Effect of cholesterol re-supplementation and atorvastatin on plaque composition in the thoracic aorta of New Zealand white rabbits.

BACKGROUND: Effects of re-supplementation of a cholesterol-enriched diet (CEDrs) on size, cholesterol content and morphology of already existing plaques are not known to date. METHODS: A group of rabbits received standard chow (SC) for 6 weeks ("negative control"; for plasma lipid measurements only). Group I-IV received 2% CED (induction) for 6 weeks; thereafter, groups II-IV have been fed a SC (= cholesterol withdrawal) for 68 weeks. Afterwards, feeding of groups II-IV was continued as follows: Group II - 10 weeks SC, group III - 4 weeks 0.5% CED (~re-supplementation), afterwards 6 weeks SC (~withdrawal again); group IV - 4 weeks 0.5% CED (re-supplementation) + atorvastatin (2.5 mg/kg body weight/day), afterwards 6 weeks SC (~withdrawal again) + atorvastatin. Plasma lipids, but also plaque size, morphology and cholesterol contents of thoracic aortas were quantified. RESULTS: After CEDrs, plasma cholesterol levels were increased. However, after withdrawal of CEDrs, plasma cholesterol levels decreased, whereas the cholesterol content of the thoracic aorta was increased in comparison with the group without CEDrs. Plaque size remained unaffected. Atorvastatin application did not change plasma cholesterol level, cholesterol content of the thoracic aorta and plaque size in comparison with the group without drug treatment. However, atorvastatin treatment increased the density of macrophages (MΦ) compared with the group without treatment, with a significant correlation between densities of MΦ (Mac-1+) and apoptotic (TUNEL+; TP53+), antigen-presenting (HLA-DR+) or oxidatively stressed (SOD2+) cells. CONCLUSIONS: In rabbits with already existing plaques, CEDrs affects plaque morphology and cellular composition, but not plaque size. Despite missing effects on plasma cholesterol levels, cholesterol content of the thoracic aorta and size of already existing atherosclerotic plaques, atorvastatin treatment transforms the already existing lesions to a more active form, which may accelerate the remodelling to a more stable plaque.

Mechanisms of the anti-proliferative and anti-inflammatory effects of the herbal fixed combination STW 5 (Iberogast®) on colon adenocarcinoma (HT29) cells in vitro.

INTRODUCTION: Several conventional pharmaceuticals like non-steroidal anti-inflammatory drugs (NSAIDS) or selective cyclooxygenase-2 (COX-2) inhibitors have been demonstrated to exert anti-proliferative effects and to induce apoptosis in a variety of cell lines, e.g. colon, stomach, or prostate cancer cells. STW 5 (Iberogast(®)), a combination of nine plant extracts, is widely used in the treatment of gastrointestinal disorders, including functional dyspepsia and irritable bowel syndrome for which the involvement of an inflammatory etiology is discussed. To investigate the possible anti-proliferative effects, STW 5 and its components have been tested by using the colon-carcinoma cell line HT-29. The analyses have been performed in comparison to acetylsalicylic acid (ASA) and diclofenac (Diclo), which are well-known to reduce colon carcinoma risk. RESULTS: STW 5 showed significant anti-proliferative and pro-apoptotic effects on HT-29 cancer cells, similar to NSAIDs under test. However, using the LDH assay, STW 5 revealed significantly lower cytotoxicity than Diclo at same concentrations. In contrast to NSAIDs, STW 5 induced COX-1/COX-2, caspase-3 and Bax mRNA expressions in HT-29 and blocked LPS mediated translocation of the NF-κB p65 from the cytoplasm into the nucleus in PMA-differentiated THP-1 macrophages. These effects might be relevant, e.g. for prevention of undesirable side effects like gastric erosions. CONCLUSION: Our data suggest that the pro-apoptotic effect of STW 5 on HT-29 cells is involving multiple targets and is possibly due to an activation of the caspase cascade via mitochondrial destabilization. Active concentrations of STW 5 are, in relation to therapeutic doses, comparable to those of ASA and Diclo, suggesting a similar favorable effect on colon carcinoma risk.

