Search

Objectives Extracts of the tubers of H arpagophytum procumbens (devil's claw, DC) inhibit different proinflammatory mediators important in the pathophysiology of osteoarthritis. Many plant-derived preparations interfere with cytochrome P450 liver enzymes, which influence their different biological activities. Therefore, the present study was designed to investigate the influence of an external metabolic activation of a DC extract on the cytotoxicity and the release of proinflammatory cytokines. Methods A screening experiment with a panel of 12 inflammatory cytokines identified three as suitable for the study: tumour necrosis factor- α ( TNF- α), interleukin ( IL) IL-6 and IL-8. They were determined using enzyme-linked immunosorbent assays in lipopolysaccharide ( LPS)-stimulated monocytic THP-1 cells, which were treated with rat liver S9 mix metabolically activated DC extract ( DCm). For the cytotoxity experiments, a WST-1 assay was used. Key findings DC dose-dependently suppressed the release of TNF-α, IL-6 and IL-8 in LPS-stimulated monocytic THP-1 cells at non-cytotoxic concentrations (50-250 μg/ml). The metabolic activation of the DC extract by S9 mix did not alternate its cytotoxicity and did not diminish its inhibitory effect. This effect was improved in the case of TNF- α inhibition as reflected by their EC50 values of 116 ± 8.2 μg/ml and 49 ± 3.5 μg/ml for DC and DCm ( P < 0.01). Conclusions Cytokines inhibitory activity of DC was not affected after its external metabolic activation. However, the amount of harpagoside and caffeic acid derivates was decreased. Other components of the extract might have contributed to its anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

Objectives Preparations containing saw palmetto berries are used in the treatment of benign prostatic hyperplasia ( BPH). There are many products on the market, and relatively little is known about their chemical variability and specifically the composition and quality of different saw palmetto products notwithstanding that in 2000, an international consultation paper from the major urological associations from the five continents on treatments for BPH demanded further research on this topic. Here, we compare two analytical approaches and characterise 57 different saw palmetto products. Methods An established method - gas chromatography - was used for the quantification of nine fatty acids, while a novel approach of metabolomic profiling using 1 H nuclear magnetic resonance ( NMR) spectroscopy was used as a fingerprinting tool to assess the overall composition of the extracts. Key findings The phytochemical analysis determining the fatty acids showed a high level of heterogeneity of the different products in the total amount and of nine single fatty acids. A robust and reproducible 1 H NMR spectroscopy method was established, and the results showed that it was possible to statistically differentiate between saw palmetto products that had been extracted under different conditions but not between products that used a similar extraction method. Principal component analysis was able to determine those products that had significantly different metabolites. Conclusions The metabolomic approach developed offers novel opportunities for quality control along the value chain of saw palmetto and needs to be followed further, as with this method, the complexity of a herbal extract can be better assessed than with the analysis of a single group of constituents. [ABSTRACT FROM AUTHOR]

An open study was carried out to assess, primarily, the safety and tolerability of Aesculus hippocastanum in the treatment of CVI. Patients underwent 8 consecutive weeks of treatment and were asked to take one 50 mg Aesculus hippocastanum tablet, twice daily. In total, 91 adverse events were reported, of which only 4 were rated as probably related to the study drug. Patients judged the tolerability of the study medication in the majority of the cases at visits 2 and 3 (90 and 95%, respectively) to be 'good' or 'fairly good.' Only 2 patients rated tolerability as poor at visit 3. For each of the symptoms investigated the difference in the median value between baseline and visit 3 was found to be statistically significant and both the ankle and lower leg circumference decreased. The PPG measurements were rejected after analysis since validation measurements carried out after the trial showed that the PPG technique had an internal error of around 30%. Nevertheless, the majority of patients rated efficacy to be 'very good' or 'good,' with only 10 patients reporting no effect by the end of the study. The results of this study indicate that Aesculaforce® 50 mg tablets are a safe, well-tolerated and efficacious treatment for Widmer stage I and II CVI. [ABSTRACT FROM AUTHOR]

Gut microbiota influences many aspects of host health including immune, metabolic, and gut health. We examined the effect of a fermented whey concentrate (FWC) drink rich in L-(+)-Lactic acid, consumed daily, in 18 healthy men ( n = 5) and women ( n = 13) in free-living conditions. Objective: The aims of this 6-weeks pilot trial were to (i) identify changes in the gut microbiota composition and fecal short chain fatty acid (SCFA) profile, and (ii) to monitor changes in glucose homeostasis. Results: Total fecal SCFA (mM) concentration remained constant throughout the intervention. Proportionally, there was a significant change in the composition of different SCFAs compared to baseline. Acetate levels were significantly reduced (-6.5%; p < 0.01), coupled to a significant increase in the relative amounts of propionate (+2.2%; p < 0.01) and butyrate (+4.2%; p < 0.01), respectively. No changes in the relative abundance of any specific bacteria were detected. No significant changes were observed in glucose homeostasis in response to an oral glucose tolerance test. Conclusion: Daily consumption of a fermented whey product led to significant changes in fecal SCFA metabolite profile, indicating some potential prebiotic activity. These changes did not result in any detectable differences in microbiota composition. Post-hoc analysis indicated that baseline microbiota composition might be indicative of participants likely to see changes in SCFA levels. However, due to the lack of a control group these findings would need to be verified in a rigorously controlled trial. Future work is also required to identify the biological mechanisms underlying the observed changes in microbiota activity and to explore if these processes can be harnessed to favorably impact host health. Clinical Trial Registration : www.clinicaltrials.gov, identifier NCT03615339; retrospectively registered on 03/08/2018., (Copyright © 2020 Smith, Maloney, Shaw, Horgan, Fyfe, Martin, Suter, Scott and Johnstone.)

