Plant Profiler

Chamomile (Chamaemelum nobile)


Synonyms / Common Names / Related Terms
(-)-alpha-bisabolol, abkit CamoCare Gold®, angelate esters, anthecotulid, anthemic acid, Anthemis arvensis, Anthemis cotula, Anthemis nobile, Anthemis nobilis, Anthemis xylopoda, anthemol, apigenin, apigetrin, apiin, Asteraceae (family), azulene, baboonig, babuna, babunah, babunah camomile, babunj, bunga kamil, cadinene, camamila, camomile, camomile sauvage, camomilla, camomille allemande (French), Campomilla, capric acid, chamaemeloside, Chamaemelum nobile L., chamazulene, chamomile flowers, chamomile mouthwash, chamomilla, chamomilla recutita, chamomillae ramane flos, chamomille commune, choline, classic chamomile, common chamomile, Compositae (family), coumarins, double chamomile, echte Kamille (German), English chamomile, farnesene, farnesol, Feldkamille (German), flavonoids, fleur de camomile, fleurs de petite camomille, Flores Anthemidis, flos chamomillae, furfural, garden chamomile, germacranolide, German chamomile, grosse Kamille (German), grote Kamille (Dutch), ground apple, guaiazulene, heniarin, Hungarian chamomile, inositol, Kamille (German), Kamillen (German), kamitsure, kamiture, kleme kamille, lawn chamomile, low chamomile, luteolin, manzanilla (Spanish), manzanilla chiquita (Spanish), manzanilla común (Spanish), manzanilla dulce (Spanish), matricaire, Matricaria chamomilla, Matricaria maritime (L), Matricaria recutita, Matricaria suaveolens, matricariae flos, matricariae flowers, matricarin, matricin, martricine, may-then, myricetin, nerolidol, nobilin, patuletin, phenolic acids, phytosterol, pin heads, proazulenes, quercimeritrin, quercitin, Romaine, romaine manzanilla, Roman chamomile, romische Kamille (German), rutin, scopoletin-7-glucoside, sesquiterpenes, Simicort®, single chamomile, spanthulenol, spiroethers, sweet chamomile, sweet false chamomile, sweet feverfew, tannins, terpenoid, tiglic acid esters, triancontane, tricontane, true chamomile, umbelliferone, whig-plant, wild chamomile.
Note: This monograph does not discuss in detail therapies using a combination of chamomile and other herbs and/or supplements.


Mechanism of Action
Pharmacology:
  • Constituents: The flowers of chamomile contain 0.4-2% (v/w) essential oil. The pharmacopoeial standard of essential oil contains no less than 4mg/kg of blue oil. Its main components are (-)-alpha-bisabolol (up to 50%) and chamazulene (1-15%). The chief constituents of Roman chamomile oil are n-butyl angelate and isoamyl angelate. The flower heads have been shown to contain approximately 0.6% bitter sesquiterpene lactones (germacranolides), including nobilin and its derivatives. Other constituents may include (-)-alphabisabolol oxide A, B and C, (-)-alpha-bisabolone oxide A, 1,8-cineole, en-yn-dicycloether, alpha-pinene, amyl and isobutyl alcohols, angelic acid esters, anthemol, anthemic acid, apigenin, choline, coumarins, farnesol, germacranolide, heniarin, inositol, lueteolin, nerolidol, nobilin, patuletin, phenolic and fatty acids, phytosterol, quercetin, scopoletin-7-glucoside, spiroethers (e.g., cis- and trans-en-yn-dicycloether), sesquiterpenes (e.g., anthecotulid), tricontane, cadinene, farnesene, furfural, spanthulenol, tiglic acid esters, flavonoids (e.g., apigenin and luteolin), proazulenes (e.g., matricarin and matricin), and umbelliferone.29 Chamazulene is formed from matricin during steam distillation of the oil. It varies in yield depending on the origin and age of the flowers.