Contribution of flavonoids and catechol to the reduction of ICAM-1 expression in endothelial cells by a standardised Willow bark extract.

INTRODUCTION: A quantified aqueous Willow bark extract (STW 33-I) was tested concerning its inhibitory activity on TNF-α induced ICAM-1 expression in human microvascular endothelial cells (HMEC-1) and further fractionated to isolate the active compounds. RESULTS: At 50 µg/ml the extract, which had been prepared from Salix purpurea L., decreased ICAM-1 expression to 40% compared to control cells without showing cytotoxic effects. Further liquid-liquid partition revealed an ethyl acetate phase with potent reduction of ICAM-1 expression to 40% at 8 µg/ml. This fraction was comprehensively characterised by the isolation of flavanone aglyca and their corresponding glycosides, chalcone glycosides, salicin derivatives, cyclohexane-1,2-diol glycosides, catechol and trans-p-coumaric acid. All compounds were investigated for their activity on TNF-α induced ICAM-1 expression. The flavonoid and chalcone glycosides were not active up to 50 µM, whereas catechol and eriodictyol at the same concentration showed a significant reduction of ICAM-1 expression to 50% of control. Interestingly, other isolated flavanone aglyca like taxifolin, dihydrokaempferol and naringenin showed only weak or moderate inhibitory activity. Eriodictyol was a minor compound in the extract, whereas the catechol content in the extract (without excipients) reached 2.3%, determined by HPLC. One of the isolated cyclohexan-1,2-diol glucosides, 6'-O-4-hydroxybenzoyl-grandidentin, is a new natural compound. CONCLUSION: As catechol is quantitatively important in Willow bark extracts it can be concluded from the in vitro data that not only flavonoids and salicin derivatives, but also catechol can probably contribute to the anti-inflammatory activity of Willow bark extracts.

Anti-inflammatory effects of the willow bark extract STW 33-I (Proaktiv(®)) in LPS-activated human monocytes and differentiated macrophages.

INTRODUCTION: Willow bark extract is frequently used in the treatment of painful rheumatological diseases, such as arthritis and back pain. Its effect has been attributed to its main component salicin, but pharmacological studies have shown that the clinical efficacy of the willow bark extract cannot be explained by its salicin content alone. Therefore different modes of action have been suggested for the anti-inflammatory effect of willow bark extract. Here, we report in vitro data revelling the effect and mode of action of the aqueous willow bark extract STW 33-I as well as a water-soluble fraction (fraction E [Fr E]) in comparison with well-known non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin (ASA) and diclofenac (Diclo) on pro-inflammatorily activated human monocytes and differentiated macrophages. RESULTS: STW 33-I and the water-soluble Fr E showed concentration-dependent and significant anti-inflammatory effects in lipopolysaccharide-activated monocytes. Both inhibited the intracellular protein expression of tumour necrosis factor-alpha (TNFα) as well as the mRNA expression of TNFα and cyclooxygenase 2 (COX-2), and the release of nitric oxide (NO). In addition, apoptosis of pro-inflammatorily activated monocytes was induced. Furthermore, treatment of activated macrophages with STW 33-I inhibited the nuclear translocation of the p65 subunit of the nuclear transcription factor-kappa B (NF-κB p65). CONCLUSIONS: The present in vitro investigations suggest a significant anti-inflammatory activity of willow bark water extract STW 33-1 and of its water-soluble fraction by inhibiting pro-inflammatory cytokines (TNFα), COX-2 and nuclear translocation of the transcription factor NF-κB in pro-inflammatorily activated monocytes. Our results provide further evidence for the therapeutic use of STW 33-I in inflammation-related disorders.

Binding of STW 5 (Iberogast) and its components to intestinal 5-HT, muscarinic M3, and opioid receptors.

