Matricaria recutita / Echte kamille

Algemene En Botanische Informatie
Familie: Asteraceae (syn. Compositae) - Samen­gesteld­bloemigen
Naam: Echte kamille (N.), Wild chamomile (E.), Camom­il­le (Fr.)
Soorten:
Echte kamille - Matricaria recu­tita L. (syn. Matri­caria cha­mo­milla)
Valse kamille - Anthemis arvensis L.
Schijfkamille - Matricaria dis­coidea DC.
Roomse kamille - Anthemis nobilis L. (cul­tivar met 'dub­bele' bloe­men)
Moederkruid - Chrysanthemum par­thenium (L.) SCHULTZ. (syn. Tana­cetum par­thenium)
Teelt, ecologie: Echte kamille is een eenjarig akkeron­kruid, zaaien in het najaar of het voorjaar.
Roomse kamille is een vaste plant, te ver­meer­deren door zaaien en scheu­ren.

Materia Medica , gebruikte delen en kwaliteit

Chamomillae flos / Matricariae flos DAB 9 / F. Helv. VII. De bloem­hoofdjes van Matricaria recutita L., ook van gecul­ti­veerde rassen met grotere bloem­hoofdjes.


Oogst: Bloemhoofdjes bij het begin van de bloei, geplukt met een speciale kam, vooral in de Midden-Europese landen (ook in het wild verza­meld).
Bewaren: In goed gesloten potten, buiten invloed van het licht.
Vervalsing: Met andere kamillesoorten. (lit. 1)

Beschrijving: Witte, lintvormige straalbloemen en gele, buisvormige schijf­bloemen, op een kegel­vor­mige, holle bloembodem zonder stro­schubben, zonder vrucht­pluis.
Reuk: ty­pisch aromatisch.
Smaak: aroma­tisch bitter.

Chamomillae flos romana, De dubbele bloemhoofdjes van Anthemis nobilis L. kunnen ook gebruikt worden, maar zouden minder werkzaam zijn. (?)

Samenstelling, inhoudstoffen
Lipofiele bestanddelen
** Etherische olie O,25-1,50 % ( vlgs DAB minstens 0,40 %)
- chamazuleen 16 % (ontstaat uit matricine door verwar­ming)
- L-alfa-bisabolol (20-50 % afhankelijk v/d soort)
terpenen (weinig in water, goed in vet oplosbaar)
Oudere olie wordt groen of bruin, verse olie is blauw

Hydrofiele bestanddelen
* Bitterstof 3,00 %
* Cumarinen (= chamillin)
** Flavonoïden o.a. luteolineglucoside, apigenine (in water oplosbaar) (lit. 1)
* Slijmstoffen tot 10,00 %

Nota's: - De werking is zowel van de lipofiele als van de hydro­fiele bestand­delen afhankelijk.
- Hydrofiel: dus waterige extracten (vooral spas­moly­tische werking).
- Lypofiel: dus alcoholische extracten (vooral an­tiflogistische werking).

Farmacologie, algemene werking
** Ontstekingsremmend en wondhelend (azuleen en L-alfa-bisa­bolol) (lit. 2)
- Stimuleert de synthese van de prostaglandines, waar­door een ulcus­pro­tectief en curatief effect ontstaat.
- Natuurlijke bisabolol is sterker werkzaam dan synthe­ti­sche.
- Effect op weefselregeneratie.
** Musculotroop spasmolytisch (bitterstof, e.o., coumari­nen, flavonen) (lit. 3)
- Opgewekte spiercontractie door o.a. histamine en seroto­nine werden door apigenine geremd (Janku).
* Koortswerend
* Anti-dysbacterieel: herstelt de darmflora
- Bacteriostatisch op o.a. gram-positieve Mycobacterium tuberculosis.
- E.o. remt de toxineproduktie van staphylococcen en strep­tococcen = ontgiftend (lit. 5)
* Stimuleert de huidstofwisseling o.a. bewezen in dierproe­ven (lit. 6)
* Aperitivum (bitterstoffen)
* Kalmerend effect op het centrale zenuwstelsel (activiteit o.a. bewezen door proeven op muizen) Hoge dosering, vooral zeer lang gebruik kan een overprikkeling veroorzaken

Nota: Krampwerend is het sleutelwoord voor de werking van Kamille.

Contra-indicaties:
- Kan allergische en irriterende huidaandoenin­gen ver­oor­zaken (?)
- Veel onderzoek, het meeste met andere soor­ten Kamille.
- Echte Kamille is weinig of niet irrite­rend (Hausen). 
Ema.europa: The clinical safety of Matricaria recutita containing preparations is good. The main risk is a sensitization in cutaneous use, which is minor. For children there are data from 817 patients with an allerginicity of 0.12% (Jeschke et al. 2009). 3,851 adults having an indication for allergy testing showed a risk of Asteraceae allergy of about 3.1% in adults. 56% thereof were allergic to matricaria (Hausen 1996).
Other specific risks for children of any age group are not deducible. Pregnant women may use herbal tea, for all other preparations there is a lack of data.
The drug interaction data are inconclusive from preclinical assessment to case reports. Nevertheless interactions regarding Cyclosporine immunosuppression after renal transplants are possible. Therefore a note should be entered in the monograph:
“For patients after renal transplantation taking high dosages for longer periods (about two months) interactions based on effects on CYP450 have been reported.”

Indicatie, medisch gebruik
Maag en darmen (lit. 1, 2, 3, 4 en 5)
** Acute en chronische ontsteking van het maagslijmvlies (rolkuur)
** Maagulcus, maagzweer (zie ook Glycyrrhiza)
** Colitis (darmontsteking) met koliek
** Darmirritatie met diarree of obstipatie (zie ook slijmstofplanten)
** Dysbacterie bv. na antibioticagebruik (Infuus + melksuiker, FOS)
* Darmreiniging (kuur darmspoelingen 37°C)

Huid (lit. 6 en 7)
** Huidirritatie, roodheid (compres en zalf)
* Geïnfecteerde wonden
* Abcessen en furunkels (zie ook Arctium lappa)
* Acné (dampbad, lotion of hydrolaat + hor­monaalkruiden)
* Jeukend en nat eczeem
* Eczeem, luiereczeem
* Impetigo (zie info)
* Allergische dermatosen (ook baden, zie ook kruiden voor de huid)
* Brandwonden 1ste en 2de graad, UV-erytheem
* Ulcus cruris, doorligwonden
* Gordelroos.

