Chamomile (Matricaria chamomilla L.): An overview
Chamomile (Matricaria chamomilla L.) is a well-known medicinal plant species from the Asteraceae family often referred to as the “star among medicinal species.” Nowadays it is a highly favored and much used medicinal plant in folk and traditional medicine. Its multitherapeutic, cosmetic, and nutritional values have been established through years of traditional and scientific use and research. Chamomile has an established domestic (Indian) and international market, which is increasing day by day. The plant available in the market many a times is adulterated and substituted by close relatives of chamomile. This article briefly reviews the medicinal uses along with botany and cultivation techniques. Since chamomile is a rich source of natural products, details on chemical constituents of essential oil and plant parts as well as their pharmacological properties are included. Furthermore, particular emphasis is given to the biochemistry, biotechnology, market demand, and trade of the plant. This is an attempt to compile and document information on different aspects of chamomile and highlight the need for research and development.
Chamomile (Matricaria chamomilla L.) is one of the important medicinal herb native to southern and eastern Europe. It is also grown in Germany, Hungary, France, Russia, Yugoslavia, and Brazil. It was introduced to India during the Mughal period, now it is grown in Punjab, Uttar Pradesh, Maharashtra, and Jammu and Kashmir. The plants can be found in North Africa, Asia, North and South America, Australia, and New Zealand. Hungary is the main producer of the plant biomass. In Hungary, it also grows abundantly in poor soils and it is a source of income to poor inhabitants of these areas. Flowers are exported to Germany in bulk for distillation of the oil.
In India, the plant had been cultivated in Lucknow for about 200 years, and the plant was introduced in Punjab about 300 years ago during the Mughal period. It was introduced in Jammu in 1957 by Handa et al. The plant was first introduced in alkaline soils of Lucknow in 1964–1965 by Chandra et al. There is no demand for blue oil as such at present in India. However, flowers of chamomile are in great demand. Presently, 2 firms, namely, M/s Ranbaxy Labs Limited, New Delhi and M/s German Remedies are the main growers of chamomile for its flowers.
Chamomile has been used in herbal remedies for thousands of years, known in ancient Egypt, Greece, and Rome. This herb has been believed by Anglo-Saxons as 1 of 9 sacred herbs given to humans by the lord. The chamomile drug is included in the pharmacopoeia of 26 countries. It is an ingredient of several traditional, unani, and homeopathy medicinal preparations.[9–12] As a drug, it finds use in flatulence, colic, hysteria, and intermittent fever. The flowers of M. chamomilla contain the blue essential oil from 0.2 to 1.9%, which finds a variety of uses. Chamomile is used mainly as an antiinflammatory and antiseptic, also antispasmodic and mildly sudorific. It is used internally mainly as a tisane (infuse 1 table-spoonful of the drug in 1 L of cold water and do not heat) for disturbance of the stomach associated with pain, for sluggish digestion, for diarrhea and nausea; more rarely and very effectively for inflammation of the urinary tract and for painful menstruation. Externally, the drug in powder form may be applied to wounds slow to heal, for skin eruptions, and infections, such as shingles and boils, also for hemorrhoids and for inflammation of the mouth, throat, and the eyes. Tabulated products from chamomile flower extracts are marketed in Europe and used for various ailments. Chamomile tea eye washing can induce allergic conjunctivitis. Pollen of M. chamomilla contained in these infusions are the allergens responsible for these reactions.
Antonelli had quoted from writings of several doctors of ancient time of the 16th and 17th century that chamomile was used in those times in intermittent fevers. Gould et al. have evaluated the hemodynamic effects of chamomile tea in patients with cardiac disease. It was found in general that the patients fell into deep sleep after taking the beverage. Pasechnik reported that infusion prepared from M. chamomilla exercised a marked stimulatory action on the secretary function of the liver. Gayar et al. reported toxicity of acetone-extract of M. chamomilla against larvae of Gulex pipens L. The other pharmacological properties include antiinflammatory, antiseptic, carminative, healing, sedative, and spasmolytic activity. However, M. chamomilla has exhibited both positive and negative bactericidal activity with Mycobacterium tuberculosis, Salmonella typhimurium, and Staphylococcus aureus.
The international demand for chamomile oil has been steadily growing. As a result, the plant is widely cultivated in Europe and has been introduced in some Asian countries for the production of its essential oil. M. chamomilla L., Anthemis nobilis L., and Ormenis multicaulis Braun Blanquet and Maire belonging to the family Asteraceae is a natural and major source of “blue oil” and flavonoids. The oil used as a mild sedative and for digestion[2024–29] besides being antibacterial and fungicidal in action.
In addition to pharmaceutical uses, the oil is extensively used in perfumery, cosmetics, and aromatherapy, and in food industry.[2730–33] Gowda et al. studied that the essential oil present in the flower heads contains azulene and is used in perfumery, cosmetic creams, hair preparations, skin lotions, tooth pastes, and also in fine liquors. The dry flowers of chamomile are also in great demand for use in herbal tea, baby massage oil, for promoting the gastric flow of secretion, and for the treatment of cough and cold. The use of herbal tea preparations eliminated colic in 57% infants. Because of its extensive pharmacological and pharmaceutical properties, the plant thus possesses great economic value and is in great demand in the European countries.
True chamomile is an annual plant with thin spindle-shaped roots only penetrating flatly into the soil. The branched stem is erect, heavily ramified, and grows to a height of 10–80 cm. The long and narrow leaves are bi- to tripinnate. The flower heads are placed separately, they have a diameter of 10–30 mm, and they are pedunculate and heterogamous. The golden yellow tubular florets with 5 teeth are 1.5–2.5 mm long, ending always in a glandulous tube. The 11–27 white plant flowers are 6–11 mm long, 3.5 mm wide, and arranged concentrically. The receptacle is 6–8 mm wide, flat in the beginning and conical, cone-shaped later, hollow—the latter being a very important distinctive characteristic of Matricaria—and without paleae. The fruit is a yellowish brown achene.
The true chamomile is very often confused with plants of the genera Anthemis. Special attention has to be paid to avoid confusion with Anthemis cotula L., a poisonous plant with a revolting smell. In contrast to true chamomile, A. cotula similar to as A. arvensis L. and A. austriaca Jacq., has setiform, prickly pointed paleae, and a filled receptacle. The latter species are nearly odorless. Although the systematic status is quite clear nowadays, there are a number of inaccuracies concerning the names. Apart from misdeterminations and confusion, the synonymous use of the names Anthemis, Chamomilla, and Matricaria leads to uncertainty with regard to the botanical identification. Moreover, the nomenclature is complicated by the fact that Linnaeus made mistakes in the first edition of his “Species Plantarum” that he corrected later on. The best-known botanical name for true chamomile is Matricaria recutita (syn. Matricaria chamomilla, Chamomilla recutita (L.) Rauschert, belonging to the genus Chamomilla and family Asteraceae. M. chamomilla is a diploid species (2n=18), allogamous in nature, exhibiting wide segregation as a commercial crop.
Chamomile, a well-known old time drug, is known by an array of names, such as Baboonig, Babuna, Babuna camornile, Babunj, German chamomile, Hungarian chamomile, Roman chamomile, English chamomile, Camomilla, Flos chamomile, Single chamomile, sweet false chamomile, pinheads, and scented mayweed, suggesting its widespread use.
The three plants, namely, A. nobilis Linn, Corchorus depressus Linn, and M. chamomilla Linn. are reported under one unani name Babuna at different places in the literature. This created a lot of confusion and misuse of the drug as an adulterant, etc. Ghauri et al. conducted a detailed taxonomic and anatomical study and concluded that Babuna belongs to the family Compositae (Asteraceae) and that the correct scientific name of Babuna is M. chamomilla L.
