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Herbal Monograph

Clove

Syzygium aromaticum (L.) Merr. & L.M.Perry

Myrtaceae

Class 2d Analgesic Antimicrobial Carminative Anti-inflammatory

Time-honored dental analgesic and warming carminative spice, rich in eugenol

Overview

Plant Description

Syzygium aromaticum is a medium-sized evergreen tree reaching 8-12 meters in height (occasionally up to 20 meters in optimal conditions), with a conical to cylindrical crown. The trunk is smooth, grey-barked, and branching begins relatively low. Leaves are opposite, simple, ovate-lanceolate, 8-13 cm long and 3-5 cm wide, with a glossy dark green upper surface, paler beneath, leathery in texture, and dotted with numerous translucent oil glands visible when held up to light. The leaves are aromatic when crushed. Flower buds (the commercial 'clove') are produced in terminal clusters (cymes) of 3-15, each bud 10-20 mm long, consisting of a long calyx tube (hypanthium) topped by four spreading sepals, and a rounded head of four unexpanded petals forming a ball (the 'nail head') that encloses numerous stamens. Buds are initially pale green, turning pink and then bright crimson-red as they approach anthesis. If allowed to open, the four petals form a small, cream-white to pale pink flower about 6 mm across. The fruit is an oblong drupe, 2.5-3 cm long, dark purplish-red when ripe, containing one or two seeds. The entire plant is intensely aromatic due to high essential oil content in all tissues, particularly the flower buds.

Habitat

Native to the Maluku Islands (Moluccas) of eastern Indonesia, specifically the small volcanic islands of Ternate, Tidore, Bacan, Makian, and Moti in the Northern Maluku province. The species requires a tropical maritime climate with high humidity (70-90%), consistent rainfall (1500-2500 mm annually with no prolonged dry season), warm temperatures (20-30 degrees Celsius, optimal 25-28 degrees), and protection from strong winds. It thrives at low to moderate elevations (sea level to 600 meters) on well-drained, deep, loamy or volcanic soils rich in organic matter with slightly acidic pH (5.5-6.5). The tree is frost-intolerant and requires consistent warmth year-round. It grows best in partial shade when young but tolerates full sun as a mature tree.

Distribution

Originally restricted to the Maluku Islands of Indonesia, clove has been cultivated throughout the tropics since the 18th century following the breaking of the Dutch VOC monopoly. Major producing countries today include Indonesia (the world's largest producer, accounting for approximately 75% of global production, centered on Sulawesi, Java, Sumatra, and Maluku), Madagascar (second largest producer), Tanzania (particularly Zanzibar and Pemba, historically a major source), Comoros Islands, Sri Lanka, India (Kerala and Tamil Nadu), and Brazil. Smaller production occurs in Malaysia, the Philippines, Grenada, and Jamaica. Indonesia both produces and consumes the most cloves globally, largely for kretek (clove cigarette) production. The Zanzibar archipelago, once the world's leading producer, remains an important source of high-quality clove buds and clove oil.

Parts Used

Dried flower bud (Flos Caryophylli)

Preferred: Whole dried bud (for infusions, decoctions, powdered in capsules) or as a starting material for tincture preparation

The dried, unopened flower bud is the primary medicinal and culinary product. It is the part referenced in all major pharmacopeial monographs (WHO, European Pharmacopoeia, Commission E, British Herbal Pharmacopoeia) and the form with the most extensive safety and efficacy data. Whole dried buds contain 15-20% essential oil, dominated by eugenol (70-90%), along with gallotannins, flavonoids, and other non-volatile constituents. The whole bud provides a broader phytochemical profile than isolated oil and is generally considered safer for internal use.

Essential oil (Oleum Caryophylli)

Preferred: Diluted topical application (1-5% in carrier oil) or in dental preparations

Steam-distilled from dried flower buds. A clear to pale yellow oil with the characteristic warm, spicy, intensely aromatic clove scent. Contains 70-90% eugenol, 5-15% eugenyl acetate, 5-12% beta-caryophyllene, and minor constituents including alpha-humulene, methyl salicylate, and vanillin. Clove bud oil is pharmacopeially distinct from clove leaf oil (which is higher in eugenol at 82-88% but lacks eugenyl acetate) and clove stem oil (intermediate profile). Bud oil is the preferred grade for medicinal and dental use. It is the concentrated form used in dentistry for topical analgesia and in zinc oxide-eugenol (ZOE) dental cements. Must be diluted before topical application due to mucous membrane and skin irritancy.

Clove leaf

Preferred: Essential oil (distilled from leaves)

Not a traditional medicinal part but increasingly used as a commercial source of eugenol through steam distillation. Clove leaf oil has a different chemical profile from bud oil: higher eugenol content (82-88%) but negligible eugenyl acetate. Leaf oil is less expensive and widely used in the fragrance, flavoring, and pharmaceutical industries as a eugenol source. Occasionally used in traditional Indonesian medicine (jamu) for topical pain relief.

Key Constituents

Phenylpropanoids (volatile)

Eugenol 70-90% of essential oil; 15-18% of dried bud by weight
Eugenyl acetate 5-15% of essential oil
Isoeugenol Trace to 0.5% of essential oil
Methyl eugenol Trace amounts (< 0.1%)

The phenylpropanoid fraction, dominated by eugenol, accounts for the majority of clove's therapeutic actions: dental analgesia, antimicrobial activity, anti-inflammatory effects, and antioxidant capacity. Eugenol is the single most clinically relevant constituent and the basis for clove's inclusion in dental pharmacopeias worldwide.

Sesquiterpenes (volatile)

Beta-caryophyllene 5-12% of essential oil
Alpha-humulene (alpha-caryophyllene) 1-3% of essential oil
Caryophyllene oxide 0.5-2% of essential oil

The sesquiterpene fraction contributes significantly to clove's anti-inflammatory properties. Beta-caryophyllene's role as a CB2 agonist provides a mechanism distinct from eugenol's COX inhibition, creating synergistic anti-inflammatory and analgesic effects. This combination of phenylpropanoid and sesquiterpene anti-inflammatory pathways may explain clove's traditional efficacy for pain conditions.

Tannins

Gallotannins (including eugeniin) 10-13% of dried bud
Ellagitannins 1-3% of dried bud

The substantial tannin content (10-13%) provides astringent, antiviral, and tissue-toning properties that complement the volatile oil actions. Tannins are particularly relevant for clove's oral health applications (tightening of gingival tissue, antiviral activity against oral herpes) and gastrointestinal uses (anti-diarrheal effect, mucosal protection).