Mondholte
** Stomatitis aphthosa en ulcerosa (spoelingen en gorgelen)
* Gingivitis, paradontitis
* Irritatie door tandprothese
* Foetor ex ore (slechte adem)
* Problemen doorkomen eerste tandjes ( Chamomilla D6)

Luchtwegen
** Rinitis, sinusitis, bronchitis, faryngitis (dampbaden + Eucalyptus)
** Neusverkoudheid, irritatie neusslijmvlies. Lauwe kamillethee door neus opsnui­ven.
* Hooikoorts
* Griep
* Bronchiaal astma bij kinderen

Anaal
* Ontstoken aambeien
* Anaaleczeem, anaalfissuren
** Pruritus ani (zitbaden)

Vaginaal, hormonaal
** Vaginitis, vulvitis         R./    Matric. fl. 33
                                               Salviae fol. 33
                                               Alchemillae hb. 33          Bereiding: infuus 2 eetlepels /1 liter/ 10'
                                                                                    Gebruik: Spoelingen en zitbaden

** Pruritis vulvae.
* Witte vloed (leucorroe)
* Na bevalling, episiotomie ( operatieve incisie waarmee de vagina-opening tijdens de bevalling wordt vergroot)
* Menstruatie gepaard met kramp en pijn (zie oa Poten­tilla anserina, zilverschoon))
* Dysmenorroe (onregelmatige, pijnlijke menstruatie)
* Beginnende menstruatieproblemen in de pubertijd van psychische aard (gevoelig en angs­tig)

Ogen
* Rode vermoeide ogen (zie ook Foeniculum en Euphra­sia)
* Conjunctivitis (bindvliesontsteking).

Haar
* Haar blonderend middel

Zenuwstelsel
* Rustgevend vooral voor kinderen in combinatie met Melissa en Hypericum

Receptuur en Bereidingswijzen

Chamomillae flos / Matricariae flos
Infuus: 1 koffielepel tot 1 eetlepel /kop 10'
Dosering: 1-2 koppen 3 x d. 1 u vóór eten
1 eetlepel = ± 2,50 g
1 koffielepel = ± 1,00 g

Pulvis: R./ Matricaria flores pulv. fl. 750 mg          Bereiding: Vers gemalen + suiker
Saccharum 250 mg                                             Dosering: 2 tot 6 x daags 1 u vóór eten

Species: R./ Matricaria 20
Foeniculi fr. 20
Althaeae rad. 20
Agropyron rhiz. 20                Bereiding: inf. 20-30'
Glycyrrhizae rad. 20             Indicaties: gastritis en maagulcus

Species 'ad cataplasmata' (DAB VI en Helv. V)
R./ Matric. cham. fl. 20
Althaeae pulv. fol. 20
Malvae pulv. fol. 20                    Bereiding: 1 eetl. mac. 30' + dec. tot brij
(Melliloti pulv. hb. 20)                 Indicaties: abces, furunkels
Lini pulv. sem. 20 (40)                Gebruik: warm toepassen

Species 'ad gargarisma' (Pahlow)
I. R./ Matric. cham. fl. 50
Salviae fol. 50

II. R./ Matric. cham. fl. 33
Tormentillae rad. 33
Tussil. farf. fol. 33

Species infantum (Wiener Vorschrift)
R./ Matric. cham. fl. 12,5
Foenic. fruct. 12,5
Althaeae rad. 25
Glycyrrhizae rad. 25                   
Agropyron rhiz. 25               Indicatie: spasmolytisch sedativum voor kinderen               

Species carminativae (Weiss)
R./ Matricaria fl. 50
Carvi fr. 10
Foeniculum fr. 10
Menthae piperita fol. 30

R./ Helv. VI.
Matricaria fl. 25
Carvi. fr. 30
Menthae fol. 20
Calami rhiz. 15
Valerianae rad. 10

Kamille-olie (Valnet) R./
Matric. fl. 20 Bereiding: 2 u verwarmen bain marie,
Olijfolie 100 10 g kamfer toevoegen.
Indicaties: reuma- en jichtpij­nen

Geschiedenis En Wetenschappelijk Onderzoek
- Galenus zegt dat Egyptenaren Kamille als toegewijd aan zon zagen en tegen koorts gebruikten.
- Dioscorides meldt ook gebruik tegen koorts.
- N. Lémery - 1667: Verzachtend, carminatief, pijnstillend voor menstrua­tieproblemen.
- Lieutaud - 1766: Spasmolyticum, koortswerend, tegen jicht- en reumapijnen.
- Dr. Cazin - 1876: Traité pratique et raisonné des plantes médicinales. Bij de beste tonise­rende, kalmerende, koorts­werende en spijsvertering-bevorde­rende kruiden.
- Caujolle en Duitse school: E.o. bactericide tegen Prot. vulg., azuleen 1/2000 bactericide bij sommige Staphylo­coccen.
- Galenus (Volgens P. Nylandt.): 'Is verwarmende en verdrog­en­de in de 1ste graad / ontdoende / verterende / pijnstil­lende.'
- Dodonaeus: 'Voor Buyckpijn ende om de Maandstonden te verwekken.' (Bloe­men in bier of wijn gekookt.)
- P. Nylandt: 'Voor Graveel en pijn in de blaas, voor buik­pijn der kleine kinderen, voor oude hoofdpijn, voor zwel­lingen en pijn in de leden.'

