Human microsomal epoxide hydrolase is the target of germander-induced autoantibodies on the surface of human hepatocytes.
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Germander, a plant used in folk medicine, caused an epidemic of cytolytic hepatitis in France. In about half of these patients, a rechallenge caused early recurrence, suggesting an immunoallergic type of hepatitis. Teucrin A (TA) was found responsible for the hepatotoxicity via metabolic activation by CYP3A. In this study, we describe the presence of anti-microsomal epoxide hydrolase (EH) autoantibodies in the sera of patients who drank germander teas for a long period of time. By Western blotting and immunocytochemistry, human microsomal EH was shown to be present in purified plasma membranes of both human hepatocytes and transformed spheroplasts and to be exposed on the cell surface where affinity-purified germander autoantibodies recognized it as their autoantigen. Immunoprecipitation of EH activity by germander-induced autoantibodies confirmed this finding. These autoantibodies were not immunoinhibitory. The plasma membrane-located EH was catalytically competent and may act as target for reactive metabolites from TA. To test this hypothesis CYP3A4 and EH were expressed with human cytochrome P450 reductase and cytochrome b(5) in a "humanized" yeast strain. In the absence of EH only one metabolite was formed. In the presence of EH, two additional metabolites were formed, and a time-dependent inactivation of EH was detected, suggesting that a reactive oxide derived from TA could alkylate the enzyme and trigger an immune response. Antibodies were found to recognize TA-alkylated EH. Recognition of EH present at the surface of human hepatocytes could suggest an (auto)antibody participation in an immune cell destruction. (+info)
Amino acids composition of Teucrium nutlet proteins and their systematic significance.
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BACKGROUND AND AIMS: Plant species are considered as a good source of dietary proteins, although the nutritional quality of proteins depends on their amino acid composition. In this work the protein content and amino acid composition of nutlets of 21 Teucrium taxa (Lamiaceae) from Spain were analysed and their nutritional quality was compared with the minimum values established by the Food and Agriculture Organization of the United Nations (FAO). In addition, the amino acid composition was evaluated as a chemical character to clarify the taxonomic complexity in this genus. METHODS: Amino acid content of nutlets was determined after derivatization with diethyl ethoxymethylenemalonate by high-performance liquid chromatography. Previously, nutlets samples were hydrolysed and incubated in an oven at 110 degrees C for 24 h. KEY RESULTS: The protein content was variable, ranging from 6.4 % in T. dunense to 43.8 % in T. algarbiense. According to the FAO values all taxa contain satisfactory amounts of leucine, threonine and valine and are deficient in lysine. The similarity analysis of Teucrium taxa using amino acid composition data did not clearly reflect the infrageneric classification of this genus. CONCLUSIONS: Annual species, such as T. spinosum, T. aristatum and T. resupinatum showed a better balanced amino acid composition. The dendrogram partly matched with the karyological complexity of Teucrium. No correlation between amino acid composition and habitat has been observed, showing that Teucrium nutlet amino acid composition may not be strongly influenced by the environment. (+info)
Pollen-stigma interference in two gynodioecious species of Lamiaceae with intermediate individuals.
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BACKGROUND AND AIMS: Intermediate individuals (perfect flowers with very high degree of pollen abortion) in a gynodioecious plant species are very rare. A study is made of male-female relationships in each flower type and how floral characters can enhance the avoidance of 'pollen discounting' and 'self-pollination' in two gynodioecious species, Teucrium capitatum and Origanum syriacum. METHODS: The relationship between stigma receptivity and pollen viability was studied in two gynodioecious protandrous species of Lamiaceae, in addition to measuring some floral morphological characters over the life span of the flowers. KEY RESULTS: Three plant types in each species were found: plants bearing hermaphrodite (or male fertile) flowers (MF), female (or male sterile) flowers (MS) and intermediate flowers (INT). Plant types differed in flower size, with MS types being shorter than the other two types. There was no difference in style length among plant types in T. capitatum. Stigma receptivity decayed with floral age and was negative and significantly correlated with pollen viability in the two species, and positive and significantly correlated with style length in O. syriacum but only in MS flowers of T. capitatum. CONCLUSIONS: Reduction in size of floral characters is associated with male sterility, except style length in T. capitatum. MF flowers have two successive reproductive impediments: self-pollination and pollen-stigma interference. In both species, self-pollination is avoided by dichogamy (negative correlation between stigma receptivity and pollen viability), and pollen-stigma interference shows two different patterns: (1) style elongation in O. syriacum is characterized by a significant length increase, final MF dimensions are greater than those of MS dimensions, and style length is positively and significantly correlated with stigma receptivity; and (2) style movement in T. capitatum is characterized by a non-significant increase in style length, final MF floral dimensions are similar to those of MS dimensions, and there is no correlation between style length and stigma receptivity. (+info)
Unusual causes of intrahepatic cholestatic liver disease.