A major safety concern with the use of herbal medicinal products (HMP) is their interactions with conventional medicines, which are often mediated via the cytochrome P450 (CYP) system. Echinacea is a widely used over-the-counter HMP, with proven immunomodulatory properties. Its increasing use makes research into its safety an urgent concern. Previously, we showed that Echinacea extracts and its alkylamides (thought to be important for Echinacea's immunomodulatory activity) mildly inhibit the enzymatic activity of the main drug metabolising CYP isoforms, but to this date, there is insufficient work on its ability to alter CYP expression levels. We now report for the first time the effect of a commercial Echinacea extract (Echinaforce) and four Echinacea alkylamides on the transcription of the major drug metabolizing enzyme CYP3A4. HepG2 cells were exposed for 96 h to clinically relevant concentrations of Echinaforce (22, 11.6 and 1.16 μg mL(-1)) or the alkylamides (1.62 and 44 nM). CYP3A4 mRNA levels were quantified using real-time reverse transcription polymerase chain reaction (RT-PCR). Neither Echinaforce nor the alkylamides produced any significant changes in the steady-state CYP3A4 mRNA levels, under these conditions. In contrast, treatment with 50 μM rifampicin resulted in a 3.8-fold up-regulation over the vehicle control. We conclude that Echinaforce is unlikely to affect CYP3A4 transcriptional levels, even at concentrations which can inhibit the enzymatic activity of CYP3A4. Overall, our data provides further evidence for the lack of interactions between Echinacea and conventional drugs.

ECHINACEA is a popular and widely used herbal medicinal product and consequently, studies of its interactions with conventional drugs are of particular importance. We have shown that ECHINACEA preparations and some common alkylamides weakly inhibit several cytochrome P450 (CYP) isoforms, with considerable variation in potency. We now report a detailed analysis of six commercial ECHINACEA liquid preparations, with emphasis on the metabolomic characterisation of the ECHINACEA compounds responsible for inhibiting CYP3A4. We separated each preparation into its ethanol- and water-soluble components, and then used (1)H-NMR together with multivariate data analysis and partial least square regression analysis to investigate the nature of the compounds responsible for CYP3A4 inhibition. The results implicated alkylamides in the CYP3A4 inhibitory activity of ECHINACEA. One of the commercial preparations (Echinaforce(R)) was further fractionated using solid phase extraction. Analysis by (1)H-NMR and mass spectroscopy (LC/MS, tandem MS, accurate mass) identified dodeca-2 E,4 E,8 Z,10 E/Z-tetraenoic acid (alkylamide 1) and a new compound (putative molecular formula C (18)H (36) NO (+)) as major components of the inhibitory fractions. In addition, the alkylamide content of all six preparations was determined by reverse phase HPLC. Levels of alkylamides 1 and 3 (undeca-2 E,4 E/ Z-diene-8,10-diynoic acid isobutylamide), correlated well with CYP3A4 inhibition. The acetylene tetradeca-8 Z-ene-11,13-diyn-2-one was shown to be present in the E. PURPUREA as well as the E. PALLIDA extracts. E. PURPUREA unlike E. PALLIDA was thought to not contain significant amounts of acetylenes. Our results directly confirm the role of alkylamides in the inhibition of CYP3A4 by ECHINACEA and uncovered a new compound which may also be involved. Extensive differences in the composition of the commercially available preparations were found. This will inevitably impact on the product efficacy, safety and pharmacological effects, especially since the differences involve alkylamides, an important class of ECHINACEA's active constituents. The metabolomic approach presented here may prove valuable as a screening or quality control tool., (Copyright Georg Thieme Verlag KG Stuttgart New York.)