Referenties

  1. H. Becker e.a.: Over flavonoïden. Dtsch. Apoth. Ztg. 121/1285 - 1981.
  2. V. Jakovlev e.a.: Over de antiflogistische werking van alfa-bisabolol, chamazuleen en matricine. Planta med. 49/67 - 1983.
  3. V. Achterrath-Tuckermann e.a.: Over de muscu­lotroop-spasmo­lytische werking van de flavo­noïden en alfa-bisabo­lol­. Planta med. 39/38 - 1980.
  4. O. Isaac, K. Thiemer: Antisep­ti­sche en ulcuspro­tectieve werking van alfa-bisabolo­l. Arzneim. Forsch. 25/1352 - 1975.
  5. M. Kienholz: Ontgiftende werking van bacterie-toxinen. Dtsch. Apoth. Ztg. 102/1076 - 1962.
  6. K. Thiemer e.a.: Invloed op de huidstofwisseling. Arzneim. Forsch. 23/756 - 1973.
  7. R. Della Loggia e.a.: Kamille-flavonen, (apigenine, luteol­ine) hebben een lokaal ontstekings­werende werking gelijk aan Indometa­cine (door crotonolie geïnduceerde dermatitis bij mui­zen). Prog. Clin. Biol. Res. 213/481 - 1986.
  8. H. Schilcher: Die Kamille. Wiss. Verlagsges. Stuttgart - 1987.
Algemene literatuur
Dr. Reinhold Carle en Dr. O. Isaac: Overzicht wetenschappelijk onderzoek Pharmaz. Entwicklung des Geschäftsbereichs Pharma der Degussa AG, Daimler­str. 25, 6000 Frankfurt I.
O. Isaac, H. Schimp­ke e.a.: Over­zicht geschie­denis. Mitt. Deut. Pharm. Ges. 35/133-170.
http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2014/07/WC500170079.pdf

Internetlinks
Info impetigo: Impetigo is een oppervlakkige huidinfectie die wordt veroorzaakt door bacteriën. Een impetigo in het gezicht wordt ook ‘krentenbaard’ genoemd. De infectie komt vooral voor bij kinderen en is zeer besmettelijk voor andere kinderen in de omgeving, zoals op school, in kinderdagverblijven, sportclubs, enz. Ook bij een wondje op de huid en bij kinderen die al een huidziekte hebben, zoals eczeem of schurft, is de kans op het ontstaan van de infectie groter. Meestal zijn kinderen met impetigo verder heel gezond. Ook volwassenen kunnen impetigo krijgen, vooral wanneer ze al een huidaandoening hebben zoals eczeem.
Impetigo komt vrij veel voor. In België zouden jaarlijks 1 op 100 kinderen in de leeftijdsgroep tussen 0 en 4 jaar besmet worden. Bij kinderen tussen 5 en 14 jaar wordt het aantal jaarlijkse gevallen geschat op 7 per 1000, tussen 15 en 24 jaar op 2 per 1.000.

Impetigo kan veroorzaakt worden door twee verschillende bacteriën: meestal gaat het om de stafylokok (Staphylococcus aureus), soms om de streptokok (groep A beta-hemolytische streptokokken of Streptococcus pyogenes). Ook menginfecties van beide kiemen zijn mogelijk. 
De infectie wordt vergemakkelijkt wanneer de huid beschadigd is door bijvoorbeeld insectenbeten of een schaafwondje. Op een gave huid kunnen de bacteriën niet binnendringen. Een letsel ontstaat steeds op de plaats waar de huid beschadigd is. Zodra de bacterie zich eenmaal in de huid genesteld heeft kan zij zich snel vermenigvuldigen en kan de impetigo zich uitbreiden over grote delen van de huid.


Anti-anxiety Effects of Chamomile Compounds.
HerbalGram. 1997;39:19 © American Botanical Council

Although its use has been traditionally recommended in mild sleep disorders in children, the use of chamomile as a mild sedative has not been substantiated in authoritative references, including the German Commission E monographs. A study using an aqueous extract of the dried flower heads of German chamomile (Matricaria recutita L., Asteraceae) investigated the affinity of several fractions of the plant for central benzodiazepine receptors in mice. Apigenin, one of the predominant flavonoids in chamomile, was found to competitively inhibit the binding of the drag flunitrazepam, benzodiazepine derivative. At doses up to 30 mg/kg, apigenin was shown to have a clear anxiolytic (anti-anxiety) activity without the sedation or muscle relaxing effects noted for benzodiazepine drags (e.g., Valium(r)) and without noticeable anticonvulsant effects. Dosages of 30 mg/kg and 100 mg/kg produced dose-dependent sedation characterized as mild. The results demonstrate that the flavonoid apigenin in chamomile produces an anti-anxiety effect without producing marked CNS depression. According to the authors of this study, chamomile from Argentina and neighboring countries is higher in free apigenin than species from other parts of the world.

This study adds chamomile to the growing list of herbal anxiolytics which includes valerian, kava, and passion flower. The anxiolytic actions of chamomile most closely compare to passion flower. Previous research identified chrysin (5,7 dihydroflavone) as the primary component in passion flower exhibiting benzodiazepine-receptor activity.(1) Valerian has potent GABA-A (gamma-aminobutyric acid, a neurotransmitter) binding activity, although the particular fraction of the plant's root having greatest activity has not been identified as is the case with chamomile and passion flower.

It is unlikely that chamomile products will be standardized on apigenin content in the next few years. In this respect and because chamomile use has been reduced to commercial tea formulations that claim to be "calming" and useful for sleep, the herb will continue to be undemtilized.

Traditional and modern phytomedicine preparations of chamomile use the flower heads just prior to blooming. In Germany alone, there are more than 90 licensed preparations of chamomile. European creams and ointments for topical application are made with a 3-10 percent chamomile concentration. Chamomile is a useful herb for small children because of its rather pleasant taste. Allergic reactions attributed to chamomile ingestion are uncommon,(2) but users should be careful of contact with the eyes. Persons with a history of allergies to the daisy family should likewise be cautioned about its use. The Commission E monographs(3) list no known contraindications for the use of chamomile, even during pregnancy and lactation.

(1.) Wolfman, C., H. Viola, A. Paladini, et al. 1994. Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacology Biochemical Behavior; 47:1-4.
(2.) Mann, C., E. J. Staba. 1986. The chemistry, pharmacology, and commercial formulations of chamomile. In: Herbs, Spices, and Medicinal Plants: Recent Advances in Botany, Horticulture, and Pharmacology (Craker, L. E., Simon, J. E., eds.). Phoenix, AZ: Oryx Press; 1:23980.
(3.) Blumenthal, M., J. Greenwald, T Hall, C. W. Riggins, R. S. Rister (Eds.), S. Klein and R. S. Rister (trans.) 1997. German Commission E Monographs. Austin, Texas. American Botanical Council.
 


