Synergistic immunomopharmacological effects of N-alkylamides in Echinacea purpurea herbal extracts

Echinacea purpurea extracts are used in the production of standardized herbal medicines for the prevention and treatment of upper respiratory infections. Unsaturated N-alkylamide lipids, the main constituent of E. purpurea and E. angustifolia preparations capable of activating the cannabinoid receptor type-2 (CB2) have been suggested to play a role as potential anti-inflammatory and immune-modulatory principles. Here we show that ethanolic E. purpurea radix and herba extracts produce synergistic pharmacological effects on the endocannabinoid system in vitro. Superadditive action of N-alkylamide combinations was seen at the level of intracellular calcium release as a function of CB2 receptor activation. Likewise, synergism of the radix and herba tinctures was observed in experiments measuring LPS-stimulated cytokine expression from human PBMCs. While the expression of the anti-inflammatory cytokine IL-10 was significantly superstimulated, the expression of the pro-inflammatory TNF-alpha protein was inhibited more strongly upon combination of the extracts. We show that N-alkylamides act in concert and exert pleiotropic effects modulating the endocannabinoid system by simultaneously targeting the CB2 receptor, endocannabinoid transport and degradation.

Medicinal herbal extracts - renal friend or foe? Part one: The toxicities of medicinal herbs

In recent years, an increasing percentage of people from industrialized countries have been using complementary and alternative medicines (CAM). This, combined with numerous warnings regarding the potential toxicity of these therapies, suggests the need for practitioners to keep abreast of the reported incidence of renal toxicity caused by the ingestion of medicinal herbs. The goal of the present two-part series, on the toxic or beneficial effects of medicinal herbs on renal health, is to provide practitioners with a summary of the most recent information as well as the means by which evidence for benefit or toxicity has been found. In this first article, we explore in vivo evidence of toxicity. Included are nephrotoxicity from aristolochic acid and other components within herbs, herb-drug interactions resulting in adverse renal effects, and renal toxicity from contaminants within the extracts. The review aims to provide a guide to encourage future toxicity studies and rigorous clinical trials.

Evaluation of micronuclei frequency in Tradescantia pallida pollen mother cells treated with ethanolic extracts isolated from Cryptocarya mandioccana, Cryptocarya moschata and Pterogyne nitens

Although herbal extracts contain several classes of compounds with pharmacological activity, they also present toxic substances with mutagenic effects. The aim of the present study was to verify the mutagenicity of Cryptocarya moschata, Cryptocarya mandioccana and Pterogyne nitens using micronucleus assay in pollen mother cells (tetrads) in Tradescantia pallida (Trad-MCN). T. pallida inflorescences were treated with different concentrations of ethanolic extracts from the selected plant species. For C. mandioccana C. moschata and P. nitens, Trad-MCN assays were carried out simultaneoulsly, followed by positive control (formaldehyde 10000 ppm), negative control (Hoagland's solution), and vehicle control (Tween 20 20% or DMSO 3%). MCN present in tetrads were quantified in 300 tetrads/inflorescence and the mean (%) and standard error (SE) were established for at least 10 inflorescences per treatment. The extracts demonstrated dose response mutagenicity (clastogenic/aneugenic effects), respectively, C. mandioccana (0.5, 1.0 and 2.0 mg/mL) and P. nitens (1.0 and 2.0 mg/mL) However, no mutagenic effect was observed to C. moschata at the concentrations evaluated in the present study. We can conclude that the C. mandioccana and P. nitens extracts demonstrated clastogenic/aneugenic effects in highest concentrations whereas C. moschata extract did not demonstrate the same effect. © 2006 Sociedade Brasileira de Toxicologia.

