Cypress

Cypress (Cupressus sempervirens L.): A Comprehensive Reference

1. Identity and Botanical Description

Taxonomic Identity

Cypress, botanically designated Cupressus sempervirens L., is also widely known as Mediterranean cypress, Italian cypress, Tuscan cypress, or Persian cypress, and is a species native to the eastern Mediterranean region and Iran. It belongs to the family Cupressaceae. The species epithet sempervirens translates from Latin as "evergreen" or "always living," reflecting the symbolic connotation of immortality and eternity attributed to the tree across many cultures.

The tree is a medium-sized coniferous evergreen growing up to 35 m (115 ft) tall, with a conic crown with level branches, and is widespread throughout the Mediterranean basin, having become endemic in similar dry-summer climates due to its ability to survive in both acidic and alkaline soils and withstand drought. Its distribution encompasses the Mediterranean region broadly, including Syria, Turkey, Cyprus, Lebanon, Palestine, and some Greek Islands, as well as the southern coasts of the Caspian Sea in Iran.

Plant Parts Used

Different plant parts are employed in medicine and industry. Male and female cones are present on the same plant. The female flowers, grouped in catkins, give rise to fruits called cypress nuts or galbules, which are the primary plant part used in herbal medicine. The galbules are harvested green and fleshy while the scales are not yet separated. Leaves, bark, and young twigs are also used across different traditions and in the production of essential oil.

Common Forms and Preparations

The crude, semi-purified, and purified extracts of C. sempervirens have long been recognized for their pharmacological activities, as evidenced by extensive use in herbal medicines, tonics, and infusions across indigenous cultures. Current commercial preparations include:

• Essential oil: Obtained by steam distillation from the leaves of C. sempervirens, with a yield of approximately 0.87% (v/w) relative to dry weight material. Used in aromatherapy, topical preparations, and fragrance.
• Hydroalcoholic and aqueous extracts of cones: Prepared from the dried female cones (galbules) for oral use in herbal tinctures, capsules, and decoctions, principally exploiting the proanthocyanidin and flavonoid content.
• Methanol and ethanol extracts: The powdered form of C. sempervirens is extracted with methanol, with the resulting extract combined, evaporated by vacuum rotary evaporation at 45°C to yield a dried powdered form. Used in research and standardized supplement preparations.
• Decoctions: Decoction of cones and young branches has been used traditionally in the treatment of hemorrhoids and to treat excessive sweating of the feet.

2. Traditional and Historical Use

Ancient Civilizations

Cypress is important in Mediterranean and Middle Eastern culture; it has long been valued for its role in symbolism, various rituals, and folk medicine. In addition to associations with death, mourning, and the underworld, cypress trees became associated with medicine and healing in Greece and Rome.

The Greek physician Hippocrates (c. 460 to 370 BCE) recommended cypress be used in a poultice associated with treating procidentia, or pelvic organ prolapse. In De Medicina, the second-century CE Greek philosopher Celsus mentioned its medicinal properties, including treatment of eye diseases.

The use of cypress in traditional medicine dates from the time of the Pharaohs, where it was applied for its astringent, tonifying, decongestant, and diuretic properties.

Medieval and Post-Classical Europe

In medieval medicine, cypress was mainly used for its anti-hemorrhoidal virtues. Traditional European herbal medicine utilized decoctions of the cones for venous insufficiency, hemorrhoids, excessive perspiration (particularly of the feet), and respiratory ailments.

Folk Medicine Across Cultures

The plant has a long history of utilization in folk medicine in many countries, mainly for cough and flu treatment. In traditional medicine, dried leaves are used in treatment of stomach pain, diabetes, inflammation, toothache, and laryngitis, and as a contraceptive. In northern Saudi Arabia, C. sempervirens is used as traditional medicine to treat cough, influenza, and rheumatism.

In Tunisia, C. sempervirens has customarily been utilized for influenza and rheumatism treatments, as an antiseptic, and against inflammation, colds, and diabetes.

In ancient Greece, cypress cones were often dipped in wine to help treat asthma and cough. Cypress essential oil was also widely used in traditional Chinese medicine and Ayurvedic medicine, which continue to attribute beneficial health properties to it.

In Iran, the cypress is both a sacred tree and a metaphor for "the graceful figure of the beloved," underscoring its deep entrenchment in regional culture and folk healing.