Herbalists don’t simply study what herb is good for what condition. Instead, each plant is analyzed on a variety of therapeutic levels. One important aspect of this is the plant’s ability to warm or cool a person. Have you ever eaten really spicy wasabi and then felt your sinuses drain? Or eaten a fresh slice of watermelon on a hot day and felt cooled and refreshed? If so, then you’ll know exactly what I am talking about. 
Every medicinal plant has these characteristics to some degree or another, and understanding these actions helps herbalists to be more effective at choosing which plant can help a particular person. 
Chamomile is relatively neutral in temperature but perhaps slightly warming. Generally, our more neutral plants can be taken by most people and in higher amounts without causing unwanted effects. 
The taste of chamomile gives us further insight into how it works. 

Chamomile: Powerfully Ally for Digestion
The taste of a plant is also very important in understanding the plant’s actions. 
For example, the bitter taste on our tongue creates a cascade of events that promotes our digestive function. From stimulating saliva (our first digestive juice) to various enzymes in the stomach, liver and pancreas, one can argue that the bitter taste is needed at every meal. 
A strongly brewed cup of chamomile provides this bitter taste, thus promoting healthy digestion. 
Chamomile can be especially beneficial for people with a “nervous stomach” as it both calms and soothes while stimulating digestive function. It can also be used by people with digestive inflammation (such as heartburn or IBS) to mediate inflammatory levels in the gut mucosa. 
Furthering helping with digestion are chamomile aromatic qualities which break up stagnant digestion. Ever had stagnant digestion? It's characterized by bloating and the feeling that there's a bowling ball in your stomach. 

Chamomile for Relaxation
Chamomile has many applications for common complaints. Besides helping to relax the nervous system chamomile also can relax muscle tissue. Women may find their menstrual cramps abated with a strong cup of chamomile tea, or diminished by rubbing their abdomen with oil infused with chamomile blossoms. 
Any mother whose colicky or teething child has been soothed to sleep (or simply quieted) by chamomile will tell you this is beneficial stuff! 

List of Issues Chamomile Can Help
Keeping in mind the above energetic considerations as well as the broader personalized considerations (diet, food intolerances, lifestyle etc). I commonly use chamomile for people with the following health issues. 
  • soothe teething, colicky or grumpy children
  • gas
  • bloating
  • diarrhea
  • leaky gut
  • tension headaches
  • difficulty sleeping
  • butterflies in stomach
  • anxiety
  • menstrual cramps
  • promote beautiful skin
  • eczema
How to make chamomile as medicine
If you’ve ever stuck a chamomile tea bag into a cup of hot water for five minutes, then you’ve experienced chamomile as a delightful and slightly sweet tea. 
To get more therapeutic results, use more chamomile and steep for longer. I generally use 1/2 cup of flowers to a pint of just-boiled water and I let it steep for 20-30 minutes. The resulting brew is decidedly less sweet and more bitter than a cup of tea but this stronger concoction provides more relief for many of the issues listed in this article. 
Besides drinking this strong infusion, it can also be used on skin as a rinse or added to bath water to relieve itching of mild rashes. 
Chamomile is also used as a tincture, a glycerite and as an infused oil. 

Special Considerations
Most people will find that chamomile is effective and safe. A small percentage of people are allergic to chamomile and will have reactions. It's always best to try new herbs and foods in small amounts. 



Kamille antroposofisch bekeken.

De wel het meest gebruikte en bekendste van alle geneesplanten is de kamille (Chamomilla reculita). In het wild komt zij niet zoveel voor; ze wordt gemakkelijk met andere samengesteldbloemigen die erop lijken verwisseld. De kamille heeft kleigrond met voldoende vochtigheid en veel zon nodig; men vindt haar ook op zouthoudende, alkalische standplaatsen: omstandigheden die in ideale vorm in Hongarije bestaan, waar dan ook de grootste oogsten vandaan komen.

Uit het zaad dat in de zomer omlaagvalt, ontwikkelen zich in de herfst allereerst kleine rozetten van zachte, fijngeveerde, bij nadere beschouwing echter enigszins vlezig aandoende blaadjes, waaraan de typische kamillegeur nog totaal ontbreekt. In plaats daarvan hebben zij een scherpe, op radijs lijkende smaak. Ook gedurende de winter, onder ijs en sneeuw, groeien de bladrozetten verder om dan bij het begin van het warmere jaargetijde een krachtige, sappig-groene, rijk van bladeren voorziene loot omhoog te stuwen. Nu pas, terwijl zij opgroeit en gaat bloeien, krijgt de kamille de ons vertrouwde gedaante. Door sterke vertakking en strekking van de stengeldelen gaan de bladeren ver uit elkaar; zij worden droger. Vanaf het begin van de bloei beginnen zij van onder naar boven geel te worden en te verwelken. Als een lichte wolk zweven aan de toppen van de vele dunne stengels de sierlijke samengestelde bloemen boven het veld. Bij de lichtste aanraking verspreiden zij hun typische, zoet-warme geur. De aanvankelijk vlakke bloemkorfjes bollen in het verloop van de bloeitijd steeds meer kegelvormig omhoog, de witte randbloempjes buigen omlaag. In de holle bloembodem is een kleine luchtruimte ingesloten. Uit de bloemen kan de blauwe etherische kamilleolie worden gedestilleerd. Bijna iedereen zal wel eens de genezende, infecties tegengaande, kramp oplossende en verwarmende wer­king ervan hebben ervaren.