Convergencia de vías de señalización en un modelo de apoptosis

La sepsis es un evento inflamatorio generalizado del organismo inducido por un daño causado generalmente por un agente infeccioso. El patógeno más frecuentemente asociado con esta entidad es el Staphylococcus aureus, responsable de la inducción de apoptosis en células endoteliales debida a la producción de ceramida. Se ha descrito el efecto protector de la proteína C activada (PCA) en sepsis y su relación con la disminución de la apoptosis de las células endoteliales. En este trabajo se analizó la activación de las quinasas AKT, ASK1, SAPK/JNK y p38 en un modelo de apoptosis endotelial usando las técnicas de Western Blotting y ELISA. Las células endoteliales (EA.hy926), se trataron con C2-ceramida (130μM) en presencia de inhibidores químicos de cada una de estas quinasas y PCA. La supervivencia de las células en presencia de inhibidores químicos y PCA fue evaluada por medio de ensayos de activación de las caspasas 3, 7 y 9, que verificaban la muerte celular por apoptosis. Los resultados evidencian que la ceramida reduce la activación de AKT y aumenta la activación de las quinasas ASK, SAPK/JNK y p38, en tanto que PCA ejerce el efecto contrario. Adicionalmente se encontró que la tiorredoxina incrementa la activación/fosforilación de AKT, mientras que la quinasa p38 induce la defosforilación de AKT.

Natural products as alternative treatments for metabolic bone disorders and for maintenance of bone health

Bone metabolism involves a complex balance between the deposition of matrix and mineralization and resorption. There is now good evidence that dietary components and herbal products can influence these processes, particularly by inhibiting bone resorption, thus having beneficial effects on the skeleton. For example, it has been reported that a number of common vegetables, including onion, garlic and parsley, can inhibit bone resorption in ovariectomized rats. Essential oils derived from sage, rosemary, thyme and other herbs inhibit osteoclast activity in vitro and in vitro and leading to an increase in bone mineral density. Soya, a rich source of isoflavones, has shown promising results and epidemiological evidence to support a use in maintaining bone health, and various traditional herbal formulae in Chinese and Ayurvedic medicine also have demonstrable effects in pharmacological models of osteoporosis. Recently, cannabinoids have been described as having positive effects on osteoblast differentiation, and the presence of cannabinoid receptors in bone tissue indicates a more complex role in bone metabolism than previously thought. The first part of this review briefly discusses normal bone metabolism and disorders caused by its disruption, with particular reference to osteoporosis and current pharmacological treatments. The effects of natural products on bone and connective tissue are then discussed, to include items of diet, herbal extracts and food supplements, with evidence for their efficacy outlined. Copyright (c) 2006 John Wiley & Sons, Ltd.

Inhibition of proinflammatory biomarkers in THP1 macrophages by polyphenols derived from chamomile, meadowsweet and willow bark.

Antiinflammatory compounds in the diet can alleviate excessive inflammation, a factor in the pathogenesis of common diseases such as rheumatoid arthritis, atherosclerosis and diabetes. This study examined three European herbs, chamomile (Matricaria chamomilla), meadowsweet (Filipendula ulmaria L.) and willow bark (Salix alba L.), which have been traditionally used to treat inflammation and their potential for use as antiinflammatory agents. Aqueous herbal extracts and isolated polyphenolic compounds (apigenin, quercetin and salicylic acid, 0–100 μM) were incubated with THP1 macrophages, and interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-) were measured. At concentrations of 10 μM, both apigenin and quercetin reduced IL-6 significantly ( p < 0.05). Apigenin at 10 μM and quercetin at 25 μM reduced TNF- significantly ( p < 0.05). Amongst the herbal extracts, willow bark had the greatest antiinflammatory activity at reducing IL-6 and TNF- production. This was followed by meadowsweet and then chamomile. The lowest effective antiinflammatory concentrations were noncytotoxic (MTT mitochondrial activity assay). The Comet assay, which was used to study the protective effect of the isolated phenols against oxidative damage, showed positive results for all three polyphenols. These are the first findings that demonstrate the antiinflammatory capacity of these herbal extracts.

Determination of synephrine in weight-loss products using high performance liquid chromatography with acidic potassium permanganate chemiluminescence detection

Adrenergic amines found in extracts of Citrus aurantium (bitter orange) evoke analytically useful chemiluminescence with acidic potassium permanganate in the presence of polyphosphates. From corrected chemiluminescence spectra, the wavelength of maximum intensity for these reactions was 680 ± 5 nm and, using flow injection analysis methodology, limits of detection for synephrine, octopamine, tyramine and hordenine were found to be between 1 × 10⁻⁹ and 1 × 10⁻⁸ M. We have applied this method of detection to the rapid determination of synephrine in dietary supplements using monolithic column chromatography.

