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Double-blind, randomized evaluation of clinical efficacy and tolerability of an apple pectin-chamomile extract in children with unspecific diarrhea.

BACKGROUND: Acute diarrhea is one of the most common childhood diseases. The main aim of therapy is oral rehydration, mostly using a glucose-electrolyte solution. Results from a previous study (DIALOG I) investigating adjuvant treatment with a medicinal preparation containing an apple pectin-chamomile extract (Diarrhoesan) indicated a significantly reduced duration of diarrhea in children. OBJECTIVES: The objective of the present clinical placebo-controlled, double-blind study (DIALOG II) was to assess the clinical efficacy and tolerability of the apple pectin-chamomile extract on a larger number of patients. METHODS: The investigation was designed as a multicenter, randomized, double-blind, placebo-controlled parallel study enrolling 255 patients presenting with acute diarrhea. Patients were aged between 6 months and 6 years and treated on an outpatient basis with either an apple pectin-chamomile preparation or placebo. As a basic medication, each child received a glucose-electrolyte solution on the first day of treatment. RESULTS: The primary outcome (primary efficacy parameter) included a combined analysis of stool frequency, stool The statistical analysis revealed a superior efficacy of the tested preparation over placebo with a significantly reduced stool frequency in the treatment group compared to the control group. The results were corroborated by efficacy assessment performed by investigators and patients. Treatment was well tolerated, with an incidence of adverse effects similar to placebo. CONCLUSION: These findings support the concept of a beneficial influence of the investigated vegetable extract in shortening the course of the disease and relieving associated symptoms.

Antidiarrheals↗

Effect of magnesium on essential oil formation of genetically transformed and non-transformed chamomile cultures.

OBJECTIVE: The importance of chamomile (Chamomilla recutita) is widely known in classical and folk medicine, with the largest group of its effective substances forming the essential oil (chamazulene, alpha-bisabolol, trans-beta-farnesene, spathulenol, cis/trans-en-in-dicycloethers). The increasing need for plant-derived high quality drugs cannot be provided by their collection in the wilderness. METHOD A: To preserve the genome of Szabadkigyo. wild type having high (-)-alpha-bisabolol content, we used biotechnological methods. RESULTS: The roots of organized culture contained beta-eudesmol, which we have identified in the intact roots. Our gas-chromatographic and mass-spectroscopic studies showed that sterile chamomile cultures generated the most important terpenoid and polyin compounds characteristics of the intact plant. We identified berkheyaradulene, geranyl-isovalerate and cedrol, as new components in these cultures. Magnesium (Mg) (370 and 740 mg/l MgSO4) has a positive effect on the growth of organized cultures and also on the quality and quantity of essential oil production. METHOD B: Another possible source of variants is available by the genetic transformation of organized cultures by infection with Agrobacterium rhisogenes. With this method, we cultivated chamomile infected by A4-Y clone and investigated the essential oil production by hairy root cultures cultivated on solid and liquid MS B-5 media. The main component of the essential oil of hairy root cultures was trans-beta-farnesene. RESULTS: We identified alpha-selinene, as a new component in these hairy roots. We studied the growth rate of A4-Y clone on the cited media, containing MgSO4 concentrations: 0; 185; 370 and 740 mg/l. The cultures grew most in medium containing 740 mg/l of MgSO4. Essential oil content was compared from hairy root cultures of different Mg containing media and measured by GC and GC-MS methods. Mg has a similar effect on hairy roots as on organized cultures.

Chamomile↗

Clinical cross-reactivity between Artemisia vulgaris and Matricaria chamomilla (chamomile).

Artemisia vulgaris is a common weed and an important source of allergens on the subtropical island of Tenerife, Canary Islands, Spain. It pollinates mainly from July to September, although, due to some local climatic conditions, it may flower throughout the year. Cross-reactivity with hazelnut, kiwi, birch, several Compositae (Ambrosia, Chrysanthemum, Matricaria, Solidago) and grass allergens has been suggested. Few studies have addressed the issue of in vivo cross-reactivity between A. vulgaris and Matricaria chamomilla. The objective of this study was to perform conjunctival and bronchial challenges with A. vulgaris and M. chamomilla and oral challenge with chamomile in 24 patients with asthma and/or rhinitis sensitized primarily to A. vulgaris. Skin prick tests with M. chamomilla were positive in 21 patients. Eighteen patients had a positive conjunctival provocation test with a A. vulgaris pollen extract and 13 patients had a positive conjunctival provocation test with a M. chamomilla pollen extract. Bronchial provocation tests with A. vulgaris were positive in 15 patients and with M. chamomilla pollen in another 16 individuals. Oral provocation tests, conducted with a commercial chamomile infusion were positive in 13 patients. Nine of these individuals were skin test positive to food allergens and 17 to others pollens of the Compositae family. This study confirms a high degree of in vivo cross-reactivity between A. vulgaris and M. chamomilla. Sensitization to A. vulgaris seems to be a primary risk factor for experiencing symptoms after the ingestion of chamomile infusions. Based on the results of bronchial provocation tests, M. chamomilla pollen could be a relevant inhalant allergen.