De vruchtjes van de kamille ontwikkelen zich spoedig na de bloei. Zij zijn niet hard en niet, zoals dikwijls bij composieten, van weerhaakjes of vleugeltjes voorzien, maar zacht en vochtig. Zij vallen in de onmiddellijke omgeving op de grond. Aldus sluit zich de levenscyclus van deze weldadige geneesplant, die in de loop van haar ontwikkeling een zo grote verandering doormaakt. De waterig-plastische bouw van de jonge, ontsprui­tende kamille wordt met het ingrijpen van de impuls om te bloeien onderworpen aan een a.h.w. plantaardig beteugeld verbrandingsproces, dat het type van de hele plant naar het droog-aromatische verschuift en in de bloemen de zachte etherische olie laat ontstaan.

Weledaberichten, 128 dec.1982



Planta Med. 1995 Jun;61(3):213-6.
Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects.
Viola H1, Wasowski C, Levi de Stein M, Wolfman C, Silveira R, Dajas F, Medina JH, Paladini AC.
The dried flower heads of Matricaria recutita L. (Asteraceae) are used in folk medicine to prepare a spasmolytic and sedative tea. Our fractionation of the aqueous extract of this plant led to the detection of several fractions with significant affinity for the central benzodiazepine receptor and to the isolation and identification of 5,7,4'-trihydroxyflavone (apigenin) in one of them. Apigenin competitively inhibited the binding of flunitrazepam with a Ki of 4 microM and had no effect on muscarinic receptors, alpha 1-adrenoceptors, and on the binding of muscimol to GABAA receptors. Apigenin had a clear anxiolytic activity in mice in the elevated plusmaze without evidencing sedation or muscle relaxant effects at doses similar to those used for classical benzodiazepines and no anticonvulsant action was detected. However, a 10-fold increase in dosage produced a mild sedative effect since a 26% reduction in ambulatory locomotor activity and a 35% decrement in hole-board parameters were evident. The results reported in this paper demonstrate that apigenin is a ligand for the central benzodiazepine receptors exerting anxiolytic and slight sedative effects but not being anticonvulsant or myorelaxant.



Anti-inflammatory effects Matricaria recutita

In vitro:
Isolated substances:
The therapeutic potential of apigenin as an anti-inflammatory agent contributing to the clinical antiinflammatory
efficacy of matricaria extracts was demonstrated in vitro through its ability to interfere
with leukocyte adhesion and adhesion protein upregulation in human endothelial cells (Gerritsen et al.
1995). It also inhibited interleukin 1α (IL-1) induced prostaglandin synthesis, tumor necrosis factor α
(TNFα), induced IL-6 and IL-8 production and blocked adhesion of leukocytes to cytokine treated
endothelial cells. In murine macrophages 3.7 and 37 µM apigenin significantly inhibited LPS-induced
IL-6 production in a dose dependent manner, but not TNFα (Smolinski and Pestka 2003). Other studies
using apigenin in cell culture models have also shown that this flavonoid has inhibitory effects on
prostaglandin E2 (PG-E2), cyclooxygenase 2 (COX-2) and nitric oxide production (Liang et al. 1999).
Chamazulene has also been shown to inhibit the inflammatory process in vitro (Safayhi et al. 1994). At
15 µM chamazulene inhibited the synthesis of leukotriene B4 in stimulated rat peritoneal neutrophilic
granulocytes by 50%. In a cell-free system 2 µM chamazulene blocked the chemical peroxidation of
arachidonic acid.
Examining histamine release from rat mast cells en-in-dicycloether partly inhibited a protamine
sulphate provoked degranulation at concentrations >100 µM, whereas neither chamazulene nor α-
bisabolol had any effect. (Miller et al. 1996).

In vivo:
Matricaria extracts:
A freeze dried extract of matricaria (no further information available) given to Wistar rats suppressed
both, the inflammatory effect and leucocyte infiltration induced by simultaneously given carrageenan
and prostaglandin E1 (Shipochliev et al. 1981).
In mice fed a diet containing 1.2% (w/w) of an ethyl acetate extract of dried M. recutita flower for 11
days, scratching behaviour induced by the compound 48/80 was suppressed in a dose- dependent
manner (Kobayashi et al. 2005). The extract was prepared with 350 g dried flowers of Matricaria
recutita extracted with 7 l ethyl acetate twice under sonication for 3 h at 70°C. The extract was filtered
and the filtrate evaporated under reduced pressure and freeze dried. (14.0 g extract). The extract at a
dose of 100, 300 and 1000 mg/kg dissolved in a vehicle of 10% ethanol, 10% Tween 80 and 80%
physiological saline solution were orally administered. Scratching behaviour induced by compound
48/80 was significantly suppressed by the upper two doses (p=0.05) with a non altered spontaneous
motor activity.
In Swiss mice the topical application of a hydroalcoholic extract of Matricaria recutita (20 g flos to
100 ml ethanol 42%V/V) to the inner surface of the ear reduced edema induced by the application of a
2.5% emulsion of croton oil (Tubaro et al. 1984). The extract contained: 0.05 mg/ml of (-)-α-
bisabolol, 0.45 mg/ml of bisabolol oxides, 0.4 mg/ml apigenin and its glucosides, 0.8mg/ml en-indicycloethers,
0.02 mg/ml azulenes). 1 ml of extract corresponds to 50 mg dry extract. The groups
with 40 animals each were treated with 0.08; 0.25; 0.75 mg dry extract. Compared to control animals
(n=104) mice treated with 0.25 mg of matricaria showed 8.5% reduction in edema and those treated
with 0.75 mg had a 23.4% reduction. No significant changes were seen in the group treated with
0.08 mg. The effect in the 0.75 mg group was similar to the positive reference treated with 0.45 mg
benzydamine used as a positive control. Neither reached the level of reduction induced by 0.15 mg
hydrocortisone (56%).

Della Loggia et al. (1990) found that topical treatment with an extract of fresh matricaria containing
51.8 mg/100 g bisabolol, 29.6 mg/100 g matricine, and 5.3 mg/100 g apigenin at a dose equivalent to
750 µg of dry product (n=25) was as effective as the reference drug 0.60 mg benzydamine (n=25) in
preventing inflammatioin in mice subjected to croton oil induced edema. The benzydamine, fresh
matricaria extract and dried matricaria extract (54.6 mg/100 g bisabolol, 16.4 mg/100 g matricine,
6.3 mg/100 g apigenin; n=26) inhibited the inflammatory response by 31.5%; 31.6% and 23.7%
respectively compared to the control group (n=41).

