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Efficacy and Safety of White Willow Bark ( Salix alba ) Extracts: Willow Bark Extract Efficacy and Safety

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Abstract

Willow bark extract has been used for thousands of years as an anti-inflammatory, antipyretic, and analgesic. In spite of its long history of use, relatively few human and animal studies have been published that confirm anecdotal observations. A small number of clinical studies have been conducted that support the use of willow bark extracts in chronic lower back and joint pain and osteoarthritis. Willow bark extracts also are widely used in sports performance and weight loss products presumably because of anti-inflammatory and analgesic activities, although no human studies have been published that specifically and directly document beneficial effects. In recent years, various in vitro and animal studies have demonstrated that the anti-inflammatory activity of willow bark extract is associated with down regulation of the inflammatory mediators tumor necrosis factor-α and nuclear factor-kappa B. Although willow bark extracts are generally standardized to salicin, other ingredients in the extracts including other salicylates as well as polyphenols, and flavonoids may also play prominent roles in the therapeutic actions. Adverse effects appear to be minimal as compared to non-steroidal anti-inflammatory drugs including aspirin. The primary cause for concern may relate to allergic reactions in salicylate-sensitive individuals. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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... More than 80% of salicin content is absorbed and then metabolized into different salicylate derivatives (Steinegger and Hövel 1972). Besides the salicinrelated constituents, other active components of willow leaves and bark such as polyphenols and flavonoids play important roles in therapeutic effects of willow (Nahrstedt et al., 2007;Shara and Stohs 2015). It has been indicated that a polyphenolic compound isolated from willow bark, 2, 3-trans procyanidin, induces relaxation in porcine coronary arteries through activation of PI3/Akt kinase signaling pathway and eNOS phosphorylation (Kaufeld et al., 2013). ...
... The antioxidant effect of standardized willow bark extract was demonstrated in serum of rats with adjuvant-induced arthritis (Khayyal et al., 2005). In addition to antioxidative and anti-inflammatory properties, willow bark is used in weight loss supplements (Shara and Stohs 2015). Moreover, in normolipidemic rabbits, aromatic water of Salix aegyptiaca decreased level of total cholesterol and this effect was comparable to that of simvastatin (Karimi et al., 2015) The aim of the present study was to evaluate the antioxidative potency of S. alba (white willow) in comparison to ASA in heart and kidney tissues of diet -induced hypercholesterolemic rabbits. ...
... Antioxidant effects of willow extract have been studied in various experiments. In addition to salicin, willow bark contains various flavonoids and polyphenols that synergistically contribute to the beneficial effects of Sa which may be more marked than ASA (Shara and Stohs 2015;Sulaiman et al., 2011). It is well-recognized that polyphenolic compounds possess several pharmacological activities, including anti-oxidant (Kumar and Pandey 2013), anti-inflammatory and hypolipidemic properties (Dudzińska et al., 2015). ...
Article
Objective Oxidative stress plays a critical role in the development of hypercholesterolemia-induced complications. This study evaluated the effects of aspirin and Salix alba hydroethanolic extract on oxidative stress in the heart and kidney of hypercholesterolemic rabbits. Materials and Methods The antioxidant activity, as well as total phenolic and salicin content of S. alba (Sa) extract were assessed by DPPH radical scavenging activity, Folin-Ciocalteu and HPLC methods, respectively. Animals were divided into two groups of control (fed with normal chow), and HD (fed with high cholesterol diet for 6 weeks). Then, hypercholesterolemic animals allocated to the following treatment groups: CHO (received HD), Sa extract (HD plus extract 60 and 120 mg/kg), and aspirin (HD plus aspirin 120 mg/kg) and received the treatments on a daily basis for 6 weeks. MDA, GSH, and nitrite concentrations as well as the activities of SOD and CAT were evaluated in cardiac and kidney tissues. Results The scavenging activity, total phenolic content and salicin were 19.1 µg/ml (IC50), 153.75 ± 3.6 mg of gallic acid/g, and 18.03 µg/mg, respectively. In comparison to CHO group, MDA levels were diminished in Sa and ASA groups but GSH levels were improved. NO metabolites increased in the heart of Sa 120 mg/kg group and in the kidney of all Sa and ASA treated groups. SOD activity increased only in the heart of Sa groups and in the kidney of Sa and ASA groups. CAT activity increased in the heart and kidney tissues of all Sa and ASA treated groups. Conclusion The results showed S. alba extract improved redox homeostasis in heart and kidney tissues of hypercholesterolemic rabbits. The extract antioxidant property may be related to its phenolic content.
... lubrication. BS and SA have both anti-inflammatory and analgesic properties due to the presence 70 of boswellic acid and salicin respectively (Kimmatkar et al., 2003;Shara and Stohs, 2015). 71 ...
... It reduces glycosaminoglycan degradation, keeping the cartilage 74 in good condition unlike NSAIDs that can induce the disruption of the glycosaminoglycan 75 synthesis, accelerating articular damage (Kimmatkar et al., 2003). Salicin has anti-inflammatory 76 and anabolic effects, as shown in canine joints (Shara and Stohs, 2015). Benefits of these natural 77 ...
... Moreover, we suspect that this reduction of TNF-α partly results from SA activity. In a recent 263 review, Shara and Stohs (2015) came to the conclusion that the anti-inflammatory activity of SA is 264 associated with down regulation of the pro-inflammatory effect of TNF-α. In addition to salicin, 265 ...
