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Clove (Syzygium aromaticum): A Comprehensive Reference

1. Identity and Botanical Classification

Botanical and Synonymous Names

Clove, scientifically designated Syzygium aromaticum L. (Myrtaceae), is also known by its older synonym Eugenia caryophyllata Thunb. It is an evergreen tree native to the Maluku Islands in Indonesia. Additional synonyms include Eugenia aromaticum and E. caryophyllata, making it one of the most ancient and valuable species of the Orient. The plant's nail-like appearance gives rise to its vernacular names in several languages, including Dutch (nagel), Spanish (clavo), and Portuguese (cravo). The English word "clove," first used in the 15th century, derives via Middle English clow of gilofer and ultimately from the Latin word clavus, meaning "nail."

Plant Morphology and Plant Part Used

The clove tree is an evergreen that grows to about 25–40 feet (8–12 meters) in height, with small, simple, opposite, gland-dotted leaves. Trees are usually propagated from seeds planted in shaded areas. Flowering begins around the fifth year; a tree can yield up to 75 pounds (34 kg) of dried buds annually. The buds are hand-picked in late summer and again in winter and then sun-dried. The commercial part of the tree is the dried flower bud, and it is indigenous to the Maluku islands in Indonesia but has recently been farmed in different places worldwide.

Geographic Distribution and Cultivation

Clove was originally found only on the Maluku Islands of Indonesia, but fierce competition between warring European nations during the 17th century that sought control of the spice trade eventually led to clove trees being transported all over the world for cultivation. Today, it is grown in numerous locations throughout the tropics including Indonesia, Zanzibar, Madagascar, Sri Lanka, and parts of the Caribbean. In 1818, plants were transferred to Zanzibar, which became the world's largest producer of cloves for more than 100 years.

Common Forms and Preparations

Clove is commercially available and used in several distinct forms:

• Whole dried buds: Buds are hand-picked and sun-dried, and vary in length from about 0.5–0.75 inches (13–19 mm).
• Essential oil (CEO): Obtained by various extraction methods including hydrodistillation, steam distillation, ultrasound-assisted extraction, microwave-assisted extraction, cold pressing, and supercritical fluid extraction.
• Polyphenolic extracts: Nonvolatile polyphenols in clove buds have been shown to be bioactive and are increasingly being used as dietary supplements.
• Dental preparations: Eugenol from clove has been incorporated into dental cement, analgesics, anesthetics, and zinc oxide-mixed temporary dental fillings.
• Culinary ground powder: Used as a spice in whole or ground form in foods and beverages worldwide.

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2. Traditional and Historical Use

Origins of Trade and Early History

Clove, native to the small islands of Maluku in Eastern Indonesia — also known as the "Spice Islands" — has been traded from one end of the world to the other, being a highly sought-after commodity in medieval Europe for medicinal and culinary purposes. During the fourteenth century, the clove trade acted as a stimulant in the establishment of commerce at ports especially in Asia and Europe, where it was traded for large profits.

Traditional Chinese Medicine (TCM)

In traditional Chinese medicine, clove is known as ding xiang or "nail spice" and was used to treat, among other things, indigestion, nausea, vomiting, and infections. In TCM, cloves help qi (life force) to descend, which is related to the Western carminative action — making it an excellent herb for the relief of nausea and vomiting, as well as for excessive flatulence and hiccoughs. Clove has been utilised in traditional Chinese medicine as a remedy for stomach ailments such as inflammation and diarrhoea.

Ayurvedic Medicine

Clove is described in Ayurveda as having a KPV− (kapha, pitta, vata) effect, meaning its predominant action is in reducing excess kapha activity in the body, which may manifest as stagnation or congestion in the tissues. Kapha may manifest as lethargy and low mood, and clove is understood to clear the orifices of the head, making way for higher clarity; it also helps to clear congestion or stagnation in the lungs. In Ayurvedic medicine, clove (known as Lavang) was considered to improve blood circulation, give relief to indigestion, enhance metabolism, and help counter stomach disorders such as gas, bloating, and nausea.

Unani Medicine and the Middle East

In the Middle East and parts of North Africa, Unani medicine — rooted in Greek and Islamic traditions — utilized cloves for both medicinal and spiritual purposes. Uses included treatment of infections, fevers, toothaches, and sore throats.