Flavonoids

Kaempferol Significant amounts (major flavonoid)
Quercetin Present in moderate amounts
Isorhamnetin Present in moderate amounts
Myricetin Present in minor amounts

The flavonoid fraction significantly enhances clove's antioxidant capacity beyond what eugenol alone provides. Clove consistently ranks among the highest-ORAC-value spices in antioxidant assays, largely due to the synergistic contribution of flavonoids, eugenol, and tannins. Flavonoids also contribute to anti-inflammatory and cardiovascular protective effects.

Triterpenoids

Oleanolic acid 2-4% of dried bud
Maslinic acid Minor amounts

Oleanolic acid contributes to clove's hepatoprotective and hypoglycemic potential, providing non-volatile bioactive compounds that complement the essential oil's actions. These triterpenoids are present in whole-bud preparations (infusions, powders) but are not found in steam-distilled essential oil.

Chromones

Biflorin Minor constituent
Isobiflorin Minor constituent

The chromone constituents are relatively unique to clove among common medicinal plants and represent an area of emerging pharmacological interest, particularly regarding cytotoxic and anti-tumor potential. Present in whole-bud preparations but absent from essential oil.

Other phenolic compounds

Vanillin Trace to 0.5% of essential oil
Gallic acid Present as free acid and in tannin structures
Methyl salicylate Trace amounts in essential oil

These minor phenolic compounds contribute to clove's exceptionally high total phenolic content and ORAC antioxidant value. Clove consistently ranks first or second among all spices tested for total antioxidant capacity in comparative studies.

Herbal Actions

Analgesic (primary)

Relieves pain

Clove is one of the most well-established herbal analgesics, with a particular affinity for dental and orofacial pain. Eugenol produces local anesthesia through reversible blockade of voltage-gated sodium channels (Nav1.2 and Nav1.7), a mechanism shared with synthetic local anesthetics like lidocaine but with a different binding site. Eugenol also inhibits COX-2 and prostaglandin synthesis, providing anti-inflammatory analgesia. The 2006 Alqareer et al. RCT demonstrated clove gel to be equivalent to 20% benzocaine gel for topical dental anesthesia. This dual mechanism (sodium channel block + COX inhibition) accounts for clove's efficacy in both acute and inflammatory pain.

[1, 4, 7]
Antimicrobial (primary)

Kills or inhibits the growth of microorganisms

Broad-spectrum antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and various fungi. Eugenol disrupts bacterial cell membranes, increases membrane permeability, and inhibits enzyme function. Clove essential oil shows MIC values of 0.25-2 mg/mL against Candida species and demonstrates activity against fluconazole-resistant strains. Particularly relevant for oral pathogens (Streptococcus mutans, Porphyromonas gingivalis) and gastrointestinal infections.

[5, 8, 9]
Carminative (primary)

Relieves intestinal gas and bloating

One of the strongest carminative spices in the Western and Ayurvedic materia medica. Eugenol and the volatile oil fraction relax smooth muscle in the gastrointestinal tract, reduce intestinal gas formation, and promote expulsion of existing gas. The warming, aromatic quality stimulates digestive secretions and promotes healthy peristalsis. Commission E approved clove for use as a carminative. In TCM, Ding Xiang is classified as a herb that warms the middle jiao and directs rebellious stomach qi downward.

[1, 4, 14]
Anti-inflammatory (primary)

Reduces inflammation

Dual anti-inflammatory mechanism: eugenol inhibits COX-2 and the arachidonic acid cascade, while beta-caryophyllene activates CB2 cannabinoid receptors to suppress NF-kappaB signaling and pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6). The flavonoid fraction (kaempferol, quercetin) adds additional NF-kappaB inhibition. This multi-target approach may explain clove's traditional efficacy for inflammatory conditions across multiple body systems.

[4, 5, 10]
Antioxidant (secondary)

Prevents or slows oxidative damage to cells

Clove possesses one of the highest ORAC (Oxygen Radical Absorbance Capacity) values of any food or spice, exceeding blueberries, turmeric, and cinnamon in comparative assays. The antioxidant activity derives from the synergistic interaction of eugenol (a phenolic chain-breaking antioxidant), gallotannins, flavonoids (quercetin, kaempferol), and gallic acid. Eugenol scavenges superoxide, hydroxyl, and peroxyl radicals. The total phenolic content of dried clove bud exceeds 200 mg GAE/g, one of the highest among botanical materials.

[4, 5]
Antispasmodic (secondary)

Relieves smooth muscle spasm

Eugenol demonstrates relaxant effects on gastrointestinal smooth muscle, reducing spasmodic contractions. This antispasmodic activity underlies clove's carminative effect and its traditional use for intestinal colic, cramping, and spasmodic digestive complaints. The mechanism involves calcium channel antagonism and direct smooth muscle relaxation.

[1, 4]
Expectorant (secondary)

Promotes the discharge of mucus from the respiratory tract

The warming, aromatic volatile oils stimulate mucus secretion and ciliary activity in the respiratory tract, promoting expectoration of thick or stagnant phlegm. Traditional use in Ayurveda (Lavanga) and TCM (Ding Xiang) for cough with cold phlegm. The warming energetic quality makes clove particularly suited for productive coughs with thin, clear, or white phlegm in cold constitutions.

[14, 15]
Diaphoretic (mild)

Promotes perspiration

Clove's warming nature gently promotes perspiration, particularly when taken as a hot infusion. Used traditionally in combination formulas for the early stages of colds and flu to 'open the exterior' and promote a mild sweat. The stimulating diaphoretic action is consistent with its warm, pungent energetics.

[3]
Immunostimulant (mild)

Stimulates and enhances immune response

Preliminary evidence suggests eugenol and clove polyphenols modulate immune function by enhancing macrophage phagocytic activity and promoting cytokine production. However, this action is less well-characterized than clove's analgesic and antimicrobial effects and is based primarily on in vitro and animal data.

[5]

Therapeutic Indications

Digestive System

well established

Dental pain (toothache, post-extraction pain)

The most evidence-backed indication for clove. Eugenol is an established topical dental anesthetic used worldwide. The Alqareer et al. (2006) RCT demonstrated that homemade clove gel was equivalent to 20% benzocaine gel for needle-insertion pain. Eugenol is included in the WHO Model List of Essential Medicines for dental use. Commission E approved clove oil for dental pain. Applied topically to the affected tooth or gum, either as diluted essential oil on a cotton pellet, or as whole clove held against the painful area.

[1, 7, 18]
well established

Flatulence and intestinal gas (bloating, distension)

Commission E approved indication. Clove has centuries of documented use across multiple traditions (Western, Ayurvedic, Chinese, Islamic) as a carminative for intestinal gas. The volatile oil relaxes gastrointestinal smooth muscle, reduces gas formation, and promotes expulsion of existing gas. Taken as infusion, tincture, or powdered bud after meals.