Amylase and glucosidase enzyme inhibitory activity of ginger (Zingiber officinale Roscoe) an in vitro study

The prevalence of type 2 diabetes has reached to an epidemic proportion in Sri Lanka. The need for achieving better control of blood glucose level has been evident in diabetes management. However it is not easy to achieve this goal in a large proportion of patients. This is partly due to limitations of currently available pharmacological agents which stimulate research on novel anti-diabetic agents with different mechanisms. Digestive enzymes have been targeted as potential avenues for modulation of blood glucose concentration through inhibition of the enzymatic breakdown of complex carbohydrates to meal derived glucose absorption. Acarbose is a widely used oral anti-diabetic drug which inhibits the α-glucosidase, enzyme responsible for breaking down of disaccharides and polysaccharides into glucose. Many herbal extracts have been found to posses similar inhibitory effects. Ginger (Zingiber officinale Roscoe) has developed a reputation in treatment of several diseases. In vitro enzymic inhibitory effect of ginger was investigated in this study. Enzymes α -amylase and α -glucosidase treated with either Acarbose or ginger extract were allowed to react with cooked rice and percentages of glucose content were measured. The glucosidase and amylase activities on the rice were inhibited by addition of ginger cause significant reduction in glucose percentages (36.86± 1.05 to 26.87± 2.17, P<0.05 and 49.04±0.65 to 35.35±2.22, P<0.05) which showed comparable results with Acarbose on glucosidase activity (36.86± 1.05 to, 27.8±1.32 P<0.05). Results of the study indicates ginger as a potential plant based amylase and glucosidase inhibitor in carbohydrate digestion but usage in glycaemic control in human has to be investigated further.

Effects of physical exercise and cinnamon extract on blood chemistry of type 1 diabetic rats

The present study was designed to analyze the effects of the association between cinnamon extract and aerobic exercise on the glycemic control and serum lipid profile of diabetic rats. Fifty Wistar male rats divided into five groups: control (C), sedentary nondiabetic rats; diabetic (D), sedentary diabetic rats; diabetic cinnamon (DC), sedentary diabetic rats that received cinnamon extract; diabetic exercise (DE), sedentary diabetic rats subjected to physical training; and diabetic cinnamon exercise (DCE), diabetic rats that received cinnamon extract and were subjected to physical training. For the induction of diabetes, the rats received alloxan. The cinnamon was administered to once a day for four weeks. The groups performed swimming exercises for one hour each day with lead overloads (3% - 5% of b.w) for five days a week for four weeks. Body weight loss was lower in the DE group compared to the other diabetic groups. The basal serum glucose of all the diabetic groups was higher compared to the control group. Group D had higher serum cholesterol concentrations compared to the DE and DCE groups. The resting blood lactate in group D was higher than the resting blood lactate in the DC and DE groups. Aerobic exercise partially counteracted the diabetic effects on body weight, serum cholesterol and blood lactate concentrations. No additional beneficial effects of cinnamon extract and aerobic exercise were observed on the parameters studied.

Análise multielementar da mucosa gástrica de roedores tratados com Alchornea glandulosa, Davilla elliptica e Davilla nitida pela técnica de fluorescência de raios-x por reflexão total

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Atividade antibacteriana de plantas medicinais frente á bactérias multirresistentes e a sua interação com drogas antimicrobianas