CULTIVATION AND CO-CULTIVATON
Soil and climatic requirements
German chamomile can be grown on any type of soil, but growing the crop on rich, heavy, and damp soils should be avoided. It can also withstand cold weather with temperature ranging from 2°C to 20°C. The crop has been grown very successfully on the poor soils (loamy sand) at the farm of the Regional Research Laboratory, Jammu. At Banthra farm of the National Botanical Research Institute, Lucknow, the crop has been grown successfully on soil with a pH of 9. Soils with pH 9–9.2 are reported to support its growth. In Hungary, it grows extensively on clayey lime soils, which are barren lands and considered to be too poor for any other crop. Temperature and light conditions (sunshine hours) have greater effect on essential oils and azulene content, than soil type. Chamomile possesses a high degree of tolerance to soil alkalinity. The plants accumulate fairly large quantity of sodium (66 mg/100 gm of dry material), which helps in reducing the salt concentration in the top soil. No substantial differences were found in the characteristics of the plants grown 1500 km apart (Hungary–Finland). Under cooler conditions in Finland, the quantity of the oxide type in the essential oil was lower than in Hungary.
The plant is propagated by seeds. The seeds of the crop are very minute in size; a thousand seeds weigh 0.088–0.153 gm. About 0.3–0.5 kg of clean seed with a high germination percentage sown in an area of 200–250 m2 gives enough seedlings for stocking a hectare of land. The crop can be grown by two methods i.e. direct sowing of the seed and transplanting. Moisture conditions in the field for direct sowing of seeds must be very good otherwise a patchy and poor germination is obtained. As direct sowing of seeds usually results in poor germination, the transplanting method is generally followed. The mortality of the seedlings is almost negligible in transplanting.
The optimum temperature for good seed germination lies between 10°C and 20°C. Nursery beds were prepared by applying good quality of farmyard manure (FYM) and compost and kept moist. The most appropriate time for raising seedlings in the nursery is soon after the cessation of monsoons in North India, that is, during the month of September. Seed germination starts within 4–5 days of sowing, and the seedlings area ready for transplanting within 4–5 weeks. Seedlings older than 5 weeks should not be transplanted; it results in a poor and indifferent crop. Based on the thermal model, appropriate time and method of sowing was studied. The study revealed that transplanting the crop was better than direct sowing, and the best time to transplant the crop was found to be from October 10 to 18 for getting higher yields. Transplanting should not be delayed beyond the end of October.
Zalecki reports that different sowing times affect the shifting of the harvesting time but do not affect the oil and chamazulene content significantly. The work on crop geometry shows that transplanting the crop at narrow spacing of 15, 20, and 30 cm, gave the highest yields of flowers.[46–49] Dutta and Singh reported that the highest yields of fresh flowers and oil content was obtained under 30 cm2 spacing. In case of varieties with a spreading habit of growth, a wider spacing of 40 cm2 is desirable.
The crop growth is slow till mid-January and picks up gradually till early February. As the season warms up, there is high activity in crop growth (increase in height, branching, bud formation) and stray flowers may be seen in the crop. Bud formation is profuse in March, there is all round growth in the plants, the early formed buds open into flowers, hence the plucking of flowers has to be also selective all through the crop cycle. With sudden rise in the temperature from 33° C to 39° C within a few days, heavy seed-setting and plant maturity will be observed in the crop. There is seed shedding and in the next year a self-germinated crop is observed.
As the roots of the plant are shallow, the plant is unable to draw moisture from the lower moist horizon of the soil and therefore needs frequent irrigation to maintain an optimum moisture level. Irrigation during the bloom period is helpful in increasing the flower yield, one additional flush of flowers is obtained and seed formation is delayed. Krθches observed that irrigation at the rosette stage increased the yield substantially. On alkaline soils, the crop is irrigated more frequently and about 6–8 irrigations are required during the crop cycle. Good performance is obtained if the soil is kept moist, but flooding should be avoided.
Manures and fertilizers
The effect of nitrogen (N) is very marked on the fresh flowers and oil yield, whereas that of phosphorus (P) and potassium (K) is negligible. Dutta and Singh observed that application of N in the form of ammonium sulfate at 40 kg/ha significantly increased fresh flower and oil yield, while the oil content decreased from 0.64 to 0.59%. Addition of organic matter increases the humus content of such soil and thereby improves the crop performance. Application of 15–25 t/ha of FYM is proved beneficial before transplanting. El-Hamidi et al. advocates the ratio of 2:2 for N2 and P for obtaining the highest yield. Application of N at a higher level caused a notable decrease in the chamazuler percentage. Paun and Mihalopa found that the application of P and K at 50 kg/ha each in autumn before sowing and application of N at 50 kg/ha in early spring was responsible for satisfactory crop growth. However, neither volatile oil nor chamazulene content was affected. On saline alkaline soils, Singh found plants showing good response to N and P fertilizers. Application of 20–25 t/ha of FYM was useful before transplanting the crop. Misra and Kapoor found the optimum dose of N and P to be between 50–60 kg N/ha and 50 kg P2O5/ha. It is reported that N significantly increased the contents of α-bisabolol and chamazulene, but significantly decreased the contents of bisabolol oxides A and B in the essential oil. N significantly increased essential oil yield per unit dry flower weight in both Bohemia and Tisane varieties. The quantity of essential oil in chamomile was inversely related to its quality in terms of α-bisabolol and chamazulenes.
No deficiency symptoms of trace elements have been observed on the crop in the country so far. Peskova has reported the good effect of the sulfates of manganese and cobalt; and borax on lime soils, whereas Koeurik and Dovjak indicated that combined application of boron and molybdenum increased dry matter significantly.
There are many herbicides for the control of weeds in M. chamomilla. Generally 3–4 weedings are required for a good crop. The application of 1–1.5 kg/ha of sodium salt of 2,4-dichlorophenoxyacetic acid (2,4-D); four weeks after transplanting gave good control of weeds for four weeks. The experimental results of researchers in other countries suggests that herbicides, such as atrazine, prometryene, propyzamide, chloropropham, mecoprop, trifluralin, linurones, give satisfactory control of weeds, but these should be used with caution. It was found that afalone was the best selective weedicide. Herbicide-treated crop had lower chamazulene content, and bisabolol content was lower in the second harvest as herbicides interfere with the metabolism of secondary products. Certain herbicides have little influence on the total essential oil content, but greater differences were found in the quantitative composition of useful substances.[55–58]
On saline–alkali soils only one thorough weeding and hoeing one month after transplanting, may be enough, as the plant once established, smothers the weed and no further weeding is required. It was reported that weed removal during 5–11 weeks after planting the crop was necessary to obtain a higher yield of the flower and oil. The uncontrolled weed growth caused 34.4% reduction in the dry flower yield as compared with the weed-free condition. The application of oxyfluorfen (0.6 kg/ha) gave higher returns.
Harvesting is the most labor-intensive operation in chamomile cultivation, accounting for a major portion of the cost of production. The success of M. chamomilla cultivation as a commercial venture lies in how efficiently and effectively one can collect the flowers at the right stage during the peak flowering season extending over a period of 3–6 weeks during March-April. Flowering is so profuse that practically every alternate day at least 30–40 units of labor will be required to be employed to pluck the flowers from an area of 0.25–0.3 ha. Flower plucking is a selective process as flowers in all stages, namely, buds, semi-opened buds, flowers in all stages of bloom appear on the plants. Flowers at the near full bloom stage give the best quality of the product, hence care has to be exercised to see that as little as possible buds, stems, leaves, and extraneous material is plucked. Flowering will be observed on plants here and there all over the field from the later half of February and these flowers are plucked at the appropriate stage. Flowers are produced in flushes and 4-5 flushes are obtained. The 2nd, 3rd, and 4th flushes are the major contributors to flower yield. The peak period of plucking is between the 2nd week of March and the 3rd week of April in North India. In normal soils, Singh obtained a maximum yield of 7637 kg of fresh flowers, the average being 3500-4000 kg/ha. In saline–alkaline soils, Singh obtained a yield of 3750 kg fresh flowers/ha. Temperature affects the number of flowers per kg. The weight of 1000 flowers is reduced from 130 to 80 gm by the 2nd week of April.