[1, 3, 4]
traditional

Nausea and vomiting (antiemetic)

A prominent traditional indication in TCM (Ding Xiang is specifically indicated for hiccup and vomiting due to stomach cold) and Ayurveda. The mechanism is attributed to clove's ability to warm the stomach, direct rebellious qi downward, and reduce gastric spasm. Evidence is primarily from traditional use across multiple systems rather than controlled clinical trials.

[4, 14, 15]
traditional

Dyspepsia and poor appetite

Traditional use as a digestive stimulant. The aromatic and pungent qualities stimulate salivary and gastric secretions, improving appetite and digestive efficiency. Used in Ayurveda to kindle agni (digestive fire) and in TCM to warm the spleen and stomach. Often combined with other warming carminatives (ginger, cardamom, fennel).

[1, 3, 15]
traditional

Diarrhea (acute, non-specific)

Traditional use based on clove's astringent (tannin) and antimicrobial properties. The gallotannin content tones intestinal mucosa, while eugenol addresses potential infectious causes. Particularly indicated in TCM and Ayurveda for diarrhea associated with cold or deficiency patterns.

[4, 14]

Respiratory System

traditional

Productive cough with cold phlegm

Traditional use across multiple systems. The warming aromatic volatile oils stimulate mucociliary clearance and thin viscous mucus. Particularly indicated for coughs with abundant clear or white sputum, worse in cold or damp conditions. Used in Ayurveda for kapha-type coughs and in TCM for lung cold with phlegm stagnation. Combined with honey as a cough preparation.

[3, 14, 15]
traditional

Sore throat and pharyngitis

Used as a gargle (diluted clove infusion or very diluted clove oil in warm water) for sore throat. The combined analgesic (eugenol), antimicrobial, and astringent (tannin) properties make it rational for oropharyngeal inflammation. Traditionally used in Indonesian, Indian, and Middle Eastern medicine for throat complaints.

[4, 5]
traditional

Bronchitis and upper respiratory infection

Supportive treatment combining expectorant, antimicrobial, and warming actions. Used as steam inhalation (a few drops of clove oil in hot water) or taken as an infusion with honey. The antimicrobial properties of eugenol may help address secondary bacterial infections.

[3, 5]

Immune System

supported

Oral candidiasis (thrush)

Clove essential oil demonstrates significant antifungal activity against Candida species (MIC 0.25-2 mg/mL), including fluconazole-resistant strains. Pinto et al. (2009) demonstrated activity against clinical isolates of C. albicans, C. tropicalis, C. krusei, and other species. Eugenol disrupts fungal cell membranes through ergosterol binding and inhibits germ tube formation. Used as a mouthwash or topical application for oral fungal infections.

[4, 8]
traditional

Common cold and influenza (early stage)

Traditional use as a warming diaphoretic in the early stages of colds and flu. The antimicrobial, diaphoretic, and expectorant properties provide symptomatic relief. Often combined with ginger and honey as a warming tea. The gallotannin eugeniin has demonstrated antiviral activity against herpes simplex virus in vitro, though clinical evidence for antiviral effects in respiratory infections is lacking.

[3, 5]

Musculoskeletal System

supported

Musculoskeletal pain and arthralgia

Topical application of diluted clove oil provides counter-irritant and analgesic effects for localized musculoskeletal pain. The combined mechanisms of sodium channel blockade (eugenol), COX-2 inhibition (eugenol), and CB2 agonism (beta-caryophyllene) provide multi-target analgesia. Used in traditional massage oil preparations in Ayurvedic medicine. Must be diluted (1-5% in carrier oil) to avoid skin irritation.

[4, 10]

Skin / Integumentary

preliminary

Fungal skin infections (dermatomycosis)

Clove oil demonstrates antifungal activity against dermatophyte species (Trichophyton, Microsporum, Epidermophyton) in vitro. Pinto et al. (2009) documented MIC values against dermatophyte clinical isolates. Used topically in diluted form (1-3% in carrier oil) for superficial fungal infections. Clinical trials in human dermatophytosis are limited.

[8]
traditional

Wound antisepsis and minor skin infections

Traditional topical antiseptic use based on clove's broad-spectrum antimicrobial properties. Diluted clove oil applied to minor cuts, abrasions, and insect bites. The combination of antimicrobial (eugenol) and mild analgesic effects is practical for minor wound care. Must be properly diluted to avoid tissue irritation.

[4, 5]

Reproductive System

traditional

Low libido and sexual debility (kidney yang deficiency pattern)

In TCM, Ding Xiang is used to warm kidney yang, and kidney yang deficiency is associated with low libido, impotence, and reproductive weakness. This indication is specific to the TCM pattern differentiation framework. Some preliminary animal studies suggest eugenol may increase testosterone levels and improve sexual behavior in male rats, but human clinical data is lacking.

[14]

Nervous System

supported

Neuralgia and neuropathic pain (topical)

Eugenol's sodium channel blocking activity provides a pharmacological basis for topical use in neuralgia. Applied as diluted oil (2-5% in carrier) to the affected area for localized nerve pain. Particularly relevant for trigeminal neuralgia and post-herpetic neuralgia due to the orofacial affinity and antiviral (eugeniin) properties. Clinical evidence is primarily from dental neuralgia contexts.

[4, 7]

Energetics

Temperature

warm

Moisture

dry

Taste

pungentaromaticsweetbitter

Tissue States

cold/depression, damp/stagnation, damp/relaxation

Clove is a quintessentially warming aromatic spice. In Western energetic herbalism, its warm-dry nature makes it specific for cold, damp, stagnant tissue states — particularly cold digestion with gas and bloating, cold-type respiratory congestion, and cold-type pain (worse in cold/damp conditions). The strong pungent and aromatic qualities disperse stagnation and stimulate circulation. In Ayurveda, Lavanga is considered pungent (katu) and bitter (tikta) in rasa (taste), with heating virya and pungent vipaka. It reduces Kapha and Vata but may aggravate Pitta in excess. In TCM, Ding Xiang is acrid and warm, entering the Spleen, Stomach, Lung, and Kidney channels. Its primary function is to warm the middle jiao, direct rebellious qi downward (stop hiccup and vomiting), and warm kidney yang. The slight sweetness rounds out the otherwise sharp pungency.

Traditional Uses

Traditional Chinese Medicine (TCM)

  • Warms the middle jiao and directs rebellious stomach qi downward to treat hiccup and vomiting due to stomach cold (the primary classical indication)
  • Warms kidney yang to treat impotence, clear urinary frequency, and soreness/cold in the lower back and knees
  • Treats diarrhea due to spleen-kidney yang deficiency (often combined with rou dou kou/nutmeg)
  • Relieves abdominal pain and distension due to cold accumulation in the middle jiao
  • Used in the classical formula Ding Xiang Shi Di Tang (Clove and Persimmon Calyx Decoction) for persistent hiccup

"Ding Xiang is acrid and warm, and enters the Spleen, Stomach, Lung, and Kidney channels. It warms the middle and directs rebellious qi downward; warms the Kidneys and assists the yang. For cold in the Stomach with vomiting, hiccup, reduced appetite, and diarrhea."