Clinical studies with the fixed herbal combination product STW 5 (Iberogast) have indicated an efficacy comparable to metoclopramide (5-HT(3) antagonist) and cisapride (5-HT(4) agonist) in functional gastro-intestinal diseases like functional dyspepsia (FD) and irritable bowel syndrome (IBS). Since serotonin (5-HT(3) and 5-HT(4)) and muscarinic M(3) receptors are known to play a central role in the etiology of FD and IBS, the extracts contained in STW 5 and several of their phytochemical components were studied in vitro for binding affinities to these receptors of the intestine. STW 5 inhibited the binding of (3)H-GR113808 and (3)H-4-DAMP to 5-HT(4) and M(3) receptors, respectively, about 10 times more potently than the binding of (3)H-GR65630 to 5-HT(3) receptors. IC(50) values for STW 5 did correspond to extract dilutions of 1:1000 (M(3) binding) and 1:2000 (5-HT(4) binding). In addition, STW 5 also potently inhibited the binding to opioid receptors with an IC(50) value of 1:2000. Of the nine herbal extracts contained in STW 5, the fresh plant extract of bitter candy tuft (Iberis amara) selectively inhibited binding to M(3) receptors, while ethanolic extracts of celandine herb and chamomile flower were selective to 5-HT(4), and liquorice root to 5-HT(3) receptors. Binding affinities to human recombinant 5-HT(3), 5-HT(4) and M(3) receptors were qualitatively similar to those of the corresponding intestinal receptors. The benzylisoquinoline alkaloid berberine had significant inhibitory action on 5-HT(4) and M(3) binding, showing IC(50) values of 40 ng/ml (100 nM) and 200 ng/ml (500 nM), respectively, but is present in the extract of celandine herb only in traces, so that also for the celandine extract a cooperative effect of several phytochemical constituents can be assumed. These in vitro data indicate that 5-HT(4) (to a lesser degree 5-HT(3)), muscarinic M(3), and opioid receptors represent target sites for the treatment of FD and IBS with STW 5 (Iberogast).

Mechanisms involved in the gastro-protective effect of STW 5 (Iberogast) and its components against ulcers and rebound acidity.

The protective effect of a commercial preparation (STW 5, Iberogast), containing the extracts of bitter candy tuft, lemon balm leaf, chamomile flower, caraway fruit, peppermint leaf, liquorice root, Angelica root, milk thistle fruit and greater celandine herb, against the development of gastric ulcers was previously reported in an earlier publication (Khayyal et al., 2001). All extracts produced a dose dependent anti-ulcerogenic effect associated with a reduced acid output, an increased mucin secretion, an increase in prostaglandin E(2) release and a decrease in leukotrienes. The effect on pepsin content was not uniform and did not seem to bear a relationship with the anti-ulcerogenic activity. The best effects were observed with the combined formulation, STW 5. Furthermore, the effect of the latter in protecting against the development of rebound gastric acidity was examined experimentally in rats and compared with the effect of some commercial antacid preparations (Rennie, Talcid and Maaloxan). A model of testing rebound acidity was developed by inducing a marginal increase in gastric acidity through the administration of indomethacin, in such a way that it could be easily neutralized, allowing any eventual secondary increase in acidity to be measured within a few hours of administration. In addition, the serum gastrin level was measured after drug treatment to establish any correlation between it and any rebound acidity. The results obtained demonstrated that STW 5 did not only lower the gastric acidity as effectively as the commercial antacid, but it was more effective in inhibiting the secondary hyperacidity. Moreover, STW 5 was capable of inhibiting the serum gastrin level in rats, an effect which ran parallel to its lowering effect on gastric acid production.

Ex vivo/in vitro absorption of STW 5 (Iberogast) and its extract components.

To correlate the pharmacological effects of the fixed herbal combination STW 5 (Iberogast) containing nine extract components with its confirmed clinical efficacy, ex vivo/in vitro absorption tests were performed. For the investigation, the everted gut sac technique and, in a pilot study, the Caco-2-cell model were used. The absorption rate of the extracts was determined by measuring characteristic marker substances of each of the individual extracts using HPLC or GC techniques. The results allow us to conclude that the investigated substances from STW 5 possess a good bioavailability, which is in accordance with the rapid onset of the therapeutic efficacy and explains its known pharmacological effects and clinical efficacy in terms of multiple drug action and multi-target therapy, respectively.

