Intestinal anti-inflammatory activity of the Serpylli herba extract in experimental models of rodent colitis.

INTRODUCTION: Nowadays, there is an increasing interest for alternative options in the treatment of inflammatory bowel diseases (IBDs) that combine efficacy and an adequate safety profile. METHODS: The intestinal anti-inflammatory effects of Serpylli herba, the officinal drug in the European Pharmacopeia composed by the aerial parts of wild thyme (Thymus serpyllum), were evaluated in the trinitrobenzenesulfonic acid (TNBS)-induced rat colitis and dextran sodium sulfate (DSS)-induced mouse colitis, which are well characterized experimental models with some resemblance to human IBD. RESULTS: S. herba extract exerted an intestinal anti-inflammatory effect in both experimental models of colitis, as evidenced both histologically, since it facilitated the tissue recovery of the damaged colon, and biochemically as showed by the improvement of the different inflammatory markers evaluated, including myeloperoxidase activity, glutathione content, and leukotriene B4 levels as well as the expression of the inducible proteins iNOS and COX-2. This beneficial effect was associated with the reduction in the expression of different cytokines, like TNFα, IL-1ß, IFNγ, IL-6 and IL-17, the chemokine MCP-1, and the adhesion molecule ICAM-1, thus ameliorating the altered immune response associated with the colonic inflammation. CONCLUSION: S. herba extract displays an anti-inflammatory effect on different models of rodent colitis that could be attributed to its immunomodulatory properties.

Ficus carica leaf extract modulates the lipid profile of rats fed with a high-fat diet through an increase of HDL-C.

Ficus carica has been traditionally used for the treatment of several metabolic syndrome-related health problems. It was the objective of this study to investigate the preventive effects of a Ficus carica (FC) leaf extract on hyperlipidemia in high fat diet (HFD)-induced obese male rats. Male Sprague-Dawley rats (180-200 g) were fed with a regular diet, HFD or a HFD + oral treatment of either 50 mg/kg or 100 mg/kg of FC or 30 mg/kg pioglitazone for six weeks. A range of parameters was evaluated including body weight development, plasma levels of total cholesterol, triglycerides (TG), low-density-lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), adiponectin, leptin, glucose, insulin, interleukin-6 (IL-6), atherogenic index (AI) and the coronary risk index (CRI). FC significantly lowered TG and IL-6 levels and elevated HDL cholesterol (p < 0.05). The effects of FC on lipid parameters were more pronounced than those of the positive control pioglitazone. FC significantly lowered AI and CRI (p < 0.01) while it had no effect on adiponectin and leptin levels. Our results demonstrate that preventive treatment with FC significantly improved the lipid profile and decreased adipogenic risk factors in HFD rats most likely mediated through an increase in HDL-C levels.

Acute blood glucose lowering effects and long-term safety of OpunDia supplementation in pre-diabetic males and females.

AIM OF THE STUDY: The aim of this study was to evaluate the acute and chronic effects of OpunDia (Opuntia ficus-indica) in obese pre-diabetic men and women. MATERIALS AND METHODS: This double-blind placebo controlled study included participants (age range of 20-50 years) randomly assigned to one of the two groups and given a 16-week supply of either the 200 mg OpunDia (n=15), or placebo (n=14). The acute phase of the study consisted of an oral glucose tolerance test (OGTT) with a 400 mg bolus of OpunDia given 30 min before orally ingesting a 75 g glucose drink. Baseline and post 16-week concentrations of glucose, insulin, hsCRP, adiponectin, proinsulin, Hb1Ac, cholesterol, and a comprehensive metabolic panel were collected along with body composition measured via densitometry (BOD POD). A repeated measures ANOVA was conducted to determine any significant interactions between group and time. Follow-up analysis was performed to determine differences among groups at each time point. Paired t-tests were performed on all variables to determine if any within group differences existed across time. RESULTS: There was a statistically significant decrease (P<0.05) in the blood glucose concentrations at the 60 (205.92+/-36.90 and 188.84+/-38.43 mg/dL, respectively), 90 (184.55+/-33.67 and 169.74+/-35.16 mg/dL, respectively) and 120 min (159.24+/-17.85 and 148.89+/-24.86 mg/dL, respectively) time points with the pre-OGTT compared to the OpunDia bolus trial. There were no between-group differences found with the OGTT time points, area under the curve, blood chemistry variables (insulin, hsCRP, adiponectin, proinsulin, Hb1Ac), diet analysis variables (carbohydrates, fat, protein and total kcals), body composition variables (fat mass, fat free mass, percent body fat and total body weight), or blood chemistry safety parameters (comprehensive metabolic panel) pre-to-post 16-week intervention. CONCLUSIONS: This study shows the acute blood glucose lowering effects and the long-term safety of the proprietary product OpunDia, thus supporting the traditional use of Opuntia ficus-indica for blood glucose management.