3. Key Phytochemical Constituents and Active Compounds

Overview of Phytochemical Profile

Approximately 109 phytochemical constituents have been identified as isolates from various parts of this plant, comprising mostly diterpenoids and biflavonoids. Chemical analysis of Cupressus sempervirens identifies phytochemicals that include monoterpenes, diterpenes, flavonoid glycosides, and bioflavonoids.

Essential Oil Constituents

A total of 20 constituents representing 98.1% of the essential oil have been identified; α-pinene (48.6%), δ-3-carene (22.1%), limonene (4.6%), and α-terpinolene (4.5%) are the main components comprising 79.8% of the oil. The oils are predominantly composed of monoterpene hydrocarbons, with α-pinene as the major constituent. Mediterranean cypress essential oil is similarly rich in α-pinene, δ-3-carene, and cedrol.

The nuts (galbules) contain an essential oil of approximately 0.2–1%, dominated by monoterpenes including α-pinene, camphene, β-phellandrene, limonene, and α-terpinene; sesquiterpenes such as cadinene; and alcohols including terpineol, borneol, linalool, sabinol, and cedrol.

Polyphenolic and Flavonoid Constituents

HPLC analysis has indicated the existence of 18 phenolic and flavonoid compounds in C. sempervirens extract. Hesperetin represents the greatest concentration (25,579.57 µg/mL), while other compounds including pyrocatechol, rutin, gallic acid, chlorogenic acid, naringenin, and quercetin are also present.

Preliminary phytochemical analysis shows the plant contains alkaloids 0.7%, flavonoids 0.22%, tannin 0.31%, saponins 1.9%, phenols 0.067%, essential oils, and many other biologically active constituents.

The galbules also contain diterpenic acids, catechin tannins (less than 5%) including proanthocyanidins, and flavonoids such as cupressuflavone, amentoflavone, rutin, and quercetin. Flavonoids specifically identified include amentoflavone and cupresflavone (mainly in the leaves), and leucoanthocyanidins.

Proanthocyanidins (Condensed Tannins)

A small amount of proanthocyanidin polymer with a molecular weight of 1,500–2,000 Daltons has been extracted from Cupressus sempervirens L. These oligomeric proanthocyanidins are considered to be among the most pharmacologically significant constituents of the plant, accounting for many of its vascular, antiviral, and connective-tissue-protective properties (see below).

Mechanisms of Action (Established in Preclinical Research)

Cypress has demonstrated angioprotective activity in the rat through procyanidol oligomers, elastase inhibitory activity in vitro, and inhibitory activity against angiotensin-converting enzyme.

In vivo, in the mouse with emphysema induced by β-aminopropionitrile (a disease chiefly caused by the destruction of alveolar elastin), the proanthocyanidins of cypress limit the breakdown of elastic lamellae and therefore the degeneration of connective tissue. The traditional use of female cypress cones to reduce symptoms of venous insufficiency or hemorrhoidal disorders is attributed to this connective tissue-protective action.

The proanthocyanidins of cypress exert a vasoconstrictive effect on small vessels while restoring the elasticity of the venous wall. Additionally, thanks to its tannin content, cypress has an astringent effect that helps tighten tissues.

Pharmacokinetic study has recommended that amentoflavone digestion is fast, and the bioavailability of bioflavonoid after oral administration is low in rats.

In pharmacokinetic assessment, administration of amentoflavone to rats was conducted intraperitoneally (10 mg/kg), intravenously (10 mg/kg), and orally (300 mg/kg).

4. Scientific Evidence by Area of Use

4.1 Antimicrobial and Antibiofilm Activity

Research has consistently shown that C. sempervirens has antimicrobial activity to varying extents, and the biological activities of the plant are strongly associated with its phytochemical content, particularly its phenolic constituents and essential oils.

In vitro antimicrobial testing showed that the methanol extract of C. sempervirens strongly inhibited the growth of test bacteria studied, except for yeast species, while the essential oil had moderate antibacterial but no anti-candida activity. Klebsiella pneumoniae was proven to be the most susceptible against the methanol extract. The exposure time of the essential oil and methanol extract for complete inhibition of cell viability of K. pneumoniae was found to be 250 µg at 30 min and 500 µg at 120 min, respectively.

In an in vitro study using HPLC-characterized extract, hesperetin was identified as the dominant phenolic compound. The well diffusion method documented antibacterial and antifungal activity against E. faecalis, E. coli, C. albicans, S. typhi, S. aureus, and M. circinelloides, with inhibition zones of 35, 33, 32, 25, 23, and 21 mm, respectively, exceeding those of standard antibiotics and antifungals.