Radical scavenging and anti-inflammatory properties of STW 5 (Iberogast) and its components.

A combination of ethanolic extracts from nine medicinal plants is successfully used in STW 5 (Iberogast((R))) for treatment of gastrointestinal disorders. To elucidate possible modes of action, the focus of this study is on antioxidant properties of the phytomedicine STW 5. In fact, functional gastrointestinal diseases, such as non-ulcer dyspepsia (NUD) and irritable bowel syndrome, are often initiated by or correlated to inflammatory processes, where oxidants such as reactive oxygen species (ROS) play a crucial role. Prominent in vivo sources of ROS generation are represented by the enzymes xanthine oxidase (XOD) or myeloperoxidase (MPO). Applying these enzymes in models in vitro, we show that STW 5 and its components possess strong antioxidant activities. Depending on the model investigated, even pro-oxidant activities of single components of STW 5 could be observed. Interestingly, these effects were absent in STW 5, indicating cooperation between the components. Moreover, if one of the component extracts of STW 5 is omitted, the antioxidant activity is reduced. Thus we conclude that all the single extracts combined in STW 5 are of importance for the therapeutic effect, working in concert. The component of STW 5 performing best in vitro differed with the model investigated, respectively, with ROS and ROS generators. In the XOD system, the extracts of lemon balm leaf and peppermint leaf showed the best antioxidant result, whereas concerning MPO driven chlorination reactions, bitter candy tuft extract was the most efficient antioxidant. Best protection against peroxynitrite induced oxidation of methionine like sulfur-compounds exhibited the STW 5 components lemon balm leaf, Matricaria flower and peppermint leaf.

Intestinal spasmolytic effects of STW 5 (Iberogast) and its components.

Functional gastro-intestinal diseases as the irritable bowel syndrome are very common in the population and are characterized by a broad spectrum of symptoms which mostly are related to spastic or paralytic intestinal function without defined histopathological changes of the tissue. Due to the multifactorial pathogenesis a multifactorial therapy with multi-target action seems to be reasonable. STW 5 (Iberogast), its constituent herbal extracts and some isolated compounds were used in an in vitro model provided by intestinal samples from guinea pig in order to test their activity on histamine-induced contractions and spontaneous motility, respectively. For comparison the known spasmolyticum papaverine was used. The results show that the lytic effect of the phytotherapeuticum on histamine-induced contraction represents additively the actions of the different components and corresponds to approx. 10 microM of papaverine. Spontaneous peristaltic motion was differently modulated by the various constituent extracts. The experiments with silibinin, glycyrrhicine, chelidonine, and protopine showed that the effects of the extracts were not comparable to those of the respective chemical constituents.

STW 5 (Iberogast) and its individual herbal components modulate intestinal electrophysiology of mice.