Use in Dentistry and as a Breath Freshener

The earliest written evidence of cloves being used as food or medicine dates back to around the year 300 B.C. During the Han Dynasty of China, clove was referenced for use as a breath freshener. In dentistry, clove essential oil was applied as an analgesic in cases of dental emergency.

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3. Key Constituents and Active Compounds

Volatile Fraction: Essential Oil

The buds contain 14–20 percent essential oil, the principal component of which is the aromatic oil eugenol. At least 30 compounds have been identified in clove essential oil; eugenol is the major compound, accounting for at least 50%, while the remaining 10–40% is made up of eugenyl acetate, β-caryophyllene, and α-humulene.

Eugenol constitutes 70% to 90% of the aromatic oil extracted from cloves. It is chemically identified as 4-allyl-2-methoxyphenol (molecular formula C₁₀H₁₂O₂; molecular weight 164.20), a phenylpropanoid belonging to the allylbenzene class. Eugenol is clear or pale yellow, with a peppery taste and a clove-like smell, and has been used to flavor food and drugs since the 19th century.

Secondary Volatile Constituents

• Eugenyl acetate (acetyl eugenol): Acetyl eugenol, a component of clove oil, has been shown to alter arachidonic acid metabolism, resulting in reduced formation of thromboxane.
• β-Caryophyllene: β-Caryophyllene, constituting about 13% of clove's essential oils, is a bicyclic sesquiterpene that exhibits broad-spectrum antimicrobial activity and anticancer effects via apoptosis induction.
• α-Humulene: A sesquiterpene co-occurring with β-caryophyllene, associated with anti-inflammatory properties.

Non-Volatile Polyphenol Fraction

The dried flower bud of Syzygium aromaticum is rich in eugenol, an antioxidant and anti-inflammatory compound that can protect the liver against injury. Clove, besides eugenol, also contains other pharmacologically active phytochemicals such as β-sitosterol and ascorbic acid. Additional active compounds elucidated from clove ethanolic extracts include phenolic compounds such as kaempferol, gallic acid, and catechin. Aqueous and alcoholic extracts of clove buds are rich in polyphenols such as gallic acid, ellagic acid, tannins, flavonoids, and their glycosides.

Regulatory Status

The FDA classifies clove essential oil as generally recognized as safe (GRAS); for this reason, it is used in perfumes, cosmetics, sanitary products, medicines, and foods.

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4. Mechanisms of Action

Anti-Inflammatory Pathways

Eugenol possesses significant antioxidant, anti-inflammatory, and cardiovascular properties, in addition to analgesic and local anesthetic activity. Several distinct molecular mechanisms underlie its anti-inflammatory action:

• Inhibition of arachidonic acid metabolites: Eugenol, the active principle of clove, inhibits 5-lipoxygenase (5-LO) enzyme through a non-competitive mechanism. Eugenol significantly inhibits the formation of leukotriene C₄ (LTC₄) in calcium ionophore A23187 and arachidonic acid–stimulated polymorphonuclear leukocyte (PMNL) cells, suggesting a beneficial role in modulating the 5-LO pathway.
• NF-κB pathway suppression: Clove exerts immunomodulatory/anti-inflammatory effects by inhibiting LPS action, and a possible mechanism probably involves the suppression of the nuclear factor-κB (NF-κB) pathway by eugenol.
• Cytokine inhibition: Clove (at 100 µg/well) inhibited IL-1β, IL-6, and IL-10 production and exerted an efficient action either before or after LPS challenge for all cytokines.
• COX pathway effects: Eugenol, a vasorelaxant and analgesic constituent of Syzygium aromaticum, also possesses strong anti-inflammatory activity.

Antimicrobial Mechanisms

Clove essential oil is hypothesized to interact with the bacterial cell wall and membrane first, destroying cell walls and membranes and causing losses of vital intracellular materials, which finally result in bacterial death. Beyond physical membrane damage, the essential oil penetrates to the cytoplasmic membrane or enters inside the cell after destruction of cell structure, and then inhibits the normal synthesis of DNA and proteins required for bacterial growth. The general mechanism of action of eugenol on bacterial biofilm includes inhibition of biofilm formation and reduced viability of biofilm-forming cells.

Antioxidant Mechanisms

Studies examining the antioxidant capacities of clove using DPPH radical scavenging assay, TEAC assay, FRAP assay, ORAC assay, hydroxyl radical scavenging assay (HRSA), and superoxide radical scavenging assay (SRSA), provide supporting evidence that clove exhibits potent antioxidant activity by scavenging free radicals. Eugenol has been shown to act as a natural antioxidant.