Diseases and pests
The various insects, fungi, and viruses have been reported, which attack the chamomile crop. The following fungi are known to attack this plant: Albugo tragopogonis (white rust), Cylindrosporium matricariae, Erysiphe cichoracearum (powdery mildew), E. polyphage, Halicobasidium purpureum, Peronospora leptosperma, Peronospora radii, Phytophthora cactorum, Puccinia anthemedis, Puccinia matricaiae, Septoria chamomillae, and Sphaerotheca macularis (powdery mildew). Also, yellow virus (Chlorogenus callistephi var. californicus Holmes, Callistephus virus 1A) causes severe damage to this plant. In the years 1960–1964 when the crop was cultivated in the Regional Research Laboratory, Jammu, no incidence of disease was reported. However, after 20 years in the month of February about two dozen plants were observed to produce symptoms resembling those of plant viruses. These plants were burnt to prevent further spread of the disease. In early March, the incidence of leaf blight caused by Alternaria spp. was observed in the crop. A spray of Benlate (0.1%) controlled the disease. Fluister reported that black bean aphids (Aphis fabae) were feeding on M. chamomilla. The insect Nysius minor caused shedding of M. chamomilla flowers, whereas Autographa chryson causes defoliation of the plant. The one spray with fosfothion 0.2%, controlled successfully aphid infestation (Doralis fabae Scop.) on chamomile. Methyl bromide (3 kg/100 m3) proved satisfactory as a fumigant against pest infestation of Ephestia elutella Hb in the desiccated herb of chamomile. Metalydacolus longistriatus in the Giza region of Egypt, was found to be associated with the roots of chamomile.
Besides damaging the cultivated crop of chamomile, fungi and insects also cause extensive damage to the dry flowers during storage and reduce the quality of the dried raw product. This is because dried chamomile, the flowers in particular, contain a large amount of hydrophilic constituents (sugars, flavonoids, mucilages, phenyl carbonic acids, amino acids, choline, salts), and also chamomile herbs are hygroscopic. Microbiological deterioration caused by fungal agents occurs in a very short time. Thus, at the marginal condition of the dry product, the most xerophilic species, molds of the species Aspergillus and Penicillium form first. The metabolism of bacteria and fungi releases more and more moisture for the more demanding organisms, such as Fusarium and Rhizopus, so the attack continues to develop in a kind of cascade effect. The metabolic excretions from the microbiological agents also make the stored product smell musty or damp, which is rated very negatively in terms of quality. In addition there is a risk that the stored product will be contaminated with mycotoxins, which are a health hazard.
The dried product is also a favorite habitat for certain insects. Larvae and beetles generally damage the stored product by eating away and polluting it with excreta and webs. This considerably reduces the quality and leads to total deterioration in a short time. The main stock pests that affect the drug are Plodia interpunctella Hb. (copper red-Indian meal moth), Ptinus latro F. (dark brown thief beetle), P. testaceus Oliv. (yellow brown thief beetle), Gibbium psylloides Gzemp. (smooth spider beetle), Lasioderma servicorne, and Stegobium paniceum.
Patra et al. reported that chamomile is grown as a winter (Rabi) season crop and, therefore, fits well in rotation with major summer (Kharif) season crops, such as paddy, maize, and others. It may follow pulses, such as green gram, pigeon pea, and other summer vegetables, such as “Okra,” cucumber, and others. It can be grown even after early maturing Brassicas; chamomile can be grown on the residual soil fertility preceding green manuring and crops that are heavily fertilized. It can be grown as an intercrop with many arable crops.
In 1999 Mishra et al. reported intercropping of celery + chamomile, ajwain + chamomile, fennel + chamomile, and sowa + chamomile, all in 1:1 ratio. Sowing of the main crop was done on 2nd November, and 8-week-old seedlings of chamomile were transplanted in the 1st week of January. Spacing of 45 × 20 cm was maintained for all the crops, dried biogas slurry was supplied at the time of land preparation, and three irrigations were given to the crops. Chamomile started blooming from the second week of March and three flower pickings (between March 25 and April 19) were done manually at an interval of 7–10 days. Also, chamomile has been found to be a suitable intercrop with aromatic grasses, such as lemon grass and palmarosa, which remain dormant in winter.
CHAMOMILE (M. CHAMOMILLA) AS A SOURCE OF NATURAL PRODUCTS
M. chamomilla belongs to a major group of cultivated medicinal plants. It contains a large group of therapeutically interesting and active compound classes. Sesquiterpenes, flavonoids, coumarins, and polyacetylenes are considered the most important constituents [Figure 1] of the chamomile drug. The coumarins are represented in M. chamomilla by herniarin, umbelliferone, and other minor ones. (Z)- and (E)-2-β-d-glucopyranosyloxy-4-methoxycinnamic acid (GMCA), the glucoside precursor of herniarin, were described as native compounds in chamomile. Eleven bioactive phenolic compounds, such as herniarin and umbelliferone (coumarin), chlorogenic acid and caffeic acid (phenylpropanoids), apigenin, apigenin-7-O-glucoside, luteolin and luteolin-7-O-glucoside (flavones), quercetin and rutin (flavonols), and naringenin (flavanone) are found in chamomile extract.
More than 120 chemical constituents have been identified in chamomile flower as secondary metabolites, including 28 terpenoids, 36 flavonoids, and 52 additional compounds with potential pharmacological activity [Table 1]. Components, such as α-bisabolol and cyclic ethers are antimicrobial, umbelliferone is fungistatic, whereas chamazulene and α-bisabolol are antiseptic. The chamomile was found to have the most effective antileishmanial activity.
German chamomile is a natural source of blue oil (essential oil). The flowers and flower heads are the main organs of the production of essential oil. It is remarkable that chamomile flower oil mainly consists of sesquiterpene derivatives (75–90%) but only traces of monoterpenes. The oil contains up to 20% polyynes. The principal components of the essential oil extracted from the flowers are (E)-β-farnesene (4.9–8.1%), terpene alcohol (farnesol), chamazulene (2.3–10.9%), α-bisabolol (4.8–11.3%), and α-bisabolol oxides A (25.5–28.7%) and α-bisabolol oxides B (12.2–30.9%),[3380–84] which are known for their antiinflammatory, antiseptic, antiplogistic, and spasmolytic properties. Among the various major constituents, α-bisabolol and chamazulene have been reported to be more useful than others. Chamazulene is an artifact formed from matricine, which is naturally present in the flowers during hydrodistillation or steam distillation. The color of the oil determines its quality. Blue color of the oil is due to sesquiterpene. The chamazulene content of the various chamomiles depends on the origin and age of the material. It decreases during the storage of the flowers.
Bisabolol has been found to reduce the amount of proteolytic enzyme pepsin secreted by the stomach without any change occurring in the amount of stomach acid, due to which it has been recommended for the treatment of gastric and upper intestinal diseases. It has also been reported to promote epithelization and granulation, and to produce a pronounced and antiphlogistic effect on paw carrageenin edema and cotton pellet granuloma of the rat. Similarly, it is recommended that, if chamomile extracts were to be used for their antiphlogistic effects then plants rich in bisabolol and chamazulene should be chosen. Also, because of the antiinflammatory properties of bisabolol, it is recommended in cosmetic preparations. The presence of cis-en-yne-dicyclo ethers, perillyl alcohol, triacontane, cadeleric hydrocarbon, and cadeleric tertiary alcohol was reported in chamomile. The other compounds, such as thujone and borneol were present in very low amounts. The main constituents of the flowers also include several phenolic compounds, primarily the flavonoid apigenin, quercetin, patuletin, luteolin, and their glucosides.
