimurium, Staphylococcus aureus, and S. epidermidis, and concluded that at the minimum volume (1 μL) the oil had activity against all bacterial species tested.

Clinical isolates of Candida albicans and fungi including Aspergillus niger ATCC 6275, A. flavus ATCC 9170, Cladosporium cladosporioides ATCC 13,276, Penicillium funiculosum ATCC 10,509, and Trichoderma viride IAM 5061 were tested, and the minimum inhibitory concentration (MIC) detected was between 10 and 30 μg/mL, while the minimum fungicidal concentration (MFC) ranged from 15 to 60 μg/mL.

All antimicrobial and antifungal evidence is in vitro. No human or animal clinical trials specifically assessing H. arenarium for infectious disease indications have been reported.

5.5 Anticancer / Antiproliferative Activity

Pharmacological data indicate that the flowers of H. arenarium are a rich source of various active compounds, including flavonoids, phenolics, polyphenols, flavones, essential oils, and coumarins. These compounds exhibit a wide range of activities including antioxidant, anticancer, immunostimulatory, anticoagulant, antibacterial, antiallergic, antitussive, bronchodilatory, and antiviral effects. Although studies have reported that H. arenarium exhibits free radical scavenging, anti-atherosclerotic, anti-inflammatory, and lipid peroxidation-reducing activities, no research had investigated the cytotoxic effects of its plant extracts on glioblastoma and breast cancer cells. Evidence for anticancer effects is at the preclinical/in vitro stage and cannot be extrapolated to clinical outcomes at this time.

5.6 Antiatherosclerotic Activity

Extracts from Helichrysum species possess a wide range of pharmacological activities such as antioxidant, antimicrobial, antiatherosclerotic, antiproliferative, antidiabetic, neuroprotective, and anti-inflammatory activities. Research specifically attributing antiatherosclerotic effects to H. arenarium flavonoids via the anti-inflammatory pathway has been published (Mao et al., 2017), but remains preclinical in nature.

5.7 Antidiabetic and Neuroprotective Properties

The antioxidant, antidiabetic, and neuroprotective properties of Helichrysum arenarium have been highlighted in recent research. These findings are based on preclinical and in vitro studies; no controlled human clinical trials for glycemic or neuroprotective endpoints have been reported specifically for H. arenarium.

6. Body Systems and Health Areas

Based on the accumulated traditional use documentation and laboratory research, H. arenarium is associated with the following body systems and health areas:

• Hepatobiliary system: According to WHO monographs, Helichrysi flos is used as a cholagogue, in the treatment of dyspeptic diseases, and in traditional medicine as a choleretic, diuretic, mild spasmolytic, hepatoprotective agent, and for detoxification.
• Digestive system: On the basis of its long-standing use, the HMPC concluded that the sandy everlasting preparation can be used for digestive disorders with a feeling of fullness and bloating. The flowers contain antibacterial constituents and bitter substances, which may also promote gastric and pancreatic secretion.
• Cardiovascular / metabolic system: Cholagogue and choleretic activities are the main reasons for its wide use in traditional medicine, and its ability to stimulate bile secretion is the most likely mechanism leading to reduced cholesterol levels.
• Urinary system: Helichrysi flos is used in Lithuanian folk medicine for healing gall-bladder and gastric disorders, cystitis, and arthritis.
• Immune / antimicrobial system: The inflorescences of H. arenarium have been used in European herbal medicine for their antimicrobial and antioxidant properties.

7. Dosage Forms and Reported Dosages

Official Dosage Guidance

The average daily dosage is 3 g of the drug or equivalent preparations, as reported in both German Commission E and WHO monographs (Blumenthal et al., 1998; WHO, 2015).

Preparation Forms

The HMPC preparation consists of dried and comminuted flowers. Herbal medicines containing this sandy everlasting preparation are usually available as herbal teas to be drunk. Use has been approved using its flowers in the form of an infusion or decoction.

Dosage Used in Clinical Studies

In the clinical trial context, the preparation used was 1 g of milled plant material (Helichrysum arenarium) immersed in hot water (200 mL, 100°C) for 10 minutes. The entire study consisted of a 4-week administration phase in which subjects were prescribed to drink 200 mL of HA tea every evening, 2 hours after dinner, followed by a 2-week follow-up phase without any supplementation.

