Eugenia aromatica
Clove/Drug Interactions:
AnalgesicsAnalgesics: The clove constituent eugenol may inhibit prostaglandin biosynthesis and thereby depress pain sensory receptors (305). Analgesic activity of various constituents of clove, including eugenol and beta-carophyllene, has been shown in animal study and in vitro (306; 307; 308; 309; 310; 311; 312; 313; 314). AnestheticsAnesthetics: Based on a randomized trial, clove gel may be as effective as oral anesthetic benzocaine 20% gel (207). Anesthetic activity of various constituents of clove, including eugenol and beta-carophyllene, has been shown in animal study and in vitro (315; 316; 317; 318). AnthelminticsAnthelmintics: Eugenol showed potent anthelmintic activity in the Caenorhabditis elegans model in vitro (319). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Clove has been associated with inhibiting platelet aggregation (146; 147; 148), increasing INR (137), and report of disseminated intravascular coagulation (137). Polysaccharides isolated from clove may have antithrombic effects in vitro (149). Therefore, use with other anticoagulants or antiplatelet agents may result in additive effects and increased bleeding risk (203). Anticonvulsant agentsAnticonvulsant agents: In animal research, essential oil of clove may induce anticonvulsant activity (374; 375). AntidiabeticsAntidiabetics: Hypoglycemia was noted after the administration of 1 teaspoon of clove oil to a seven month-old infant (4). In animal research, eugenol demonstrated antidiabetic effects (139), although conflicting animal evidence exists (302). AntihistaminesAntihistamines: According to animal and in vitro evidence, clove, specifically the eugenol in clove, may have antihistamine activity (403; 404; 405). AntihypertensivesAntihypertensives: Based on animal evidence, eugenol may decrease arterial blood pressure and myocardial contractile force (142; 143; 144). Anti-inflammatoriessAnti-inflammatoriess: Based on in vitro and animal evidence, eugenol may act as an anti-inflammatory agent (27; 406; 407; 408; 409; 410; 411; 412; 413; 314). In animal study, eugenol possessed greater antipyretic properties than acetaminophen when given intravenously in small doses to rabbits (414). AntilipemicsAntilipemics: In healthy humans, 150mg of eugenol daily for three weeks did not increase plasma apo A-I, apo A-II, HDL cholesterol, or HDL phospholipids (415). Although in animal research, clove aqueous extract reduced serum cholesterol and TG levels (301). AntineoplasticsAntineoplastics: In laboratory and animal evidence, eugenol may display features of apoptosis (9; 416; 417), and eugenol and other clove constituents may display antimutagenic or antiproliferative effects (418; 419; 420; 33; 421; 422; 423). In vitro, clove extract may reduce intracellular cAMP levels and modulate cell signaling through protein kinase A (424). There is a lack of available human data for interactions with clove and antineoplastics. AntiprotozoalsAntiprotozoals: Based on in vitro evidence, clove may exhibit trypanocidal activity against Trypanosoma cruzi epimastigote and bloodstream trypomastigote forms by inhibiting parasite growth (425). Based on in vitro study, adulticidal, nymphicidal, ovicidal, and general antiparasitic activities were observed with clove oil (68; 426; 427; 428; 70; 429; 430; 431; 432; 433), and eugenol has demonstrated acaricidal activities (6; 7; 434; 435). AntispasmodicsAntispasmodics: According to secondary sources, clove may act as an antispasmodic.AntiviralsAntivirals: Based on in vitro evidence, clove essential oil and eugenol may possess antiviral properties against herpes simplex virus (HSV) (436; 437), hepatitis C virus (HCV) (438), and human cytomegalovirus (CMV) and murine CMV (MCMV) (439; 440). CNS depressantsCNS depressants: In case report and review, CNS depression has been reported (4; 253). Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Based on rat study, clove may induce cytochrome P450 enzymes, particularly CYP2E1 (441; 442) and potentially decrease levels of drugs metabolized by these enzymes. Dental and periodontal agentsDental and periodontal agents: The application of eugenol to an enamel-dentin bonding agent resulted in reduced dentinal adhesion when a dentin bonding agent that dissolves the smear layer in a self-conditioning adhesive system was used (443). The effects of eugenol on bonding strengths when resin cement is used have been examined (444); however, additional details are lacking. Dermatologic agentsDermatologic agents: Allergic stomatitis secondary to eugenol has also been reported (285). Some people may experience skin irritation or painful sensations from clove leading