Administration, Oral↗

Efficacy of chamomile-extract spray for prevention of post-operative sore throat.

A randomized, double-blind study was carried out to assess the effect of 111 mg of Chamomile extract spray compared with normal saline spray (placebo) administered before intubation on post-operative sore throat and hoarseness. One hundred and sixty-one ASA (American Society of Anesthesiologists) physical status I, II elective surgical patients were recruited. Forty-two out of 80 patients (52.5%) in the Chamomile group scored no post-operative sore throat in the post-anesthesia care unit compared with 41 out of 81 patients (50.6%) in the placebo group, p=0.159. Post-operative sore throat and hoarseness both in the post-anesthesia care unit and 24 hour after operation were not statistically different. There was no statistically significant relationship between sore throat or hoarseness and ASA physical status, sex, history of smoking, grade of laryngoscopic view, number of intubation attempts, condition during intubation and condition of extubation. However, there was significant correlation between use of oral airway and sore throat in the post-anesthesia care unit and 24 hours after operation (p=0.031 and 0.002 respectively). Chamomile extract spray administered before intubation, therefore, can not prevent post-operative sore throat and hoarseness.

Administration, Topical↗

Headspace-solid-phase microextraction fast GC in combination with principal component analysis as a tool to classify different chemotypes of chamomile flower-heads (Matricaria recutita l.).

Headspace-solid-phase microextraction gas chromatography-principal component analysis (HS-SPME GC-PCA) is proposed as a complementary or alternative method to essential oil (EO) GC-PCA in order to discriminate between flower-heads of chamomile of different chemotypes. Ninety-two EOs and the headspaces sampled by HS-SPME of the corresponding chamomile flower-heads were examined by conventional GC and fast GC (F-GC) and the results submitted to statistical analysis by PCA. HS-SPME F-GC-PCA showed itself to be a rapid technique by which to distinguish chamomile flower-head chemotypes a produced results in agreement with the accepted EO classification. Using this method, the analysis time was reduced from at least 4.5 h with EO conventional GC to less than 1 h with HS-SPME F-GC. This approach can thus successfully be used as an analytical decision maker in order to reduce the number of time-consuming EO conventional GC analyses by limiting them to those samples that cannot unequivocally be classified. The EO conventional GC and HS-SPME F-GC results of PCA were very uniform, but they did not provide quantitative correlations between the components as determined by the two methods. A different statistical approach and a larger number of samples will be needed in order to correlate components in the headspace sampled by SPME and those in the corresponding EO quantitatively through a function.

Chromatography, Gas↗

A study of the production of essential oils in chamomile hairy root cultures.

The active substances in chamomile (Matricaria recutita L.) belong to chemically different structural types. The largest group of medically important compounds forming the essential oils are primarily chamazulene, (-)-alpha-bisabolol, bisabololoxides, bisabolonoxide A, trans-beta-farnesene, alpha-farnesene, spathulenol and the cis/trans-en-in-dicycloethers. Flavonoids, coumarins, mucilages, mono- and oligosaccharides also have pharmacological effects. We studied the production of essential oils in genetically transformed cultures. Sterile juvenile chamomile plants were infected with A4-Y strains of Agrobacterium rhizogenes. They are known plant pathogens and are capable of inducing so-called hairy roots. The transfer DNA segment of the Ri-virulence plasmid of A. rhizogenes becomes integrated in the genome of the plant cells. The isolated hairy roots grow rapidly on hormone-free media. In order to obtain bacteria-free media, we cultured the transformed roots on Murashige-Skoog (MS) medium supplemented with carbenicillin (800 mg/l). To study the production of essential oils, the clones were propagated on liquid and solid MS and Gamborg (B5) media, respectively. According to gas chromatography, the composition of the essential oil of hairy root cultures on different media was found to be similar, but differing in proportion. The main component of the essential oil which was identified by gas chromatography and mass spectrometry was trans-beta-farnesene, as in the intact roots.