  • Up to 50% of essential oil of chamomile contains alpha-bisabolol (terpenoid) and is reported to have anti-inflammatory, antibacterial, antimycotic, and ulcer-protective properties.40,28,15, 41 The precise mechanism of action remains unclear, but it has been theorized that azulenes activate the pituitary-adrenal system to release cortisone and prevent the discharge of histamine.11
  • Allergenic effects: The allergenic properties documented for chamomile have been attributed to anthecotulid, a sesquiterpene lactone, azulines, and matricarin. The prerequisite for allergenic activity is thought to be an exocyclic alpha-methylene group. Both histamine release and inhibition of histamine discharge have been advanced as mechanisms for the potential antiallergenic action of azulenes. The discharge of histamine from tissues is prevented by activating the pituitary-adrenal system to release cortisone. The activity of chamazulene and guaiazulene are about equal, but less effective than prochamazulene.
  • Anticoagulant effects: Coumarins in German chamomile, such as umbelliferone, may possess anti-coagulant properties, although this mechanism has not been well studied.12
  • Anithyperlipidemic effects: In animal models, chamomile has shown some cholesterol-lowering activities.29
  • Anti-inflammatory effects: Several constituents of chamomile, including apigenin-7-glucoside3, luteoline, terpene compounds, herniarine, matricin, chamazulene, (-)-alpha-bisabololoxides A and B, and (-)-alpha-bisabolol, patuletin, umbelliferone, quercetin, myricetin, rutin, and spiroethers, have been studied for their anti-inflammatory activities Most studies, however, have found that the whole extracts were more active than their individual constituents. Chamazulene, alpha-bisabolol, and apigenin have the highest anti-inflammatory actions against proinflammatory agents. Matricin, the precursor of chamazulene, demonstrates anti-inflammatory activity superior to chamazulene. In vitro, chamomile extract has been found to inhibit both cyclooxygenase and lipooxygenase, and therefore, inhibits prostaglandins and leukotrienes.18
  • Chamazulene inhibits leukotriene B4 from forming intact cells with the inhibitory concentration at a dose of 2mcM in laboratory research.19 Both bisabolol and bisabolol oxide have been shown to inhibit 5-lipoxygenase. Intradermal application of liposomal apigenin-7-glucoside inhibited skin inflammation caused by xanthine-oxidase and cumene hydroperoxide in rats in a dose-dependent manner.20 Apigenin inhibits histamine and serotonin release. Luteolin, a flavonoid contained in the essential oil of chamomile, has anti-inflammatory activity similar to indomethacin.
  • In mice, hydroalcoholic extracts of chamomile induced a reduction of edema similar to the nonsteroidal anti-inflammatory agent used as reference (benzydamine).21 More recently, a CO2 extract of chamomile was found to be more active as an anti-inflammatory agent than the hydroalcoholic extract.2 Spiroethers, apigenin, luteolin, and quercetin, found in the oil of German chamomile, are purported to have anti-inflammatory and smooth muscle relaxing effects.11 Alpha-bisabolol blocked carrageenan-induced rat paw edema.22
  • Antimicrobial effects: Antimicrobial activity of chamomile has been studied in vitro and the results have been encouraging; however, human data remains lacking. Chamomile oil is actively antibacterial and fungicidal at concentrations of at least 25mg/mL, as is the chamomile constituent bisabolol at concentrations of at least 1mg/mL. Alpha-Bisabolol, luteolin, quercitin, and apeginin have been theorized to possess antibacterial properties.11 The coumarin constituent, hernearin, may also have antibacterial and antifungal properties in the presence of ultraviolet light. High molecular weight polysaccharides with immunostimulating activity have been isolated from German chamomile.30 Two such studies demonstrated that gram-positive bacteria were more susceptible than gram-negative bacteria to chamomile