to a rash, hives, burning, irritation, dry peeling lips, blanching, chemical burns, lack of feeling, and sweating on skin exposed to clove. In human research, itching was reported following application of 1% clove oil to the anus either topically or internally, however the investigators noted that it was unclear whether the side effect was associated with clove oil or lignocaine (209). In addition, mild pain, local irritation, and burning were reported following application of SS cream (a clove combination product) (288). Topical use of undiluted clove oil may irritate the skin (212) and cause contact dermatitis (204). In animal research, Tiger Balm? Red (containing 5% cassia oil plus 5% clove oil) caused irritation consisting of erythema, eschar formation, and some edema, to which a degree of tolerance developed, whereas a formulation with only 2% clove oil was better tolerated and produced less irritation (163). Drugs that may cause adverse dental effectsDrugs that may cause adverse dental effects: Based on a cohort study of men who smoked clove cigarettes, clove may cause adverse dental effects (158). Topical use of clove oil may also result in oral tissue sensitivity, local tissue irritation, and damage to dental pulp or the supporting periodontium (anecdotal). EstrogensEstrogens: In vitro, eugenol has been shown to exert antiestrogenic effects and was able to displace [(3)H]17beta-estradiol from isolated alpha- and beta-human estrogen receptors (150). Fertility agentsFertility agents: Based on in vitro and animal evidence, eugenol and clove oil may exert a potent spermicidal action (140; 141). HepatotoxinsHepatotoxins: Based on case reports, ingested clove oil may be hepatotoxic (3; 2). Theoretically, concurrent use of clove and hepatotoxic agents may increase the risk of liver damage. However, in animal study, oral administration of eugenol to male rats lowered lipid peroxide levels in a model of iron-induced liver damage and lowered liver and serum lipid peroxide levels, serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (445). ImmunosuppressantsImmunosuppressants: Based on in vitro study, eugenol may inhibit macrophage function and modulate immune reactions (151; 152; 153). Based on in vitro and animal study, clove or its constituents have demonstrated other immunomodulatory effects (154; 155; 156). Clove administration to mice did not, however, influence the Th1/Th2 cytokine balance (157). InsecticidesInsecticides: Significant correlations among adulticidal, nymphicidal, and ovicidal activities against Trialeurodes vaporariorum (greenhouse whitefly), the cockroach, the garden chafer (Phyllopertha horticola), Megalurothrips sjostedti Tryb., the Japanese termite (Reticulitermes speratus Kolbe), the Formosan subterranean termite (Coptotermes formosanus Shiraki), Meloidogyne incognita (Kofoid and White) Chitwood, Leptotrombidium chiggers (larvae), and the cotton leaf-worm Spodoptera littoralis (Boisd.) were observed with clove leaf oil (68; 426; 427; 428; 70; 429; 430; 431; 432). Eugenol has demonstrated acaricidal activity against house the dust mites Dermatophagoides farinae and Dermatophagoides pteronyssinus (6; 7; 434; 435), and to repel mosquitos (446; 447). Clove oil has been used to control Varroa jacobsoni (Oudemans) infestation in honeybee colonies (433). NephrotoxinsNephrotoxins: Based on a case report, ingested clove oil may be nephrotoxic (4). Tyrosinase inhibitorsTyrosinase inhibitors: Based on in vitro evidence, methanolic extract of Syzygium aromaticum may exhibit mushroom tyrosinase inhibitory activity (448). VasodilatorsVasodilators: Based on animal and in vitro evidence, eugenol from clove may have vasorelaxant properties (449; 450; 451). Clove/Herb/Supplement Interactions:
Agents that may cause adverse dental effectsAgents that may cause adverse dental effects: Based on a cohort study of men who smoked clove cigarettes, clove may cause adverse dental effects (158). Topical use of clove oil may also result in oral tissue sensitivity, local tissue irritation, and damage to dental pulp or the supporting periodontium (anecdotal). AnalgesicsAnalgesics: The clove constituent eugenol may inhibit prostaglandin biosynthesis and thereby depress pain sensory receptors (305). Analgesic activity of various constituents of clove, including eugenol and beta-carophyllene, has been shown in animal study and in vitro (306; 307; 308; 309; 310; 311; 312; 313; 314). AnestheticsAnesthetics: Based on a randomized trial, clove gel may be as effective as oral anesthetic benzocaine 20% gel (207). Anesthetic activity of various constituents of clove, including eugenol and beta-carophyllene, has been shown in animal study and in vitro (315; 316; 317; 318). AnthelminticsAnthelmintics: Eugenol showed potent anthelmintic activity in the Caenorhabditis elegans model in vitro (319). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Clove has been associated with inhibiting platelet aggregation (146; 147; 148), increasing INR (137), and report of disseminated intravascular coagulation (137). Polysaccharides isolated from clove may have antithrombic effects in vitro (149). Therefore, use with other anticoagulants or antiplatelet agents may result in additive effects and increased bleeding risk (203). AnticonvulsantsAnticonvulsants: In animal research, essential oil of clove may induce anticonvulsant activity (374; 375). AntihistaminesAntihistamines: According to animal and in vitro evidence, clove, specifically the eugenol in clove, may have antihistamine activity (403; 404; 405). Anti-inflammatoriesAnti-inflammatories: Based on in vitro and animal evidence, eugenol may act as an anti-inflammatory agent (27; 406; 407; 408; 409; 410; 411; 412; 413; 314). In animal study, eugenol possessed greater antipyretic properties than acetaminophen when given intravenously in small doses to rabbits (414). AntilipemicsAntilipemics: In healthy humans, 150mg of eugenol daily for three weeks did not increase plasma apo A-I, apo A-II, HDL cholesterol, or HDL phospholipids (415). Although in animal research, clove aqueous extract reduced serum cholesterol and TG levels (301). AntineoplasticsAntineoplastics: In laboratory and animal evidence, eugenol may display features of apoptosis (9; 416; 417), and eugenol and other clove constituents may display antimutagenic or antiproliferative effects (418; 419; 420; 33; 421; 422; 423). In vitro, clove extract may reduce intracellular cAMP levels and modulate cell signaling through protein kinase A (424). There is a lack of available human data for interactions with clove and antineoplastics. AntiparasiticsAntiparasitics: Based on in vitro evidence, clove may exhibit trypanocidal activity against Trypanosoma cruzi epimastigote and bloodstream trypomastigote forms by inhibiting parasite growth (425). Based on in vitro study, adulticidal, nymphicidal, ovicidal, and general antiparasitic activities were observed with clove oil (68; 426; 427; 428; 70; 429; 430; 431; 432; 433), and eugenol has demonstrated acaricidal activities (6; 7; 434; 435). AntispasmodicsAntispasmodics: According to secondary sources, clove may act as an antispasmodic.AntiviralsAntivirals: Based on in vitro evidence, clove essential oil and eugenol may possess antiviral properties against herpes simplex virus (HSV) (436; 437), hepatitis C virus (HCV) (438), and human cytomegalovirus (CMV) and murine CMV (MCMV) (439; 440). CNS depressantsCNS depressants: In case report and review, CNS depression has been reported (4; 253). Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Based on rat study, clove may induce cytochrome P450 enzymes, particularly CYP2E1 (441; 442) and potentially decrease levels of drugs metabolized by these enzymes. Dental and periodontal agentsDental and periodontal agents: The application of eugenol to an enamel-dentin bonding agent resulted in reduced dentinal adhesion when a dentin bonding agent that dissolves the smear layer in a self-conditioning adhesive system was used (443). The effects of eugenol on bonding strengths when resin cement is used have been examined (444); however, additional details are lacking. Dermatologic agentsDermatologic agents: Allergic stomatitis secondary to eugenol has also been reported (285). Some people may experience skin irritation or painful sensations from clove leading to a rash, hives, burning, irritation, dry peeling lips, blanching, chemical burns, lack of feeling, and sweating on skin exposed to clove. In human research, itching was reported following application of 1% clove oil to the anus either topically or internally, however the investigators noted that it was unclear whether the side effect was associated with clove oil or lignocaine (209). In addition, mild pain, local irritation, and burning were reported following application of SS cream (a clove combination product) (288). Topical use of undiluted clove oil may irritate the skin (212) and cause contact dermatitis (204). In animal research, Tiger Balm? Red (containing 5% cassia oil plus 5% clove oil) caused irritation consisting of erythema, eschar formation, and some edema, to which a degree of tolerance developed, whereas a formulation with only 2% clove oil was better tolerated and produced less irritation (163). Fertility agentsFertility agents: Based on in vitro and animal evidence, eugenol and clove oil may exert a potent