Fennel

Fennel/Drug Interactions:

  • GeneralGeneral: Based on animal study, pretreatment with fennel essential oil may enhance the percutaneous absorption of various drugs like trazodone (125).
  • AnalgesicsAnalgesics: In animal study, oral administration (200mg/kg) of methanolic fennel fruit extract displayed inhibitory effects, acute and subacute inflammatory activity, and central analgesic effects (126). Human trial has demonstrated analgesic effects (127; 16; 93).
  • AntibioticsAntibiotics: In animal study, concurrent use of fennel and ciprofloxacin may lead to decreased bioavailability of ciprofloxacin (70). Theoretically, fennel may also interfere similarly with other fluoroquinolone antibiotics. In various studies, fennel displayed antibacterial effects against pathogens such as Mycobacterium tuberculosis, Escherichia coli, Listeria monocytogenes, Bacillus spp., Salmonella typhimurium, Shigella dysenteriae, Pseudomonas aeruginosa, Staphylococcus aureus, Campylobacter jejuni, Helicobacter pylori, and multidrug-resistant Acinetobacter baumannii (128; 129; 130; 8; 131; 132; 133; 134; 135; 136; 9; 137; 138; 139; 140; 141; 10; 12; 142; 143). Rats immunized with fennel honey challenged Staphylococcus aureus infection (11).
  • Anticoagulant agentsAnticoagulant agents: In animal study, Foeniculum vulgare essential oil and anethole (its main constituent) displayed antithrombotic and antiplatelet activity as well as destabilizing clot effect (71). The phenylpropanoids of fennel have also displayed antiplatelet activity against ADP, arachidonic acid, and the thromboxane A2 agonist U46619 (144).
  • Antidiabetic agentsAntidiabetic agents: Essential oil of fennel seed has been reported to stimulate pancreatic alpha-cells and insulin secretion in diabetic rat model (61). In laboratory study, fennel was found to inhibit aldose reductase (22).
  • AntifungalsAntifungals: In various studies, essential oil of fennel and bitter fennel have been found to exert varying levels of antifungal effects against Aspergillus niger, Aspergillus parasiticus, Alternaria alternata, Fusarium oxysporum, Candida albicans, Botrytis cinerea, Rhizoctonia solani, and Sclerotinia sclerotiorum (145; 130; 146; 147; 14; 148; 149; 150; 137; 151).
  • Antihypertensive agentsAntihypertensive agents: In animal study, fennel has displayed hypotensive activity (62; 63). The aqueous extracts of Foeniculum vulgare leaves administered intravenously as lyophilized boiled water extract produced a dose-related reduction in arterial blood pressure without affecting heart rate or respiratory rate; this effect appeared to be related to histamine antagonism and not to adrenergic, muscarinic, ganglionic, or serotonergic receptors effects (62).
  • Anti-inflammatoriesAnti-inflammatories: The effects of anethole (a main constituent) may be mediated by modulation of tumor necrosis factor (TNF)-induced cellular responses (6). Anethole may interfere with TNF signaling; led to the activation of NF-kappaB, AP-1, JNK, MEK, and apoptosis; and may suppress NF-kappaB-dependent gene expression induced by TNF. NF-kappaB controls the expression of some genes involved in carcinogenesis and inflammation (152).
  • AntineoplasticsAntineoplastics: In various studies, fennel has demonstrated anticancer effects (153; 154).
  • Antiobesity agentsAntiobesity agents: In animal study to examine the effect of inhalation of essential oils on body weight, feed intake, and food efficiency rate, fennel lowered food efficiency rate but not feed intake (155). However, in another animal feed experimental study, the essential oil of fennel added to the diet resulted in a reduction of feed amount and intake (156).
  • AntispasmodicsAntispasmodics: Fennel seed increased gastrointestinal motility and acted as an antispasmodic at high doses. Fennel extracts produced a reduction in acetylcholine-induced contraction and decreased maximum possible contractility (157).
  • Cholinesterase inhibitorsCholinesterase inhibitors: In lab study, constituents of essential oils like those found in fennel have displayed high inhibitory activity against acetyl- and butyrylcholinesterase (158).
  • Cytochrome P450: substrates, inhibitors, inducersCytochrome P450: substrates, inhibitors, inducers: Based on lab study, fennel has been found to time-dependently inhibit cytochrome P450 3A4 (66; 67; 68). Fennel constituents, including 5-methoxypsoralen (5-MOP), have displayed the strongest inhibition and inhibitory effects. 5-MOP showed the characteristics of time-dependent inhibition, requirement of NADPH, lack of protecting effect of nucleophiles, and recovery of CYP3A4 activity by the competitive inhibitor (66).
  • DiureticsDiuretics: Fennel has been traditionally used as a diuretic (159). In animal study, oral administration of fennel water extract resulted in diuretic and natriuretic effects (63). Fennel was found to increase water, sodium, and potassium excretion (63).
  • EstrogensEstrogens: In clinical trial, fennel has been studied for conditions like hirsutism due to its possible estrogenic activity (64). Fennel was found to increase uterine weight in mice and shorten double-time cell growth in breast cancer cells (160).
  • Gastrointestinal agentsGastrointestinal agents: Fennel and herbal teas containing fennel, like ColiMil?, are traditionally and popularly used to improve a variety of gastrointestinal disorders (161; 24; 24; 162). In experimental study, enzymes like pancreatic trypsin, lipase, and amylase have been stimulated by fennel (161; 163). In animal and in vitro study, fennel has demonstrated further gastrointestinal effects (164; 165; 166).
  • Glaucoma agentsGlaucoma agents: In animal study, aqueous extract of fennel displayed oculohypotensive activity comparable to timolol (69).
  • ImmunosuppressantsImmunosuppressants: In laboratory study, fennel extract displayed immunomodulatory NF-kappaB activity (65).
  • Iron saltsIron salts: In experimental study, fennel displayed iron ion-chelating activity (167).
  • TrazodoneTrazodone: Based on animal study, pretreatment with fennel essential oil may enhance the percutaneous absorption of various drugs like trazodone (125).
  • VasodilatorsVasodilators: In animal study, fennel displayed vasorelaxant effects (63; 71). The essential oil and anethole (its main constituent) displayed a NO-independent vasorelaxant effect (71).
  • VasopressorsVasopressors: In animal study, fennel displayed vasorelaxant effects (63; 71). The essential oil and anethole (its main constituent) displayed a NO-independent vasorelaxant effect (71).