Absence of mutagenic effects of a particular Symphytum officinale L. liquid extract in the bacterial reverse mutation assay.

Comfrey (Symphytum officinale L.) root is traditionally used for the topical treatment of contusions, strains and sprains. Besides allantoin and rosmarinic acid, which are discussed as pharmacologically active principles, the drug contains pyrrolizidine alkaloids (PAs) known for their hepatotoxic, carcinogenic and mutagenic properties. The topical herbal medicinal products Kytta-Salbe f and Kytta-Plasma f contain a PA-free liquid extract from comfrey root as active substance. The aim of this study was to demonstrate the absence of genotoxic effects of this special extract in the bacterial reverse mutation assay (Ames test). Briefly, comfrey root liquid extract was investigated for its ability to induce gene mutations in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 with and without metabolic activation using the mammalian microsomal fraction S9 mix. Reference mutagens were used to check the validity of the experiments. Comfrey root fluid extract showed no biologically relevant increases in revertant colony numbers of any of the five tester strains, neither in the presence nor in the absence of metabolic activation. In conclusion, the comfrey root fluid extract contained in Kytta-Salbe f and Kytta-Plasma f was not mutagenic in the bacterial reverse mutation assay.

In vitro anti-cancer activity of two ethno-pharmacological healing plants from Guatemala Pluchea odorata and Phlebodium decumanum.

Many traditional healing plants successfully passed several hundred years of empirical testing against specific diseases and thereby demonstrating that they are well tolerated in humans. Although quite a few ethno-pharmacological plants are applied against a variety of conditions there are still numerous plants that have not been cross-tested in diseases apart from the traditional applications. Herein we demonstrate the anti-neoplastic potential of two healing plants used by the Maya of the Guatemala/Belize area against severe inflammatory conditions such as neuritis, rheumatism, arthritis, coughs, bruises and tumours. Phlebodium decumanum and Pluchea odorata were collected, dried and freeze dried, and extracted with five solvents of increasing polarity. We tested HL-60 and MCF-7 cells, the inhibition of proliferation and the induction of cell death were investigated as hallmark endpoints to measure the efficiency of anti-cancer drugs. Western blot and FACS analyses elucidated the underlying mechanisms. While extracts of P. decumanum showed only moderate anti-cancer activity and were therefore not further analysed, particularly the dichloromethane extract of P. odorata inhibited the cell cycle in G2-M which correlated with the activation of checkpoint kinase 2, and down-regulation of Cdc25A and cyclin D1 as well as inactivation of Erk1/2. In HL-60 and MCF-7 cells this extract was a very strong inducer of cell death activating caspase-3 followed by PARP signature type cleavage. The initiating death trigger was likely the stabilization of microtubules monitored by the rapid acetylation of alpha-tubulin, which was even more pronounced than that triggered by taxol. The dichloromethane extract of P. odorata contains apolar constituents which inhibit inflammatory responses and exhibit anti-cancer activity. The strong proapoptotic potential warrants further bioassay-guided fractionation to discover and test the active principle(s).

Modulation of GABAA receptors by valerian extracts is related to the content of valerenic acid.

Valeriana Officinalis L . is a traditionally used sleep remedy, however, the mechanism of action and the substances responsible for its sedative and sleep-enhancing properties are not fully understood. As we previously identified valerenic acid as a subunit-specific allosteric modulator of GABAA receptors, we now investigated the relation between modulation of GABAA receptors by Valerian extracts of different polarity and the content of sesquiterpenic acids (valerenic acid, acetoxyvalerenic acid). All extracts were analysed by HPLC concerning the content of sesquiterpenic acids. GABAA receptors composed of alpha 1, beta 2 and gamma 2S subunits were expressed in Xenopus laevis oocytes and the modulation of chloride currents through GABAA receptors (IGABA) by Valerian extracts was investigated using the two-microelectrode voltage clamp technique. Apolar extracts induced a significant enhancement of IGABA, whereas polar extracts showed no effect. These results were confirmed by fractionating a highly active ethyl acetate extract: again fractions with high contents of valerenic acid exhibited strong receptor activation. In addition, removal of sesquiterpenic acids from the ethyl acetate extract led to a loss of I (GABA) enhancement. In conclusion, our data show that the extent of GABAA receptor modulation by Valerian extracts is related to the content of valerenic acid.

Achillea millefolium L. s.l. revisited: recent findings confirm the traditional use.