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Background: Rheumatoid arthritis has seen a significant increase in both incidence and prevalence and its treatments show limited efficiency due to their undesirable effects on patient health. Therefore, major interests lie in the development of treatments with drugs derived from plants or other natural sources with little adverse effects as an alternative to current treatments. Hypothesis/Purpose: The present study evaluates the therapeutic effects of glucosamine against rheumatoid arthritis in combination with hyaluronic acid, resin extract of Boswellia serrata or a bark extract of Salix alba on an animal model. We suggest that combinations with plants could improve the attenuation of arthritis symptoms and articular inflammation. Study design: We used Freund's complete adjuvant on rats as models of rheumatoid arthritis. Individuals were separated into eight experimental groups: a control group without arthritis, one with arthritis and without treatment, and six other groups receiving a daily therapeutic treatment from days 14 to 29. Methods: Hind-paw thickness and arthritis scores were measured at days 0, 3, 6 and 9 post-induction, and then every day from days 12 to 29 with a digital caliper and a score system respectively. At the end of the treatment, the mRNA content of three pro-inflammatory cytokines from cartilage was measured using real-time PCR. The total antioxidant activity was evaluated with an Antioxidant Assay Kit. Results: Treatments with Boswellia serrata and Salix alba (Glu+Hyal A+Bosw, Glu+Bosw+Sal, Glu+Bosw and Glu+Hyal A+Sal) saw significant reductions in hind-paw thickness and arthritis scores at the end of the experiment when compared to the untreated group. Expression of pro-inflammatory gene IL 17A was also reduced, but only the Glu+Hyal A+Sal combination significantly decreased the expression of IL-1β and TNF-α. The total antioxidant activity in blood plasma significantly increased in groups treated with plant extracts. Conclusion: The addition of Boswellia serrata and/or Salix alba attenuates clinical signs of rheumatoid arthritis in Freund's complete adjuvant-induced arthritis in rats likely due to both their anti-inflammatory and antioxidant properties.
... Phenolic constituents of Salix reticulata (Salicaceae) and antiproliferative activity of an extract and individual compounds were investigated in immortalized human non-tumorigenic keratinocytes (HaCaT). A MeOH extract from aerial parts afforded several flavonoids, including luteolin and apigenin glycosides (2-5 and 9) and catechin (1), two procyanidin fractions, and the phenolic glucosides picein (6), triandrin (7), and salicortin (8). In an adenosine triphosphate assay, the MeOH extract reduced cell viability by approximately 60 % at a concentration of 100 µg/mL. ...
... Phenolic glucosides included picein (6) [15], triandrin (7) [16], and salicortin (8) [17]. In addition, a mixture of dimeric procyanidins ( The major constituents luteolin-7-O-β-glucopyranoside (2) and picein (6) were quantified in S. reticulata aerial parts by HPLC-UV analysis. The content of luteolin-7-O-β-glucopyranoside was found to be 1221 ± 25 mg/100 g dry weight, and that of picein 817 ± 5 mg/100 g dry weight. ...
... To our knowledge, this is the first study on anti-migratory and antiproliferative effects of salicortin (8) and picein (6) in HaCaT cells. For salicortin, which did not show any significant effects in our experiments, in vitro anti-inflammatory activity has been shown earlier by Kwon et al. [26]. ...
Article
Phenolic constituents of Salix reticulata (Salicaceae) and antiproliferative activity of an extract and individual compounds were investigated in immortalized human non-tumorigenic keratinocytes (HaCaT). A MeOH extract from aerial parts afforded several flavonoids, including luteolin and apigenin glycosides (2-5 and 9) and catechin (1), two procyanidin fractions, and the phenolic glucosides picein (6), triandrin (7), and salicortin (8). In an adenosine triphosphate assay, the MeOH extract reduced cell viability by approximately 60 % at a concentration of 100 µg/mL. Cell proliferation was assessed with a BrdU incorporation ELISA assay. The extract inhibited proliferation of HaCaT cells in a concentration-dependent manner, with approximately 50 % inhibition at 100 µg/mL. In time-lapse assays, the extract showed distinct inhibitory effects on cell migration at concentrations of 12.5, 25, and 50 µg/mL. The activity of selected constituents was also determined. Luteolin-7-O-β-glucuronide (3) significantly inhibited cell proliferation at concentrations of 10 and 50 µM. In contrast, luteolin-7-O-β-glucopyranoside (2) and a procyanidin fraction (P1) had only weak effects, while picein (6) and salicortin (8) did not affect cell proliferation. Luteolin-7-O-β-glucuronide (10 µM) and, to a lesser extent, the procyanidin fraction (10 µg/mL) also inhibited cell migration.
... Ancient Egyptians and Sumerians used willow bark and leaves against inflammatory conditions caused by injury and to relieve joint pain. Moreover, the Khoikhoi people of South Africa and the Indigenous peoples of North America, having discovered these properties completely independently, used the willow extracts to cure fever, osteoarthritis and headache (Al-Khalifa, 1993;Lichterman, 2004;Shara and Stohs, 2015;Volmink, 2008;Wood, 1993). ...
... The active agent that is responsible for analgesic, antipyretic and anti-inflammatory properties of willow is salicin. Salicin is metabolized by intestinal flora into saligenin, and then further metabolized by the liver into salicylic acida substance that differs from aspirin through a lack of an acetyl group (Shara and Stohs, 2015). ...
... Aspirin was then patented in the United States on February 27, 1900. Initially it was sold as a powder, however in 1904 aspirin became the first industrially produced drug available in tablet form worldwidea fact indicative of its wide commercial success (Lichterman, 2004;Shara and Stohs, 2015). ...