Analgesic and Local Anesthetic Mechanisms

Eugenol, the major constituent of clove oil, has been widely used for its anesthetic and analgesic action in dentistry. Mechanisms of action include inhibition of prostaglandin synthesis, modulation of inflammatory pathways, and direct effects on nociceptors.

Antifungal Mechanisms

Growth inhibition caused by eugenol derivatives is probably a consequence of two different mechanisms — accumulation of compounds in the fungal membrane due to lipophilic interactions and Michael-type reactions between eugenol derivatives and components of the fungal membrane, or production of reactive oxygen species (ROS) by enzymatic reduction of nitro compounds.

Glucose Homeostasis Mechanisms

Clove and its essential oils (eugenol and acetyl eugenol) have been shown in preclinical studies to modulate pathways involved in glucose homeostasis. In cell-free assays, polyphenolic clove extract (PCE) inhibited α-amylase activity and α-glucosidase activity. In another study using a cell-free assay, a polyphenol-rich clove extract inhibited glycogen phosphorylase b (IC₅₀ = 0.86 µg/mL), the enzyme responsible for converting liver glycogen to glucose.

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5. Scientific Evidence by Area of Use

5.1 Dental Analgesia and Oral Health

Eugenol is used as a mild rubefacient in dentifrices and as an obtundent for hypersensitive dentine, caries, or pulp. It has also been used in dental cement, analgesics, anesthetics, and zinc oxide-mixed temporary dental fillings.

Clinical Evidence: A systematic review identified 21 clinical studies evaluating phytotherapeutic agents for dental pain management; the most consistent evidence supports eugenol and ginger, while curcumin and cannabidiol (CBD) showed variable but promising outcomes. The phytotherapeutic agents demonstrating the strongest analgesic properties in dental applications include clove oil (eugenol), turmeric (curcumin), capsaicin, and ginger powder. Clinical applications included management of pulpitis, postextraction pain, temporomandibular disorders, and oral mucositis. Evidence supports the analgesic efficacy of eugenol in toothache management, though standardization of preparations and larger RCTs are needed to establish optimal dosing regimens and long-term safety profiles.

Antiplaque and Antigingivitis Evidence: A comparative clinical study found that newly formulated herbal mouthrinse (containing clove) and commercially available mouthrinse were beneficial clinically as antiplaque and antigingivitis agents. The newly formulated mouthrinses showed significant reduction in microbial colony-forming units (CFU) at 21 days, supporting the regular use of herbal mouthrinse as an antiplaque, antigingivitis, and antimicrobial rinse.

Evidence strength: Moderate for dental analgesia (eugenol is the best-supported phytotherapeutic agent in systematic review). Limited and largely in vitro or small-scale for antiplaque/antigingivitis applications.

5.2 Antimicrobial Activity

Clove ethanolic extract (CEE) is an effective antimicrobial agent against Gram-positive (Staphylococcus epidermidis, Staphylococcus aureus) and Gram-negative (Proteus mirabilis, Escherichia coli, Klebsiella pneumoniae) urinary tract infection-causing pathogens; the extract also exhibits strong antioxidant activities. In clove bud essential oil, eugenol was the major component (76.23%), and the oil exhibited strong antibacterial activity against Staphylococcus aureus ATCC 25923, with a minimum inhibitory concentration (MIC) of 0.625 mg/mL.

Clove essential oil (CEO) contains a high amount of phenolic compounds with several biological activities, including antibacterial, antifungal, insecticidal, and antioxidant properties. Eugenol's known antibacterial, antiviral, antifungal, anticancer, anti-inflammatory, and antioxidant properties have led to its long use in areas such as cosmetology, medicine, and pharmacology.

Evidence strength: Primarily in vitro; robust laboratory data across multiple pathogens, but controlled human clinical trials specifically for infectious disease treatment are lacking.

5.3 Antioxidant Properties

Clove's antioxidant capacity — reported at 90.31% DPPH scavenging at 35 µg/mL — and anti-inflammatory effects, including inhibition of TNF-α and IL-1β, are well-documented. In one in vitro study, clove at concentrations of 0.25, 0.50, and 1.00 mg/mL inhibited the formation of advanced glycation end-products (AGEs) by 86.3%, 88.6%, and 95.2%, respectively.