spermicidal action (140; 141). HepatotoxinsHepatotoxins: Based on case reports, ingested clove oil may be hepatotoxic (3; 2). Theoretically, concurrent use of clove and hepatotoxic agents may increase the risk of liver damage. However, in animal study, oral administration of eugenol to male rats lowered lipid peroxide levels in a model of iron-induced liver damage and lowered liver and serum lipid peroxide levels, serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (445). HypoglycemicsHypoglycemics: Hypoglycemia was noted after the administration of 1 teaspoon of clove oil to a seven month-old infant (4). In animal research, eugenol demonstrated antidiabetic effects (139), although conflicting animal evidence exists (302). HypotensivesHypotensives: Based on animal evidence, eugenol may decrease arterial blood pressure and myocardial contractile force (142; 143; 144). ImmunosuppressantsImmunosuppressants: Based on in vitro study, eugenol may inhibit macrophage function and modulate immune reactions (151; 152; 153). Based on in vitro and animal study, clove or its constituents have demonstrated other immunomodulatory effects (154; 155; 156). Clove administration to mice did not, however, influence the Th1/Th2 cytokine balance (157). InsecticidesInsecticides: Significant correlations among adulticidal, nymphicidal, and ovicidal activities against Trialeurodes vaporariorum (greenhouse whitefly), the cockroach, the garden chafer (Phyllopertha horticola), Megalurothrips sjostedti Tryb., the Japanese termite (Reticulitermes speratus Kolbe), the Formosan subterranean termite (Coptotermes formosanus Shiraki), Meloidogyne incognita (Kofoid and White) Chitwood, Leptotrombidium chiggers (larvae), and the cotton leaf-worm Spodoptera littoralis (Boisd.) were observed with clove leaf oil (68; 426; 427; 428; 70; 429; 430; 431; 432). Eugenol has demonstrated acaricidal activity against house the dust mites Dermatophagoides farinae and Dermatophagoides pteronyssinus (6; 7; 434; 435), and to repel mosquitos (446; 447). Clove oil has been used to control Varroa jacobsoni (Oudemans) infestation in honeybee colonies (433). NephrotoxinsNephrotoxins: Based on a case report, ingested clove oil may be nephrotoxic (4). PhytoestrogensPhytoestrogens: In vitro, eugenol has been shown to exert antiestrogenic effects and was able to displace [(3)H]17beta-estradiol from isolated alpha- and beta-human estrogen receptors (150). Tyrosinase inhibitorsTyrosinase inhibitors: Based on in vitro evidence, methanolic extract of Syzygium aromaticum may exhibit mushroom tyrosinase inhibitory activity (448). VasodilatorsVasodilators: Based on animal and in vitro evidence, eugenol from clove may have vasorelaxant properties (449; 450; 451). Clove/Food Interactions:
TeaTea: The addition of clove to black and peppermint tea may have synergistic effects on their antioxidant activity (458). Clove/Lab Interactions:
Blood glucoseBlood glucose: Reduced blood glucose was noted after the administration of 1 teaspoon of clove oil to a seven month-old infant (4). Blood pressureBlood pressure: In animal research, eugenol may reduce blood pressure (142; 143). Coagulation panel (INR)Coagulation panel (INR): Acute ingestion of clove oil may lead to an increase in INR (137). Hormone panel (estrogens)Hormone panel (estrogens): In vitro, eugenol has been shown to exert antiestrogenic effects and was able to displace [(3)H]17beta-estradiol from isolated alpha- and beta-human estrogen receptors (150). Kidney function testsKidney function tests: Based on a case report, ingested clove oil may be nephrotoxic (4). Lipid profileLipid profile: In healthy humans, 150mg of eugenol daily for three weeks did not increase plasma apo A-I, apo A-II, HDL cholesterol, or HDL phospholipids (415). In animal research, clove aqueous extract reduced serum cholesterol and TG levels (301). Liver function testsLiver function tests: Several case reports describe liver damage in children after the ingestion of clove oil (137; 2; 137; 138). However, based on animal evidence, oral administration of eugenol to male rats lowered liver and serum lipid peroxide levels, serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (445). Protein kinase A levelsProtein kinase A levels: Based on in vitro evidence, clove extract may reduce intracellular cAMP levels and modulate cell signaling through protein kinase A (424). Tyrosinase levelsTyrosinase levels: Based on in vitro evidence, methanolic extract of Syzygium aromaticum may exhibit mushroom tyrosinase inhibitory activity (448). Urine testsUrine tests: Proteinuria and urinary abnormalities were observed in a seven month-old infant given one teaspoon of clove oil (4).