Article
Aspirin (acetylsalicylic acid), the oldest synthetic drug, was originally used as an anti-inflammatory medication. Being an irreversible inhibitor of COX (prostaglandin-endoperoxide synthase) enzymes that produce precursors for prostaglandins and thromboxanes, it has gradually found several other applications. Sometimes these applications are unrelated to its original purpose for example its use as an anticoagulant. Applications such as these have opened opportunities for new treatments. In this case, it has been tested in patients with cardiovascular disease to reduce the risk of myocardial infarct. Its function as an anticoagulant has also been explored in the prophylaxis and treatment of pre-eclampsia, where due to its anti-inflammatory properties, aspirin intake may be used to reduce the risk of colorectal cancer. It is important to always consider both the risks and benefits of aspirin's application. This is especially important for proposed use in the prevention and treatment of neurologic ailments like Alzheimer's disease, or in the prophylaxis of myocardial infarct. In such cases, the decision if aspirin should be applied, and at what dose may be guided by specific molecular markers. In this revived paper, the pleiotropic application of aspirin is summarized.
... The extract is obtained from the activeprinciple of the plant, using an adequate procedure, using either water, or an equivalent hydro-alcoholic solvent with a concentration of maximum 80% ethanol V / V. Enayat and Banerjee (2009) showed that the willow bark extracts are high in polyphenols, flavonoids, catechins, gallic acid, cafeic acid, vanillin, p-coumaric acid, mirycetin, epigallocatechin gallat, rutin, quercetin, salicin. These phenolic compounds are responsible for the antioxidant activity of the willow bark extract and contribute to its antiparasitic effect (Shara et al., 2015). The phenolic compounds have bactericide (Gordon and Wareham, 2010) and bacteriostatic (Etxeberria et al., 2013) properties, they depress the adhesion of pathogen bacteria (E. ...
... coli, Clostridium spp.), improve nutrient utilization and animal performance (Viveros et al., 2011;Dueñaset al., 2015;Breneset al., 2016). Despite their long history of utilization, rather few animal studies have been published, which to confirm these observations (Shara et al., 2015). Due to the presence of hydroxyl groups, the polyphenols have the capacity of incorporating in to the lipid membranes thus increasing their permeability, which makes the pathogen bacteria more sensitive to antibacterial compounds (Chiva-Blanch and Visoli, 2012;Paszkiewicz et al., 2012). ...
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A feeding trial was performed on 60, Cobb 500 broiler chicks (14-28 days) assigned to 2 groups (C, E) housed in an experimental hall with 32˚C air temperature, 36% humidity and 23 h light regimen. The conventional diet (C), with corn and soybean meal as basic ingredients, had 3082.48 kcal/kg metabolisable energy and 19.99% crude protein. Unlike the diet of C group, the diet of experimental group (E) had 1% willow bark extract (Salix alba). At the age of 28 days, 5 broilers/group were slaughtered and samples of caecal content were collected for bacteriological examination. Compared to group C, the pathogenic bacteria, Enterobacteriacee and Escherichia coli (colony forming units), were significantly (P≤0.05) lower in the caecum content, while the units of lactobacilli were significantly (P≤0.05) higher in group E. Throughout the experimental period, under heat stress, no mortalities were recorded.The inclusion of 1% willow bark extract in broiler diets (14-28 days) reared under heat stress reduced the proliferation of pathogenic bacteria and stimulated the growth of favourable bacteria such as lactobacilli in the gut.
... 4 La corteza del sauce blanco (Salix alba) ha sido usada durante siglos debido a sus propiedades antipiréticas, antiinfl amatorias y analgésicas. 5 Varios grados del extracto están comercialmente disponibles y contienen, por ejemplo, 15, 25 o 50 % de salicina, sustancia que fi nalmente se metaboliza en ácido acetilsalicílico. 5 Los antiinfl amatorios no esteroideos (AINE) son responsables de 21 a 25 % de los eventos adversos relacionados con el consumo de medicamentos y constituyen la segunda causa de hipersensibilidad a fármacos en el mundo y la primera en Latinoamérica. ...
... 5 Varios grados del extracto están comercialmente disponibles y contienen, por ejemplo, 15, 25 o 50 % de salicina, sustancia que fi nalmente se metaboliza en ácido acetilsalicílico. 5 Los antiinfl amatorios no esteroideos (AINE) son responsables de 21 a 25 % de los eventos adversos relacionados con el consumo de medicamentos y constituyen la segunda causa de hipersensibilidad a fármacos en el mundo y la primera en Latinoamérica. 6,7 Las reacciones que provocan pueden manifestarse con una variedad de síntomas (respiratorios, cutáneos, anafi láctico y de otros órganos específi cos), los cuales pueden presentarse con diferentes tiempos de inicio después de la ingesta del fármaco. ...
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Are natural analgesic products safe in patients with allergy to non-steroidal anti-infl ammatory drugs? ¿Son seguros los productos naturales analgésicos en los pacientes con alergia a los antiinfl amatorios no esteroideos? Este artículo debe citarse como: Chérrez-Ojeda I, Calderón JC, Calero E, Terán C, Chérrez A. ¿Son seguros los productos naturales analgésicos en los pacientes con alergia a los antiinfl amatorios no esteroideos? Rev Alerg Mex Abstract Background: Nonsteroidal anti-infl ammatory drugs (NSAID)-induced hypersensitivity reactions can be clinically apparent with asthma, rhinosinusitis, anaphylaxis or rash. Although natural anti-infl ammatory products can have similar components, they are not subjected to rigorous quality control standards. Case report: The case is presented of a 22-year-old female with NSAID allergy who attended with facial and laryngeal angioedema associated with pruritus in eyelids and pharynx. She developed these symptoms fi fteen minutes after taking an over-the-counter (OTC) natural anti-infl ammatory product. She received treatment with epinephrine, antihistamines and corticosteroids. Conclusion: Diff erent natural anti-infl ammatory products are freely available both OTC and online. Some contain dangerous substances that can cause important, and even lethal. side eff ects. Allergologists, dermatologists and general practitioners should be able to recognize that the consumption of these products, which is widely spread, can cause angioedema.