    • Fennel/Herb/Supplement Interactions:

  • GeneralGeneral: Based on animal study, pretreatment with fennel essential oil may enhance the percutaneous absorption of various topical agents (125).
  • AnalgesicsAnalgesics: In animal study, oral administration (200mg/kg) of methanolic fennel fruit extract displayed inhibitory effects, acute and subacute inflammatory activity, and central analgesic effects (126). Human trial has demonstrated analgesic effects (127; 16; 93).
  • AntibacterialsAntibacterials: In various studies, fennel displayed antibacterial effects against pathogens such as Mycobacterium tuberculosis, Escherichia coli, Listeria monocytogenes, Bacillus spp., Salmonella typhimurium, Shigella dysenteriae, Pseudomonas aeruginosa, Staphylococcus aureus, Campylobacter jejuni, Helicobacter pylori, and multi-drug resistant Acinetobacter baumannii (128; 129; 130; 8; 131; 132; 133; 134; 135; 136; 9; 137; 138; 139; 140; 141; 10; 12; 142; 143; 70). Rats immunized with fennel honey challenged Staphylococcus aureus infection (11).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In animal study, Foeniculum vulgare essential oil and anethole (its main constituent) displayed antithrombotic and antiplatelet activity as well as destabilizing clot effect (71). The phenylpropanoids of fennel have also displayed antiplatelet activity against ADP, arachidonic acid, and the thromboxane A2 agonist U46619 (144).
  • AntifungalsAntifungals: In various studies, essential oil of fennel and bitter fennel has been found to exert varying levels of antifungal effects against Aspergillus niger, Aspergillus parasiticus, Alternaria alternata, Fusarium oxysporum, Candida albicans, Botrytis cinerea, Rhizoctonia solani, and Sclerotinia sclerotiorum (145; 130; 146; 147; 14; 148; 149; 150; 137; 151).
  • Anti-inflammatoriesAnti-inflammatories: The effects of anethole (a main constituent) may be mediated by modulation of tumor necrosis factor (TNF)-induced cellular responses (6). Anethole may interfere with TNF signaling; led to the activation of NF-kappaB, AP-1, JNK, MEK, and apoptosis; and may suppress NF-kappaB-dependent gene expression induced by TNF. NF-kappaB controls the expression of some genes involved in carcinogenesis and inflammation (152).
  • AntineoplasticsAntineoplastics: In various studies, fennel has demonstrated anticancer effects (153; 154).
  • Antiobesity agentsAntiobesity agents: In animal study to examine the effect of inhalation of essential oils on body weight, feed intake, and food efficiency rate, fennel lowered food efficiency rate but not feed intake (155). However, in another animal feed experimental study, the essential oil of fennel added to the diet resulted in a reduction of feed amount and intake (156).
  • AntioxidantsAntioxidants: Fennel has displayed antioxidant activity in animal and laboratory study (168; 169; 126; 170; 171; 15; 172; 173; 174; 175; 153; 176; 177; 178; 167; 7; 139; 136; 179; 180).
  • AntispasmodicsAntispasmodics: Fennel seed increased gastrointestinal motility and acted as an antispasmodic at high doses. Fennel extracts produced a reduction in acetylcholine-induced contraction and decreased maximum possible contractility (157).
  • Cytochrome P450: substrates, inhibitors, inducersCytochrome P450: substrates, inhibitors, inducers: Based on lab study, fennel has been found to time-dependently inhibit cytochrome P450 3A4 (66; 67; 68). Fennel constituents, including 5-methoxypsoralen (5-MOP), have displayed the strongest inhibition and inhibitory effects. 5-MOP showed the characteristics of time-dependent inhibition, requirement of NADPH, lack of protecting effect of nucleophiles, and recovery of CYP3A4 activity by the competitive inhibitor (66).
  • DiureticsDiuretics: Fennel has been traditionally used as a diuretic (159). In animal study, oral administration of fennel water extract resulted in diuretic and natriuretic effects (63). Fennel was found to increase water, sodium, and potassium excretion (63).
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: Fennel and herbal teas containing fennel, like ColiMil?, are traditionally and popularly used to improve a variety of gastrointestinal disorders (161; 24; 24; 162). In experimental study, enzymes like pancreatic trypsin, lipase, and amylase have been stimulated by fennel (161; 163). In animal and in vitro study, fennel has demonstrated further gastrointestinal effects (164; 165; 166).
  • Glaucoma agentsGlaucoma agents: In animal study, aqueous extract of fennel displayed oculohypotensive activity comparable to a glaucoma agent (69).
  • Hormonal herbs and supplementsHormonal herbs and supplements: In clinical trial, fennel has been studied for conditions like hirsutism, due to its possible estrogenic activity (64). Fennel was found to increase uterine weight in mice and shorten double-time cell growth in breast cancer cells (160).
  • HypoglycemicsHypoglycemics: Essential oil of fennel seed has been reported to stimulate pancreatic alpha-cells and insulin secretion in a diabetic rat model (61). In laboratory study, fennel was found to inhibit aldose reductase (22).
  • HypotensivesHypotensives: In animal study, fennel has displayed hypotensive activity (62; 63). The aqueous extracts of Foeniculum vulgare leaves administered intravenously as lyophilized boiled water extract produced a dose-related reduction in arterial blood pressure without affecting heart rate or respiratory rate; this effect appeared to be related to histamine antagonism and not to adrenergic, muscarinic, ganglionic, or serotonergic receptors effects (62).
  • ImmunomodulatorsImmunomodulators: In laboratory study, fennel extract displayed immunomodulatory NF-kappaB activity (65).
  • Insect repellentsInsect repellents: The essential oils of sweet fennel have displayed insecticidal and larvicidal effects against Anopheles dirus, Aedes aegypti, Culex, Armigeres, and a variety of aphids (30; 181; 182; 183). Constituents of Foeniculum vulgare fruit oil, particularly p-anisaldehyde and fenchone, displayed acaricidal activity against Dermatophagoides spp. (184). Constituents of fennel essential oil, including carvacrol and thymol, may act as nematicides (185).
  • IronIron: In experimental study, fennel displayed iron ion-chelating activity (167).
  • PeonyPeony: In animal study, fennel fruit was found to enhance the bioavailability of paeoniflorin, a constituent of red peony root (186).
  • ProbioticsProbiotics: Based on in vitro study, the essential oil and hexane extract of fennel have displayed antimicrobial activity against probiotic bacteria (187).
  • VasoconstrictorsVasoconstrictors: In animal study, fennel displayed vasorelaxant effects (63; 71). The essential oil and anethole (its main constituent) displayed a NO-independent vasorelaxant effect (71).
  • VasodilatorsVasodilators: In animal study, fennel displayed vasorelaxant effects (63; 71). The essential oil and anethole (its main constituent) displayed a NO-independent vasorelaxant effect (71).