Besides the capitula, the shoot (leaves and stem) and root of the plant also contain essential oil. Earlier investigations on the oil of this herb reported the presence of (Z)-3-hexenol, (E)-β-farnesene, α-farnesene, germacrene D, (E)-nerolidol, spathulenol, hexadec-11-yn-11,13-diene, and (Z)- and (E)-en-yn-dicycloethers, whereas the root oil was reported to contain linalool, nerol, geraniol, β-elemene, (E)-β-farnesene, α-farnesene, spathulenol, τ-cadinol, τ-muurolol, β-caryophyllene, cis-caryophyllene, caryophyllene oxide, chamomillol, hexadec-11-yn-11,13-diene, cis- and trans-en-yn-dicycloethers, and chamomile esters I and II. These oils were devoid of chamazulene and α-bisabolol and its oxides were present as minor constituents. α-Humulene, hexadec-11-yn-13,15-diene, phytol, isophytol, and methyl palmitate were detected for the first time from M. chamomilla.
All these and other compounds were found in different amounts and ratios in various parts of the inflorescence depending on the growth stage and the time of picking during the day. The quantity of α-bisabolol and α-bisabolol oxides A and B in the flowers reached a maximum at full bloom and then declined. Farnesene content of the flowers decreased gradually with their growth and development. The accumulation of essential oils in the flowers continued during drying. Harvesting at the early flowering phase and drying in shaded places is recommended. Franz, in pot trials, showed that the oil content was the lowest in decaying heads and highest in one week of flower initiation. Farnesene and bisabolol were highest in the flower buds and lowest in the decaying flowers. Chamazulene and bisabolol oxide content increased from buds to fully developed flower buds
BIOCHEMISTRY AND BIOTECHNOLOGY
Effect of nitrogen on M. chamomilla
Environmental stress, irrespective of its nature, enhances reactive oxygen species (ROS) formation, thereby activating both protective mechanism and cellular damages. Tissue damage occurs when the capacity of antioxidative systems becomes lower than the amount of ROS generated. To protect cells under stress conditions and maintain the level of ROS, plants possess several enzymes to scavenge ROS. Important in regulating intracellular hydrogen peroxide (H2 O2) are catalase (CAT) and peroxidases (guaiacol peroxidase [GPX]). A previous study has shown that both CAT and GPX increase their activity under conditions of N starvation in rice leaves. Moreover, both CAT and GPX showed the highest activities, while H2O2 accumulation and superoxide dismutase activity was the lowest in the leaves of bean plants cultivated with the lowest N dosage compared with the highest N dosage. Since growth of the leaves and roots was the highest in the lowest N dosage, this could be an indication that removal of H2O2 occurs also under optimal nutrient conditions. Additionally, this indicates that the highest N dose is toxic and drastically depresses the growth of the plants. Phenolic compounds are potent inhibitors of oxidative damage due to availability of their phenolic hydrogen. Their involvement in H2O2 detoxification through peroxidases is well established. Enhancement of phenylalanine ammonia-lyase (PAL) activity and higher accumulation of leaf phenolics and root exudation of phenolics under phosphate and N deficiency were recorded.
In a previous study, Kovacik et al. reported that with prolonged N deficiency the majority of detected phenolic acids and coumarin-related compounds increased in chamomile leaf rosettes. Recently Kovacik and Backor showed that N deficiency enhanced root growth and inhibited shoot growth in M. chamomilla plants. Chlorophyll composition was not affected by N stress, but N and soluble proteins decreased in both the rosettes and the roots. PAL activity was enhanced in N-deficient rosettes and tended to decrease by the end of the experiment, while in the roots PAL activity was maintained. The total phenolic contents increased in both rosettes and roots under N deficiency. N-deficiency also affects peroxidase and CAT activities as it decreased them in the rosettes, while it increased them in the roots. Furthermore, lipid per oxidation status increased in N-deficient roots, indicating that antioxidative protection was insufficient to scavenge ROS being generated. Surprisingly, H2O2 content was lower in N-deficient roots, while in the leaves it increased.
Effect of Cd and Cu on M. chamomilla
Heavy metals have become one of the main biotic stress agents for living organisms because of their increasing use in the developing field of industry causing high bioaccumulation and toxicity. Heavy metal toxicity usually depends on the metal amounts accumulated by plants. Cadmium (Cd) has no known physiologic function in plants, whereas Copper (Cu) is an essential plant micronutrient. Being a redox active metal, Cu generates ROS, whereas Cd is a redox inactive metal unable to catalyze the generation of ROS via Fenton–Haber-Weiss reactions. Nevertheless, Cd may induce the expression of lipoxygenases in plant tissues, and thus indirectly causes oxidation of polyunsaturated fatty acids. Cu has a greater ability to cause lipid peroxidation than redox inactive metals, such as Cd; this fact was previously demonstrated also in Cd- and Cu-treated chamomile. Hydrogen peroxide is the main ROS being formed from superoxide radical and scavenged by specific enzymes. Therefore, regulated production of ROS and maintenance of “redox homeostasis” are essential for the physiologic health of organisms.
Plants develop different mechanisms enabling them to cope with metal accumulation in the tissues and ROS formation induced by the presence of metals. Kovacik and Backor studied the Cd and Cu uptake by 4-week-old chamomile plants and their effect on selected antioxidative enzyme activities, such as CAT, GPX, and glutathione reductase (GR) up to 7 days of exposure to 3, 60, and 120 μM Cd or Cu. Cd content in the rosettes was 10-fold higher in comparison with Cu, whereas Cu was preferentially accumulated in the roots. The increase of CAT and GPX activity was similar in the rosettes of Cd- and Cu-treated plants, indicating the nonredox active properties of Cd and low Cu accumulation. In the roots, Cu showed strong pro-oxidant effect, as judged from extreme stimulation of CAT and GPX, followed by an increase in H2O2 and malondialdehyde (MDA). However, alleviation of oxidative stress (ca. 93- to 250-fold higher activity in 120 μM Cu-treated roots) seemed to be more important. Cd had substantially lower influences and stimulated GR activity more than that by Cu.
Kovacik et al. reported that Cu decreased dry mass production, water, chlorophyll, and N content in both the leaf rosettes and roots at 120 μM. Most of the 11 phenolic acids detected increased in 60 μM Cu but in the 120 μM treatment their contents were lower or not significantly different from the control. Among the coumarin-related compounds, (Z)- and (E)-GCMAs increased in 60 and 120 μM Cu, whereas herniarin rose in the 3 and 60 μM Cu. The amounts of umbelliferone were not affected by any of the doses tested. The MDA content of the leaf rosette was not affected by the exposure of plants to 120 μM Cu, but a sharp increase was observed in the roots. At 120 μM Cu stimulated a 9-fold higher K+ loss than the 60 μM treatment, whereas at the lowest concentration it stimulated K+ uptake. Cu accumulation in the roots was 3-, 49-, and 71-fold higher than the leaf rosettes in the 3, 60, and 120 μM Cu treatments, respectively. The 120 μM Cu dose is limiting for chamomile growth.
Chamomile is reported to accumulate high amounts of Cd preferentially in the roots and also in anthodia,[140–142] indicating that it belongs to the group of facultative metallophytes or metal excluders. Grejtovsky et al. studied the effects of Cd on secondary metabolites of chamomile, and did not observe any changes in apigenin-7-O-glucoside and other derivatives in anthodia. On the other hand, the quantities of two coumarins in the leaves, herniarin and umbelliferone, as well as herniarin glucosidic precursors (Z)- and (E)-GMCAs, were affected by foliar application of Cu2+ ions and biotic stress. These two stress factors resulted in a decrease in the GMCAs, but an increase in herniarin as well as umbelliferone compared with the control. However, nutritional starvation, such as N deficiency, did not cause this pattern of coumarins dynamics, indicating the presence of other mechanisms governing their accumulation.