Preclinical Dosage Data

In animal research on choleretic activity, intravenous administration of three flavonoids from sandy everlasting (kaempferol-3-glycoside, naringenin-5-glycoside, and apigenin) was applied at a dose of 4 mg/100 g body weight.

Market Availability

H. arenarium inflorescences are the only herbal medicinal product from the Helichrysum genus (Asteraceae family) approved by the HMPC and currently available on the market as such.

8. Safety Considerations and Interactions

Side Effects

The EU monograph supports the use of H. arenarium for digestive disorders, feeling of fullness and bloating, and, importantly, no side effects are reported. At the time of the HMPC assessment, no side effects had been reported with these medicines.

Overdose

No case of overdose has been reported.

Interactions

No drug interactions are known.

Fertility and Reproductive Safety

No fertility data are available.

Asteraceae Allergy Risk

As a member of the Asteraceae (Compositae) family, individuals with known hypersensitivity to other Asteraceae plants (e.g., chamomile, ragweed, chrysanthemum) should be aware of the potential for cross-reactivity. This is a class-level consideration for all Asteraceae-family botanicals.

Evidence Limitations and General Research Gaps

All existing data on the chemical composition and biological activities of H. arenarium remain nevertheless scarce and do not establish a clear chemical composition of the flowers and their connection with the cited biological activities. The connection between phenolic content and antimicrobial activities has not been fully established in the literature. No large randomized controlled trials assessing efficacy and long-term safety for any clinical indication have been completed to date.

9. Regulatory Status Summary

H. arenarium inflorescences are the only herbal medicinal product from the Helichrysum genus approved by the HMPC and currently available on the market as such. The HMPC assessment covers the medicinal uses of sandy everlasting, and its conclusions are taken into account by EU Member States when evaluating applications for the licensing of herbal medicines containing sandy everlasting.

References

• Pljevljakušić et al. (2018). Sandy Everlasting (Helichrysum arenarium (L.) Moench): Botanical, Chemical and Biological Properties. Frontiers in Plant Science. PMC6090377.
• Pljevljakušić et al. (2018). Sandy Everlasting (Helichrysum arenarium (L.) Moench): Botanical, Chemical and Biological Properties. Frontiers in Plant Science.
• Sandy Everlasting (Helichrysum arenarium (L.) Moench): Botanical, Chemical and Biological Properties. PubMed Abstract.
• Brezeanu et al. (2022). Helichrysum arenarium: From Cultivation to Application. Applied Sciences, 12(20), 10241.
• Helichrysum arenarium. Encyclopedia MDPI.
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• Chemical Profile and Antimicrobial Activity of the Essential Oils of Helichrysum arenarium (L.) Moench. and Helichrysum italicum (Roth.) G. Don. PMC9002512.
• Antioxidant and Toxic Activity of Helichrysum arenarium (L.) Moench and Helichrysum italicum (Roth) G. Don Essential Oils and Extracts. PMC8879542.
• A Comparative Study of the Antioxidative Effects of Helichrysum italicum and Helichrysum arenarium Infusions. Antioxidants, 2021. PMC7998896.
• Kenig et al. (2022). Helichrysum italicum and Helichrysum arenarium infusions in reversing the traits of metabolic syndrome: a double-blind randomized comparative trial. Food & Function.
• Kenig et al. (2022). Helichrysum italicum and Helichrysum arenarium Infusion Consumption Affects the Inflammatory Status and the Composition of Human Gut Microbiota in Patients with Traits of Metabolic Syndrome. PMC9601527.
• European Medicines Agency (EMA). Helichrysi flos — Herbal Medicinal Product.
• EMA/HMPC. Final European Union Herbal Monograph on Helichrysum arenarium (L.) Moench, flos.
• EMA. Sandy Everlasting (Helichrysum arenarium (L.) Moench, flos) — Summary for the Public.
• Antunes Viegas et al. (2014). Helichrysum italicum: From traditional use to scientific data. Journal of Ethnopharmacology.
• Les et al. (2017). Everlasting flower (Helichrysum stoechas Moench) as a potential source of bioactive molecules. Industrial Crops and Products.
• Phytochemical Study of Phenolic Compounds from Helichrysi flos by LC-DAD-MS. SpringerLink.
• ClinicalTrials.gov. NCT04866628: Clinical Trials of Two Helichrysum Infusions in Adults.
• Phytochemical Profile and Anticancer Potential of Helichrysum arenarium Extracts on Glioblastoma, Bladder Cancer, and Breast Cancer Cells. PMC11859872.