The essential oil of Cupressus sempervirens L. presented antibacterial activity against Gram-positive and Gram-negative bacteria, showing the largest inhibition zones with B. subtilis and E. coli.

The antimicrobial action of Cupressus sempervirens essential oils was more evident against Gram-positive compared to Gram-negative bacteria.

Evidence strength: These bioactivities originate from animal studies in vivo and in vitro studies, and are still considered inconsequential for direct clinical inference. In vitro bioactivity cannot fully elucidate the biologic effect in vivo, while animal models are essential for pharmacological research before clinical use. The bioactivities in vitro need to be explored through comprehensive future research.

4.2 Antiviral Activity

In a published study, the aim was to search for new antiviral agents from herbal medicines. Ethanol extracts of C. sempervirens, C. sempervirens var. horizontalis, and C. sempervirens cv. Cereiformis were used to test their influence on herpes simplex virus type 1 (HSV-1). HeLa cell monolayers were infected with HSV-1, and antiviral activity was assessed using the Hematoxylin and Eosin method. Results showed that all three plants have antiviral activity against HSV-1 virus, with the most active extract being that from C. sempervirens. Among the different plant parts tested, the fruit extract possessed the strongest anti-HSV activity. The authors concluded that all extracts tested showed significant antiviral potency.

Proanthocyanidins from cypress have been tested against different viruses, including DNA viruses, RNA viruses, enveloped and non-enveloped viruses.

In vivo, in patients with herpes lesions, local application of cream containing 5% proanthocyanidins has been reported to decrease the number of herpes lesions. However, the scale of available clinical evidence is limited.

Evidence strength: Primarily in vitro and animal-based. One small clinical application was reported for topical proanthocyanidin cream in herpes, but large-scale controlled clinical trials are absent from the published literature.

4.3 Antioxidant Activity

Tunisian C. sempervirens essential oil has exhibited significant antioxidant activities in ABTS and DPPH assays, surpassing the effects of the synthetic reference antioxidant BHT.

From the DPPH assay, promising antioxidant activity was recorded for C. sempervirens extract with an IC₅₀ of 8.97 µg/mL. Moreover, ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC) assays confirmed the antioxidant activity of the extract, expressed as ascorbic acid equivalent (AAE) of 366.9 ± 0.2 µg/mg and 102 ± 0.2 µg/mg of extracts, respectively.

Evidence strength: All data are from in vitro assays. No human clinical trials establishing clinically meaningful antioxidant effects are available.

4.4 Antidiabetic Activity

α-Amylase and α-glucosidase inhibition percentages were determined to express the antidiabetic activity of C. sempervirens extract in vitro, with a promising IC₅₀ value of 27.01 µg/mL for α-amylase compared to that of acarbose (50.93 µg/mL), while the IC₅₀ value for α-glucosidase was 19.21 µg/mL compared to 4.13 µg/mL for acarbose.

Dried leaves of C. sempervirens have traditionally been used to treat diabetes, and the percentages of α-amylase and α-glucosidase inhibition have been determined to assess the plant extract's potential as an antidiabetic.

Evidence strength: Preliminary; in vitro enzyme inhibition only. No human clinical trials exist. The α-glucosidase IC₅₀ for the extract (19.21 µg/mL) compares less favorably to acarbose (4.13 µg/mL), indicating the extract is less potent on this target in vitro.

4.5 Anticoagulant Activity

Prothrombin time (PT) and activated partial thromboplastin time (APTT) assays have revealed the role of C. sempervirens extract as an anticoagulant agent when compared with the activity of heparin. A dedicated study by Ulusal et al. (2007) also documented this anticoagulant effect, published in Phytotherapy Research.

Evidence strength: In vitro and limited animal data only. No controlled human trials. The anticoagulant property is considered a significant safety-relevant pharmacological characteristic (see Safety section).

4.6 Venous Insufficiency and Hemorrhoidal Disorders

In vitro antiviral activity, vasoconstrictive effects on small vessels, and restoration of the elasticity of the venous wall have all been proposed mechanisms related to traditional use in venous insufficiency. The traditional use of female cypress cones to reduce symptoms of venous insufficiency or hemorrhoidal disorders is attributed to this connective tissue-protective action.