Kovacik et al. reported that the dry mass accumulation and N content were not significantly altered under low (3 μM) and high (60 and 120 μM) levels of Cd. However, there was a significant decline in the chlorophyll and water content in the leaves. Among coumarin-related compounds, herniarin was not affected by Cd, whereas its precursors (Z)- and (E)-GCMAs increased significantly at all the levels of Cd tested. Cd did not have any effect on umbelliferone, a stress metabolite of chamomile. Lipid peroxidation was also not affected by even 120 μM Cd. Cd accumulation was approximately 7- (60 μM) to 11-fold (120 μM) higher in the roots than that in the leaves. At high concentrations, it stimulated K+ leakage from the roots, whereas at the lowest concentration it could stimulate K+ uptake. This supported the hypothesis that metabolism was altered only slightly under high Cd stress, indicating that chamomile is tolerant to this metal. Preferential Cd accumulation in the roots indicated that chamomile could not be classified as a hyperaccumulator and, therefore, it is unsuitable for phytoremediation.
Effect of amino acids on M. chamomilla
Amino acids can act as growth factors of higher plants because they are the building blocks of protein synthesis, which could be enzymes important for metabolic activities. There is evidence that ornithine is a precursor of polyamines that are essential in the regulation of plant growth and development. Proline has been shown to accumulate in the plant tissue under various conditions. The suggested functions of the accumulated proline are osmoregulation, maintenance of membrane and protein stability, growth, seed germination, and provision of storage of carbon, nitrogen, and energy.
Gamal el-Din and Abd-el-Wahed investigated the effect of different concentrations of ornithine, proline, and phenylalanine on vegetative growth, essential oil, and some biochemical constituents of chamomile. They observed that all the amino acids significantly increased the plant height, number of branches, number of flower head, fresh and dry weights of the aerial parts, and flower head per plant. Foliar application of 50 mg/L ornithine and 100 mg/L proline or phenylalanine resulted in greater effect as compared with other treatments. This regulatory effect of amino acids on growth could be explained by the notion that some amino acids (eg, phenylalanine and ornithine) can effect plant growth and development through their influence on the gibberellin biosynthesis. The total phenol and total indole contents in the vegetative aerial parts were significantly increased by all the amino acids. The maximum effect showed ornithine, proline, and phenylalanine at a concentration of 150 mg/L. Proline or phenylalanine at 50 or 150 mg/L decreased the total carbohydrates, whereas 150 mg/L of ornithine had such effect. The greatest increase in the oil percentage and yield were obtained at 150 mg/L of ornithine and 100 mg/L of proline or phenylalanine.
Effect of salicylic acid on M. chamomilla
Salicylic acid (SA) is a well-known endogenous plant signal molecule involved in many growth responses and in disease resistance. Stimulation of growth after exposure to SA has been recorded in some plant species, such as wheat, soybean, and maize. It can also contribute to stress tolerance by stimulating highly branched metabolic responses. The effect of exogenous SA depends on numerous factors, including the species and developmental stage, the mode of application, and the concentration of SA. A range of plant physiologic reactions to SA application are known. Pastirova et al. have shown that accumulation of coumarin-related compounds in chamomile was affected by exogenous SA application at a dose of 2 mM. Kovacik et al. reported that SA exhibited both growth-promoting and growth-inhibiting properties at doses of 50 and 250 μM, respectively. The latter being correlated with the decrease of chlorophylls, water content, and soluble proteins. In terms of phenolic metabolism, it seems that the higher SA dose has a toxic effect, based on the sharp increase in PAL activity, which is followed by an increase in total soluble phenolics and lignin accumulation. GPX activity was elevated at a dose of 250 μM SA. However, PAL activity decreased with prolonged exposure to SA, indicating its inhibition. Accumulation of coumarin-related compounds (umbelliferone and herniarin) was not affected by SA; whereas (Z)- and (E)-GCMAs increased in the rosettes at 250 μM SA.
Tissue culture studies
Tissue culture is the culture and maintenance in vitro of plant cells or organs in sterile, nutritionally and environmentally supportive conditions. It has applications in research and commerce. In commercial settings, tissue culture is often referred to as micropropagation, which is really only one form of a set of techniques. Micropropagation refers to the production of whole plants from cell cultures derived from explants, the initial piece of tissue put into culture of meristem cells. Two types of tissue culture of M. chamomilla were isolated, namely, E40 and BK2 derived from leaf and stem, respectively. These cultures were also maintained in modified Murashige and Skoog medium and essential oil was present in both types of tissue culture and chromatograms of both essential oils showed similarity. Szoke et al. obtained callus tissues from root, stem, and flower clusters of wild chamomile. They studied the dynamics of growth of callus tissues on the basic growth medium containing 2,4-D and kinetin in light and in dark. It was observed that the growth of inflorescence callus, either cultured in light or dark, was sensitive to added growth regulators. It grew better with kinetin + 2,4-D. Use of 10% coconut milk instead of kinetin + 2,4-D was effective in improving the growth. Differences in the composition of essential oil in the three parts studied were attributed to the level of tissue organization. Cellarova et al. has dealt with the possibility of morphogenesis induction in callus tissue cultures of some representatives of M. chamomilla. Shoot in calli has been induced by 0.1 mg/L kinetin or by combination of 0.5 mg/L kinetin and 0.5 mg/L alpha naphthyl acetic acid (NAA) added to Murashige and Skoog medium. Rhizogenesis took place without any other addition of auxin.
IMPROVED VARIETIES OF CHAMOMILE AS A SOURCE OF DRUG
The world market currently has chamomile drug of various origins and therapeutical values. The medicinal value of the plant material was evaluated by the content of essential oil and the content of chamazulene, etc. The quality of blue oil (essential oil) is determined by its color. As the name indicates, bluer the oil better is the quality, because blue color serves as the chemical marker for the presence of terpenoids and flavonoids, chiefly chamazulene and α-bisabolol. For manufacturing chamomile extracts of antiphlogistic effectiveness, only such types of chamomile should be used, which exhibit a high content of (-)-α-bisabolol and the synthetic racemic bisabolol. Thus, chamomile of a particular chemical composition is used as drug as it shows specific pharmacological activity.
As efficient methods for determining the drug constituents and effectiveness have been developed, the content of (-)-α bisabolol and its oxides in the flowers has become an important indicator of drug quality and value. As a result, four basic types of chamomile A, B, C, and D are recognized, according to the qualitative and quantitative composition of the essential oil.
-Chemical type A (dominant component of essential oil is bisabolol oxide A).
-Chemical type B (dominant component of essential oil is bisabolol oxide B).
-Chemical type C (dominant component of essential oil is (-)-α-bisabolol).
-Chemical type D ((-)-α-bisabolol and bisabolol oxide A and B present in 1:1 ratio approx.).
The major suppliers of chamomile for the world market, which are Poland, Hungary, Germany, Argentina, and Czecho-Slovakia, have recently initiated intensive plant improvement programs to produce plants with high levels of essential oils with a defined chemical composition. The varieties “Bona,” “Kosice-II,” and the cultivar “koice-1” have been developed through selection and breeding efforts. Normally, these new types have over twice the essential oil content of the older “Bohemia” variety, and “Bona” and “Kosice-II” have chemical profiles much higher in (-)-α-bisabolol and chamazulene [Table 2].
German chamomile was introduced in India during the 17th century. But its commercial cultivation remained marginalized mainly due to poor yield of flowers coupled with low oil content and poor oil quality. No attempt was ever made to scientifically organize the cultivation of such valuable cash crop. As a result of germplasm enhancement and exploitation program, an improved variety, Vallary, was developed and finally released for commercial cultivation in India. It is the first ever genetically improved variety of German chamomile, bred specially for agroclimatic conditions of North Indian plains. Its oil is highly viscous and dark blue in color, indicative of high concentration of terpenoids and flavonoids.
German chamomile enjoys good domestic and international market. It is the fifth top selling herb in the world and is a major food cosmetic and pharmaceutical additive. It sold either as flower head or as blue oil. “Blue oil” is the commercial trade name of chamomile oil in the international market, which fetches about Rs. 40,000 for a kilogram. The world production of chamomile blue essential oil was estimated by the USDA to be 5.4 t, in the year 1989.