oil.31 It was most effective against Staphylococcus aureus, Streptococcus mutans, and Streptococcus salivarius; with also Bacillus megatherium, Leptospira icterohaemorrhagiae, and Trichomonocidal bactericidal activity.32 It was also found to be somewhat effective as a fungicidal against Candida albicans.31 Concentrated chamomile extracts also inhibited the growth of several strains of fungi.1 The hydro-alcoholic extract of chamomile completely inhibited growth of group B Streptococcus.32 Two additional in vitro studies showed that chamomile blocked the aggregation of Helicobacter pylori33 and numerous strains of Escherichia coli.34 Methanol extracts of Matricaria recutita flowers had a MIC >100mcg/mL against 15 Helicobacter pylori strains in vitro35 Chamomile methanol and chloroform extracts have also shown strong activity against several strains of Arcobacter.36 An ethanolic extract of the entire plant has been reported to inhibit the growth of poliovirus and herpes virus. The volatile oil of chamomile also inhibited Bacillus subtilis in vitro. German chamomile esters and lactones showed activity against Mycobacterium tuberculosis and Mycobacterium avium. Another in vitro study found that chamomile tea contains no flavonoids and are inactive against Bacillus cereus (strain RM3190) incubated at 21°C for 3, 15, 30, and 60 minutes.37 Chamazulene, alpha-bisabolol, flavonoids, and umbelliferone displayed antifungal properties against Trichophyton mentagrophytes and Trichophyton Rubrum.38
  • Antineoplastic effects: Antineoplastic effects of apigenin, a flavonoid compound in chamomile, have been studied in animals, and it was discovered that it strongly absorbed ultraviolet light.42 Applied topically, apigenin reduced the number of UVB-induced squamous cell carcinomas in mice and may prove to be a useful sunscreen ingredient. Apigenin was found to suppress 12-O-tetradecanoyl-phorbol-13-acetate-induced tumor promotion in mouse skin, presumably through inhibition of protein kinase C.4 It was also found to induce G2/M cell cycle arrest in mouse keratinocytes.5 Blue azulene inhibits succinodehydrogenase in tumor cells and was found to be more potent than the action of the green fraction.43 In a study observing the immunomodulatory effects of Matricaria chamomilla, the extract was found to have almost no stimulatory effect, although it did increase cell proliferation.44 Sesquiterpenoids, nobilin, and its epoxy- and dehydro- derivatives have demonstrated antitumor activity against human tumor cells in vitro.
  • Antioxidant effects: Chamomile has shown moderate antioxidant activities in vitro29, and some of this activity may be due to its apigenin content, which has exhibited anti-inflammatory properties.3
  • Anxiolytic effects: Chamomile has shown some anxiolytic effects.29
  • Bone effects: An extract containing Matricaria chamomile, Sideritis euboea, Sideritis clandestine, and Pimpinella anisum was associated with selective estrogen receptor modulators (SERMs property) against osteoporosis.9 It stimulated osteoblastic cell differentiation and exhibited antiestrogenic effects on breast cancer cells without proliferative effects on cervical adenocarcinoma cells.
  • Cardiac effects: Apigenin was found to increase the atrial rate in rats.23 Apigenin relaxed the thoracic aorta by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels in an animal study. A dose of 0.2mL/kg was stated to exhibit hypotensive effects, as well as cardiac and respiratory depressant properties.17
  • Cytochrome P450 effects: Crude essential chamomile oil demonstrated the inhibition of four cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A4), with CYP1A2 being more sensitive than the other isoforms.14 Three constituents of the oil, namely chamazulene, cis-spiroether, and trans-spiroether, showed to be potent inhibitors of this enzyme, also being active towards CYP3A4. CYP2C9 and CYP2D6 were less inhibited; only chamazulene and alpha-bisabolol revealed a significant inhibition of the latter.