[14]

Ayurveda

  • Lavanga is used as a dipana (appetizer) and pachana (digestive) to kindle agni and burn ama (toxins)
  • Carminative for adhmana (flatulence) and gulma (abdominal tumors/masses)
  • Antiemetic for chardi (vomiting) especially due to kapha or vata imbalance
  • Kasa (cough) and shvasa (asthma) of kapha origin with cold, abundant phlegm
  • Mukha roga (oral diseases) including dantavedana (toothache) and mukha paka (stomatitis)
  • Placed in the mouth to freshen breath and promote salivation (mukha shodhana)
  • Applied as paste or oil for shula (pain) in joints and muscles

"Lavanga is katu-tikta in rasa, laghu-snigdha in guna, with ushna virya and katu vipaka. It is kaphavatahara (pacifies kapha and vata) and is indicated in chardi, trishna, kasa, shvasa, hikka, and mukha roga."

[15]

Unani / Islamic Medicine

  • Qaranful is classified as hot and dry in the second degree
  • Used for strengthening the stomach and liver
  • Treatment of nausea, vomiting, and intestinal gas
  • Dental pain relief and oral hygiene (the Prophet Muhammad is reported to have recommended miswak, and clove was used similarly)
  • Aphrodisiac and tonic for reproductive weakness
  • Used in compound formulas (majun, jawarish) for digestive complaints
  • Applied topically for headache and joint pain

"Qaranful (clove) is hot and dry in the second degree. It strengthens the stomach, liver, and heart. It is beneficial for nausea, flatulence, and colic. Applied to the tooth, it relieves toothache."

[16]

European Herbalism (Medieval to Eclectic)

  • Introduced to Europe via Arab trade routes by the 4th-6th century CE; widely used in medieval compound medicines
  • Included in theriac and mithridate (complex polypharmacy preparations)
  • Used by the Eclectic physicians as a local anesthetic, rubefacient, and stimulating carminative
  • King's American Dispensatory (1898) recommends clove oil for toothache, flatulent colic, and as a corrective adjunct to griping purgatives
  • Gerard's Herball (1597) describes cloves as 'hot and dry in the third degree' and beneficial for the head, heart, and stomach
  • Applied to umbilicus in folk medicine to treat infant colic
  • Used as a pomander ingredient (studded in oranges) as an aromatic antimicrobial in plague times

"Oil of Cloves, dropped into a carious tooth, relieves toothache. The infusion of Cloves is a pleasant stomachic and carminative. Dose of the oil, 1 to 5 minims."

[3, 17]

Indonesian / Southeast Asian Traditional Medicine (Jamu)

  • Cengkeh is native to the Maluku Islands and central to Indonesian traditional medicine (jamu)
  • Used in warming jamu preparations for masuk angin (a 'wind entering the body' condition with bloating, chills, and malaise)
  • Included in jamu gendong (ambulant/carried jamu) preparations for digestive complaints
  • Clove oil applied to temples and forehead for headache
  • Whole cloves chewed for nausea during pregnancy (traditional practice, though safety not established)
  • Used in traditional birthing practices as a warming aromatic
  • Cultural significance extends beyond medicine: kretek (clove cigarettes) are a major cultural and economic product

[4]

Modern Research

rct

Topical dental anesthesia: Clove gel versus benzocaine

Randomized, subject-blinded controlled trial comparing homemade clove gel, 20% benzocaine gel, and two placebos as topical anesthetics for needle insertion pain in the oral cavity.

Findings: Seventy-three adult volunteers received topical agents applied to the maxillary canine buccal mucosa for 5 minutes before two needle sticks. Pain response was measured using a 100 mm visual analogue scale (VAS). Both clove gel and benzocaine gel produced significantly lower mean pain scores compared to their respective placebos (p=0.005). Critically, no statistically significant difference was found between clove gel and benzocaine gel pain scores, demonstrating equivalence of the natural clove preparation with the standard pharmaceutical topical anesthetic.

Limitations: Single-center study with relatively small sample size (73 subjects). The clove gel was a homemade preparation without standardized eugenol content, making exact dose determination and reproducibility challenging. Only needle-insertion pain was assessed, not sustained dental pain or post-procedural pain. Subject-blinded but not double-blinded (operators could distinguish preparations).

[7]

narrative review

Comprehensive review of Syzygium aromaticum pharmacology

Review covering the botanical, chemical, pharmacological, and toxicological aspects of Syzygium aromaticum (clove), with particular emphasis on eugenol, the main bioactive compound, and its diverse biological activities.

Findings: Clove essential oil and eugenol demonstrate a wide spectrum of pharmacological activities: analgesic (sodium channel blockade), antimicrobial (effective against both Gram-positive and Gram-negative bacteria, yeasts, and molds), anti-inflammatory (COX-2 and NF-kappaB inhibition), antioxidant (one of the highest ORAC values among all spices), and antifungal (active against Candida and Aspergillus species). Antidiabetic potential was noted through alpha-glucosidase inhibition and enhancement of insulin sensitivity. Anti-tumor activity was observed in multiple cell lines in vitro. The WHO has established an acceptable daily intake of 2.5 mg/kg body weight for clove oil.

Limitations: Narrative review synthesizing heterogeneous studies with variable methodologies. Many pharmacological activities demonstrated only in vitro or in animal models. Limited human clinical trial data for most indications beyond dental analgesia. Dose-response relationships for most activities not well characterized in humans.

[4]

narrative review

Chemical composition and biological activities of clove essential oil

Short review of the chemical composition and biological activities of clove essential oil (Eugenia caryophyllata / Syzygium aromaticum), focusing on antimicrobial, antioxidant, anti-inflammatory, and anesthetic properties.

Findings: The essential oil demonstrated antimicrobial activity against pathogenic bacteria (including Staphylococcus aureus, Escherichia coli), antiviral activity against herpes simplex virus (HSV-1 and HSV-2) attributed to the gallotannin eugeniin, antifungal activity against Candida species and Aspergillus niger, and significant antioxidant capacity. Anti-inflammatory activity was demonstrated through inhibition of prostaglandin synthesis and suppression of COX-2 expression. The anesthetic activity was attributed to eugenol's interaction with sodium channels.

Limitations: Short review format with limited depth of analysis. Heavy reliance on in vitro studies. Antiviral activity against HSV attributed to tannin fraction (eugeniin) rather than essential oil per se. Variable study methodologies make direct comparisons difficult.