The medicinal plant sector in India is unorganized and it is difficult to get regular update of statistics vis-à-vis the demand and supply, collection, and economics of chamomile. Also, worldwide production figures are difficult to isolate due to small-scale farming and the fact that statistics generally do not quote chamomile separately from herbs. In 1995, the worldwide production was estimated to be approximately 500 t of dried flower per annum from large-scale farming. In 1998, this figure raised to 1000 t of dried flower per annum from large-scale farming.
Price is largely regulated by supply and demand in the world. In 1991, the world price for dried chamomile flower ranged from US $ 1,000/t for low grade to approximately US $ 16,000/t for high oil content flower. Bulk botanical herbs, in 1997, was advertising organically grown chamomile on the Internet at US $ 28 per pound (US $ 61.73 per kg). Recently, it is selling at the rate of US $ 700 per kg. With the current trends, these prices should increase within the next two years.
There is a great demand for chamomile in the world market because of its extensive medicinal values and impeccable pharmacological properties. Also, there has been an increase in the use of natural substances instead of synthetic chemicals because many herbal medicines are free from side effects, easy to obtain, considered healthy, and create income. It is a well-established fact that chamomile plant diversity is being threatened by unregulated harvesting of natural populations and expansion of urban centers. So it is advisable to cultivate chamomile for better quality control of the target bioactive components. This approach also allows for the production of uniform plant material at predetermined intervals in the required quantities. A strong need is felt to screen the different chemotypes of chamomile growing at different phytogeographical locations. Similarly, biodiversity studies at morphologic, biochemical, and genetic levels will enable the research community to realize the extent of variability within the existing germplasm of chamomile, and hence help in the conservation of the plant. However, there is still a wide scope for exploring different aspects of chamomile.
In India, it appears that there is a good potential for chamomile cultivation as a commercial medicinal and industrial crop. Because of the high international market price of chamomile, it is necessary to promote this valuable crop as a commercial crop mainly for export of chamomile oil from India.
Source of Support: Nil
Conflict of Interest: None declared
- 1. Stinking mayweedN Z J Agric1979138213
- 2. New aspects of cultivating chamomileHerba Polonica197925359
- 3. Introduction of some of the important exotic aromatic plants in Jammu and KashmirIndian Perfumer19571429
- 4. Cultivation of plants for perfumery industry at LucknowIndian Perfumer197316404
- 5. Experimental cultivation of some essential oil bearing plants in saline soils, Matricaria chamomilla LPerfum Essent Oil Rec196859871
- 6. Recent progress in chamomile research- medicines of plant origin in modern therapy19891st edCzecho-SlovakiaPrague press
- 7. Herbal medicine past and present19901st edUSADuke University Press
- 8. Natural pharmacy (in Slova)19861st edPrirodaBratislava
- 9. Chamomile (Chamomilla recutita): Economic botany, biology, chemistry, domestication and cultivationJ Med Aromat Plant Sci1998201074109
- 10. J Med Aromat Plant Sci20012361723
- 11. Progress in Essential OilsPerfume Flavorist1987123552
- 12. The chemistry, pharmacology and commercial formulations of chamomileHerbs, Spices and Medicinal Plants- Recent Advances in Botany, Horticulture and Pharmacology1986PhoenixOryx Pres23580
- 13. Phytochemical investigation of apigenin glycosides of Matricaria chamomillaPharmazie1962173014
- 14. The British herbal compendium19921st edLondonBritish Herbal Medicine Association
- 15. The chemistry, pharmacology and commercial formulations of chamomileHerbs, spices and medicinal plants- recent advances in botany, horticulture and pharmacology2002USAHaworth Press Inc23580
- 16. The lipophilic compounds of a Turkish Matricaria chamomilla variety with no chamazuline in the volatile oilInt J Crude Drug Res1990281457
- 17. Medicinal plants and authentic guide to natural remedies19881st edLondonW. Foulsham and Co. Ltd
- 18. Allergic conjunctivitis to chamomile teaAnn Allergy19906512732
- 19. Matricaria chamomilla L. and Anthemis nobilis L. in intermittent fevers in medicinesBiol Abstr1928621145
- 20. Cardiac effect of chamomile teaJ Clin Pharmacol1973134759
- 21. Cholagogic action of extracts prepared from wild chamomile (Matricaria chamomilla)Farmakol Toksikol1996294689
- 22. Toxicity of certain plants to Culex pipens L.larvae (Diptera: Culicidae)Bull Soc Entomol (Egypt)19685246775
- 23. Chamomile a medicinal plantJ Herbs Spices Med Plants19921014
- 24. Isolation of a genotype bearing fascinated capitula in chamomile (Chamomilla recutita)J Med Aromat Plant Sci1999211722
- 25. Variability of content and composition of essential oil in various chamomile cultivators (Matricaria chamomilla L.)Herba Hungarica198928218
- 26. Vallary: An improved variety of German chamomilePafai J1996181720
- 27. Induced floral mutants and their productivity in German chamomile (Matricaria recutita)Indian J Agric Sci1993632733
- 28. Traditional cultivation of Babunah Chamomilla recutita (L.) Rauschert syn. Matricaria chamomilla L. LucknowBull Medico-Ethnobotanical Res198014717
- 29. Cultivations of German chamomile – a reviewCurr Res Med Aromat Plants1983526978
- 30. AnonymousA superior variety of German chamomile identified. CIMAP Newsletter19932013
- 31. Vital oils19911st edLondonEbury Press
- 32. Analysis of essential oils by gas chromatography and mass spectrometry19761st edNew YorkJohn Wiley and Sons, Inc
- 33. Recent advances in biosynthesis of alkaloidsComprehensive natural product chemistry (CONAP)1999OxfordElsevier Publisher2569
- 34. Influence of Plant density, Nitrogen and Phosphorus on growth, yield and essential oil content of chamomile (Matricaria chamomilla Linn.)Indian Perfumers19913516872
- 35. AnonymousAzulene in pharmacy and cosmetics. Dragoco Rep196916235
- 36. Efficacy of herbal tea preparation in infantile colicJ Pediatr19931226502
- 37. Study on the assessments of plants/herbs, plant/herb extracts and their naturally or synthetically produced components as additives for use in animal production CFT/EFSA/FEEDAP/2005/01200515569
- 38. Plant sourcesChamomile: industrial profiles20051st edBoca RatonCRC Press3942
- 39. Encyclopedia of common natural ingredients used in food, drugs, and cosmetics19962nd edNew YorkJohn Wiley and Sons
- 40. Correct scientific name of “Babuna” used widely as a drug in unani system of medicinePak J Sci Ind Res198427203
- 41. Matricaria chamomilla Linn. – A remunerative crop for saline alkali-soilsIndian Forester19781046317
- 42. Experiments with the cultivation of chamomile (Matricaria chamomilla)Herba Hungarica196651417
- 43. Lucknow Extension BulletinLucknow (NBRI): Economic Botany Information Service1979
- 44. Comparative examination of chamomile varieties grown in Finland and HungaryHerba Hungarica1988274555
- 45. Cultivation and fertilizing of the tetraploid Matricaria chamomilla L.IThe sowing time Herba Polonica19711736775
- 46. Effect of different spacings on fresh flower and oil yield of Matricaria chamomillaIndian J Agron19649112
- 47. Elaboration of cultural practices for chamomile (Matricaria chamomilla L.). An Inst Cercot Pentrru Cereale Plants Tehn Fund, Ser B Agrochim AgrotechnPasuni Finete19663466370
- 48. Utilization of saline-alkali soils for agro-industry without reclamationEcon Bot19702443942