... 4 La corteza del sauce blanco (Salix alba) ha sido usada durante siglos debido a sus propiedades antipiréticas, antiinfl amatorias y analgésicas. 5 Varios grados del extracto están comercialmente disponibles y contienen, por ejemplo, 15, 25 o 50 % de salicina, sustancia que fi nalmente se metaboliza en ácido acetilsalicílico. 5 Los antiinfl amatorios no esteroideos (AINE) son responsables de 21 a 25 % de los eventos adversos relacionados con el consumo de medicamentos y constituyen la segunda causa de hipersensibilidad a fármacos en el mundo y la primera en Latinoamérica. ...
... 5 Varios grados del extracto están comercialmente disponibles y contienen, por ejemplo, 15, 25 o 50 % de salicina, sustancia que fi nalmente se metaboliza en ácido acetilsalicílico. 5 Los antiinfl amatorios no esteroideos (AINE) son responsables de 21 a 25 % de los eventos adversos relacionados con el consumo de medicamentos y constituyen la segunda causa de hipersensibilidad a fármacos en el mundo y la primera en Latinoamérica. 6,7 Las reacciones que provocan pueden manifestarse con una variedad de síntomas (respiratorios, cutáneos, anafi láctico y de otros órganos específi cos), los cuales pueden presentarse con diferentes tiempos de inicio después de la ingesta del fármaco. ...
Article
Full-text available
Background: Nonsteroidal anti-inflammatory drugs (NSAID)-induced hypersensitivity reactions can be clinically apparent with asthma, rhinosinusitis, anaphylaxis or rash. Although natural anti-inflammatory products can have similar components, they are not subjected to rigorous quality control standards. Case report: The case is presented of a 22-year-old female with NSAID allergy who attended with facial and laryngeal angioedema associated with pruritus in eyelids and pharynx. She developed these symptoms fifteen minutes after taking an over-the-counter (OTC) natural anti-inflammatory product. She received treatment with epinephrine, antihistamines and corticosteroids. Conclusion: Different natural anti-inflammatory products are freely available both OTC and online. Some contain dangerous substances that can cause important, and even lethal. side effects. Allergologists, dermatologists and general practitioners should be able to recognize that the consumption of these products, which is widely spread, can cause angioedema.
... 4 La corteza del sauce blanco (Salix alba) ha sido usada durante siglos debido a sus propiedades antipiréticas, antiinfl amatorias y analgésicas. 5 Varios grados del extracto están comercialmente disponibles y contienen, por ejemplo, 15, 25 o 50 % de salicina, sustancia que fi nalmente se metaboliza en ácido acetilsalicílico. 5 Los antiinfl amatorios no esteroideos (AINE) son responsables de 21 a 25 % de los eventos adversos relacionados con el consumo de medicamentos y constituyen la segunda causa de hipersensibilidad a fármacos en el mundo y la primera en Latinoamérica. ...
... 5 Varios grados del extracto están comercialmente disponibles y contienen, por ejemplo, 15, 25 o 50 % de salicina, sustancia que fi nalmente se metaboliza en ácido acetilsalicílico. 5 Los antiinfl amatorios no esteroideos (AINE) son responsables de 21 a 25 % de los eventos adversos relacionados con el consumo de medicamentos y constituyen la segunda causa de hipersensibilidad a fármacos en el mundo y la primera en Latinoamérica. 6,7 Las reacciones que provocan pueden manifestarse con una variedad de síntomas (respiratorios, cutáneos, anafi láctico y de otros órganos específi cos), los cuales pueden presentarse con diferentes tiempos de inicio después de la ingesta del fármaco. ...
Article
Full-text available
Background: Nonsteroidal anti-inflammatory drugs (NSAID)-induced hypersensitivity reactions can be clinically apparent with asthma, rhinosinusitis, anaphylaxis or rash. Although natural anti-inflammatory products can have similar components, they are not subjected to rigorous quality control standards. Case report: The case is presented of a 22-year-old female with NSAID allergy who attended with facial and laryngeal angioedema associated with pruritus in eyelids and pharynx. She developed these symptoms fifteen minutes after taking an over-the-counter (OTC) natural anti-inflammatory product. She received treatment with epinephrine, antihistamines and corticosteroids. Conclusion: Different natural anti-inflammatory products are freely available both OTC and online. Some contain dangerous substances that can cause important, and even lethal. side effects. Allergologists, dermatologists and general practitioners should be able to recognize that the consumption of these products, which is widely spread, can cause angioedema.
... It contains Salicin, which is converted to acetylsalicylic acid inside intestine. The willow bark has been used to treat pain, inflammation, osteoarthritis, aches and to reduce fevers [129]. In fact, short period of willow bark supplement (240 mg salicin/day for 2-week) decreases joint pain in patients with osteoarthritis [130], while longer period (6-week) does not seem to improve this symptom [131]. ...
... However, no studies were conducted to investigate the ergogenic effect of this herb on muscle performance in athletes, which present a limitation of his actual use in sports field. Shara and Stohs [129] suggested that adverse effects appear to be minor when compared to non-steroidal antiinflammatory drugs such as aspirin. ...