  • Gastrointestinal effects: In vitro, alpha-bisabolol has been found to inhibit the induction of ulceration by indomethacin, stress, or ethanol.15 In rats, bisabolol (from chamomile oil), taken orally at doses between 0.8mg/kg and 80mg/kg, provided protection against gastric toxicity of 200mg/kg of acetylsalicylic acid. Cis-spiroether has been implicated to have antiulcer activity. Intraperitoneal administration of apigenin significantly reduced intestinal transit time in mice. Apigenin (12.5-50mg/kg) slowed down castor oil-induced diarrhea. Alpha-bisabolol decreased the proteolytic activity of pepsin by 50%. In a rat study, Matricaria recutita flower extract significantly reduced upper gastrointestinal transit.6
  • Hepatic effects: Chamomile oil has been reported to increase bile secretion and concentration of cholesterol in bile, following the administration of 0.1mL/kg by mouth to cats and dogs. The ability of the volatile oil to regenerate liver tissue in partially hepatectomized rats has been attributed to the azulene constituents. The application of chamomile extract (Kamillosan®) increased the oxidative phosphorylation in rat liver mitochondria.45
  • Hypoglycemic effects: The flavonoid glucoside chamaemeloside, found in Chamaemelum nobile, has in vivo hypoglycemic activity comparable to free 3-hydroxy-3-methylglutaric acid (HMG).16
  • Renal effects: The volatile oil has been documented to reduce the serum concentration of urea in rabbits with experimentally induced uremic conditions.8 In a rat study, a combination of birch, hawthorn, strawberry, cornsilk, chamomile flowers (Matricariae flos), and horsetail had a significantly greater diuretic effect than horsetail herb extract alone or hydrochlorothiazide suspension (p<0.05).39
  • Sedative effects: In a case series intending to examine the cardiac effects of chamomile, the authors observed that 10 out of 12 patients undergoing cardiac catheterization fell asleep shortly after drinking chamomile tea.10 However, there is limited evidence supporting the sedating effects of chamomile. In one mouse model, it was concluded that the apigenin component of chamomile is a ligand for benzodiazepine receptors, and exerts slight sedative effects.13 In contrast to diazepam, chrysin and apigenin do not cause reductions in memory. Lyophilized infusion of chamomile administered intraperitonealy in mice displayed a depressive effect on the central nervous system.26 Prolongation of hexobarbital-induced sleeping time and reduction in activity in mice has been documented.
  • In an in vitro study, ethanolic extracts of chamomile flower had selective binding affinities to 5-HT(4) receptors.7
  • Spasmolytic effects: alpha-Bisabolol and apigenin are considered spasmolytic.24,11,25 10mg of Apigenin reduced spasm comparably to 1mg of papaverine. Flavonoids and coumarins are smooth muscle relaxants with the coumarins, herniarin, and umbelliferone possessing minor smooth muscle relaxant activities. Smooth muscle relaxant properties have also been documented for a cis-spiroether constituent.46,24,27,47 Enhancement of uterine tone in guinea pigs and rabbits has been reported for an aqueous extract at a concentration of 1-2mg extract/cm3.48 Farnesol also has sedative and spasmolytic effects in vitro.
Pharmacokinetics:
  • Absorption: Chamomile did not affect iron bioavailability when administered with meals based on wheat flour and fortified with ferrous sulfate.49
  • Metabolism: Herbal teas in rats were investigated to observe their hepatic effects on phase I and phase II metabolism.50 In rats, CYP1A2 metabolism was decreased significantly (p<0.05) by 39% from the control value; however, CYP2D and CYP3A were not affected. There was also no change in the activity of glutathione-s-transferase. CYP3A4 inhibition might occur with chamomile, currently seen in vitro, which can decrease metabolism, increase serum concentration, and possibly cause drug toxicity.51
  • A study revealed that there are strong intersubject variations of chamomile metabolite in urine.52 The urinary excretion of hippurae and glycine increased with depleted creatinine concentrations in some subjects. The metabolite profile persisted for two weeks after chamomile tea ingestion, suggesting that the metabolic effects were prolonged two weeks after stopping daily ingestion.

References
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