- 49. Cultivation and fertilizing of the tetraploid form of Matricaria chamomilla L. II. Spacing and density of sowingHerba Polonica197218708
- 50. Effect of nitrogen, phosphorus and potassium singly and in combination on oil content of Matricaria chamomillaSymposium on “Production and Utilization of Medicinal and Aromatic Plants in India”1961JammuRRL11
- 51. The effect of fertilizer levels on growth yield and oil production of Matricaria chamomillaLloydia19652824551
- 52. Cultivation of Matricaria chamomillaSupplement to cultivation and utilization of aromatic plants1997Jammu-TawiRegional Research Laboratory (CSIR)24153
- 53. Effect of trace elements on the yield and quality of pharmaceutical chamomile flowers (Matricaria chamomilla) and peppermint leaves (Mentha piperita) var. rubescensIzvestiia Akadmii Nauk Lat SSR196871119
- 54. Effect of molybdenum and boron dry matter production and drug yield in chamomile (Matricaria chamomilla)Nase Liecive Rastliny1979166974
- 55. Vergleichende Untersuchungen Uber sekundare Inhaltsstoffe bei pflanzentumoren, Blite Kraut und wurzel der Matricaria chamomilla LPlanta Med19793632232
- 56. First finding on chemical weed control in chamomile (Matricaria chamomilla)Pharmazie1969241703
- 57. Influence of herbicides and some heavy metals on growth of Matricaria chamomilla L.and the biosynthesis of essential oilActa Horticulture19787333941
- 58. Herbicides in the cultivation of Matricaria chamomilla. I. Influence of herbicides on flower production and weedPlanta Med19773137889
- 59. Comparative efficacy of thiobencarb, nitrofen and oxyflurofen in German chamomile (Matricaria chamomilla L.)Indian Perfumer19893322831
- 60. Cultivation of Matricaria chamomillaCultivation and utilization of medicinal and aromatic plants1982Jammu-TawiRegional Research Laboratory (CSIR)6538
- 61. The food plants of the black bean of aphid A.fabaeTijdschrift Plantenzic Kien1950556987
- 62. Nyrius minor Dist. (Lygaeidae: Namiptera) – A pest pf Matricaria chamomillaIndian J Entomol196224646
- 63. Storage of dry drugChamomile: industrial profiles2005Boca RatonCRC Press2113
- 64. Handbuch fur arzte, apotheker und andere naturwissenschaftler19871st edGermanyWissenschaft Verlagsgesellschaft
- 65. Matricaria recutita cultivation2005LucknowFarm Bulletin CIMAP7
- 66. Effect of drying Matricaria chamomilla flowers on chemical composition of essential oilJ Med Aromat Plant Sci19992110205
- 67. Coumarins of Matricaria recutitaKhim Prirod Sojed199168534
- 68. HPLC determination of coumarins in Matricaria chamomillaPlanta Med1981434123
- 69. Simultaneous and quantitative analysis of glycosideShoyakugaku Zasshi199347348
- 70. Seasonal variation in the production of the head and accumulation of glycosides in the head of Matricaria chamomillaActa Horticulture19953907582
- 71. Pharmacological potential of Matricaria recutita-A reviewInt J Pharm Sci Drug Res20102126
- 72. Essential oil of Chamomilla recutita (L.) Rausch. From IranJ Essent Oil Res2002144078
- 73. Essential oil content and composition of German chamomile (Matricaria chamomilla L.) at different irrigation regimesJ Agron200654515
- 74. Flavonoid in Matricaria chamomilePlanta Med19803921930
- 75. On the flavones of chamomile (Matricaria chamomilla L.) and a new acetylated apigenin-7-glucosidePlanta Med19803712430
- 76. Therapy with chamomile-experience and verificationDisch Apoth Ztg198012056770
- 77. A study of the production of essential oils in chamomile hairy root culturesEur J Drug Metab Pharmacokinet1999243038
- 78. CRC handbook of medicinal herbs19851st edBoca RatonCRC Press297414
- 79. Screening of medicinal plants for antileishmanial and antimicrobial activityActa Hortic199642623542
- 80. Chemical study of Matricaria chamomilla L-IIFitoterapia198354515
- 81. Pharmacological investigations with compounds of ChamomillaPlanta Med19793511824
- 82. Phytochemical study of a new hybrid chamomile variety. II. Essential oilPharm Zentralle196910881323
- 83. Active chemical constituents of Matricaria chamomilla L. syn. Chamomilla recutita (L.) RauschertChamomile-industrial profiles2005Boca RatonCRC Press5576
- 84. Plant Drug Analysis19841st edHeidelbergSpringer-Verlag3234
- 85. α-Bisabolol – an agent, anti-inflammatory pour products cosmetiquePerfume Cosmet Aromes198457557
- 86. Valuation of anti-inflammatory activity of a chamomile extract after topical applicationPlant Med198450359
- 87. Encyclopedia of common natural ingredients used in food, drugs and cosmetics19801st edNew YorkJohn Wiley and sons11012
- 88. Pharmacological investigations with compounds of chamomile II.New investigations on the antiphlogistic effects of (-)-α-bisabolol and bisabolol oxidesPlanta Med19793512540
- 89. Pharmacological investigations with compounds of chamomile V.Investigations on the spasmolytic effect of compounds of chamomile and Kamillosan® on the isolated guinea pig ileumPlanta Med1980393850
- 90. The essential oil19521st edNew YorkD. Van Nostrand Company Inc
- 91. The essential book of herbal medicine19791st edLondonArkana Penguin Books
- 92. Pharmacological investigations with compounds of chamomile VI.Investigations on the antiphlogistic effects of chamazulene and matricinePlanta Med1983496773
- 93. Content of the active principles in various parts of Matricaria chamomillaAtti-Conv Naz Olii Essenz Sui Deriv Agrum19756071306
- 94. The essential oil of Matricaria chamomillaJ Tech Assoc India1961165961
- 95. Zusammensetzung und accumulation des etherischenol in Matricaria chamomilla Radix. 2. Mitt. ZNaturforsch19833815961
- 96. Dynamics of some components of chamomile essential oilRef Zhurnal1980107601
- 97. Content and composition of the essential oil in flower heads of Matricaria chamomilla L. during its ontogenetical developmentPlanta Med1979362823
- 98. Indian medicinal plants-an illustrated dictionary20071st edNew YorkSpringer-Verlag
- 99. Dietary intake of the flower extracts of German chamomile (Matricaria recutita L.) inhibited compound 48/80-induced itch-scratch responses in micePhytomedicine20031065764
- 100. Antiproliferative and apoptotic effects of chamomile extract in various human cancer cellsJ Agric Food Chem20075594708
- 101. Antihyperglycemic and antioxidative potential of Matricaria chamomilla L. in streptozotocin-induced diabetic ratsNat Med20086228493
- 102. Anti-inflammatory activity of some Iraqi plants using intact ratsJ Ethnopharmacol1989261638
- 103. In vitro antimicrobial activity of plants in Acute Otitis ExternaBraz J Otorhinolaryngol20087411824
- 104. Antipruritic effect of the single oral administration of German chamomile flower extract and its combined effect with antiallergic agents in ddY miceJ Ethnopharmacol200510130812
- 105. Preliminary studies towards utilization of various plant extracts as antisolar agentsInt J Cosmet Sci19961887101
- 106. Therapie unspezifischer Magenbeschwerden mit Kamillosan®Kassenarzt19781836056
- 107. An animal model for the study of chamomilla in stress and depression: pilot studyHomeopathy2008971414
- 108. Antiulcerogenic effect of some gastrointestinally acting plant extracts and their combinationArzneimittelforschung20015154553
- 109. A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorderJ Clin Psychopharmacol20092937882
- 110. Acaricidal activity of aqueous extracts of camomile flowers, Matricaria chamomilla, against the mite Psoroptes cuniculiMed Vet Entomol2004182057
- 111. In vitro susceptibility of Helicobacter pylori to botanical extracts used traditionally for the treatment of gastrointestinal disordersPhytother Res20051998891
- 112. Hepatoprotective activity of aqueous ethanolic extract of Chamomile capitula in paracetamol intoxicated albino ratsAm J Pharmacol Toxicol200611720