    • Fennel/Food Interactions:

  • EggsEggs: Fennel feed additive was found to alter the smell and taste of hen eggs (188).
  • Iron-containing foodsIron-containing foods: In experimental study, fennel displayed iron ion-chelating activity (167).

    • Fennel/Lab Interactions:

  • Blood pressureBlood pressure: In animal study, fennel displayed hypotensive activity (62; 63).
  • Coagulation panelCoagulation panel: In animal study, Foeniculum vulgare essential oil and anethole (its main constituent) displayed antithrombotic and antiplatelet activity as well as destabilizing clot effect (71). The phenylpropanoids of fennel have also displayed antiplatelet activity against ADP, arachidonic acid, and the thromboxane A2 agonist U46619 (144).
  • ElectrolytesElectrolytes: Fennel has been traditionally used as a diuretic (159). In animal study, oral administration of fennel water extract resulted in diuretic and natriuretic effects (63). Fennel was found to increase water, sodium, and potassium excretion (63).
  • Hormone panelHormone panel: In humans, fennel has been studied for conditions like hirsutism, due to its possible estrogenic activity (64). Fennel was found to increase uterine weight in mice and shorten double-time cell growth in breast cancer cells (160).
  • Intraocular pressureIntraocular pressure: In animal study, aqueous extract of fennel displayed oculohypotensive activity comparable to timolol (69).
  • IronIron: In experimental study, fennel displayed iron ion-chelating activity (167).
  • Liver function testsLiver function tests: In animal study, essential oil of fennel displayed hepatoprotective effects against carbon tetrachloride-induced liver injury (189). Decreased levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and bilirubin were noted.