The antiulcerogenic properties of Matricaria chamomilla hydroalcoholic extract (MCE) on ethanolinduced
gastric mucosal injury were investigated by Cemek et al. (2010) in rats. Airdried Matricaria
recutita (plant part and status not specified) was pulverized. 100 g plant material was extracted with
1 l Ethanol 37% in a soxhlet apparatus. The extract was lyophilized. Group 1 (7 rats each) received
ethanol, groups 2-6 received 25, 50, 100, 200, 400 mg MCE/kg, group 7 received famotidine + ethanol
as positive control. After the induction of gastric mucosal injury, all groups were sacrificed; the gastric
ulcer index (total ulcer area/total gastric area) was calculated, and malondialdehyde (MDA) and
reduced glutathione (GSH) in whole blood and gastric tissue, and serum ascorbic acid, retinol, and
beta-carotene levels were measured in all groups. MCE clearly has a protective effect against ethanolinduced
gastric mucosal lesions (Control (ethanol) 20.67±1.6; MCE-25+ethanol 18.79±2.8; MCE-
50+ethanol 11.87±1.2; MCE-100+ethanol 15.96±1.7; MCE-200+ethanol 8.61±2.7; MCE-400+ethanol
10.29±2.7), and this effect, at least in part, depends upon the reduction in lipid peroxidation and
augmentation in antioxidant activity.

Al Hindawi et al. 1989 tested Matricaria recutita flowers. Approximately 50 g of dried plant material
was extracted with 80% ethanol (3 x 500 ml; no information whether V/V or m/m) by shaking for 3 h
at room temperature. The supernatant was evaporated at 40°C. The residue was dissolved and
resuspended in distilled water using a minimum amount of Tween 80. Each g of the dried extract was
equivalent to 4.05 g of the fresh plant material. 400 mg/kg extract reflecting 1.62 g fresh plant
equivalent /kg inhibited rat paw edema at 41.1% of control (P>0.01).

Essential oil:
Kobayashi et al. (2005) determined the antipruritic effect of the matricaria essential oil. The essential
oil groups (100, 300 and 1000 mg/kg) reduced the scratching behaviour significantly with 300
(p<0.01) and 1000 mg/kg (p<0.001).
Della Loggia et al. (1990) found that topical treatment with the matricaria essential oil containing
55.6 mg bisabolol/100 g , 4.7 mg chamazulene/100 g , but no matricine or apigenin at a dose
equivalent to 30 μg essential oil showed no effect in preventing inflammatioin in mice subjected to
croton oil induced edema (6.6% inhibition n=25).

Isolated substances:
(-)-α-bisabolol was able to decrease leukocyte migration, protein extravasations and the amount of
TNF-α to the peritoneal cavity in response to carrageenan induced rat paw edema. Additionally, (-)-α-
bisabolol reduced neutrophil degranulation in response to phorbol-myristate-acetate (Rocha et al.2011).
Proinflammatory cytokine production was inhibited in mice treated with 50 mg apigenin/kg for 1 h
then injected with stimulant Lipopolysaccharide (LPS) (Smolinski and Pestka 2003). Apigenin inhibited
LPS-induced IL-6 (65% less than control) and/or TNFα production (76% less than control) in serum of
the mice. Apigenin showed anti-inflammatory activity in carrageenan induced rat paw edema (Al
Hindawi et al. 1989; Gerritsen et al. 1995).

Panés et al. (1996) injected male Sprague-Dawley rats intraperitoneally with rTNF (rat Tumor necrosis
factor) and induced a significant increase in ICAM-1 expression (intracellular adhesion molecule 1) in
different organs (lung 38%, kidneys 29%, liver 67%, heart 197%, skeletal muscle 257%, mesentery
176%).Treatment with apigenin 100 mg/kg significantly decreased ICAM-1 expression after rTNF
administration in all organs. It completely abrogated the rTNF induced upregulation in lung, liver and
brain. It significantly attenuated the ICAM-1 responses in heart, pancreas and mesentery and blocked
ICAM-1 upregulation in skeletal muscle.

Hempel et al. (1998) tested constituents of topical Matricaria preparations in inflammations of the
mouse ear induced by arachidonic acid, phorbolmyristate acetate and oxazolone. Bisabololoxide A and
B showed an anti-inflammatory effect comparable to bisabolol. Matricin and chamazulen (1x10-6 molar
each) seemed to be a little less effective, but it has to be considered the slow transformation from
matricin to chamazulene at the skin. The En-in ether, predominantly the cis form, showed a good antiinflammatory
effect contrarily to in vitro data. Apigenine was more effective than apigenine-7-
glycoside. The constituent with known therapeutic activity is according to the data not a single one but
the effectiveness results from the interplay of different constituents as described.
In rats, both apigenin and α-bisabolol inhibited the development of gastric ulcers induced by
indomethacin, stress and alcohol (Szelenyi et al. 1979). In this study, α-bisabolol was also shown to
reduce healing times in ulcers induced by either chemical stress or heat coagulation.

Assessors comment:
In vitro pharmacological data for the constituents of matricaria recutita containing extracts and in vivo
data for different extracts as well as constituents thereof show in several experiments a decrease of
Assessment report on Matricaria recutita L., flos and Matricaria recutita L., aetheroleum
EMA/HMPC/55837/2011 Page 36/62
the inflammatory reaction documented by controls. These data exist not for all herbal preparations
included in the monograph. Furthermore the concentrations/dosages used are relatively high.

Wound healing Matricaria recutita

In vivo:
Matricaria extracts:
Wound healing activity was determined by Nayak et al. (2007) using excision, incision and dead space
wound models. Sprague-Dawley rats were divided into two groups of six for each model: animals in
the test group were treated with the aqueous extract of M. recutita (120 mg/kg/day) (no further
specification), which was mixed in their drinking water. Animals in the control group were maintained
with plain drinking water. Healing was assessed by the rate of wound contraction, period of
epithelialisation, wound-breaking strength, granulation tissue weight and hydoxyproline content on
days 1, 5, 10, 15. Wound contraction and epithelisation were significantly better in the test group
resulting in a healing 3 days earlier under matricaria, differing from day 10 on. Wound breaking
strength in incision wounds was significantly higher in the test group (control 428.30 g ±14.47/ test
654.10±16.50; p= 0.02).