Catechins and flavanolic oligomers from Cupressus sempervirens L. have been compared for their in vitro elastase inhibitory and in vivo angioprotective activity.

Evidence strength: Mechanistic rationale is plausible based on preclinical studies; however, well-designed human clinical trials in venous insufficiency or hemorrhoids specifically studying cypress preparations are not available in the accessible peer-reviewed literature.

4.7 Benign Prostatic Hyperplasia (BPH)

Labda-8(17),12,14-trien-19-oic acid contained in Cupressus sempervirens fruits has been found to suppress benign prostatic hyperplasia in human in vitro and rat models by inhibiting androgens and STAT-3 signaling.

Eight essential diterpenes were identified, with the strongest diterpene (labda-8(17),12,14-trien-19-oic acid) showing an IC₅₀ of 37.5 µM against antiproliferative action in BPH stromal cells in humans. There was significant inhibition of STAT-3 activation (phosphorylation) in BPH stromal cells and inhibition of androgen-sensitive KLK3/PSA. The diterpene fraction inhibited rat prostatic hyperplasia, causing apoptotic marking in stromal cells with lower expressions of Bcl-2/Bax, IGF-I, TGF-β, and PCNA.

In vitro and animal research shows that cypress fruit extract inhibits proliferation of stromal cells in benign prostatic hyperplasia and induces apoptosis of stromal cells.

Evidence strength: In vitro and rat model data only; no human clinical trials have been published.

4.8 Anticancer / Cytotoxic Activity

Using the sulforhodamine B assay, the essential oil of Cupressus sempervirens ssp. Pyramidalis was investigated for antiproliferative activity in renal adenocarcinoma cells and C32 amelanotic melanoma cells. The leaf oil of C. sempervirens ssp. Pyramidalis showed the maximum cytotoxic action with an IC₅₀ estimate of 104.90 µg/mL against these cell lines.

Strong cytotoxic activity of taxodione isolated from Cupressus sempervirens cones has also been documented.

Evidence strength: Entirely preclinical (in vitro cell-line data). No human trials. These findings should be regarded as exploratory only.

4.9 Hepatoprotective Activity

An in vivo study conducted over 4 weeks showed that pre-treatment with C. sempervirens extract (250 mg/kg/day, orally) demonstrated a safety index in normal rats and hepatoprotective action against paracetamol-induced liver toxicity (4 g/kg body weight, orally), compared to silymarin (100 mg/kg/day, orally) as a positive control.

Evidence strength: Rat model only. No human clinical trials. Numerous in vivo and in vitro studies have provided support for the traditional uses of C. sempervirens, but further research is required for isolating more active constituents and for validating clinical utilization in herbal formulations for humans, including investigation of potential toxicity.

4.10 Neurobiological Effects

The dichloromethane, acetone, ethyl acetate, and methanol extracts of the cones and leaves of Cupressus sempervirens var. horizontalis and var. pyramidalis were investigated for their in vitro neurobiological effects. These investigations focused on antioxidant capacity and enzyme inhibitory actions relevant to neurodegeneration, including acetylcholinesterase and butyrylcholinesterase inhibition. Recent pharmacological discoveries have shown effects of the extracts on the central nervous system.

Evidence strength: In vitro enzyme inhibition only. No human clinical data.

4.11 Anti-inflammatory Activity

Pharmacological investigations of Cupressus sempervirens have shown anti-inflammatory properties, among other biological activities. The anti-inflammatory effect of the essential oil was investigated using an acetic acid-induced capillary permeability test in animal models. Traditional use for inflammation, including toothache and laryngitis, is well documented across multiple ethnobotanical surveys.

Evidence strength: Animal model and in vitro data only. No controlled human trials.

4.12 Antiparasitic and Antileishmanial Activity

The antileishmanial potential of C. sempervirens extract has been reported against different forms, including amastigote and promastigote of Leishmania major and L. infantum.

Evidence strength: In vitro only.