- 113. The immunomodulating activity of the heteropolysaccharides from German chamomile (Matricaria chamomilla) during air and immersion coolingEksperimental′naia i Klinicheskaia Farmakologiia199962525
- 114. Inhibition of poliovirus replication by an extract of Matricaria chamomilla (L)Comptes Rendus de l′Academie des Sciences-III198530128994
- 115. The effect of German chamomile (Marticaria recutita L.) extract and tea tree (Melaleuca alternifolia L.) oil used as irrigants on removal of smear layer: a scanning electron microscopy studyInt Endod J2006391905
- 116. Lousicidal, ovicidal and repellent efficacy of some essential oils against lice and flies infesting water buffaloes in EgyptVet Parasitol200916425766
- 117. Greek plant extracts exhibit selective estrogen receptor modulator (SERM)-like propertiesJ Agric Food Chem200452695661
- 118. Study of benzodiazepine like effects of Matricaria recutita on morphine withdrawal syndrome in adult male ratsPak J Med Sci2008247359
- 119. Presence of Clostridium botulinum spores in Matricaria chamomilla (chamomile) and its relationship with infant botulismInt J Food Microbiol200812135760
- 120. Wild chamomile (Matricaria recutita L.) mouthwashes in methotrexate-induced oral mucositisPhytomedicine200512257
- 121. Uterotonic action of extracts from a group of medicinal plantsVeterinarno-Meditsinsiki Nauki198118948
- 122. Inhibitory effect of essential oils against herpes simplex virus type 2Phytomedicine200815718
- 123. Comparative analysis between Chamomilla recutita and corticosteroids on wound healing. An in vitro and in vivo studyPhytother Res2009232748
- 124. Antioxidants, oxidative damage and oxygen deprivation stress: a reviewAnn Bot20039117994
- 125. Phenols and antioxidative status of Raphanus sativus grown in copper excessPhysiol Plant2003118218
- 126. Effects of nitrogen deficiency on gas exchange, chlorophyll fluorescence, and antioxidant enzymes in leaves of rice plantsPhotosynthetica20044235764
- 127. Phenolic compounds and oxidative metabolism in green bean plants Ander nitrogen toxicityAust J Plant Physiol2000279738
- 128. Structure-antioxidant activity relationships of flavonoids and phenolic acidsFree Radic Biol Med19962093356
- 129. Changes in the concentration of phenolic compounds and exudation induced by phosphate deficiency in bean plants (Phaseolus vulgaris L.)Plant Soil2004267419
- 130. Phenylalanine ammonia-lyase activity and phenolic compounds accumulation in nitrogen deficient Matricaria chamomilla leaf rosettesPlant Sci20071723939
- 131. Changes of phenolic metabolism and oxidative status in nitrogen deficient Matricaria chamomilla plantsPlant Soil200729725565
- 132. Signalling responses in plants to heavy metal stressActa Physiol Plant20072917787
- 133. Oxidative stress in Arabidopsis thaliana exposed to cadmium in due to hydrogen peroxide accumulationPlant Sci200516811320
- 134. Oxidative mechanisms in the toxicity of metal ionsFree Radic Biol Med19951832136
- 135. The activity and localization of lipoxygenases in Arabidopsis thaliana under cadmium and copper stressesPlant Growth Regul20064829
- 136. Phenolic compounds composition and physiological attributes of Matricaria chamomilla grown in copper excessEnviron Exp Bot20086214552
- 137. Matricaria chamomilla is not a hyperaccumulator, but tolerant to cadmium stressPlant Growth Regul20065023947
- 138. Molecular biomarkers of oxidative stress in aquatic organisms in relation to toxic environmental pollutantsEcotoxicol Environ Saf20066417889
- 139. Oxidative status of Matricaria chamomilla plants related to cadmium and copper uptakeEcotoxicology2008174719
- 140. Cadmium and zinc interactions in trace element accumulation in chamomileJ Plant Nutr200528138396
- 141. Effect of high cadmium concentrations in soil on growth, uptake of nutrients and some heavy metals of Chamomilla recutita (L.) RauschertJ Appl Bot20007416974
- 142. Hypericum perforatum L. and Chamomilla recutita (L.) Rausch accumulation of some toxic metalsPharmazie20035835960
- 143. The influence of soil cadmium eliminating sorbents on Chamomilla recutitaJ Environ Sci Health1998B3330716
- 144. Quantitative changes of secondary metabolites of Matricaria chamomilla by abiotic stressZ Naturforsch200459c5438
- 145. Umbelliferone, a stress metabolite of Chamomilla recutita (L.) RauschertJ Plant Physiol200115810857
- 146. Nitrogen deficiency induced changes of free amino acids and coumarin contents in the leaves of Matricaria chamomilla LActa Physiol Plant20062815964
- 147. Metabolism and function of polyamines in plants: recent development (new approaches)Plant Growth Regul20013413548
- 148. PolyaminesAnnu Rev Plant Physiol19853611743
- 149. Nitrogen containing compounds and adaptation of plants to salinity stressBiol Plant200043491500
- 150. Endogenous ornithine and arginine contents and dark induced praline accumulation in detached rice leavesJ Plant Physiol19991556658
- 151. The effects of exogenous proline and praline analogues on in vitro shoot organogenesis in ArabidopsisPlant Growth Regul2001342037
- 152. The regulatory role for proline metabolism in stimulating Arabidopsis thaliana seed germinationPlant Growth Regul2003394150
- 153. Effect of some amino acids on growth and essential oil content of chamomile plantInt J Agric Biol2005737680
- 154. Alkaloid biology and metabolism in plants19781st edNew YorkPlenum Press
- 155. Salicylic acid and disease resistance in plantsCrit Rev Plant Sci19991854775
- 156. Characterization of salicylic acid-induced genes in Chinese cabbagePlant Cell Rep200321102734
- 157. Changes in the hormonal status of wheat seedlings induced by salicylic acid and salinityPlant Sci200316431722
- 158. Effects of salicylic acid on the growth of roots and shoots in soybeanPlant Physiol Biochem1998365635
- 159. Salicylic acid induced changes on some physiological parameters symptomatic for oxidative stress and mineral nutrition in maize (Zea mays L.) grown under salinityJ Plant Physiol200716472836
- 160. Induction of a biotic stress tolerance by salicylic acid signalingJ Plant Growth Regul200726290300
- 161. A role for salicylic acid and NPR1 in regulating cell growth in ArabidopsisPlant J20012820916
- 162. Salicylic acid induces changes of coumarin metabolites in Matricaria chamomilla LPlant Sci200416781924
- 163. Salicylic acid induced changes to growth and phenolic metabolism in Matricaria chamomilla plantsPlant Cell Rep20092813543
- 164. Tissue culture of Matricaria chamomilla L.: I. Isolation and maintenance of the tissue culture and preliminary phytochemical investigationsPlanta Med19763025868
- 165. Differences in the essential oil composition in isolated roots, root callus tissues and cell suspensions of Matricaria chamomillaIzvestiia Akadmii Nauk SSSR-Seriia Biolgicheskaia198069439
- 166. Effect of growth regulators on biomass formation in callus culture of chamomile (Matricaria chamomilla)Herba Hungarica1979184157
- 167. Tissue culture of the wild chamomileFiziologiya Rastenii (Mosc)19772483240
- 168. Morphogenesis in callus tissue cultures of some Matricaria and Achillea speciesBiol Plant1982244306
- 169. Recent knowledge in quality evaluation of camomile blossoms respectively camomile oil. 2. Quality evaluation of the volatile oil in Flores Chamomillae. Grading of commercial camomiles into 4 respectively 5 chemical typesPlanta Med19732313244
- 170. CultivationChamomile: Industrial profiles20051st edBoca RatonCRC Press77165
- 171. CIMAP releases the variety vallary of German chamomileCIMAP Newsl1995226
- 172. Matricaria recutita (German chamomile). The Australian New Crops Newsletter1999
1 11 about 7 p., last cited on 2010 July 19Available from: http://www.newcrops.uq.edu.au/newslett/ncn11166.htm
- 173. Cultivation prospects of German chamomile in South IndiaNat Prod Radiance200761357