Article
Full-text available
The use of herbal medicinal products and supplements has increased during last decades. At present, some herbs are used to enhance muscle strength and body mass. Emergent evidence suggests that the health benefits from plants are attributed to their bioactive compounds such as Polyphenols, Terpenoids, and Alkaloids which have several physiological effects on the human body. At times, manufacturers launch numerous products with banned ingredient inside with inappropriate amounts or fake supplement inducing harmful side effect. Unfortunately up to date, there is no guarantee that herbal supplements are safe for anyone to use and it has not helped to clear the confusion surrounding the herbal use in sport field especially. Hence, the purpose of this review is to provide guidance on the efficacy and side effect of most used plants in sport. We have identified plants according to the following categories: Ginseng, alkaloids, and other purported herbal ergogenics such asTribulus Terrestris, Cordyceps Sinensis. We found that most herbal supplement effects are likely due to activation of the central nervous system via stimulation of catecholamines. Ginseng was used as an endurance performance enhancer, while alkaloids supplementation resulted in improvements in sprint and cycling intense exercises. Despite it is prohibited, small amount of ephedrine was usually used in combination with caffeine to enhance muscle strength in trained individuals. Some other alkaloids such as green tea extracts have been used to improve body mass and composition in athletes. Other herb (i.e. Rhodiola, Astragalus) help relieve muscle and joint pain, but results about their effects on exercise performance are missing.
... Salicylic acid (SA) is a phenolic phytohormone which is found in plants (White willow (Salix alba). This natural source of salicylic acid (Fig. 1) plays role in plant growth and development, photosynthesis, transpiration, ion uptake and transport [1]. SA also induces specific changes in leaf anatomy and chloroplast structure. ...
... It plays a role in the resistance to pathogens by inducing the production of pathogenesis-related proteins [3]. It is involved in the systemic acquired 1 Young Researchers and Elite Club, Shiraz Branch, Islamic Azad University, Shiraz, Iran * Mohamadpour.f.7@gmail.com © Mohamadpour F., 2019 resistance (SAR) in which a pathogenic attack on one part of the plant induces resistance in other parts [4]. ...
... It contains Salicin, which is converted to acetylsalicylic acid inside intestine. The willow bark has been used to treat pain, inflammation, osteoarthritis, aches and to reduce fevers [129]. In fact, short period of willow bark supplement (240 mg salicin/day for 2-week) decreases joint pain in patients with osteoarthritis [130], while lon- ger period (6-week) does not seem to improve this symptom [131]. ...
... However, no studies were conducted to investigate the ergogenic effect of this herb on muscle performance in athletes, which present a limitation of his actual use in sports field. Shara and Stohs [129] suggested that adverse effects appear to be minor when compared to non-steroidal anti- inflammatory drugs such as aspirin. ...
Article
ABSTRACT Background: Nutritional practices targeting improved exercise performance and training adaptations are considered to be ergogenic aids. Currently, the majority of attention is given to the macronutrients carbohydrate and protein, while micronutrients are considered to a lesser scale. Though literature does exist, very little attention is given to fruit and respective fruit extracts. Scope and Approach: Fruit as a whole, contains macro- and micronutrients, fiber, minerals, vitamins, a number of bioactive phytochemicals, including phenolic compounds such as anthocyanins and ellagitannins and intuitively should be considered a regular part of an athletes diet. The primary aim of this review is to review the extant literature and provide a narrative overview of studies involving fruit, respective fruit extracts, and their effects on exercise performance and recovery. Included in this review are blackcurrant, grapes, pomegranate, cherry, banana, watermelon and blueberry. Key Findings and Conclusions: There appears to be a consistent pattern in the literature for fruits extracts to improve antioxidant capacity. Data supporting performance improvements are less compelling. While the health affects of whole fruits is intuitive, there is a paucity of studies examining whole fruits as part of an athletic diet. Key Words: Fruit; Fruit Extracts; Anti-oxidant; Exercise; Sport; Performance
... It is a precursor to acetylsalicylic acid and has documented anti-inflammatory properties [12], including an inhibitory effect on TNF-a [13]. Whereas TNF-a inhibitors are typically administered via injection, salicin is ingested [14] and has no noted serious side effects [15,16], fewer even than its synthetic counterpart, aspirin, and other non-steroidal anti-inflammatory drugs (NSAIDs), all of which can damage the gastrointestinal mucosa [17]. ...
... Perhaps most interestingly, we examined the underlying mechanism of these relationships and found that NRF2 accounted for much of salicin's effects on cellular senescence in endothelial cells. NRF2, therefore, can be considered a key mechanism underlying the effectiveness of salicin as a preventive treatment for vascular disease.Brief human trials have found salicin to have minimal side effects comparable to, or perhaps even less than, aspirin and other NSAIDs, specifically when it comes to gastrointestinal side-effects [15,16]. However, as many of the negative effects of NSAID and steroid treatment are longterm, it is important for future research to explore the longterm impact of taking salicin, both in terms of its preventive effects and its potential side effects. ...
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Cellular senescence is strongly tied to vascular disease. The current study aims to examine ways that endothelial cellular senescence can be prevented and the mechanisms by which prevention of senescence occurs. Human umbilical vein endothelial cells were exposed to TNF-α to induce senescence; then salicin was administered in two doses – 50 and 100 µM – to establish a dose-dependent effect of salicin on SA-β-Gal, G1 cell cycle arrest, expression of p21 and PAI-1, p53 acetylation at K382, NRF2 and oxidative stress. NRF2 was examined as a mediating mechanism of salicin’s impact on cellular senescence and was found to account for salicin’s impact on SA-β-Gal, p21, PAI-1 and p53. Together, these results provide a compelling case that salicin has a substantial impact on numerous factors tied to cellular senescence in human endothelial cells. Thus, treatment with salicin may hold promise as a means of preventing aging-related vascular disease. Furthermore, salicin appears to operate via a functional pathway that is different from that affected by anti-inflammatory drugs (e.g. aspirin).
... Numbers of clinical human and animal trials with willow bark extracts provide some confusing results. Some prove its effectiveness while the others not, but general conclusion is rather supporting the view that willow bark extract is effective as an analgesic and anti-inflammatory agent (Shara and Stohs 2015). ...