Martins et al. (2009) treated 125 wistar rats in 5 groups with: no drugs (group I), Matricaria
(commercially in Brazil available matricaria preparation AdMuc; no further specification) (group II),
topical triamcinolone acetonide (group III), clobetasole propionate cream (group IV); clobetasole
propionate paste (group V). Under anaesthesia traumatic ulcers were applied with an 3 mm circular
scalpel. After 1, 3, 5, 7, 14 days each 5 rats were sacrificed to evaluate the grade of wound healing
(grade 1 total healing, grade 5 epithelial ulcer and acute inflammatory infiltrate). In the clinical
analysis all rats of the matricaria group had healed ulcers at 5 days whereas the other groups reached
that status after 14 days. The wound healing in the corticosteroid groups were significantly lower than
in the control group. To check the influence of the different tested preparations a viability testing was
done with an established cell line of human gingival fibroblasts (FMMI) using MTT reduction. The
matricaria replicates (n=8) showed the least viability.
Thirty male Wistar rats (250-300 g) were randomly divided by Jarrahi et al. (2008) into three groups,
as control, vehicle, and treatment. Second-degree burning was induced in 20% of whole surface area
of animal body by placing the back of animal into boiling water for 8 s. Animals of control group
received no treatment. Animals of vehicle and treatment groups were treated topically by olive oil and
extract dissolved in olive oil (100 g Matricaria recutita flowers added to 100 ml olive oil) twice a day
respectively from the first day of burn induction to complete wound healing. Control group and vehicle
group showed no differences, but the difference between control and verum was statistically significant
(p=0.05) and all the wounds were healed 11 days earlier than in the control group.
Assessors comment:
In vivo data of Matricaria recutita containing extracts showed in rats a better wound healing than the
controls.

Gastrointestinal effects Matricaria recutita

In vitro:
Matricaria extracts:
Using the isolated guinea pig ileum Forster et al. demonstrated the effectiveness of an ethanol extract
of matricaria (ratio herbal substance:extraction solvent= 1:3.5; extraction solvent: ethanol 31%
(m/m)) on spasms induced by acetylcholine and histamine. At doses of 2.5 and 10 ml/l the matricaria
extract increased the median effective dose (DE50) of acetylcholine and histamine in a dose-related
manner, also when the effect of ethanol was subtracted. Nevertheless, the effect was far less than that
of the usual therapeutic atropine dose (recalculated to the in vitro system) (Forster et al. 1980).
The cyclic nucleotides cAMP and cGMP regulate the smooth muscle tone of the intestinum causing
relaxation. Inhibition of phosphodiesterases (PDEs), which catalyse the hydrolysis of cAMP and cGMP to
5’-AMP and 5’-GMP, is one of the mechanisms operated by spasmolytic drugs. The effect of matricaria
on cAMP- and cGMP-phosphodiesterases (PDE) was investigated by Maschi et al. 2008. Human platelet
cAMP-PDE and recombinant PDE5A1 were assayed in the presence of infusions prepared from sifted
flowers and capitula. LC-ESI-MS/MS analysis showed different compositions in infusions made with
dried flowers (infusion with hot water, lyophilized, DER: 3.5:1). Matricaria inhibited cAMP-PDE activity
(IC50 = 17.9-27.2 µg/ml), while cGMP-PDE5 was less affected (-15% at 50 µg/ml). Flavonoids showed
an inhibitory effect (IC50 = 1.3-14.9 µM), contributing to around 39% of the infusion inhibition.

Isolated substances:
The antispasmodic effects of different matricaria compounds have been examined in isolated guinea
pig ileum. According to Achterrath-Tuckermann et al. (1980) compounds contained in both aqueous
and oil extracts of the plant are effective antispasmodics in isolated guinea pig ileum. Compared to
papaverine, a smooth muscle relaxing drug α-bisabolol was 91% as effective on spasms induced with
barium chloride while bisabolol oxides A and B were 46-50% as effective. Among the flavonoids tested
apigenin was 3.3 times more potent than papaverine, followed by quercetin (72% as active), patuletin
(68%) and luteolin (44%).

In vivo:
Chamomile extracts:
The effect of ColiMil as phytotherapeutic formulation and its herbal components (methanolic Matricaria
recutita flowers extract, aqueous Foeniculum vulgare fruit extract and aqueous Melissa officinalis aerial
parts extract) (no further information available) on upper gastrointestinal transit was investigated in
mice in vivo. Reference drug was loperamide (~0.25 mg/mous). Oral administration of the herbal
formulation (0.4-0.8 ml/mice, corresponding to 0.89-1.78 mg methanolic Matricaria recutita extract)
dose-dependently delayed upper gastrointestinal transit (lower dosage: 17%; higher dosage: 24%).
Matricaria recutita extract itself (0.89 and 1.78 mg/mouse) reduced motility significantly (lower
dosage: 10%; higher dosage: 15%). Loperamid reduced motility by 17% (Capasso et al. 2007).

Isolated substances:
Apigenin, at 12.5-50 mg/kg administered i.p. reduced both small and large intestinal transit time in
mice with castor oil induced diarrhea (Di Carlo et al. 1993).
Assessors comment:
Antispamodic effects of extracts and compounds of extracts were described in vitro and in vivo. The
clinical relevance of the effects seen in vitro seems to be low, while the effects seen in vivo were seen
with a methanolic extract with no further details. A correlation to the extracts/indications of the
monograph is not possible, however, a certain plausibility concerning the antispasmodic effects can be
retrieved from such data

Antimicrobial activity Matricaria recutita

Matricaria extracts:
An ethanolic extract of matricaria inhibited the growth of herpes and polio virus (Aggag and Yousef
1972, Vilaginès et al. 1985).
In general aqueous extracts of matricaria were more effective against molds and yeast, while alcoholic
extracts showed higher activities against bacteria (Al-Ismail and Talal 2003).
Antimicrobial activity of the aqueous extract of M. recutita against various microorganisms
(Pseudomonas aeruginosa, beta haemolytic streptococci, Enterobacter agglomerans, Escherischia coli,
Staphylococcus aureus) was assessed. These germs were resistant to the extract (Nayak et al. 2007).