5. Body Systems and Health Areas Associated with Cypress

Enormous pharmacological properties have been found for C. sempervirens, including antiseptic, anti-inflammatory, antispasmodic, antioxidant, antimicrobial, hepatoprotective, wound-healing, anticoagulant, antihyperlipidemic, anticancer, neurobiological, antidiabetic, and antiosteoporotic activities. Across the published literature, the following body systems are principally associated with the plant:

• Circulatory and vascular system: Venous insufficiency, hemorrhoids, angioprotection, anticoagulation.
• Respiratory system: Traditional use for cough, influenza, asthma, cold.
• Integumentary / musculoskeletal system: Wound healing, anti-inflammatory, skin antimicrobial, rheumatism.
• Urogenital system: Benign prostatic hyperplasia (preclinical), diuretic use (traditional).
• Gastrointestinal system: Stomach pain, hemorrhoids, gastric ulcer (preclinical).
• Endocrine / metabolic: Antidiabetic enzyme inhibition (in vitro), antihyperlipidemic (preclinical).
• Hepatic system: Hepatoprotective (animal model).
• Nervous system: Acetylcholinesterase inhibition (in vitro).
• Immune / infectious disease: Antimicrobial, antiviral (HSV-1, retroviruses), antileishmanial.

6. Dosage Forms and Reported Dosages

No standardized clinical dosing regimen for Cupressus sempervirens has been established by a major regulatory body. The appropriate dose of cypress depends on several factors such as the user's age, health, and other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for cypress.

The following dosages appear in the specific studies cited above:

• Hepatoprotective animal study: Extract at 250 mg/kg/day administered orally to rats over 4 weeks, with silymarin at 100 mg/kg/day as comparator.
• Amentoflavone pharmacokinetics (animal): Amentoflavone was administered to rats intraperitoneally (10 mg/kg), intravenously (10 mg/kg), and orally (300 mg/kg).
• Antimicrobial in vitro: Complete inhibition of K. pneumoniae cell viability was achieved at 250 µg of essential oil at 30 minutes and 500 µg of methanol extract at 120 minutes.
• Topical proanthocyanidin cream (herpes): Local application of cream containing 5% proanthocyanidins was reported to decrease herpes lesion count.
• Antidiabetic in vitro: IC₅₀ for α-amylase inhibition was 27.01 µg/mL and for α-glucosidase was 19.21 µg/mL.

7. Safety Considerations and Interactions

General Safety Profile

Pharmacological effects identified include anti-inflammatory, antioxidant, antidiabetic, antiviral, and anti-malignancy properties; however, these bioactivities originate from animal studies in vivo and in vitro, and are still considered preliminary.

Anticoagulant / Bleeding Risk

Cypress might prolong bleeding time and increase the risk of bruising and bleeding; individuals with a bleeding disorder should use cypress with caution. Cypress may increase the risk of bleeding during and after surgery; it should be stopped at least 2 weeks before a scheduled surgery. This risk is directly supported by published pharmacological findings of anticoagulant activity.

Allergic Contact Dermatitis

A documented safety concern is skin allergy. Samaran et al. (2020), published in Contact Dermatitis, reported allergic contact dermatitis to Cupressus sempervirens resin and cross-reaction with colophonium. People who are sensitive to cedar, peaches, or adhesive bandages might have allergic reactions to cypress. The plant can cause allergies, especially in people already allergic to conifers.

Essential Oil Toxicity

The toxicological profiles of the majority of medicinal plant essential oils have not been fully elucidated, and toxicity testing in a varied range of in vitro studies using animal models is crucial for determining the safety profile of essential oils. The essential oil contains constituents that are toxic at high doses; cypress essential oil is considered toxic if the dose is exceeded.

Cypress essential oil is rich in cedrol, which has a sedative effect and is part of the composition of some sleep-promoting drugs.

Pregnancy and Lactation

Cypress essential oil is considered neurotoxic and oxytocic. Because it stimulates uterine musculature, the essential oil form of the plant is totally contraindicated in pregnancy. Use in lactation is also not recommended.

Drug Interactions

The most clinically significant interaction concern is with anticoagulant and antiplatelet medications. Cypress may slow blood clotting, which would be additive with warfarin, heparin, aspirin, clopidogrel, and related drugs. The anticoagulant property of C. sempervirens extract has been demonstrated in vitro via prolongation of both prothrombin time (PT) and activated partial thromboplastin time (APTT), compared with the activity of heparin. There are no published human interaction studies.

Overall Evidence Characterization

Numerous in vivo and in vitro studies have provided support for the traditional uses of C. sempervirens, but further research work is required toward isolating more active constituents and for validating its clinical utilization in herbal formulations for humans, as well as investigating any potential toxicity for future clinical studies. As of the most current comprehensive reviews, bioactivities identified in research originate from animal studies in vivo and in vitro, and are still considered inconsequential for direct clinical inference without confirmatory human trials.

References

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