... Proper selection of extraction solvents is essential for isolation of wide range phytochemicals having different polarities. The composition of the final extract may influence extract efficacy when used in therapy or as active food ingredient (Shara and Stohs 2015) Recently, significant emphasis on developing ''green'' technologies of extraction is more often observed (Attard et al. 2015). Non-toxic, cheap and environmentally friendly solvents and their lower amounts are very desirable in the case of clean technology of extraction. ...
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The use of natural compounds derived from agricultural crops and other plants as health promoting chemicals gains tremendous growing interest in various industrial sectors as well as among people worldwide. These chemicals have been more and more employed by the food industry as food additives, functional food ingredients, nutraceuticals, by feedstuffs industry, but also by the cosmetic and pharmaceutical industries. The general idea for this interest is to use natural products as potential alternatives to synthetic chemicals. On the other hand, some plants characterized by high yield and being used as energy crops also contained significant amount of bioactive compounds. This review focuses on the wide spectrum of the phytochemicals present in available biomass plants. It is supposed that extraction of bioactive chemicals from energy crops before their energetic use may increase economical effectiveness, providing simultaneously a double benefit in the form of phytochemicals and bioenergy as value added products. This remains in line with bioeconomy, which is defined by European Commission as “the production of renewable biological resources and the conversion of these resources and waste streams into value added products, such as food, feed, bio-based products and bioenergy”. However, the issue is still a challenging effort due to the high costs, technology readiness and regulatory hurdles.
... Willow bark was included as part of the Materia Medica in the first volume of the U. S. Pharmacopeia published in 1820 [6]. Today, willow bark is used for the treatment of pain, particularly, LBP, osteoarthritis (OA), headaches, and inflammatory conditions such as tendinitis and bursitis [7]. ...
... Fig. 3Chemical structures of some salicylate derivatives found in willow bark: salicin (1); salicylaldehyde (2); salicylic acid (3); acetylsalicylic acid (4); salicortin (5); 2′-O-acetylsalicortin (6); (−)-tremulacin(7). ...
Article
Willow bark (Salix spp.) is an ingredient in some dietary supplements. No serious adverse effects were reported from trials of willow bark extracts delivering 120 – 240 mg salicin (the purported active constituent) daily for up to 8 weeks. All studies involved adults only; none involved special subpopulations such as pregnant or breastfeeding women, or children. The most common adverse effects associated with willow bark are gastrointestinal; a few allergic reactions were also reported. Some publications advise caution when taking willow bark. There is a risk of increased bleeding in vulnerable individuals, salicylates cross the placenta and are eliminated slowly in newborns, some persons are sensitive or allergic to aspirin, and children are at risk of Reye syndrome. Concurrent use with other salicylate-containing medicines increases these risks. Metabolism of 240 mg salicin from willow bark could yield 113 mg of salicylic acid, yet dietary supplement products are not required to be labeled with warnings. In contrast, over-the-counter low-dose aspirin (81 mg strength), which delivers 62 mg salicylic acid, is required by law to include cautions, warnings, and contraindications related to its use in pregnant and nursing women, children, and other vulnerable subpopulations, e.g., those using anticoagulants. In the interest of protecting public health, the United States Pharmacopeia has included a cautionary labeling statement in the United States Pharmacopeia Salix Species monograph as follows: “Dosage forms prepared with this article should bear the following statement: ‘Not for use in children, women who are pregnant or nursing, or by persons with known sensitivity to aspirin.’”
... For the initial experiments conducted in this study, we used willow bark extract (WBE). Willow bark (Salix sp., Salicaceae) has been used for thousands of years as an anti-inflammatory, analgesic and antipyretic agent, and the therapeutic use of standardized willow bark extracts against lower back pain is well-established by clinical trials (Shara and Stohs, 2015) 1 . Willow bark extracts are usually standardized to their content of salicylic alcohol derivatives with the main constituent salicin. ...
... Willow bark extracts are usually standardized to their content of salicylic alcohol derivatives with the main constituent salicin. However, their clinical efficacy cannot be fully explained by the presence of this group of constituents, and other compound classes like flavonoids and proanthocyanidin derivatives are thought to contribute to the activity as well Shara and Stohs, 2015). Therefore, in the current study, we aimed to investigate the whole range of constituents and their putative microbial metabolites by a metabolomics approach, and to elucidate the interplay between the extract's constituents and human gut microbiota by 16S rRNA sequencing. ...
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Herbal preparations are complex mixtures of natural products, many of which are able to reach the distal gut due to low oral bioavailability. There, they can influence the microbial communities, and can be metabolized into potentially absorbable bioactive compounds by the intestinal bacteria. This aspect has often been disregarded when searching for the active principles of medicinal plants and herbal medicinal products. The aim of this study was to establish an interdisciplinary platform to unravel interactions of herbal medicine and intestinal microbiota, using a combined LC-MS metabolomics and 16S rRNA microbiome sequencing approach. Willow bark extract (WBE), a herbal medicinal product with a long history of traditional use and a well-established anti-inflammatory activity, was incubated with human fecal suspension under anoxic conditions. Samples were taken after 0.5, 4, and 24 h of incubation. Microbiome analyses revealed that incubation with WBE had a marked effect on microbial community composition and functions. For example, the proportion of Bacteroides sp. was clearly enhanced when the fecal sample used in this study was incubated with WBE. LC-MS analysis showed that WBE constituents were readily metabolized by fecal bacteria. Numerous microbial metabolites could be annotated, allowing the construction of putative microbial degradation pathways for the main groups of WBE constituents. We suggest that studies of this type help to increase the knowledge on bioactive principles of medicinal plants, since gut microbial metabolites might have been underestimated as a source of bioactive compounds in the past.
