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Origins:

Camomile (Camomilla volgare o Matricaria Chamomilla) is a very common plant which can be found around the margins of fields and in uncultivated and sunny areas. 

An officinal plant known since ancient times it is distinguished by the particular and pleasant scent of its small yellow flowers that once collected and dried are used for - apart from the well known tisane and infusion - the extraction of the functional active components useful in the pharmaceutical and cosmetic field. 

Introduction:

Chamomile is an annual plant belongs to Asteraceae (Compositae) family. The flowers have an active substance which is called essential oil and the most important its constituent is chamazulene that is used widely in pharmaceutical food perfumery and flavouring industry (Kacuric 1979; Galambosi and Holm 1991). The annual world consumption of chamomile flowers is more than 4000 ton (Franz et al. 1986). Medicinal plants production is mainly dependant on ecological condition. In this respect management of environmental parameters is very critical. By using correct planting time and plant density it will be possible to control radiation interception by plants. In Iran there are more than 7500 plant species which most of them have valuable active substances. One of the most important of them is chamomile that grows wildly in various ecological zones of Iran. Recently its cultivation in Tehran Lorestan Khoozestan Fars and Isfahan provinces has started and several drugs have produced from its essential oil. This is very important to reduce chemical drugs and increase individual health.

The question of the right planting time of chamomile in relation to its yield and essential oil content has been subject of discussion several times (Franz et al. 1985). Although it is stated that chamomile should be sown in autumn but it is dependant on ecological condition and objective of production. For example in spring sowing flavonoid and chamazulene content in flowers are higher than autumn sowing (Galambosi 1992; Letchamo and Vomel 1992) while flower yield is higher in autumn. There are no studies on spring cultivation of chamomile in these regions and chamomile is planted in autumn. One of the problems in these provinces is finding out the adaptability and correct cultivation practices. Chamomile is a long day plant and planting time has major effects on flowering and its quantitative and qualitative yield (Franz et al. 1986; Salamon 1992). Then by choosing correct time of planting and plant density growth and development will accordance with optimum temperature and solar radiation and subsequently yield will increase. 

Present studies have shown that German chamomile may be successfully cultivated possessing a great potential in Khojir region in Tehran province. Therefore it became imperative to find out the optimum planting time and plant density of chamomile to exploit its yield potential for its recommendation to the farmers of this region. 

The Camomile contains an essential oil which - although its composition and quantity (which varies from its place of origin and time of harvest) hasn't been thoroughly studied - has azulenes and bisabolol compounds of fundamental importance.

In books relative to this subject anti-inflammatory and  anti-allergic properties have been associated to these compounds let alone their capability to repair the skin tissues. 

There are actually two herbs commonly called chamomile: Roman (common) chamomile and German (Hungarian chamomile wild chamomile scented mayweed). Roman chamomile (Chamaemelum nobile Anthemis nobilis) is native in southwestern and northwestern regions of Europe (Spain France England) and is scattered around the eastern Mediterranean the Balkans and Crimea. German chamomile (Matricaria recutita Chamomilla recutita) is originally native to southeastern and southern Europe. It is one of the most commonly distributed medicinal herbs all over the world except the tropical and the arctic regions. Both chamomiles are used in traditional herbalism and medicine; however German chamomile is more frequently preferred for medicinal use. In addition chamomile extract and essential oils are frequently used as components in several cosmetic and hygienic products. 

Chemical Composition and Pharmacological Action: 

Chamomilla recutita the sun-loving plant of the plains is rich in active ingredients and has remained one of the most popular herbs since ancient times. There are different classes of active constituents which have been isolated and used individually in medical practice and cosmetics. The plant contains 0.24%–1.9% volatile oil which is a wonderful blend of different individual oils. This oil extracted from flower heads by steam distillation can range in color from brilliant blue to deep green when fresh but fades over time to dark yellow. Despite fading the oil does not lose its potency. The oil contains a-bisabolol (up to 50%) chamazulene cyclic sesquiterpenes which directly reduce inflammation and are mild antibacterials. The essential oil also contains bisabolol oxides farnesene and spiro-ether which have anti-inflammatory and antispasmodic actions. 