O controle de micro-organismos infecciosos multirresistentes às vezes é ineficaz mesmo com o desenvolvimento de novos antibióticos. Diversos extratos de plantas medicinais têm efeitos antimicrobianos o que pode representar uma alternativa terapêutica para doenças infecciosas, principalmente quando associados aos antibióticos de uso clínico. O objetivo do trabalho foi avaliar a atividade antibacteriana de plantas medicinais sobre bactérias multirresistentes e os efeitos de sua interação com drogas antimicrobianas. Foi determinada a atividade antibacteriana de extratos e frações das plantas Eleutherine plicata (marupazinho), Geissospermum vellosii (pau-pereira) e Portulaca pilosa (amor-crescido) frente a isolados de Staphylococcus aureus Oxacilina Resistente (ORSA) e de Pseudomonas aeruginosa multirresistente, provenientes de processos clínicos humanos, assim como a interação destes produtos vegetais com drogas antimicrobianas de uso clínico. A atividade antibacteriana foi determinada pelo método de disco difusão em ágar Muller Hinton e a Concentração Inibitória Mínima (CIM) pela técnica de microdiluição em placas utilizando caldo Muller Hinton como meio de cultura e resazurina a 0,01% como revelador de crescimento bacteriano. Os extratos e frações foram testados nas concentrações de 500, 250, 125, 62,5, 31,2 e 16,2 μg/mL dissolvidos em DMSO a 10%. As plantas E. plicata e G. vellosii demonstraram atividade contra os isolados ORSA com CIM de 125 μg/mL, enquanto que P. pilosa teve ação sobre os isolados de P. aeruginosa multirresistentes com CIM de 250 μg/mL. Ocorreram 25% de sinergismo e apenas 5% de antagonismo entre as 120 interações de produtos vegetais e drogas antimicrobianas testadas. Frente aos isolados ORSA houve sinergismo com as drogas ciprofloxacina, clindamicina e vancomicina tanto com os derivados de E. plicata como os de G. vellosii. Os produtos de P. pilosa potencializaram a ação das drogas aztreonam, cefepime e piperacilina+tazobactam frente aos isolados de P. aeruginosa multirresistentes. Os resultados comprovaram o potencial das plantas E. plicata, G. vellosii e P. pilosa no controle de infecções bacterianas envolvendo fenótipos multidrogas resistentes (MDR) e que a sua interação com drogas antibacterianas pode representar uma nova alternativa na terapia destas infecções.

Drying of Phytochemical Preparations in a Spouted Bed: Perspectives and Challenges

This article presents an overview of relevant issues to be considered in the development of standardized phytochemical preparations, focusing on the use of the spouted bed as a drying method. Aspects related to the effects of feed composition properties and processing parameters on system performance and product quality are addressed. From the information presented, it can be concluded that the spouted bed technology can be successfully applied for production of high-quality phytochemical preparations suitable for food and pharmaceutical purposes, considering the requirements for product safety, quality, and efficacy. Nevertheless, it should be emphasized that, at this time, the proposed technology is appropriate for small-scale production, mainly due to difficulties concerning scale-up, modeling, and the simulation of spouted bed systems, and also for predicting product properties and system behavior during operation.

Provisional Biopharmaceutical Classification of Some Common Herbs Used in Western Medicine

The aim of this study was to classify some markers of common herbs used in Western medicine according to the Biopharmaceutical Classification System (BCS). The BCS is a scientific approach to classify drug substances based upon their intestinal permeability and their solubility, at the highest single dose used, within the physiologically relevant pH ranges. Known marker components of twelve herbs were chosen from the USP Dietary Supplement Compendium Monographs. Different BCS parameters such as intestinal permeability (P-eff) and solubility (C-s) were predicted using the ADMET Predictor, which is a software program to estimate biopharmaceutical relevant molecular descriptors. The dose number (D-0) was calculated when information from the literature was available to identify an upper dose for individual markers. In these cases the herbs were classified according to the traditional BCS parameters using Peff and Do. When no upper dose could be determined, then the amount of a marker that is just soluble in 250 mL of water was calculated. This value, M-x, defines when a marker is changing from highly soluble to poorly soluble according to BCS criteria. This biopharmaceutically relevant value can be a useful tool for marker selection. The present study showed that a provisional BCS classification of herbs is possible but some special considerations need to be included into the classification strategy. The BCS classification can be used to choose appropriate quality control tests for products containing these markers. A provisional BCS classification of twelve common herbs and their 35 marker compounds is presented.