STW 5 (Iberogast), a phytomedicine agent consisting of a fixed combination of nine individual plant extracts, is widely used in the treatment of dyspepsia and motility related disorders. Little if anything is known on the possible influence on electrophysiological properties of intestinal smooth muscle by which STW 5 causes its beneficial effects. The aim of the present study was to investigate whether herbal extracts influence electrophysiological parameters of large and small intestine. For this purpose intracellular recordings of smooth muscle cell (SMC) of the circular muscle layer of different parts of mouse intestine were performed using standard microelectrode techniques. The resting membrane potential (RMP), excitatory and inhibitory neurotransmission in proximal colon, the frequency and the amplitude of slow waves in small intestine were investigated. The RMP of SMC was -46.4+/-3.8 mV, n=11 in the colon and -59+/-1.3 mV, n=15 in small intestine. STW 5 significantly depolarized the RMP of colonic (16.6+/-2.2 mV, n=6, p<0.05) and jejunal (9.6+/-1.6 mV, n=7, p<0.05) SMC. This depolarizing effect can be mainly attributed to the constituents of chamomile flower, Angelica root and greater celandine herb. Following the electrical field stimulations (EFSs), junction potentials are influenced in a distinct manner. Excitatory junctions potentials (EJPs) of the colon were not significantly reduced (13.1+/-4.8 vs. 10.1+/-2.8 n.s., n=6) but fast (fIJP) and slow (sIJP) inhibitory junction potentials of the murine colon are reduced significantly by STW 5 (fIJP: 21.6+/-8.1 vs. 11.6+/-2.1 and sIJP: 12.1+/-3.3 vs. 6.1+/-1.3 n=6, p<0.05). The basal frequency of small intestinal slow waves was 39.5+/-1.4 min(-1) and the amplitude was 23.1+/-0.9 mV, n=15. STW 5 significantly reduced amplitude and frequency of the slow waves (11.7+/-0.8 mV; 33.5+/-3.4 min(-1), n=6, p<0.05). This effect on slow waves represents the summation of effects of the nine individual phytoextracts. Whereas Angelica root and chamomile flower completely blocked the slow wave activity, bitter candy tuft increased the frequency and amplitude, greater celandine herb reduced frequency and amplitude of the slow wave, peppermint leaf reduced frequency and left amplitude unchanged and liquorice root, caraway fruit and lemon balm leaf had no effects in basic electrophysiological properties of SMC. This study demonstrates that STW 5 causes changes in SMC RMP, excitatory and inhibitory neurotransmission and slow wave rhythmicity. These effects represent a summation effect of different constituents of this phytotherapeuticum and prove that STW 5 has characteristic effects on intestinal electrophysiology.

STW 5 (Iberogast) reduces afferent sensitivity in the rat small intestine.

INTRODUCTION: A limited number of drugs are available for the treatment of functional dyspepsia and irritable bowel syndrome. The efficacy of STW 5 (Iberogast) was previously shown in clinical trials. Since visceral hypersensitivity seems to be the prime pathomechanism of functional gastro-intestinal disorders, the aim of this study was to explore whether STW 5 reduces intestinal afferent sensitivity in the upper gastrointestinal tract. METHODS: Two groups of male Wistar rats were pretreated with either the herbal preparation STW 5 or its vehicle (30.8% ethanol). Then, after 2h, general anesthesia was induced by pentobarbitone (60 mg kg(-1)i.p.) and extracellular multi-unit afferent recordings were obtained from mesenteric afferents innervating the proximal jejunum. The intestinal afferent nerve response to increasing doses of 5-HT and bradykinin were quantified as well as afferent discharge following a ramp distension of the adjacent intestinal loop from 0 to 60 cm H(2)O. RESULTS: Afferent discharge to 5-HT and bradykinin increased dose-dependently. Following the different doses of 5-HT, the peak in afferent nerve discharge was always reduced after pretreatment with STW 5 compared to controls with a response of 110+/-5 imp s(-1) after STW 5 and 128+/-3 in vehicle controls at the maximum dose (40 microg kg(-1); p<0.05; mean+/-SEM). For bradykinin, afferent responses were reduced following STW 5 at the 20 and 40 microg kg(-1) dose but not at 10 microg kg(-1) (40 microg kg(-1)176+/-7 imp s(-1) following STW 5 versus 200+/-6 imp s(-1) in controls; p<0.05). The ramp distension of the intestinal loop stimulated a rise in intestinal afferent nerve discharge that was always lower in the STW 5 pretreated group compared to vehicle controls with the exception of the discharge rate at the pressure level of 0 and 20 cm H(2)O (all other pressures up to 60 cm H(2)O p<0.05). CONCLUSIONS: Sensitivity of intestinal afferents to mechanical and chemical stimuli is reduced following treatment with the herbal preparation STW 5. This mechanism may help to explain why STW 5 relieves dyspeptic and bowel symptoms in patients.

Antioxidative properties of the gastrointestinal phytopharmaceutical remedy STW 5 (Iberogast).