Background: In Chinese medicine, Ginkgo biloba is used for a variety of indications. In the current study, the safety and efficacy of a traditional fresh plant extract was investigated in patients with mild cognitive impairment., Patients and Methods: 59 elderly patients were treated for 6 weeks with a twice daily tablet containing 90 mg of fresh plant Ginkgo biloba extract. The patients suffered from age-related mild cognitive impairment of the non-Alzheimer type assessed by the DemTect score and the presence of symptoms, such as forgetfulness, memory problems, and difficulties in concentration. At the end of the treatment period, safety was primarily assessed by the occurrence of adverse events and efficacy by the DemTect score, the SF-12 quality of life questionnaire, and the change in cognitive symptoms, as well as the judgment of the investigators and patients., Results: At the final visit, the SF-12 mental score had increased significantly from 48.3 +/- 10.1 to 51.3 +/- 7.9, whereas the SF-12 body score (44.5 +/- 9.2 to 45.3 +/- 8.1) and the DemTect score (15.9 +/- 2.0 to 16.0 +/- 2.3) had not changed significantly. About half of all patients experienced an improvement in their memory and their ability to concentrate, as well as a decrease in symptoms of forgetfulness. The majority of investigators and patients judged the treatment to be effective. The tablets were very well tolerated and, as a treatment for their cognitive impairment, highly accepted (90% would take them again)., Conclusion: This newly developed, holistic fresh leaf extract of Ginkgo biloba is a safe, effective, and, at least, adjuvant treatment option for patients with mild cognitive impairments., (Copyright 2009 S. Karger AG, Basel.)

Establishing the pharmacological basis for efficacy of herbal medicinal products (HMPs) is a continuous challenge. In this context, also the question of bioavailability, the elucidation of metabolic pathways and their pharmacokinetics is of major interest. These data are relevant to link results from pharmacological IN VITRO assays and clinical studies. A better understanding of the pharmacokinetics and bioavailability of phytopharmaceuticals can also help in designing rational dosage regimes. The preparations used in the present pharmacokinetic single-dose study are different ECHINACEA PURPUREA formulations (Echinaforce) with various excipients. The concentrations of the active compounds (alkamides) in the administered products have been in the low mg range per dose. Due to the expected necessary detection of ng ranges, a sensitive and selective LC-ESI-MS-based method that is capable of monitoring plasma levels of traces of active constituents in humans was developed and validated. The resulting maximum concentrations (mean +/- standard deviation) of dodeca-2 E,4 E,8 Z, 10 E/ Z-tetraenoic acid isobutylamides in plasma were 0.22 +/- 0.07 ng/mL after administration of Echinaforce tablets, 0.22 +/- 0.15 ng/mL after taking Echinaforce Junior tablets and 0.23 +/- 0.16 ng/mL after administration of an Echinacea sore throat spray. The areas under the curve were 0.22 ng/mL x h, 0.20 ng/mL x h and 0.23 ng/mL x h, respectively.

Background: Phytotherapy is a third approach for treating lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). The lipido-sterolic extract of the fruit of Serenoa repens is one of the more widely used phytotherapeutic agents in this regard., Materials and Methods: The effect of an ethanolic extract of S. repens (10-1000 microg/ml) was tested in hormone-sensitive LNCaP, MCF-7 and hormone-insensitive DU 145, MDA MB231 prostate, breast carcinoma cell lines, renal Caki-1, urinary bladder J82, colon HCT 116 and lung A 549 cancer cells. Its cell growth inhibitory and apoptosis-inducing effects were tested using WST-1 assay and flow cytometry (Annexin V/PI stain) and/or by colorimetric assay (APOPercentage assay)., Results: The S. repens extract induced a dose-dependent antiproliferative effect on all human malignant cells tested, with GI50 values between 107 and 327 pmicro/ml. In hormone-sensitive prostate LNCaP and breast MCF-7 cell lines, the effect of extract expressed in GI50 was 2.2- and 2.5-fold more potent (p < 0.01) than in hormone-insensitive DU 145 and MDA MB231 cells. The proportion of apoptotic cells, except in A549 cells, lay between 22.5-36.3%. S. repens extract did not induce apoptosis in lung cancer A 549 cells., Conclusion: This study showed that the antiproliferative effect exerted by the ethanolic extract of S. repens is at least triggered by induction of apoptosis. These in vitro data provide some information that may be useful for clinical use and render S. repens extract an interesting tool for new applications.

An open study was carried out to assess, primarily, the safety and tolerability of Aesculus hippocastanum in the treatment of CVI. Patients underwent 8 consecutive weeks of treatment and were asked to take one 50 mg Aesculus hippocastanum tablet, twice daily. In total, 91 adverse events were reported, of which only 4 were rated as probably related to the study drug. Patients judged the tolerability of the study medication in the majority of the cases at visits 2 and 3 (90 and 95%, respectively) to be "good" or "fairly good." Only 2 patients rated tolerability as poor at visit 3. For each of the symptoms investigated the difference in the median value between baseline and visit 3 was found to be statistically significant and both the ankle and lower leg circumference decreased. The PPG measurements were rejected after analysis since validation measurements carried out after the trial showed that the PPG technique had an internal error of around 30%. Nevertheless, the majority of patients rated efficacy to be "very good" or "good," with only 10 patients reporting no effect by the end of the study. The results of this study indicate that Aesculaforce 50 mg tablets are a safe, well-tolerated and efficacious treatment for Widmer stage I and II CVI.