... For the initial experiments conducted in this study, we used willow bark extract (WBE). Willow bark (Salix sp., Salicaceae) has been used for thousands of years as an anti-inflammatory, analgesic and antipyretic agent, and the therapeutic use of standardized willow bark extracts against lower back pain is well-established by clinical trials (Shara and Stohs, 2015) 1 . Willow bark extracts are usually standardized to their content of salicylic alcohol derivatives with the main constituent salicin. ...
... Willow bark extracts are usually standardized to their content of salicylic alcohol derivatives with the main constituent salicin. However, their clinical efficacy cannot be fully explained by the presence of this group of constituents, and other compound classes like flavonoids and proanthocyanidin derivatives are thought to contribute to the activity as well Shara and Stohs, 2015). Therefore, in the current study, we aimed to investigate the whole range of constituents and their putative microbial metabolites by a metabolomics approach, and to elucidate the interplay between the extract's constituents and human gut microbiota by 16S rRNA sequencing. ...
... Adverse effects of bark extracts appear to be minimal. The primary risk may relate to allergic reactions in salicylate-sensitive individuals [57,58]. ...
... Generally, the extracts of Salix bark have been regarded as being safe, although sensitive individuals may get allergic reactions due to salicylates. Studies have also shown that there are other salicin-related compounds that contribute to various effects, which may also concern cytotoxicity [57]. ...
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Biocolourants have been investigated as alternatives to synthetic dyes. However, natural origin per se is not a label of harmlessness and research is needed to obtain safe dyes. We studied the cytotoxicity of the extracts from fungal (Cortinarius semisanguineus, Tapinella atrotomentosa) and plant (Tanacetum vulgare, Salix phylicifolia) sources and the woollen fabrics dyed with the extracts. Cytotoxicity in vitro using hepa-1 mouse hepatoma cells for 24 h and 72 h exposure was observed as the highest tolerated dose. All biocolourants produced intensive colour on fabrics with fastness properties from moderate to good. The Salix and Cortinarius samples did not show any cytotoxic effects, whereas the Tanacetum and Tapinella samples had slightly higher test values but were not interpreted as being significantly toxic. Higher than zero values of the undyed fabrics showed the importance of examining their toxicity as well. It was found that the cytotoxicity of the samples dyed with the biocolourants did not differ significantly from the undyed wool fabric. The concentrations of dyes used in the assays were very low, imitating the dose of the user. In addition to colouring properties, natural dyes may have pharmaceutical and antibacterial properties which would enhance the interest in using them in products for added value. (This article belongs to the Special Issue Fungal Secondary Metabolites)
... So far, there are many in vivo and in vitro studies that have proved the antioxidant properties of willow extracts [7][8][9]. A good antibacterial activity of Salix alba was reported [10], positively correlated with its antioxidant potential [11]. ...
... Data on total phenolic content of Salix alba powder used in this study revealed a high level of TPC. There are many studies showing that Salix alba bark is a natural source of phenolic compounds with antioxidant activity [8,9,11]. Compared to data reported by [6] on total phenolic content of ethanolic extracts of S. alba bark, our results are 2.4 times higher. ...
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The paper aimed to analyse the effect of dietary Salix alba L. bark powder (SAB) on broiler performance in terms of oxidative stress parameters in liver and gut microflora. One hundred and eighty Cobb 500 broiler chicks (14 days) were allotted to three homogeneous treatments (SAB 0%; SAB 0.025%; SAB 0.05%). The broilers were housed in an environmentally controlled space (10 replicates, six broilers/replicate). Compared to dietary control treatment (SAB 0%), the other treatments included 0.025% SAB (SAB 0.025%) and 0.05% SAB (SAB 0.05%). The results showed that SAB powder used in broiler diet had a high total phenolic content. Regarding the performance results, significant differences between experimental and control treatments were recorded only for average daily feed intake (35–42 days). The broilers fed with SAB powder had a significantly lower hepatic level of malondialdehide and glutathione, a higher total antioxidant capacity than those fed control treatment, and demonstrated a positive effect on the development of non-pathogenic bacteria (lactobacilli) but a decrease in the population of pathogenic ones (E. coli, staphylococci). Our findings suggested that dietary 0.05% SAB powder could be an effective solution to impede the oxidative stress in broiler liver and to improve gut microflora.
... S. alba (white willow) was chosen for risk assessment. Apart from its use in medicine (Shara and Stohs, 2015) and as a food supplement, Salix bark is used in plant protection and is registered in the European Union (EU) as a basic substance (Marchand, 2015). Salix bark uses as a fungicide, having an eliciting action on the crop's self-defence mechanisms, are approved (Matyjaszczyk, 2018). ...
... Tree bark is not typical component of meals in Europe and, when discussing the topic, people were generally surprised that it is consumed in food at all. However, it is consumed as an ingredient of weight-loss supplements (Sharpe et al., 2006) as well as sports performance products (Shara and Stohs, 2015). Some food supplements contain white willow bark as one of numerous components, plus willow bark is sold for human consumption as a powder. ...
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This Technical Report contains a description of the activities within the work programme of the EUFORA Fellowship on the risk assessment of white willow in food. The bark of different varieties of willow has had a long history of medical use as a means to reduce fever and as a painkiller. Willow bark is also used in weight loss and sports performance food supplements. The labelling of these products usually does not mention any restrictions to the length of use. The recommended doses for foods differ, sometimes exceeding doses recommended for pharmaceuticals. A systematic literature review on adverse effects potentially resulting from oral exposure to white willow (Salix alba) was performed. The aim of the study was to assess the risk for humans when consuming white willow bark in food. The preliminary results show that despite the long history of use only very limited data on toxicity of white willow bark are available. However, anaphylactic reactions in people with a history of allergy to salicylates may occur. Some other adverse effects of salicylates are considered to be of low relevance for the long-time consumption of white willow bark, mainly due to relatively low concentrations of salicin and the presence of compounds with gastroprotective action. However, it seems that the content of heavy metals, mainly cadmium, should be further addressed in risk assessment of white willow bark in food.