Chamomile↗

New terpenoids in cultivated and wild chamomile (in vivo and in vitro).

The effect of Chamomilla recutita (L.) Rauschert is made up by several groups of active substances, among which terpenoids in the inflorescences are of greatest importance. Among cultivated species, the Hungarian BK-2 contains more chamazulene in its essential oil than the German Degumil type, which is mainly cultivated for its (-)-alpha-bisabolol. Both components have important antiinflammatory activities. Among wild chamomile populations in Hungary, a population was found in the area of Szabadkigyós containing significant amounts-on average 48%-of (-)-alpha-bisabolol in its inflorescence oil. In vitro cultures were made from this population to obtain propagation material containing a high number of active substances. The intact roots contained no (-)-alpha-bisabolol but the sesquiterpene alcohol beta-eudesmol as new compound was identified by our group. Sterile plantlets, cultured in vitro, were multiplied for phytochemical investigations. Pharmacologically important compounds of the essential oils were followed in great detail. The amount of in vitro cultured terpenoids and polyin compounds was compared with that of in vivo plants. These volatile compounds were identified by comparing their retention times with those of authentic standards, essential oils of known composition and peak enrichment. The confirmation of identity was done by comparison of their mass spectra with those reported in the literature and reference compounds. The percentage evaluation of each component was made by area normalisation. Gas chromatography (GC) and mass spectrometry (MS) showed that sterile chamomile cultures generated the most important terpenoid and polyin compounds characteristic of the parent plant. We identified germacrene-D, berkheyaradulene, 4-(2', 4', 4'-trimethyl-bicyclo[4.1.0]hept-2'-en-3'-yl)-3-buten-2-one, geranyl-isovalerate and cedrol as new components in these sterile cultures.

Biological Specimen Banks↗

Inhibitory effect of chamomile essential oil on the sister chromatid exchanges induced by daunorubicin and methyl methanesulfonate in mouse bone marrow.

Different preparations of chamomile (Matricaria chamomilla) are used to treat various diseases, including inflammation and cancer; however, no studies on the plant's antigenotoxic capacity have been made. The aim of the present work was to determine the inhibitory effect of the chamomile essential oil (CO), on the sister chromatid exchanges (SCEs) produced by daunorubicin and methyl methanesulfonate (MMS) in mouse bone marrow cells. CO was analyzed and was found to contain 13 compounds, mainly bisabolol and its oxides, chamazulene, farnesene, germacrene and other sesquiterpenes. Initially, a toxic and a genotoxic analysis of CO were made; both showed negative results. To determine whether CO can inhibit the mutagenic effects induced by daunorubicin, one group of mice was administered corn oil, another group was treated with the mutagen (10 mg/kg), a third group was treated with 500 mg/kg of CO; three other groups were treated first with CO (5, 50 and 500 mg/kg) and then with 10 mg/kg of daunorubicin. In the case of MMS, the experimental groups consisted of the following: the negative control group which was administered corn oil, a group treated with 25 mg/kg of MMS, a group treated with 1000 mg/kg of CO, and three groups treated first with CO (250, 500 and 1000 mg/kg) and then with MMS (25 mg/kg). The results indicated a dose-dependent inhibitory effect on the SCEs formed by both mutagens. In the case of daunorubicin, a statistically significant result was observed in the three tested doses: from the lowest to the highest dose, the inhibitory values corresponded to 25.7, 63.1 and 75.5%. No alterations were found with respect to the cellular proliferation kinetics, but a reduction in the mitotic index was detected. As regards MMS, the inhibitory values were 24.8, 45.8 and 60.6%; no alterations were found in either the cellular proliferation kinetics or in the mitotic indices. Our results suggest that CO may be an effective antimutagen that could be considered for further study.

Animals↗

Beta-eudesmol, a new sesquiterpene component in intact and organized root of chamomile (Chamomilla recutita).

Gas chromatography (GC) and GC-mass spectrometry are used to identify a new sesqiterpene, beta-eudesmol, which seems to be a characteristic essential oil component of the intact and in vitro organized root of chamomile [Chamomilla recutita (L.) Rauschert]. It is identified on three types of stationary phases by GC. The confirmation of identity is carried out by comparison of mass spectra with those reported in the literature and measured from a reference compound. The percentage evaluation of the oil component is made by area normalization, on the basis of three parallel measurements. Among the cultivated and wild chamomile species examined, the wild species from the areas of Szeghalom contain the highest quantity of beta-eudesmol (9.25% in the total essential oil).