Important flavonoids have been identified in German chamomile including apigenin luteolin and quercetin. Recent research indicates that they display more or less inhibitory effects on certain malignant cell proliferation in vitro.Some alkylated flavonoids such as chrysoplenin chrysoplenol and jaceidin also have been traced. These compounds have recently been shown to possess anti-inflammatory and antispasmodic activity. Other classes of compounds identified are coumarins herniarin and umbelliferone. These have anti-inflammatory properties. In addition Matricaria recutita contains phenolic carboxylic acids such as vanillic anisic syringic and caffeic acids. Other relevant constituents are anthemic acid anthemidine tannin and matricarin. 

Roman chamomile contains up to 0.6% of sesquiterpene lactones of the germacranolide type mainly nobilin and 3-epinobilin. Some of the important flavonoids identified in matricaria such as apigenin luteolin and apiin are also found in Roman chamomile as is phenolic carboxylic acids (caffeic ferulic) coumarins and thiophene derivatives. 

Laboratory analysis:

Flowers were dried in an air ventilated oven at 35º C for 5 days. The extraction of the essential oil content per unit dry flower weight was based on steam distillation using Clevenger apparatus. The composition of the essential oil was determined using gas chromatography technique (GC) and Chamazulene content was determined by gas chromatography by mass spectrometry technique (GC/MS).

Statistical analysis:

Data ware subjected to statistical analysis using ANOVA a statistical package available from SAS. Means comparisons were done by Duncan multiple range test at 5% level. 

Nitrogen Application Affects Yield and Content of the Active Substances in Camomile Genotypes:

Camomile [Chamomilla recutita (L.) Rausch.] is an important medicinal plant whose multitherapeutic cosmetic and nutritional values have been established through years of traditional and scientific applications (Mann and Staba 1986; Schilcher 1987). Reports concerning the effect of nitrogen on growth yield and content of the active substances in camomile is contradictory and fragmentary. The objectives of this study was to compare the response of a diploid and two tetraploid camomile genotypes to low and high levels of nitrogen fertilization. A two year (1986-1987) pot experiment was conducted with three camomile genotypes under 5 different N levels. 

METHODOLOGY:

Seeds of three camomile genotypes a diploid (2n=18) and two tetraploids (BK2-39 and R-43 2= 36) were obtained from the breeding program of the Institute of Agronomy and Plant Breeding I Justus Liebig University Giessen. The essential oil composition and morphology of these lines were previously described (Letchamo and Vömel 1989; Letchamo 1990).

Seedlings were raised in a greenhouse and transferred to 5 liter Mitscherlich pots filled with 2.0 kg of soil (RH loess serosiom) and 4.0 kg of sand. Four plants/pot with 8 replications of each variant were planted in spring 1986 and 1987. Five levels of N (NH4NO3) were used as follows. N0 = no nitrogen N1 = 0.4 g N/pot N2 = 0.8 g N/pot N3 = 1.2 g N/pot and N4 = 1.6 g N/pot. During planting we applied 1.5 g/pot CaCO3 5.0 g/pot Fe 5.0 g/pot Mn 2.5 g/pot Cu 2.5 g/pot Zn 0.5 g/pot B and 0.05 g/pot Mo. The flowers were hand harvested at the medium stage of their development (Letchamo 1990) and dried at 38°C for 72 h. Circulatory steam distillation (2.0 g of the dry sample) was carried out in a Neoclevenger type apparatus (in 500 ml volume round bottomed flask with 300 ml deionized water) for 2 h using n-Pentan as a distillation receiver (Hölzl and Demuth 1979). The essential oil content was determined gravimetrically. Essential oil samples were diluted in 1 ml toluol and analyzed using Carlo Erba Instruments Model GC-6000 Vega Series-2; equipped with a flame ionization detector (FID) interfaced with a Spectrophysics Integrator Sp. San Jose California for chromatography data acquisition processing and quantitation. A 30 m x 0.25 mm id fused silica capillary column packed with a stationary phase of 0.25 µm thickness was used for the separation of volatiles. Carrier gas flow rate was 30 ml N/min; sample size was 1 ul direct injection with Hamilton Microliter syringe. Injector system was split-splitless with 1:20 ratio. Injection port temperature was 220°C detector oven temperature was adjusted to 240°C. Column temperature was programmed at 120°C for 0 min. 120° to 150°C at 30°C/min for 2 min. 150deg. to 175°C 10 min. 175°C to 220°C at 30°C/min. n-Hexadecane was used as an internal standard. The data were analyzed using analysis of variance following established statistical procedures (Dospechov 1979; Köhler et al. 1984) using SPSS/pc .