[5]

in vitro

Antimicrobial activity of clove essential oil against bacteria

Study evaluating the microbicidal activity of clove essential oil against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, examining the influence of concentration, temperature, and organic matter on bacterial death kinetics.

Findings: Clove essential oil (containing 83.13% eugenol) showed microbicidal activity against all three test organisms. The activity was concentration-dependent, with 0.4% essential oil showing faster bacterial killing than 0.2%. Temperature influenced activity: higher temperature (37 degrees C) enhanced bactericidal effect compared to lower temperature (21 degrees C). The presence of organic matter partially reduced but did not eliminate antimicrobial activity. The mechanism involves eugenol and other phenolic compounds denaturing bacterial proteins and disrupting cell membrane phospholipid integrity.

Limitations: In vitro study only; in vivo antimicrobial efficacy not assessed. Limited number of bacterial species tested. Concentration of 0.2-0.4% essential oil may not reflect achievable concentrations in clinical use. Organic matter interference is relevant to clinical settings but only assessed with a single organic load.

[9]

in vitro

Antifungal activity against Candida, Aspergillus, and dermatophyte species

Comprehensive in vitro evaluation of clove essential oil and eugenol against clinical and reference strains of Candida, Aspergillus, and dermatophyte species, using CLSI standard protocols for antifungal susceptibility testing.

Findings: Clove essential oil (85.3% eugenol) showed inhibitory activity against all 58 tested fungal strains. MIC values ranged from 0.25-2 mg/mL against Candida species, including fluconazole-resistant strains (a clinically significant finding). Aspergillus species were also inhibited. Both oil and eugenol significantly reduced ergosterol content in yeast cell membranes and completely or almost completely inhibited germ tube formation in C. albicans at sub-MIC concentrations. The mechanism involves direct binding to ergosterol in fungal cell membranes, disrupting membrane integrity.

Limitations: In vitro study; clinical efficacy in human fungal infections not established. MIC values determined by broth microdilution may not directly predict in vivo efficacy. Essential oil composition may vary between batches and sources. Dermatophyte results less extensive than Candida data.

[8]

in vitro

Beta-caryophyllene as a dietary CB2 receptor agonist

Identification and characterization of beta-caryophyllene as the first dietary cannabinoid: a sesquiterpene component of clove, black pepper, and other plants that selectively activates the cannabinoid type 2 (CB2) receptor.

Findings: Beta-caryophyllene was identified as a selective full agonist of the CB2 receptor with a binding affinity (Ki) of 155 nM. It selectively activates CB2 without activity at CB1 receptors (the receptor responsible for psychoactive effects of THC). In macrophage cell cultures, beta-caryophyllene inhibited LPS-induced pro-inflammatory cytokine expression (TNF-alpha, IL-1beta) through CB2-mediated suppression of NF-kappaB signaling. Oral administration in mice attenuated carrageenan-induced inflammation. As a GRAS-listed food component, beta-caryophyllene represents a safe, non-psychoactive dietary anti-inflammatory acting through the endocannabinoid system.

Limitations: Primary characterization study. Anti-inflammatory effects demonstrated in vitro and in acute mouse inflammation models; chronic inflammatory conditions not assessed. The contribution of beta-caryophyllene to the overall anti-inflammatory effect of whole clove in clinical use is difficult to quantify separately from eugenol's effects. Concentration of beta-caryophyllene delivered from typical clove doses may differ from experimental concentrations.

[10]

in vitro

Eugenol inhibition of cytochrome P450 enzymes

In vitro evaluation of eugenol's effects on the activity of human liver microsomal cytochrome P450 enzymes CYP1A2, CYP2C9, CYP2D6, and CYP3A4.

Findings: Eugenol demonstrated significant inhibitory activity against CYP2C9, with suppression of 62-67% even at the lowest tested concentration (1 micromolar). Moderate inhibition of CYP1A2 was observed (23-40% inhibition at 1-100 micromolar). Minimal effects were seen on CYP2D6 and CYP3A4 at physiologically relevant concentrations. The strong CYP2C9 inhibition is particularly clinically relevant because CYP2C9 metabolizes warfarin, phenytoin, and several NSAIDs, suggesting a pharmacokinetic basis for potential drug interactions.

Limitations: In vitro study using human liver microsomes; clinical translation uncertain. Eugenol concentrations tested (1-100 micromolar) may not accurately reflect hepatic portal concentrations achieved from typical oral clove consumption. The study tested pure eugenol, not whole clove extract; other clove constituents may modulate CYP effects. No clinical studies confirm these interactions at dietary or typical therapeutic doses of clove.

[11]

case series

Eugenol hepatotoxicity at high doses

Analysis of eugenol-induced hepatotoxicity based on case reports and toxicological data, with parallels to acetaminophen hepatotoxicity mechanism.

Findings: Ingestion of concentrated clove oil (eugenol) at doses of 10 mL or more can cause severe hepatocellular injury presenting as acute hepatic necrosis, similar to acetaminophen overdose. The mechanism involves oxidation of eugenol by hepatic peroxidases to a reactive quinone methide intermediate that depletes glutathione and causes oxidative damage to hepatocytes. N-acetylcysteine (the acetaminophen antidote) has been used successfully to treat eugenol-induced hepatic failure. At therapeutic doses and normal dietary intake, eugenol has not been implicated in liver injury. The WHO and FDA recognize eugenol as GRAS at typical dietary exposure levels.

Limitations: Case series and toxicological analysis; all reported cases involved accidental or intentional ingestion of large quantities of concentrated essential oil, far exceeding any therapeutic or dietary use. The hepatotoxic threshold is well above doses encountered in herbal practice. Risk is specifically with concentrated essential oil ingestion, not with use of whole clove buds.

[12, 19]

Preparations & Dosage

Infusion (Tea)

Strength: 1-3 g dried buds per 200-250 mL water; approximately 1:65-1:200 ratio

Lightly crush 3-5 whole dried clove buds (to expose internal tissues and essential oil glands) and place in a cup. Pour 200-250 mL of freshly boiled water over the buds. Cover tightly (essential to retain volatile oils) and steep for 10-15 minutes. Strain and drink while warm. For a stronger carminative effect, increase to 5-8 buds. Can be combined with other warming carminatives (ginger slices, fennel seeds, cardamom pods) for a digestive tea blend.

Adult:

1-3 g dried clove buds (approximately 5-15 buds) per cup, 2-3 cups daily

Frequency:

2-3 times daily, ideally after meals for carminative effect

Duration:

May be used short-term (1-2 weeks) for acute digestive complaints or periodically as needed. Long-term daily use at culinary doses is traditional and generally safe.