Chamomile↗

[Surveillance of phytotherapeutic drugs in the state of Minas Gerais. Quality assessment of commercial samples of chamomile].

Marketing of medicinal plants and phytotherapeutic products is spreading all over the world. In order to assess the commercialization of medicinal plants and phytotherapeutic products in the State of Minas Gerais, we identified and tested for the presence of adulterants and active ingredients in 27 samples of chamomile. All the samples consisted of Matricaria recutita flowers, but they were badly fragmented, a result of excessive handling and poor preservation. All samples contained contaminants, and insects were observed in 63% of the samples sold in drugstores. Only 50% of the samples in each group had the essential oils needed to produce antiinflammatory activity. Flavonoids and other phenolic constituents with a spasmolytic effect were detected in only 20% of the samples from each group. Results with chamomile indicated the poor quality with which medicinal plants and phytotherapeutic products are marketed and confirm the need for surveillance of such products in Brazil.

Anticarcinogenic Agents↗

Isolation, identification and stability of acylated derivatives of apigenin 7-O-glucoside from chamomile (Chamomilla recutita [L.] Rauschert).

The major flavonoids in the white florets of chamomile (Chamomilla recutita [L.] Rauschert) were rapidly purified using a combination of polyamide solid-phase extraction and preparative HPLC. From the combined LC/MS, LC/MS/MS, and NMR data the apigenin glucosides were identified as apigenin 7-O-glucoside (Ap-7-Glc), Ap-7-(6"-malonyl-Glc), Ap-7-(6"-acetyl-Glc), Ap-7-(6"-caffeoyl-Glc), Ap-7-(4"-acetyl-Glc), Ap-7-(4"-acetyl,6"-malonyl-Glc), and a partially characterised apigenin-7-(mono-acetyl/mono-malonylglucoside) isomer. Malonyl and caffeoyl derivatives of Ap-7-Glc have not previously been identified in chamomile. The two mono-acetyl/mono-malonyl flavonoids have not previously been reported in any plant species. These acylated glucosides are unstable and degrade to form acetylated compounds or Ap-7-Glc. The degradation products formed are dependent on the extraction and storage conditions, i.e. temperature, pH and solvent.

Acetylation↗

Metabolomic strategy for the classification and quality control of phytomedicine: a case study of chamomile flower (Matricaria recutita L.).

In order to improve the accuracy and consistency of control phytomedicine preparations worldwide, regulatory authorities are requesting research into new analytical methods for the stricter standardisation of phytomedicines. Such methods have to be both objective and robust, and should address the reproducibility of the content of the chemical profiles. NMR-based metabolomics, which combines high-resolution (1)H-NMR spectroscopy with chemometric analysis, has been employed as an innovative way to meet those demands. In this paper, chamomile flowers from three different geographical regions, namely, Egypt, Hungary and Slovakia were characterised using 1H-NMR spectroscopy followed by principal component analysis. It was found that the origin, purity and preparation methods contributed to the differences observed in prepared chamomile extracts. In addition, this method also enabled the elucidation of the molecular information embedded in the spectra responsible for the observed variability. The metabolomic strategy employed in the current study should provide an efficient tool for the quality control and authentication of phytomedicines.

Flowers↗

Modulation of lipopolysaccharide-induced proinflammatory cytokine production in vitro and in vivo by the herbal constituents apigenin (chamomile), ginsenoside Rb(1) (ginseng) and parthenolide (feverfew).

Dietary supplements are not subject to the same pre-market approval as conventional drugs, thus the true efficacy and, in cases, safety of these products is not known. The objective of this study was to evaluate the potential anti-inflammatory properties of three herbal constituents, apigenin (chamomile), ginsenoside Rb(1) (ginseng) and parthenolide (feverfew) on lipopolysaccaharide (LPS)-induced proinflammatory cytokine production, and to determine if effects in cell culture could predict results in an intact animal model. Murine macrophage cells and mice were treated with the stimulant LPS and herbal constituents, and resultant culture supernatant and serum, respectively, were evaluated for interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha by ELISA. All three constituents inhibited LPS-induced IL-6 and/or TNF-alpha production in culture. Inhibition of these two cytokines was observed in mice, but did not display the same patterns of inhibition as cell culture data. The results suggest that all three constituents possessed anti-inflammatory properties, but that cell culture data can only be used to approximate potential effects in animals, and must be confirmed using appropriate animal models.