Morphological Changes and Flower Yield:

Plant height the straw yield number of productive tillers primary branches and volume of the flower heads significantly increased due to the increased levels of N application. Similar results were reported by Franz and Kirsch (1974) and Meawad et al. (1984) by applying N with K and some growth regulators at different levels respectively. Maximum response for straw was not reached by BK2-39 and R-43 even at N4. The straw yield of tetraploids however showed a significant growth with increased N application up to N4. A remarkably relaxed vegetative growth with thick leaves and branches was observed particularly by BK2-39 and R-43 at N4. At this N concentration the two tetraploid genotypes flowered ca. 8 days later than the control and lower levels of nitrogen (N1 N2 and N3) and remained dark green throughout the vegetation period.

The number of the flower heads and the drug yield (g/pot) significantly increased due to additional levels of nitrogen application in all the genotypes. The drug and straw yield of the diploid did not show much difference between N3 and N4. A difference of 1.9 and 6.1 g/pot between N3 and N4 was obtained for drug and straw respectively. The maximum drug yield response for this genotype was reached at N3 as further additions of N did not result in further increase. Similarly the drug yield difference between N3 and N4 was only 0.8 g/pot of the tetraploid BK2-39 with a maximum being at N3. The weight of individual flower heads increased only up to N2 in the diploid and BK2-39 and up to N3 in R-43. The difference was 11.2 g/pot for BK2-39 and 11.8 g/pot for R-43.

Components Identified:

1)     18-cineole (6.8%); 2) E-beta-farnesene (2.5%); 3) bisobolol oxide B (9.2%); 4) alpha-bisabolol (6.0%); 5) bisabolene oxide (4.4%); 6) bisabolol oxide A (40.3%); 7) chamazulene (29.7%) [All peaks confirmed by GC-MS]

CHEMICAL CONSTITUENTS:
Alpha Bisabolol Apigenin Axillarin Azulene Borneol Caffeic Acid Caprylic Acid Chamazulene Chlorogenic Acid Chrysoeriol Chrysosplenol Fructose Furfural Gentisic Acid Geraniol Glucose Herniarin Hyperoside Isorhamnetin Jaceidin Kaempferol Linoleic Acid Luteolin Mucilage Oleic Acid P-Coumaric Acid Palmitic Acid Patuletin Perillyl Alcohol Quercetin Quercetin-3-Galactoside Salicylic Acid Sinapic Acid Tannin Thujone Umbelliferone Xylose.

GC Chromatogram:

 

 

Structure of Major Compounds:

 

Oxygen free radical-related reactions are implicated in numerous pathophysiological conditions such as inflammation gastric ulceration neuronal degeneration and tumor promotion. Chamazulene was found to produce a significant protection against lipid peroxidation induced by Fe2 /ascorbate. Active oxygen species attacking membrane lipids (mainly polyunsaturated fatty acids) generate inflammatory responses and tissue damage. Therefore chamazulene as a potent antioxidant with low IC50 (18 µM) is comparable to known antioxidants such as quercetin (IC50 17 µM) or propyl gallate (IC50 10 µM) which have therapeutic value in the anti-inflammatory processes. Oxygen free radicals are also essential for the activation of 5-lipoxygenase enzyme a key enzyme in leukotriene production. Since leukotrienes are involved in the initiation and maintenance of a variety of inflammatory diseases it was reasonable to test the effect of chamazulene on leukotriene synthesis. Indeed chamazulene inhibited the formation of leukotriene B4 in rat peritoneal neutrophilic granulocytes in a concentration-dependent manner. 