Essential oil:
Essential oils extracted from matricaria have exhibited some antimicrobial activity against certain
species of bacteria, fungi and viruses in vitro. German matricaria oils were slightly more effective
against 25 different gram-positive and gram-negative bacteria and 20 strains of Listeria
monocytogenes than oil from Roman matricaria (Chamaemelum nobile) but neither was as effective as
Marrocan Matricaria (Ormensis multicaulis) (Lis-Balchin et al. 1998). The efficacy of these oils was 8-
56%. The antifungal activities of the German matricaria oils against Aspergillus niger, Aspergillus
orchraeus and Fusarium culmorum were 63-75% inhibition.
Soliman and Badeaa (2002) reported antifungal activities of M. chamomilla oil against Aspergillus
flavus and A. parasiticus as well as F. moniliforme. The highest used concentration (3000 ppm)
demonstrated the highest inhibition (91-95%).

Effects on the central nervous system Matricaria recutita

Aqueous extracts of matricaria flowers:
Della Loggia et al. (1982) employed a lyophilized aqueous extract of matricaria prepared with 50 g
flowers infused for 5 min with 1 l boiling water to study basal motility, exploratory and motor activities
of Swiss NOS mice. Long-term motility was reduced by 57.1% within 10 min of treatment with
360 mg/kg matricaria i.p. (n=15) and reached a maximum inhibition of 92.1-97.5%, compared to
controls (n=15) 1.5-2.5 h later; motor coordination was not affected. Short-term motor activity was
reduced by 90% with a dose of 180 mg/kg i.p. (n=24). Locomotor activity was reduced by 46.0% and
56.5% and the number of head-dippings reduced by 34.4% and 39.4% with doses of 180-320 mg/kg
i.p. respectively. Matricaria administered at 160 and 320 mg/kg i.p. (n=16/group) potentiated
hexobarbital-induced sleep in mice by 37.1% and 62.7% respectively, compared to controls given
100 mg/kg of the barbiturate alone.

Shinomyia et al. (2005) observed that a matricaria extract, prepared by refluxing water in 1 h, has
benzodiazepine-like hypnotic activity to be antagonized by flumazenil, a BDZ receptor antagonist, at a
dose of 3 mg/kg. The substance showed a significant antagonistic effect on the shortening in sleep
latency induced by matricaria extract at a dose of 300 mg/kg. No significant effects were observed
with the matricaria containing extract on total times of wakefulness, non-rapid eye movement (nonREM)
sleep and REM sleep.

Essential oil:
In a study of ovarectomized rats Yamada et al. (1996) found that inhaling the vapour of matricaria oil
reduced a stress-induced increase in plasma adrenocorticotropic hormone (ACTH) levels. Diazepam coadministered
with the matricaria oil vapour, further reduced ACTH levels , while flumazenil, a
benzodiazepine (BDZ) receptor antagonist blocked the effect of matricaria oil vapour on ACTH.

Isolated substances:
Viola et al. (1995) tested a purified fraction of an aqueous matricaria extract containing apigenin
administered i.p. to examine its effects on anxiolytic, sedative, locomotor, myorelaxant and
anticonvulsive activities in mice. At 3 mg/kg, a dose similar to those used for benzodiazepines,
apigenin significantly increased the percentage of entries and time spent in the open arms of an
elevated plus maze, behaviors indicative of an anxiolytic effect. Doses up to 10 mg/kg produced no
changes in spontaneous ambulatory locomotor activity: at 30 and 100 mg/kg there was a 26% and
46% reduction in activity, respectively, and a moderate decrease in the head-dipping behaviors
indicating a mild sedative effect. At 100 mg/kg apigenin had no myorelaxant effect, in contrast to
3 mg/kg diazepam. In mice treated with doses up to 80 mg/kg apigenin no significant anticonvulsant
activity was found after challenge with 50-80 mg/kg of the seizure inducing pentylneterazole; however
at 20, 40, 80 mg/kg apigenin increased the onset time of convulsions by approximately 2 fold
compared to controls.

Avallone et al. (2000) tested much lower doses (0.5-10 mg/kg apigenin) without being able to show an
anxiolytic effect. At 1 mg/kg the number of entries and time spent in the open arms of an elevated
plus maze were higher than the control group, but did not reach statistical significance. The authors
reported similarly that apigenin had no myorelaxant effect up to 50 mg/kg and no effect on picrotoxin
(6-8 mg/kg) induced convulsions at 25 and 50 mg/kg apigenin. But apigenin reduced significantly the
time of latency in the onset of convulsions. Open filed tests showed significant reductions in locomotor
activities compared with controls at apigenin doses of 25 and 50 mg/kg but not at 12.5 mg/kg
indicating a sedative effect at higher doses similar to Viola et al. (1995). The lack of effect with the
addition of a benzodiazepine agonist to apigenin treated animals suggests that the sedative properties
of apigenin may not be due to a direct effect on benzodiazepine receptors, but to other
neurotransmitters.

Salgueiro et al. (1997) observed that 10 mg/kg apigenin administered to Wistar rats either pre- or
post-training had no effect on training or test session performance of inhibitory avoidance , active
avoidance or habituation to an open field , unlike diazepam which had an amnestic effect on animals
subjected to the same tests. Also in contrast to diazepam, apigenin had no effect on the tail-flick test,
indicating the lack of an analgesic effect. These results also suggest that apigenin affects
benzodiazepine receptors differently than classical benzodiazepine receptor ligands such as diazepam.
According to Medina et al. (1998) the separation index (ratio between the maximal anxiolytic dose and
the minimal sedative dose) for diazepam is 3 while for apigenin is 10. Compounds, other than
apigenin, present in extracts of matricaria can also bind benzodiazepine and GABA receptors in the
brain and are thought to be responsible for some of the sedative effects; however many of these
compounds are unidentified (Avallone et al. 1996).
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