Since inflammation is a common mechanism of many gastrointestinal diseases, reactive oxygen metabolites may play an important role in their pathophysiology. Therefore it is interesting to know, whether phytopharmaceuticals known to modulate gastrointestinal motor function reveal also antioxidative properties. We tested STW 5 (Iberogast), its constituent nine different plant extracts, and some isolated compounds which are present in STW 5 for characterizing their antioxidative and radical quenching activities. The test assays consisted in pure chemical and complex cellular systems in which different types of reactive species were produced. Quantification of the effects was based on chemiluminescence reactions. The results show that all extracts contribute to the effect of the complete remedy STW 5, in the chemical systems in a strongly additive manner, in the cellular systems in a supraadditive manner. The largest contributions resulted from the extracts from peppermint and melissa leaves. Comparison of effects from isolated phytochemical compounds from the extracts with that of the extracts itself shows that usually the extract is more effective than the monosubstance which indicates also the synergism within the whole plant extracts. This means that the plant extracts present in STW 5 provide strong radical quenching activities that could also be involved in the therapeutic gastrointestinal actions.

The herbal preparation STW 5 (Iberogast) desensitizes intestinal afferents in the rat small intestine.

INTRODUCTION: Visceral hypersensitivity in the upper gastrointestinal tract is a potential pathomechanism of functional dyspepsia. The herbal preparation STW 5 (Iberogast) provides symptomatic relief for this condition. We aimed to investigate whether STW 5 modulates intestinal afferent sensitivity. METHODS: The herbal preparation STW 5 or vehicle (30.8% ethanol) were administered orally in male Wister rats. After 2 h animals were anaesthetized and extracellular multi-unit intestinal afferent nerve recordings were secured from the neurovascular bundle of the mesentery in the proximal jejunum. Afferent discharge to ramp distension of the intestinal loop (0-60 cm H2O) and dose-response curves for i.v. bradykinin (10, 20 and 40 microg kg(-1)) and 5-HT (5, 10, 20 and 40 microg kg(-1)) were recorded. RESULTS: Baseline discharge was not different between the vehicle and treatment group. Ramp distension was followed by a pressure dependent increase in afferent nerve discharge that was decreased following STW 5 pretreatment for all distending pressures reaching 147 +/- 8 impulses s(-1) (imp s(-1)) following STW 5 vs 171 +/- 5 imp s(-1) following vehicle at 60 cm H2O (mean +/- SEM; P < 0.05). A dose-dependent increase in afferent discharge was observed for 5-HT and bradykinin. Following STW 5 pretreatment, afferent discharge was reduced at all doses of 5-HT to 110 +/- 5 at the maximum dose after STW 5 and 128 +/- 3 imp s(-1) in controls (all P < 0.05). Afferent discharge to bradykinin was similarly reduced at 20 and 40 microg kg(-1) but not at 10 microg kg(-1) of bradykinin with a discharge rate of 176 +/- 7 imp s(-1) following STW 5 and 200 +/- 6 imp s(-1) in controls at 40 microg kg(-1) (P < 0.05). CONCLUSIONS: The preparation STW 5 reduces intestinal afferent nerve discharge following chemical and mechanical stimuli, while baseline discharge is not affected. This effect of STW 5 on afferent sensitivity may contribute to its therapeutic relief of dyspeptic symptoms.

Thin-layer chromatography and multivariate data analysis of willow bark extracts.

In most cases the pharmacological activity of plant extracts is not assigned to single components and often not all active ingredients are known. Approaches other than those considering single compounds only to analyze plant material have proven helpful for a better characterization of extracts in their entirety. In this study extracts of willow bark are analyzed by high-performance thin-layer chromatography (HPTLC) and two different pharmacological tests [the 2,2'-azobis (2-amidinopropane) dihydrochloride reaction and the xanthine/xanthine oxidase reaction] with the help of multivariate data analysis. Described are two models using the results of the chromatographic study of 22 various extracts of willow bark and their pharmacological properties. The chromatographic data are obtained by a special TLC scanner that enables measurement of HPTLC tracks simultaneously in the range of lambda = 200-400 nm. Additionally, the developed models are used to predict the activity of another three extracts of willow bark demonstrating the quality of the model.