Yarrow (Achillea millefolium L. s.l.) is traditionally used in the treatment of inflammatory and spasmodic gastro-intestinal disorders, hepato-biliary complaints and inflammation. Now we could show that the flavonoids mediated the antispasmodic properties of yarrow, whereas the dicaffeoylquinic acids caused the choleretic effects. Moreover, we observed an in vitro-inhibition of human neutrophil elastase, a protease involved in the inflammatory process, by extracts and fractions from yarrow, which suggests additional mechanisms of antiphlogistic action. The presented results confirm the traditional use of yarrow.

Achillea millefolium L. s.l. -- is the anti-inflammatory activity mediated by protease inhibition?

Achillea millefolium L. s.l. is traditionally used not only in the treatment of gastro-intestinal and hepato-biliary disorders, but also as an antiphlogistic drug. As various proteases, for instance human neutrophil elastase (HNE) and matrix metalloproteinases (MMP-2 and -9), are associated with the inflammatory process, the aim of this study was to test a crude plant extract in in vitro-protease inhibition assays for understanding the mechanisms of anti-inflammatory action. Furthermore, two fractions enriched in flavonoids and dicaffeoylquinic acids (DCQAs), respectively, were also tested in order to evaluate their contribution to the antiphlogistic activity of the plant. The extract and the flavonoid fraction inhibited HNE showing IC(50) values of approximately 20 microg/ml, whereas the DCQA fraction was less active (IC(50)=72 microg/ml). The inhibitory activity on MMP-2 and -9 was observed at IC(50) values from 600 to 800 microg/ml, whereas the DCQA fraction showed stronger effects than the flavonoid fraction and the extract. In conclusion, the in vitro-antiphlogistic activity of Achillea is at least partly mediated by inhibition of HNE and MMP-2 and -9. After the recently described spasmolytic and choleretic effects the obtained results give further insights into the pharmacological activity of Achillea and confirm the traditional application as antiphlogistic drug.

Distribution of phenolic compounds in Middleeuropean taxa of the Achillea millefolium L. aggregate.

Achillea millefolium L. s.l. is a cytogenetically, morphologically, and chemically polymorphic aggregate. Besides the sesquiterpenes that possess chemotaxonomic relevance and mediate the antiphlogistic activity, the plant contains phenolic compounds such as dicaffeoylquinic acids and flavonoids causing choleretic and spasmolytic effects. To evaluate their contribution to the chemotaxonomy of European taxa of the A. millefolium group, we developed a SPE-HPLC/UV method that allows quantification of the phenolic constituents in the different taxa. The investigated species displayed differences in the quantitative and qualitative composition of phenolic acids and flavonoids. Hence, they seem to be of chemotaxonomic significance, especially for the distinction of the diploid taxa. Combining the obtained results with the data of the sesquiterpene analyses gives a comprehensive insight into the distribution of those pharmacologically relevant plant constituents in the A. millefolium group.

Antioxidant activity of isoflavones and biflavones isolated from Godoya antioquiensis.

Two biflavones, ochnaflavone (1) and 2",3"-dihydroochnaflavone (2), and two isoflavones, 5,7,4'-trihydroxy-3',5'-dimethoxyisoflavone (piscigenin) (3) and 5,4'-dihydroxy-7,3',5'-trimethoxyisoflavone (4), a new natural compound, were isolated from the leaves of Godoya antioquiensis (Ochnaceae). Their structures were determined on the basis of spectral data and by comparison with data reported in the literature. The isolated compounds were evaluated for their radical scavenging activity using the NBT (nitrobluetetrazolium)/hypoxanthine superoxide and the .OH/luminol chemiluminescence methods. The isolated isoflavones were found to exhibit a strong hydroxyl radical scavenging activity and a moderate inhibition of the superoxide anion, whereas the two biflavones were inactive in the superoxide anion assay and showed a low hydroxyl radical scavenging activity.

Investigation of the spasmolytic activity of the flavonoid fraction of Achillea millefolium s.l. on isolated guinea-pig ilea.

The spasmolytic activity of a flavonoid fraction of a commercial sample of yarrow (Achillea millefolium s.l.), its main flavonoids as well as quercetin and two flavonoid metabolites were investigated on isolated terminal guinea-pig ilea. The aglycones quercetin, luteolin and apigenin exhibited the highest antispasmodic activities with IC50 values of 7.8 micromol/L, 9.8 micromol/L and 12.5 micromol/L, respectively. Rutin and the flavonoid metabolites homoprotocatechuic acid and homovanillic acid showed no significant effects on contractility of the terminal ilea. From the results on the spasmolytic activity of the flavonoid fraction, the glycosides and the respective aglycones it is concluded that in tea prepared from yarrow the concentration of the flavonoids is high enough to exert a spasmolytic effect in the gut, which is mainly caused by blockade of the calcium inward current, but additionally also by mediator-antagonistic effects.