Pediatric:

Not recommended for children under 6. Children 6-12: half adult dose (1-2 buds per cup) under practitioner guidance. Sweeten with honey for palatability.

Infusion is the simplest and safest preparation for internal use. The hot water extracts both volatile (eugenol, beta-caryophyllene) and non-volatile (tannins, flavonoids) constituents. Covering during steeping is essential because eugenol is volatile and will be lost to evaporation in an uncovered vessel. The resulting tea has a warm, spicy, mildly numbing taste. This preparation provides a lower eugenol dose than essential oil or tincture forms, making it appropriate for self-care and for those who prefer a gentler approach.

[1, 3]

Tincture

Strength: 1:5, 60-70% ethanol (dried bud)

Use dried, lightly crushed clove buds. Standard maceration: 1:5 ratio in 60-70% ethanol (the high alcohol concentration is needed to efficiently extract the eugenol and other volatile oil components). Macerate in a sealed glass jar for 2-4 weeks with daily agitation. Press and filter through fine muslin or coffee filter. The resulting tincture should be a dark amber-brown liquid with the intense aroma and warming taste of clove. Store in amber glass dropper bottles away from light and heat.

Adult:

0.5-2 mL (10-40 drops) three times daily, diluted in a small amount of warm water

Frequency:

2-3 times daily after meals for digestive indications

Duration:

Short to medium-term use (2-4 weeks). Reassess if symptoms persist.

Pediatric:

Not recommended for children under 12 due to alcohol content and potent volatile oil concentration

Tincture provides a convenient, concentrated preparation with a standardizable dose. The high alcohol concentration is necessary for adequate extraction of eugenol and other phenylpropanoids. A lower menstruum concentration (e.g., 45%) will produce a tincture enriched in tannins and flavonoids but with less volatile oil. Some practitioners combine the two approaches for a full-spectrum preparation. The tincture is potent and pungent; always dilute in water before taking. Can be added to formulations with other digestive herbs (ginger, fennel, peppermint).

[3, 6]

Essential Oil

Strength: Undiluted (dental topical on cotton pellet) or 1-5% dilution in carrier oil (skin application). WHO acceptable daily intake for eugenol: 2.5 mg/kg body weight.

Use pharmacopeial-grade clove bud essential oil (steam-distilled from dried flower buds of Syzygium aromaticum). For dental pain: apply 1-2 drops of undiluted or minimally diluted oil to a small cotton pellet and place directly on the affected tooth or adjacent gum tissue. Hold in place for 1-2 minutes. For topical pain relief: dilute to 1-5% in a carrier oil (olive, coconut, or jojoba) before applying to skin. For mouthwash: add 2-3 drops to 200 mL warm water, stir vigorously, and use as a gargle/mouthwash (spit, do not swallow). Never ingest essential oil.

Adult:

Dental topical: 1-2 drops (approximately 0.05-0.1 mL) applied to cotton pellet, up to 3-4 times daily for acute toothache. Topical (skin): 1-5% dilution in carrier oil. Mouthwash: 2-3 drops per 200 mL water.

Frequency:

For dental pain: every 2-4 hours as needed, short-term use only (1-3 days maximum pending dental evaluation)

Duration:

Short-term use only. Dental pain requiring clove oil for more than 2-3 days requires professional dental evaluation. Topical use for musculoskeletal pain: up to 2 weeks.

Pediatric:

Not recommended for children under 12. Keep clove essential oil out of reach of children. Accidental ingestion by children has caused serious adverse effects including hepatotoxicity and seizures.

Essential oil is the most concentrated and potent preparation and carries the highest risk of adverse effects. It is the form used in dental practice and the subject of the Commission E positive monograph for dental analgesia. The oil should be pharmaceutical-grade clove BUD oil (not leaf or stem oil, which have different constituent profiles). Undiluted application is acceptable only for dental use on a small cotton pellet applied directly to the painful site. Never apply undiluted clove oil to large skin areas. Never ingest clove essential oil; serious hepatotoxicity has been reported from ingestion of as little as 10 mL. Keep away from children. Avoid contact with eyes and mucous membranes (other than the specific dental application site).

[1, 2, 12]

Capsule / Powder

Strength: 500 mg crude powder per capsule. Standardized extracts: varies by manufacturer.

Dried clove buds, finely powdered (ground to pass through a 60-80 mesh sieve), filled into vegetarian or gelatin capsules. Alternatively, standardized clove extract powder encapsulated. The powder should have the characteristic dark brown color and intense aromatic odor of fresh clove.

Adult:

Crude powder: 500-1000 mg (1-2 capsules of 500 mg) 2-3 times daily with meals. Total daily dose: 1-3 g powdered clove bud.

Frequency:

2-3 times daily with meals

Duration:

Short to medium-term use (2-4 weeks) for digestive complaints. Periodic use as needed.

Pediatric:

Not well-established. Not generally recommended for children under 12.

Capsules are convenient for those who find the taste of clove too strong for infusions or tinctures. Powdered whole clove bud provides the full spectrum of volatile and non-volatile constituents. However, ground clove loses essential oil rapidly due to increased surface area and volatilization; encapsulation should occur promptly after grinding, and capsules should be stored in airtight containers. The powder form may cause gastric irritation in sensitive individuals; taking with food mitigates this. Enteric-coated capsules are available commercially for those who experience upper GI discomfort.

[3, 4]

Decoction

Strength: 3-5 g dried buds per 400-500 mL water; approximately 1:80-1:130

Lightly crush 3-5 g of dried clove buds. Add to 400-500 mL of cold water in a covered pot. Bring to a gentle boil, then reduce heat and simmer gently for 10-15 minutes with the lid on (prolonged boiling drives off volatile oils). Strain immediately. The decoction will be darker and more astringent than an infusion due to greater extraction of tannins.

Adult:

3-5 g dried buds decocted in 400-500 mL water. Drink in 2-3 divided portions throughout the day.

Frequency:

Preparation taken in 2-3 divided doses daily

Duration:

Short-term use for acute complaints (diarrhea, colic). 3-7 days.

Pediatric:

Not recommended for children under 6. Children 6-12: half adult dose under practitioner guidance.

Decoction extracts more tannins and non-volatile constituents than infusion, making it more appropriate when astringent effects are desired (e.g., for diarrhea or as an astringent gargle). However, the prolonged heating drives off some volatile oil, reducing the eugenol content compared to a covered infusion. This trade-off means decoction is preferred for tannin-dependent indications and infusion is preferred for carminative and volatile-oil-dependent indications. In TCM practice, Ding Xiang is typically added to decoctions near the end of cooking (hou xia, 'added later') to preserve volatile oil content.