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We report five cases with unusual causes of intrahepatic cholestasis, including consumption of Teucrium polium (family Lamiaceae) in the form of tea, Stauffer's syndrome, treatment with tamoxifen citrate for breast cancer, infection with Coxiella Burnetii (acute Q fever), and infection with Brucella melitensis (acute brucellosis). (+info)
Comparison of the phenolic component profiles of skullcap (Scutellaria lateriflora) and germander (Teucrium canadense and T. chamaedrys), a potentially hepatotoxic adulterant.
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Mass spectroscopic fingerprinting method for differentiation between Scutellaria lateriflora and the germander (Teucrium canadense and T. chamaedrys) species.
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Scutellaria lateriflora, commonly known as skullcap, is used as an ingredient in numerous herbal products. However, it has been occasionally adulterated/contaminated with Teucrium canadense and T. chamaedrys, commonly known as germander, which contain hepatotoxic diterpenes. Due to the morphological similarities between the two genera, analytical methodologies to distinguish authentic S. lateriflora from the Teucrium species are needed to ensure public safety. In this study, a direct-injection electrospray ionization/MS method was used to generate spectral fingerprints of extracts from 21 skullcap and germander samples at a rate of 90 s/sample. MS fingerprints were analyzed by principal component analysis. The newly developed method offers a rapid and easy way to differentiate between skullcap and germander samples. (+info)
The effect of "Teucrium polium L." extracts on insulin release from in situ isolated perfused rat pancreas in a newly modified isolation method: the role of Ca2+ and K+ channels.
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BACKGROUND: "Teucrium polium L." (TP) has been long recommended in Iranian folk medicine for its anti-diabetic activities. We attempt here to evaluate the effect of TP extract on insulin secretion in rat pancreas. METHODS: Rat pancreas was isolated in situ and perfused with Krebs solution containing low glucose (LG, 2.8 mM) or high glucose (HG, 16.7 mM) as perfusate. The aqueous extract (Aq. E) and methanolic extract (Met. E) of TP aerial parts and two partition fractions of Met. E were added to perfusate to evaluate insulin release. Diazoxide (DZX) and verapamil (VPM) were also used for assessing the probable mechanism of the effects. In each experimental group, the peak and baseline of insulin levels in effluent samples were compared. The GC/MS analysis was carried out to detect active ingredients in the extracts. RESULTS: Adding Met. E to the LG caused a significant increase (P<0.05) in insulin release from the basal level of 0.17 +/- 0.05 microg/l to a peak value of 3.94 +/- 1.29 microg/l. when Met. E was introduced to the HG, there was a further protracted stimulation of insulin release from 2.15 +/- 1.35 microg/l to 6.16 +/- 0.52 microg/l. Both DZX and VPM when added separately to the LG, led to inhibition of Met. E induced insulin secretion. The Aq. E and fractions had no significant effect on insulin secretion. Only in the Met. E, the component 5-hydroxy-4',7-dimethoxyflavone (apigenin-4',7-dimethylether) was detected. CONCLUSION: It can be concluded that the insulinotropic properties of TP extracts can be attributed to the presence of apigenin existing only in Met. E, but not in Aq. E and fractions. Moreover, certain types of K+ and Ca2+ channels take part in this effect. (+info)