Chamazulene an active ingredient of chamomile is a potent antioxidant valuable in the anti-inflammatory process: 

(–)-bisabolol was studied in experimental ulcer models with rats. One of the following were used to induce ulcers: 20 mg/kg indomethacin 3.5 mL 50% ethanol 0.05 mL 80% acetic acid or stress produced by periodic noise. (–)-bisabolol inhibited occurrence of ulcers induced by indomethacin stress or ethanol and shortened healing time of acetic acid-induced ulcers.

The influence of chamazulene a-bisabolol and one of the dicycloethers (components of essential oil) was studied on protamine sulfate-provoked degranulation of mast cells from Lewis-1a rats. The degranulation effect was determined by measuring histamine liberation. Chamazulene and -bisabolol had no distinct inhibition but dicycloether above 10-4 M inhibited degranulation. 

A systematic comparison of spasmolytic action of the hydrophilic and lipophilic compounds of chamomile was carried out on isolated guinea pig ileum. Series of tests showed that the total extract and some of the ingredients had a dose-dependent spasmolytic effect on the smooth muscles of the intestine. The lipophilic (-) -bisabolol bisabolol oxides showed a marked papaverine-like musculotropically spasmolytic action while the essential oil had the least effect. The chamomile flavones apigenin luteolin patuletin and quercetin were also very active in their spasmolytic action. These studies showed that the lipophilic as well as the hydrophilic components take part in the therapeutic action. 

Sedative Hypnotic Analgesic:

The anxiolytic effect of apigenin was tested in mice.18 Apigenin isolated from the aqueous extract of Matricaria recutita had a clear anxiolytic activity in mice as tested in the elevated plus-maze. A dosage up to 10 mg/kg produced no sedation or muscle relaxant effect. However a 10-fold increase in dosage produced a mild sedative effect. Binding studies of apigenin on synaptosomal membrane prepared from bovine cerebral cortex showed significant affinity for the central benzodiazepine receptor. Apigenin competitively inhibited the binding of flunitrazepam a benzodiazepine receptor ligand with a Ki of 4 µM and had no effect on muscarinic receptor 1-adrenoceptors and on the binding of muscimol to GABAA receptors.18 The authors concluded that apigenin is a ligand for the benzodiazepine receptors exerting anxiolytic and slight sedative effects but not being anticonvulsant or myorelaxant. 

The effect of chamomile tea on the cardiovascular system is unclear. Twelve patients with cardiac disease underwent cardiac catheterization. Hemodynamic data obtained prior to and 30 min. after ingestion of chamomile tea demonstrated a small but statistically significant (p < 0.05) increase in the mean brachial artery pressure. No other significant hemodynamic changes were observed.19 However 10 of 12 patients fell into deep sleep shortly after drinking the tea. 

Antimicrobial Activity of Essential Oil:

The volatile oil prepared from flower heads (fresh or dried) by steam distillation has been tested against Gram-positive (Staphylococcus aureus Bacillus subtilis) and Gram-negative bacteria (E. coli Pseudomonas aeruginosa) as well as a fungus Candida albicans. Oil concentrations above 0.05% were very effective against the Gram-positive bacteria and Candida. The Gram-negative bacteria were relatively less sensitive20 except for Bacillus subtilis. The antibacterial effect may depend on the concentration of chamazulen bisabolol and bisabolol oxides in the extract. Even at low concentrations <100-µg/mL a-bisabolol and its spiro-ether were effective antibacterial agents and exhibited fungicide activity. 

A partial antiviral effect of aqueous and hydroalcoholic extract of Matricaria chamomilla has also been described in cell culture and animal studies. The aqueous extract lowered the tick-borne encephalitis virus titer in kidney cells and induced the resistance in virus-infected mice. In addition hydroalcoholic extract in the early stage of poliovirus development inhibits cellular and viral RNA synthesis. 