[3, 14]

Poultice

Strength: Ground clove paste at approximately 1:1-1:2 with carrier medium

Grind dried clove buds to a coarse powder. Mix with a small amount of warm water or warm carrier oil (sesame, coconut) to form a thick paste. Optionally add a pinch of ground ginger for enhanced warming effect. Apply the paste to the affected area, cover with a clean cloth or gauze, and leave in place for 15-30 minutes. Test on a small area first to assess sensitivity. Remove immediately if burning or excessive irritation occurs.

Adult:

Apply topically to affected area as a paste or compress. Use 1-2 teaspoons of ground clove per application.

Frequency:

1-2 times daily for localized pain or inflammation

Duration:

Short-term use only (1-5 days). Discontinue if irritation develops.

Pediatric:

Not recommended for children due to skin sensitivity and potential irritation.

This traditional preparation is used for localized musculoskeletal pain, dental abscess (external face application), and headache (applied to temples). The counter-irritant and analgesic properties of eugenol provide warming pain relief. Always use on intact skin only; avoid open wounds. The poultice should produce a pleasant warming sensation; burning or stinging indicates the need for more dilution or shorter application time. Wash area thoroughly after removal.

[3]

Safety & Interactions

Class 2d

Other specific use restrictions apply (AHPA Botanical Safety Handbook)

Contraindications

absolute Known hypersensitivity to eugenol, clove, or other Myrtaceae plants

Allergic contact dermatitis and contact stomatitis to eugenol are well-documented, particularly in dental professionals with occupational exposure. Cross-sensitivity with other eugenol-containing plants (allspice, cinnamon leaf) may occur. Individuals with confirmed eugenol allergy should avoid all clove products including bud oil, leaf oil, and whole buds.

absolute Internal use of undiluted essential oil

Ingestion of concentrated clove essential oil is potentially lethal. Ingestion of as little as 10 mL of clove oil has caused hepatocellular necrosis, disseminated intravascular coagulation (DIC), and multi-organ failure. Eugenol is hepatotoxic at high concentrations through formation of reactive quinone methide intermediates that deplete glutathione. Undiluted clove oil should never be swallowed. This contraindication applies to essential oil only, not to whole clove buds or properly prepared infusions and tinctures.

relative Application of undiluted essential oil to mucous membranes (except brief dental topical use)

Undiluted clove oil causes tissue irritation and chemical burns on mucous membranes and sensitive skin. Brief application to a small dental area on a cotton pellet is acceptable clinical practice, but broad application of undiluted oil to oral mucosa, genital mucosa, or large skin areas can cause tissue necrosis. Always dilute to 1-5% for skin application.

absolute Children under 2 years of age (essential oil)

Clove essential oil should not be used on or given to infants and toddlers. Case reports document serious adverse effects in young children from accidental ingestion of clove oil, including hepatotoxicity, seizures, and central nervous system depression. The immature hepatic detoxification capacity of young children increases susceptibility to eugenol toxicity. Whole clove bud preparations in culinary amounts are considered lower risk but still not recommended as a therapeutic agent for this age group.

Drug Interactions

Drug / Class Severity Mechanism
Warfarin and other coumarin anticoagulants (Anticoagulants) moderate Dual mechanism: (1) eugenol inhibits platelet aggregation via thromboxane synthesis inhibition, producing additive antiplatelet effects; (2) eugenol potently inhibits CYP2C9 (the primary enzyme metabolizing S-warfarin), potentially increasing warfarin plasma levels and prolonging INR. In vitro studies demonstrated 62-67% CYP2C9 inhibition at concentrations as low as 1 micromolar.
Aspirin, clopidogrel, and other antiplatelet agents (Antiplatelet agents) moderate Eugenol inhibits platelet aggregation through inhibition of thromboxane synthesis and arachidonic-acid-induced platelet aggregation. Additive antiplatelet effect when combined with pharmaceutical antiplatelet agents.
NSAIDs (ibuprofen, naproxen, diclofenac) (Non-steroidal anti-inflammatory drugs) minor Eugenol shares the COX inhibition mechanism with NSAIDs. Concurrent use could theoretically produce additive COX inhibition and increase the risk of gastrointestinal side effects (ulceration, bleeding). Additionally, several NSAIDs are CYP2C9 substrates, and eugenol's CYP2C9 inhibition could theoretically alter their metabolism.
Insulin, metformin, sulfonylureas, and other antidiabetic medications (Hypoglycemic agents) theoretical Eugenol and oleanolic acid demonstrate hypoglycemic activity in animal models through alpha-glucosidase inhibition and enhancement of insulin sensitivity. Additive hypoglycemia is theoretically possible when combined with pharmaceutical antidiabetic agents.
CYP2C9 substrate drugs (phenytoin, losartan, celecoxib, glipizide) (CYP2C9 substrates) theoretical Eugenol potently inhibits CYP2C9 in vitro (62-67% inhibition at 1 micromolar). Drugs primarily metabolized by CYP2C9 could theoretically accumulate to higher plasma levels when combined with therapeutic clove use, increasing the risk of dose-dependent adverse effects.

Pregnancy & Lactation

Pregnancy

possibly unsafe

Lactation

insufficient data

Culinary use of clove as a spice in food amounts is generally considered safe during pregnancy and has a long history of traditional dietary use. However, therapeutic doses and concentrated essential oil preparations should be avoided during pregnancy. Eugenol has demonstrated uterotonic activity in animal studies, and the emmenagogue classification in some traditional systems raises concern. The essential oil is contraindicated during pregnancy due to its concentrated eugenol content and hepatotoxic potential. No controlled studies in pregnant or breastfeeding women have been conducted. The EMA monograph and most safety references recommend against therapeutic use during pregnancy and lactation due to insufficient safety data. Brief topical dental use of clove oil for acute toothache during pregnancy may be acceptable as a lower-risk alternative to certain medications, but this should be discussed with a healthcare provider.