Herbal extracts modulate the amplitude and frequency of slow waves in circular smooth muscle of mouse small intestine.

BACKGROUND: Herbal preparations like STW 5 (Iberogast) are widely used drugs in the treatment of dyspepsia and motility-related disorders of the gastrointestinal tract. STW 5 is a phytotherapeutic agent consisting of a fixed mixture of 9 individual plant extracts. The electrophysiological mechanisms of action of STW 5 remain obscure. AIM: The aim of the present study was to investigate whether herbal extracts influence electrophysiological parameters of the small intestine. For this purpose, the resting membrane potential (RMP) and the slow wave rhythmicity of smooth muscle cells of mouse small intestine were observed. METHODS: Intracellular recordings of smooth muscle cells of the circular muscle layer of mouse small intestine were performed using standard microelectrode techniques. After dissection of the mucosa, the small intestine was placed in an organ bath and a microelectrode was applied on a circular smooth muscle cell. The RMP and the amplitude of slow waves were measured in millivolts. RESULTS: The RMP of smooth muscle cells was -59 +/- 1.3 mV. This RMP was significantly depolarized by STW 5 (9.6 +/- 1.6 mV); the depolarizing effects can be mainly attributed to the constituents of matricariae flos, angelicae radix and chelidonii herba. The basal frequency of small intestinal slow waves was 39.5 +/- 1.4 min(-1) and the amplitude was 23.1 +/- 0.9 mV. STW 5 significantly reduced the amplitude and frequency of the slow waves (11.7 +/- 0.8 mV; 33.5 +/- 3.4 min(-1)). This effect on slow waves represents the sum of the effects of the 9 phytoextracts. Whereas angelicae radix and matricariae flos completely blocked slow wave activity, Iberis amara increased the frequency and amplitude, chelidonii herba reduced the frequency and amplitude of the slow waves, mentae piperitae folium reduced the frequency and left amplitude unchanged and liquiritae radix, carvi fructus and melissae folium had no effects. CONCLUSION: Herbal extracts cause changes in smooth muscle RMP and slow wave rhythmicity, up to reversible abolition, by blockade of large conductance Ca2+ channels and other not yet identified mechanisms. In herbal preparations like STW 5 these effects add up to a total effect and this study indicates that herbal preparations which are widely used in dyspepsia and motility-related disorders have characteristic, reproducible, reversible effects on small intestinal electrophysiology.

Antioxidative effects of lemon oil and its components on copper induced oxidation of low density lipoprotein.

Oxidation of low density lipoprotein (LDL) has been implicated in atherogenesis since several years. Therefore many researchers are looking for potent antioxidants which are able to inhibit LDL-oxidation and thus lower the risk for atherosclerosis. In particular several flavonoids have been investigated for their antioxidant capacity and it was shown that many factors influence the ability of flavonoids to retard LDL-oxidation, among others their lipophilic character. Since essential oils and some of their components which are highly lipophilic, have been shown to possess antioxidant properties, their effects on copper-induced LDL-oxidation were analysed. Plasma was incubated with different terpenoid substances and subsequently the LDL was isolated. It could be demonstrated that the terpenoids were enriched in LDL after incubation with plasma. To follow the kinetics of copper induced LDL-oxidation formation of conjugated dienes as well as loss of tryptophan fluorescence were measured. Furthermore the antioxidants alpha-tocopherol, beta-carotene and lycopene were quantified in LDL. It could be shown that particularly lemon oil and one of its components, gamma-terpinene, are efficiently slowing down the oxidation of LDL. This effect is independent of alpha-tocopherol stability in LDL, whereas the loss of carotenoids during oxidation is strongly retarded.

Biochemical activities of extracts from Hypericum perforatum L. 5th communication: dopamine-beta-hydroxylase-product quantification by HPLC and inhibition by hypericins and flavonoids.