Animals↗

Analytical and preparative supercritical fluid extraction of chamomile flowers and its comparison with conventional methods.

Supercritical fluid extraction (SFE) was compared with Soxhlet extraction, steam distillation and maceration for the isolation of the active components present in chamomile flowerheads. The obtained fractions were analysed by GC-MS and reversed-phase HPLC. The yield of essential oil achieved by a 30-min extraction with pure CO2 at 90 atm and 40 degrees C was 4.4 times higher than that produced by steam distillation performed for 4 h. The recovery of the flavonoid apigenin obtained by supercritical CO2 after a 30-min extraction at 200 atm and 40 degrees C was 71.4% compared to Soxhlet extraction performed for 6 h and 124.6% compared to maceration performed for 3 days. However, the highly polar flavonoid apigenin-7-glucoside was not extracted by 100% CO2 (recovery values < 1.1%). Its extraction efficiency was markedly improved by the addition of the polar modifier methanol (5%, v/v) to the CO2 fluid, yet the obtained recoveries were unsatisfactory (14.6-19.5%). The SFE method was scaled-up for preparative applications using a pilot plant with three separation stages operating in series. Large-scale SFE was technically feasible with pure CO2 as the extracting fluid. However, the use of CO2 modified with organic solvents was not effective at the pilot-plant scale.

Chamomile↗

Suitability of two root-mining weevils for the biological control of scentless chamomile, Tripleurospermum perforatum, with special regard to potential non-target effects.

The biology and host range of the two root-mining weevils Diplapion confluens Kirby and Coryssomerus capucinus (Beck), two potential agents for the biological control of scentless chamomile Tripleurospermum perforatum (Mérat) Laínz, were studied in the field in southern Germany and eastern Austria, and in a common garden and under laboratory conditions in Delémont, Switzerland from 1993 to 1999. Both weevils were univoltine, and females started to lay eggs in early spring. Diplapion confluens had three and C. capucinus five instars. Larvae of both species were found in the field from mid-April until the end of July; later instars preferentially fed in the vascular cylinder of the shoot base, root crown or root. Although larvae of both species occupy the same temporal and spatial niche within their host plants, they occurred at all investigated field sites together, and showed a similar distribution within sites. No negative or positive interspecific association was detected. Host-specificity tests including no-choice, single-choice, and multiple-choice tests under confined conditions, as well as tests under field conditions with natural and augmented insect densities revealed that both herbivores were specific to plant species in the tribe Anthemideae. However, their development to mature larva or adult on several cultivated plants, as well as on one plant species native to North America, rendered them unsuitable for field release in North America. It was concluded that to investigate non-target effects reliably, host-specificity tests with biological control agents should be carried out under a variety of conditions, particularly with augmented insect densities, as are expected to occur naturally after release.

Animals↗

Anthecotulide: purification, analytical data, absence from chamomile preparations, stability and reactivity, and anti-infective testing.

The sesquiterpene lactone anthecotulide (1) was extracted from Anthemis cotula in 0.7% w/w yield. A pure standard was prepared by preparative TLC and used for quantitative determination of 1 with a TLC scanner. The constitution of 1 was corroborated and the double-bond configuration determined. It was stable at room temparature in air and reacted very slowly with glutathione. It was not detectable in 34 chamomile (Matricaria recutita) preparations and did not show antibacterial activity against a range of clinically important strains at a concentration of <10 microg/mL.

Anthemis↗

["More is not better"--evaluation of toxicologic risks of the heavy metals, lead and cadmium, and the herbicides, linuron, fluazifop-P-butyl and cycloxydim in dried Chamomile flowers (Chamomilla recutita L. Rauschert)].

Cadmium and all three enumerated herbicide residues in dried samples of industrially grown true chamomile were found to be above the suggested and accepted tolerance values. The results are discussed with regard to the current Croatian regulation and FAO/WHO recommendations on herbicides and to human toxicology risk assessment. The paper gives a critical evaluation of the herbicide overuse in agricultural practice and strongly discouraged such practice. The authors advocate prospective use of plants as natural indicators of environmental contamination and toxicological burden of the human food chain.

Cadmium↗