Adverse Effects

common Local tissue irritation and chemical burn (topical essential oil use) — The most frequently reported adverse effect. Undiluted or inadequately diluted clove oil causes a burning sensation, erythema, and potential tissue necrosis on skin and mucous membranes. Severity is dose-dependent and exposure-time-dependent. Self-limiting when diluted preparations are used. Proper dilution (1-5% in carrier) prevents this in most individuals.
uncommon Allergic contact dermatitis or contact stomatitis — Allergic reactions to eugenol are well-documented, particularly in dental professionals with repeated occupational exposure (prevalence of 1-2% in the general population for eugenol patch test positivity). Manifests as erythema, vesiculation, and pruritus at the application site. Oral manifestations include stomatitis and gingivitis. Cross-reactivity with balsam of Peru and cinnamon possible.
uncommon Gastrointestinal irritation (nausea, epigastric discomfort, diarrhea) — Can occur with oral ingestion of concentrated preparations (tincture, capsules) on an empty stomach. The pungent volatile oil irritates gastric mucosa. Mitigated by taking with food. Self-limiting with dose reduction.
rare Hepatotoxicity (concentrated essential oil ingestion) — Reported only with ingestion of large quantities of concentrated clove essential oil (10 mL or more), not with standard herbal preparations or culinary use. Presents as acute hepatocellular necrosis with elevated transaminases, similar to acetaminophen overdose. N-acetylcysteine is the appropriate antidote. Risk is limited to accidental or intentional essential oil ingestion.
very-rare Seizures (essential oil poisoning in children) — Reported in young children following accidental ingestion of clove essential oil. CNS depression and seizures may occur along with hepatotoxicity. Represents a poisoning scenario rather than a therapeutic adverse effect. Highlights the importance of keeping essential oils out of reach of children.
rare Pulpal necrosis (with prolonged direct dental application) — Prolonged or repeated application of concentrated eugenol directly into a tooth cavity can cause irreversible damage to the dental pulp. This is a known risk of dental eugenol use and one reason why temporary ZOE restorations are used with caution by dentists. Brief topical application for pain relief does not typically cause this effect.

References

Monograph Sources

  1. [1] German Commission E (Bundesinstitut fur Arzneimittel und Medizinprodukte). Commission E Monograph: Caryophylli flos (Clove) and Caryophylli floris aetheroleum (Clove Oil). Bundesanzeiger (Federal Gazette), Monograph published 1988; English translation in Blumenthal M, et al. The Complete German Commission E Monographs. Austin: American Botanical Council, 1998 (1998) . ISBN: 978-0-9655555-0-0
  2. [2] European Medicines Agency (EMA), Committee on Herbal Medicinal Products (HMPC). Community Herbal Monograph on Syzygium aromaticum (L.) Merr. et L.M. Perry, floris aetheroleum. European Medicines Agency, London. Doc. Ref. EMA/HMPC/572834/2009 (2012)
  3. [3] Hoffmann D. Medical Herbalism: The Science and Practice of Herbal Medicine. Rochester, VT: Healing Arts Press (2003) . ISBN: 978-0-89281-749-8
  4. [4] Cortes-Rojas DF, de Souza CRF, Oliveira WP. Clove (Syzygium aromaticum): a precious spice. Asian Pacific Journal of Tropical Biomedicine (2014) ; 4 : 90-96 . DOI: 10.1016/S2221-1691(14)60215-X . PMID: 25182278
  5. [5] Chaieb K, Hajlaoui H, Zmantar T, Kahla-Nakbi AB, Rouabhia M, Mahdouani K, Bakhrouf A. The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzygium aromaticum L. Myrtaceae): a short review. Phytotherapy Research (2007) ; 21 : 501-506 . DOI: 10.1002/ptr.2124 . PMID: 17380552
  6. [6] British Herbal Medicine Association. British Herbal Pharmacopoeia: Caryophylli Flos. Bournemouth: British Herbal Medicine Association (1983) . ISBN: 978-0-903032-07-4

Clinical Studies

  1. [7] Alqareer A, Alyahya A, Andersson L. The effect of clove and benzocaine versus placebo as topical anesthetics. Journal of Dentistry (2006) ; 34 : 747-750 . DOI: 10.1016/j.jdent.2006.01.009 . PMID: 16530911
  2. [8] Pinto E, Vale-Silva L, Cavaleiro C, Salgueiro L. Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species. Journal of Medical Microbiology (2009) ; 58 : 1454-1462 . DOI: 10.1099/jmm.0.010538-0 . PMID: 19589904
  3. [9] Nunez L, Aquino MD. Microbicide activity of clove essential oil (Eugenia caryophyllata). Brazilian Journal of Microbiology (2012) ; 43 : 1255-1260 . DOI: 10.1590/S1517-83822012000400003 . PMID: 24031950
  4. [10] Gertsch J, Leonti M, Raduner S, Racz I, Chen JZ, Xie XQ, Altmann KH, Karsak M, Zimmer A. Beta-caryophyllene is a dietary cannabinoid. Proceedings of the National Academy of Sciences USA (2008) ; 105 : 9099-9104 . DOI: 10.1073/pnas.0803601105 . PMID: 18574142
  5. [11] Sunyoto T, et al.. Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes. Journal of Herbal Medicine (2024) . DOI: 10.1016/j.hermed.2024.100890
  6. [12] Hartnoll G, Moore D, Douek D. Near fatal ingestion of oil of cloves. Archives of Disease in Childhood (1993) ; 69 : 392-393 . DOI: 10.1136/adc.69.3.392 . PMID: 8215557
  7. [13] Janes SE, Price CS, Thomas D. Essential oil poisoning: N-acetylcysteine for eugenol-induced hepatic failure and analysis of a national database. European Journal of Pediatrics (2005) ; 164 : 520-522 . DOI: 10.1007/s00431-005-1664-0 . PMID: 15895251

Traditional Texts

  1. [14] Bensky D, Clavey S, Stoger E. Chinese Herbal Medicine: Materia Medica, 3rd Edition. Ding Xiang (Flos Caryophylli). Seattle: Eastland Press (2004) . ISBN: 978-0-939616-42-8
  2. [15] Bhavamishra (translated by Bulusu Sitaram). Bhavaprakasha Nighantu (Indian Materia Medica): Karpuradi Varga - Lavanga. Varanasi: Chaukhambha Orientalia. Original text ca. 16th century CE. (2006) . ISBN: 978-81-7637-020-1
  3. [16] Ibn Sina (Avicenna). Al-Qanun fi al-Tibb (The Canon of Medicine), Book II: Qaranful (Clove). Original text ca. 1025 CE. Multiple modern translations and commentaries available. (1025)
  4. [17] Felter HW, Lloyd JU. King's American Dispensatory, 18th Edition: Caryophyllus. Cincinnati: Ohio Valley Company (1898)

Pharmacopeias & Reviews

  1. [18] World Health Organization. WHO Model List of Essential Medicines, 23rd List (2023): Eugenol (dental use). Geneva: World Health Organization (2023)
  2. [19] US Environmental Protection Agency (EPA). Eugenol: Toxicological Review and Hazard Assessment. US EPA Integrated Risk Information System (IRIS) (2002)
  3. [20] Council of Europe. European Pharmacopoeia, 11th Edition: Clove (Caryophylli flos) and Clove Oil (Caryophylli floris aetheroleum). Strasbourg: European Directorate for the Quality of Medicines (EDQM) (2023)

Last updated: 2026-03-02 | Status: review

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Full botanical illustration of Syzygium aromaticum (L.) Merr. & L.M.Perry

Public domain, Köhler's Medizinal-Pflanzen (1887), via Wikimedia Commons