Evidence strength: Strong in vitro antioxidant data; translation to human clinical outcomes has not been established by adequately powered clinical trials.

5.4 Blood Glucose Regulation and Metabolic Effects

Preclinical evidence: Clove (Syzygium aromaticum flower bud) ethanol extract significantly suppressed an increase in blood glucose level in type 2 diabetic KK-Aʸ mice, and results indicate that clove has potential as a functional food ingredient for the prevention of type 2 diabetes, with hypoglycemic effects mediated via PPAR-γ activation. In a rat model, intraperitoneal administration of clove essential oil (CEO) at 20 mg/kg body weight was investigated, and administration of CEO to diabetic rats showed a significant decline in blood glucose levels, total cholesterol, and xanthine oxidase, compared to the streptozotocin control group.

Human/Clinical evidence: An open-label pilot study tested whether polyphenolic clove extract (PCE) supplementation (250 mg once daily for 30 days) could influence glucose metabolism in 13 otherwise healthy volunteers stratified into two groups according to initial preprandial glucose levels: Group I (n=7) ≤100 mg/dL, and Group II (n=6) between 101 and 125 mg/dL. These findings underscore the therapeutic utility of PCE for maintaining healthy glucose metabolism and warrant further larger-scale clinical trials. The study has notable limitations: it was open-label (non-blinded, non-randomized), very small (n=13), and had a conflict of interest disclosed — two authors were employed by the manufacturer of the tested PCE ingredient.

To the best of current knowledge, there is no completed systematic review of eugenol's activity in experimental models of diabetes in the published literature, and there is a paucity of information regarding the therapeutic efficacy of eugenol in clinical trials.

Evidence strength: Preliminary. Animal and in vitro evidence is promising; the single human pilot study is methodologically limited. Larger, controlled, randomized clinical trials are needed before clinical conclusions can be drawn.

5.5 Anti-Inflammatory Effects

Eugenol's vast range of pharmacological activities is well-researched and includes antimicrobial, anti-inflammatory, analgesic, antioxidant, and anticancer activities, among others. The anti-inflammatory effects observed in laboratory settings include inhibition of key inflammatory enzymes and cytokines (see Section 4, above). Animal studies have demonstrated reduction in arthritic markers. Controlled human clinical trials evaluating systemic anti-inflammatory effects of clove supplementation are currently sparse.

Evidence strength: Mechanistic and preclinical data are well-documented; robust human clinical evidence for systemic inflammatory conditions is lacking.

5.6 Antifungal Activity

Clove oil, containing the major component eugenol, has been reported to demonstrate therapeutic properties including antifungal effects. Laboratory studies indicate activity against multiple fungal species, including Candida spp. These data are primarily in vitro.

Evidence strength: In vitro only; no adequately powered human clinical trials on antifungal efficacy have been identified.

5.7 Anticancer Properties

β-Caryophyllene exhibits anticancer effects via apoptosis induction in ovarian and lung cancer cell lines. Eugenol can induce apoptosis via the caspase-dependent pathway in human osteosarcoma cells. These findings are from cell-based and animal studies.

Evidence strength: Entirely preclinical (cell culture and animal models). No human clinical trial evidence for anticancer effects is currently available.

5.8 Hepatoprotective Effects

The dried flower bud of Syzygium aromaticum is rich in eugenol, an antioxidant and anti-inflammatory compound that can protect the liver against injury. Eugenol (derived from the clove tree) reduces CYP2E1 activity, lipid peroxidation, protein oxidation, and inflammatory markers; improves antioxidant status; prevents DNA damage; and increases expression of the COX-2 gene in preclinical rat models. Clove extracts have been shown to prevent thioacetamide-induced hepatotoxicity by decreasing hepatic biomarkers (AST, ALT, and ALP) and increasing levels of total plasma protein and albumin in animal models.

Evidence strength: Preclinical (animal models) only; no controlled human clinical trial data currently available.

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6. Body Systems Associated with Clove

• Oral/Dental System: Analgesic for toothache and pulpitis; antiplaque and antigingivitis activity; dental cement ingredient.
• Gastrointestinal System: Traditionally used as a carminative for flatulence, nausea, vomiting, and indigestion; preclinical evidence for gastroprotective effects.
• Metabolic/Endocrine System: Preclinical and preliminary human evidence for glucose homeostasis modulation; lipid-lowering effects in animal models.
• Immune System: Anti-inflammatory and immunomodulatory activity via cytokine and NF-κB pathway modulation.
• Hepatic System: Preclinical hepatoprotective and antioxidant effects; paradoxically, hepatotoxic at overdose.
• Respiratory System: It is believed that cloves' anti-inflammatory and anti-free-radical properties may help alleviate various illnesses, supporting good lung function.
• Cardiovascular System: Antiplatelet effects attributed to eugenol and acetyl eugenol.