Extracts from the herb "St. John's wort" (Hypericum perforatum L.) exhibit beneficial effects on patients suffering from mental depressions. Lack of catecholamine neurotransmitters may be one biochemical mechanism for this problem under discussion. It has been recently reported that alcoholic extracts from Hypericum perforatum inhibit dopamine-beta-hydroxylase (D-beta-H) with an I50 of 0.1 mumol/l on the basis of total hypericin content and with an I50 of 21 mumol/l with pure commercial hypericin. As test system polarographic determination of oxygen uptake with tyramine as a substrate analogue was used. In the present paper the quantification of the enzymatic activity and the potential influence of inhibitors are reported using dopamine as substrate and product (noradrenaline) quantification by HPLC. With this test system it could be shown that D-beta-H is strongly inhibited by pseudohypericin (I50 = approx. 3 mumol/l) and hypericin (I50 = approx. 5 mumol/l), whereas the I50-values of various flavonoids (quercitrin, isoquercitrin, hyperoside, rutin, quercetin, amentoflavone, kaempferol) are in the range of 50 mumol/l or higher.

Biochemical model reactions indicative of inflammatory processes. Activities of extracts from Fraxinus excelsior and Populus tremula.

All processes of oxygen activation include very reactive intermediates. Therefore, aerobic cells must cope with--and to some extent also adapt to--oxidative stress provoked for example by infections or intoxications, where these reactive intermediates accumulate. All inflammatory processes include such oxygen activating processes where reactive oxygen species (ROS) are produced. Dependent on the strength of these impact(s), several symptoms indicate the deviation from normal, steady-state metabolism. Intrinsic radical scavenging processes or compounds administered with food thus have to warrant metabolic control within certain limits. Antioxidants which in many cases are free radical scavengers or quenchers of activated states comprise a vast number of classes of organic molecules including phenolics as the most prominent ones. In this publication the activities of extracts from Fraxinus excelsior, Populus tremula and Solidago virgaurea as components of the drug Phytodolor and their mechanisms of protection from oxidative damage are summarized. In addition, new results on tyrosine nitration, a process characteristic for sites of inflammation, and its inhibition by these plant extracts, is reported.

Psychotherapeutic aspects of the martial arts.

Formerly understood by Western thought as only a set of fighting skills, the Martial Arts (MAs) have come to be seen, in the psychological literature about the MAs, as a comprehensive approach to both physical and mental health. The MAs enhance self-esteem through the provision of physical activity and group experience, and the teaching of relaxation, concentration, assertiveness, and directiveness and honesty in communication. Thus, they are understood to be a legitimate form of therapy, for both "neurotic" and some chronically mentally ill patients. It is proposed in this paper, that the MAs can also be a useful supplement to verbal psychotherapy, as they foster and expose feelings through a physical modality, which can then be observed and analyzed in the modality of verbal psychotherapy. A case report illustrates how the MAs produce feelings and reveal problems, which are brought into the psychotherapy arena and analyzed.

Hyperthermic treatment of rabbit corneas.

Well defined heat doses (temperature X time) were applied to normal rabbit corneas in an effort to determine thermal tolerance, and to examine the effects of heat on this tissue. A purely conductive heater was chosen to minimize intraocular penetration, and avoid findings attributable to nonthermal effects of inductive sources. The etched element heater was sewn to 38 rabbit corneas. Thirty-six were treated to temperatures of 38, 45, 52 and/or 59 degrees centigrade for durations of 5, 15, or 45 min. Three eyes were treated at each time-temperature interval and sacrificed at either time 0, 1 day or 1 week follow-up. Histologic examinations were performed on all corneas. A corneal haze was first noted at 45 degrees C X 45 minutes X 1 day follow-up. This correlated with a mild stromal edema on light microscopy. Higher thermal doses produced a spectrum of damage, with complete destruction of all keratocytes and endothelial cells at 59 degrees C X 45 min. At levels greater than 45 degrees C x 45 min, heat damage was noted to be increased at 24 hr followup. Some recovery was noted by 1 week follow-up, with the exception of the 59 degrees C X 15 or 45 min groups. These two heat doses induced a drop-out of cellular elements with evidence of disintegration and fragmentation of collagen fibrils. Conductive heating of up to 45 degrees C X 15 min appeared well tolerated by normal rabbit corneas.