Topical Applications:

Chamomile preparations are widely used in skin care products to reduce cutaneous inflammation and other dermatological diseases. In a double-blind trial chamomile extract was tested on 14 patients after dermabrasion of tattoos. The drying effect on weeping wound areas was followed as an objective parameter. Researchers observed statistically significant decreases of the wound areas as well as a drying tendency. Anti-inflammatory activity of witch hazel distillate (Hamamelis virginiana) applied topically on 24 patients was compared to chamomile and to 1% hydrocortisone cream. Erythema and moist desquamation which are side effects of radiotherapy were treated with chamomile cream and almond ointment. Fifty women who had undergone breast cancer surgery were included in the study. Each woman received 2 Gy per treatment 5 times a week (6 MeV electron beam on the scar area). Researchers found a small advantage in the protection (skin changes appeared later) in the chamomile cream group but in the comparison no statistically significant differences were observed in the areas tested.26 In another clinical test erythema was induced by UV irradiation and was treated with either hamamelis extract with phosphatidylcholin emulsion chamomile cream or 1% hydrocortisone. Skin blanching was quantified by visual scoring and chromametry. Both the hamamelis and the chamomile reduced redness but the hydrocortisone had a greater effect when compared to the herb cream. 

In a recent in vivo study with nine female volunteers chamomile flavons—apigenin luteolin and apigenin 7-O-ß-glukoside—adsorbed at the skin surface and penetrated into deeper skin layers. This observation supports their use as topical antiphlogistic agents to treat inflammations in deep tissues. 

The anti-inflammatory effects of a hydroalcoholic extract of Chamomilla recutita was tested in mice (1 mL of extract contained 50 mg of dry product). A 2.5% emulsion of croton oil was used on the ears of animals to produce edema. A dose-dependent response was observed when chamomile extract was used to reduce edema. 

Stomatitis is a frequent dose-limiting side effect of 5-fluorouracil-based (5-FU) chemotherapy. The ulceration can be painful and may limit future cytotoxic therapy. In a randomized trial 164 patients used chamomile mouthwash or placebo along with 30-min. oral cryotherapy to reduce developing stomatitis from 5-FU treatment. In a 14-day trial chamomile or placebo was administered 3 times daily starting at the first day of chemotherapy. Combined results from this trial did not support significant differences between chamomile- and placebo-treated groups. However subset analysis based on gender revealed that chamomile might be beneficial for males but detrimental for females. No plausible explanation was found for these results. 

Regarding products geared towards body treatment the Camomile extracts are important components in the preparation of creams tonics and lotions for the soothing of irritated and inflamed skin (that is for those products destined to the care of sensitive delicate and easily irritable  skins) and also for delicate detergents (specific types as in personal hygiene). In all these uses other plant extracts with the same soothing sedative and refreshing properties can be used with great advantage together with the Camomile (e.g. Calendula Hamamelis Horse-Chestnut etc.).

The Camomile extracts are used in the interesting preparation of lotions with a low alcohol content destined to the depurative treatment for the cleansing of the skin (to facilitate the opening and cleansing of the pores) and the preparation of a subsequent treatment with a moisturizing and nourishing milk or cream. 

An identical effect has been seen in cosmetic products containing Camomile extracts in treating acne and the external treatment of rosacea. These extracts used to sooth and aid the respiration of the skin are also indicated for the preparation of aftershaves post-suntan creams let alone in baby skin-care products (delicate detergents oils and creams). 

The derivatives of the Camomile are widely used in trichology (refreshing and soothing shampoos for itchy and irritated scalps and shampoos which lighten the hair colour).

Conclusion:

Chamomile has been used in herbal medication since ancient times is still popular today and probably will continue to be used in the future. Recent research on heteropolysaccharides isolated from chamomile flowers showed immunomodulating action. Apigenin a plant flavonoid found in chamomile showed inhibitory effect of TPA-mediated tumor promotion and antimutagenicity. Initial studies also showed the topical use of apigenin reduced UV-induced skin tumorogenesis. Acute HIV-1 infection of H9 and C8166 cell cultures could be suppressed by certain flavonoids including apigenin. This might be a potential therapeutic strategy to maintain the cellular state of HIV-1 latency. With a large list of recent basic research accruing chamomile is a perfect example of a herb having diverse therapeutic uses.

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