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7. Dosage Forms and Reported Dosages

The following dosages are reported in research sources and are not recommendations:

• Polyphenolic clove extract (PCE) — human pilot study: PCE supplementation at 250 mg once daily for 30 days was evaluated for its effect on preprandial and 2-hour postprandial glucose levels.
• Clove bud powder — animal study: Diabetic rats were placed on dietary regimens containing 20–40 g kg⁻¹ clove bud powder.
• Clove essential oil — animal study: The effect of intraperitoneal administration of clove essential oil (CEO) at 20 mg/kg body weight was investigated in a rat diabetes model.
• Hydroalcoholic clove extract — hepatoprotection animal study: All clove extract doses of 50, 150, and 300 mg/kg prevented hepatotoxicity damage in a rat model.
• In vitro macrophage study: Macrophages were incubated with clove or eugenol at 5, 10, 25, 50, or 100 µg/well for 24 hours.
• Safe intake reference for eugenol: High concentrations of eugenol can be toxic; a dose of 2.5 mg/kg body weight is regarded as safe.

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8. Safety Considerations and Interactions

General Toxicological Profile

Various acute and chronic toxicity studies of clove oil have reported an oral LD₅₀ of 3,597.5 mg/kg, with no adverse effects reported in subchronic toxicity tests at NOAEL levels of 900–2,000 mg/kg/day. The oral LD₅₀ of eugenol was reported as 2,650–3,000 mg/kg body weight.

Hepatotoxicity at High Doses

Eugenol, also called clove oil, is used widely as a flavoring for foods and teas and as an herbal oil used topically to treat toothache. In therapeutic doses, eugenol has not been implicated in causing serum enzyme elevations or clinically apparent liver injury, but ingestions of high doses — as with an overdose — can cause severe liver injury. The acute liver injury of eugenol overdose presents clinically with acute hepatic necrosis, a pattern similar to that of acetaminophen hepatotoxicity. Ingesting as little as 10 mL of clove oil has been reported to cause hepatotoxicity, which can be treated with N-acetylcysteine.

Drug Interactions: Cytochrome P450 Enzyme Inhibition

Potential herb-drug interactions are noted when eugenol is administered simultaneously with medications metabolized by CYP enzymes, most notably CYP2C9, CYP2D6, and CYP3A4. In one study, a dose-related inhibition of the CYP1A2 enzyme was detected with eugenol, and eugenol at 100 µM inhibited CYP3A4 activity by 67%. Drug interactions are likely to appear when herbs containing eugenol are concurrently consumed with medications metabolized via these CYPs; as a result of inhibition or stimulation of these CYP enzymes, drugs' plasma levels might increase or decrease, potentially changing pharmacological effects and enhancing the probability of toxic drug reactions.

Anticoagulation and Platelet Effects

Eugenol is known to inhibit platelet aggregation and alter arachidonic acid metabolism in human platelets. This effect may be additive or synergistic with anticoagulant drugs (e.g., warfarin) or antiplatelet agents, potentially increasing bleeding risk at supraculinary concentrations.

Blood Sugar Interactions

In animal studies, clove intake showed anti-hyperglycemic, hypolipidemic, and antioxidant properties under hyperglycemic conditions; treatment of diabetic animals with pure eugenol also reduced blood glucose levels. This raises the theoretical possibility of additive hypoglycemic effects when clove supplements are used concurrently with antidiabetic medications, though human evidence confirming this interaction is currently absent.

Allergic Sensitization

Eugenol is a phenolic aromatic compound with known antibacterial, antiviral, antifungal, anticancer, anti-inflammatory, and antioxidant properties. However, high concentrations can be toxic. Eugenol is a recognized contact allergen, particularly in dental practice and cosmetics; sensitization can occur with repeated topical exposure at high concentrations.

N-Acetylcysteine for Overdose

N-acetylcysteine has been used to treat patients with eugenol or clove oil overdose; while not proven to be effective for eugenol overdose in humans, it has been shown to be effective in preventing hepatic injury in animal models.

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