Valerian: No Evidence for Clinically Relevant Interactions

In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients

Chemical Profile and Antimicrobial Activity of the Fungus-Growing Termite Strain Macrotermes Bellicosus Used in Traditional Medicine in the Republic of Benin

The fungus growing termite species Macrotermes bellicosus (M. bellicosus) is used in nutrition and traditional medicine in the Republic of Benin for the treatment of infectious and inflammatory diseases. Previous findings demonstrated evidence of anti-inflammatory and spasmolytic properties of M. bellicosus. The aim of the present study was to evaluate the antimicrobial potential of different extracts of M. bellicosus samples and determine the chemical profile of an ethanolic M. bellicosus extract. Chemical profiling was conducted using centrifugal partition chromatography and 13C-NMR, followed by MALDI-TOF MS. Major identified compounds include hydroquinone (HQ), methylhydroquinone (MHQ), 3,4-dihydroxyphenethyl glycol (DHPG), N-acetyldopamine (NADA) and niacinamide. The fatty acid mixture of the extract was mainly composed of linoleic and oleic acid and highlights the nutritional purpose of M. bellicosus. Using the Kirby–Bauer disc diffusion and broth microdilution assay, an antibacterial activity of M. bellicosus samples was observed against various clinical strains with a highest growth inhibition of S. aureus. In addition, HQ and MHQ as well as fractions containing DHPG, niacinamide and NADA inhibited S. aureus growth. The reported antimicrobial activity of M. bellicosus and identified active substances provide a rationale for the traditional medicinal use of M. bellicosus

Adenosine A1 receptor: Functional receptor-receptor interactions in the brain

Over the past decade, many lines of investigation have shown that receptor-mediated signaling exhibits greater diversity than previously appreciated. Signal diversity arises from numerous factors, which include the formation of receptor dimers and interplay between different receptors. Using adenosine A1 receptors as a paradigm of G protein-coupled receptors, this review focuses on how receptor-receptor interactions may contribute to regulation of the synaptic transmission within the central nervous system. The interactions with metabotropic dopamine, adenosine A2A, A3, neuropeptide Y, and purinergic P2Y1 receptors will be described in the first part. The second part deals with interactions between A1Rs and ionotropic receptors, especially GABAA, NMDA, and P2X receptors as well as ATP-sensitive K+ channels. Finally, the review will discuss new approaches towards treating neurological disorders

Cytotoxic effects of capsaicin and capsicum extracts on neuroblastoma cells

Capsaicin, a hot pepper alkaloid, has been shown to stimulate the release of serotonin and dopamine in SH-SY5Y neuroblastoma cells. Binding on vanilloid receptor 1 (TRPV1) is one of the cellular mechanisms responsible for this effect. On the other hand TRPV1 are involved in cell proliferation and apoptosis. The aim of the present experiments was to investigate the effect of the potential anticancer agent capsaicin on B104 neuroblastoma cells. Materials and methods: MTT and LDH assays were used to determine viability and cell death in B104 neuroblastoma cells. Capsicum ethanolic extracts isolated from 4 different genotypes of hot species of Capsicum annuum L. and capsaicin solutions in different concentrations and time of exposures were investigated. Results: Capsaicin (500nM, 1 μM, 10μM) did not influence significantly viability or cell death of B104 cells when it was applied for 1 or 24 hours incubation. There was a significant cytotoxicity of high concentrations of capsaicin (100μM), after 24 hours incubation and for capsaicin (250μM), even when cells are treated for 1 hour. Interestingly, ethanolic capsicum extracts which contained capsaicin (0.5mM to 2.1mM) did not show any cytotoxic effect. We assume therefore, that other compounds (carotenoids, vitamins, and other polyphenolic substances) within the ethanolic extract interact antagonistic with the cytotoxic effect of capsaicin. Conclusion: Our results indicate that capsaicin in high concentration has cytotoxic effects on neuroblastoma cells. The effects are time and concentration dependent. Our data are in line with previous findings in which capsaicin increased caspase-3 activity after treatment for 24 hours

Adenosine receptors as a target in colonic inflammation

The purine nucleoside adenosine, which is involved in several physiological functions, regulates a wide variety of immune and inflammatory responses and acts as modulator of gut functions. Although it is present at low concentrations in the extracellular space, stressful conditions, such as inflammation, can markedly increase its extracellular level up to micromolar range. Recent evidence suggests a prominent role of A2Areceptors (A2AR) and A2B receptors (A2BR) in the pathophysiology of inflammation (Sitkovsky and Lukashev 2005, Palmer and Trevethick 2008). In the current study we investigated the role of A2AR and A2BR to regulate contractility in untreated and inflamed rat colon preparations using specific receptor agonists and antagonists.<br>Inflammation was induced by intraluminal instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS, 0.01/0.1M, 30min). mRNA-expression was determined using RT-PCR. Contractions were measured isometrically in an organbath setup. All four adenosine receptor subtypes were expressed in untreated colon preparations. Activation of A1, A2B, and A3 receptor with specific agonists reduced the acetylcholine (ACh, 10?M)-induced contractions, while activation of A2BR enhanced. After incubation with TNBS morphologically damages in colonic mucosa and muscle walls were detectable followed by reduced ACh-contractions. The TNBS-mediated decrease of ACh-contractions as well as the morphological damages were partially normalized by co-incubation of TNBS with the A2AR agonist 2-p-[carboxyethyl]phenethylamino-5'-N-ethylcarboxamido-adenosine (CGS 21680, 10?M) or the A2BR antagonist 4-(2,3,6,7-tetrahydro-2,6-dioxo-1-propyl-1H-purin-8-yl-benzenesulfonic acid<br>(PSB 1115, 100?M).<br>In this study using an in-vitro inflammatory model, we demonstrate that the A2AR agonist CGS 21680 or the A2BR antagonist PSB 1115 effectively conteracted the development of TNBS-induced disturbances in colon preparations, so qualifying adenosine receptors as potential targets in colonic inflammation