... However, with a variety of analgesic ingredients, Pain Bloc-R matched the efficacy of acetaminophen potentially by targeting multiple pain pathways with its ingredients. Vitamin D [15], white willow bark [16], and Angelica root extract [17] serve as anti-inflammatory agents. The antioxidant properties of acetyl L-carnitine and Benfotiamine can potentially reduce neuroinflammation and alleviate pain caused by peripheral neuropathy [41]. ...
Article
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The lack of effective treatment for chronic discomfort without negative side effects highlights the need for alternative treatments. Pain Bloc-R is a natural health product composed of vitamins B6, B12, D, white willow bark extract, Angelica root extract, acetyl L-carnitine HCl, caffeine, L-theanine, Benfotiamine, and L-tetrahydropalmatine. The objective of this study was to compare the effects of Pain Bloc-R, acetaminophen, and placebo on unresolved aches and discomfort as assessed by the brief pain inventory (BPI) and modified Cornell musculoskeletal discomfort questionnaires. This randomized, double-blind, placebo-controlled, crossover study consisted of three 7-day periods with Pain Bloc-R, acetaminophen, or placebo, each separated by a 7-day washout. Twenty-seven healthy adults (ages 22–63 years) were randomized to receive the three interventions in different sequences. The BPI “pain at its worst” scores were significantly lower when participants took Pain Bloc-R than when they took acetaminophen (21.8% vs. 9.8% decrease, p = 0.026) after seven days of supplementation. Pain Bloc-R achieved a significant improvement in the “pain at its least” score, significantly decreased the interference of discomfort in walking, and significantly decreased musculoskeletal discomfort total scores (34%, p = 0.040) after seven days. In a post hoc subgroup analysis based on age and gender, male participants ≤45 years taking Pain Bloc-R reported significant reductions in pain severity and pain interference vs. acetaminophen. Pain Bloc-R performed as well as acetaminophen in managing unresolved non-pathological pain in otherwise healthy individuals.
... Recent years have witnessed the growing popularity of natural remedies, which increased the demand for high-quality herbal material [1,2]. Willow bark is commonly used in the production of natural alternatives to aspirin because of similar medicinal properties to acetylsalicylic acid (synthetic aspirin): it delivers analgesic, antipyretic, anti-inflammatory and anti-rheumatic effects [3][4][5], and it is used as a cold remedy and an alternative treatment for rheumatic diseases [6][7][8][9]. ...
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In this study, the genetic diversity and structure of 13 natural locations of Salix purpurea were determined with the use of AFLP (amplified length polymorphism), RAPD (randomly amplified polymorphic DNA) and ISSR (inter-simple sequence repeats). The genetic relationships between 91 examined S. purpurea genotypes were evaluated by analyses of molecular variance (AMOVA), principal coordinates analyses (PCoA) and UPGMA (unweighted pair group method with arithmetic mean) dendrograms for both single marker types and a combination of all marker systems. The locations were assigned to distinct regions and the analysis of AMOVA (analysis of molecular variance) revealed a high genetic diversity within locations. The genetic diversity between both regions and locations was relatively low, but typical for many woody plant species. The results noted for the analyzed marker types were generally comparable with few differences in the genetic relationships among S. purpurea locations. A combination of several marker systems could thus be ideally suited to understand genetic diversity patterns of the species. This study makes the first attempt to broaden our knowledge of the genetic parameters of the purple willow (S. purpurea) from natural location for research and several applications, inter alia breeding purposes.
... WWB suppresses inflammatory molecules and reduces oxidative stress in human endothelial cells [11,12] . In vitro and in vivo studies evidenced that the anti-inflammatory activity of WWB is associated with the downregulation of the inflammatory mediators TNF-α and NF-κB [13] . In 2010, a paper by Gopaul et al. [14] described the ability of salicin to reduce the visible signs of skin aging when applied topically, thus showing anti-aging capabilities. ...
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Background: Acne vulgaris is a common skin defect, usually occurring during adolescence, but often it can persist in adults leaving permanent face scarring. Acne is usually treated with topical drugs, oral antibiotics, retinoids, and hormonal therapies, but medicinal plants are increasingly employed. Objective: To investigate the protective role of white willow bark (WWB) and 1,2-decanediol (DD) on the damage caused by lipopolysaccharides (LPS) on human adult keratinocytes (HaCaT). Methods: HaCaT were exposed to LPS alone or in association with WWB and DD. Epidermal viability, metabolic modulation, inflammatory activity, and cell migration were assessed with both common standardized protocols or high-throughput screening systems. Results: The preincubation of HaCaT with WWB and DD (used separately or in combination) differently prevented the alterations induced by LPS on HaCaT in terms of growth factor release (IGF, EGF, VEGF), cytokine production (IL-1α, IL-6, IL-8), or expression of the transcription factor FOXO-I. Moreover, they partially restore wound repair lowered by LPS. Conclusions: These results suggest that both natural compounds were able to differently affect several functions of LPS-stressed keratinocytes suggesting their potential role for the prevention of acne vulgaris, without adverse effects.
... Active phytochemicals. Although traditionally salicin was considered as the active principle, there are opinions that this substance cannot explain the whole range of effects of WBE, and that other phytochemicals might be involved, such as polyphenols and flavonoids, which showed inhibitory activity on COX-2 and decreased synthesis of pro-inflammatory mediators in vitro, in human monocytes and differentiated macrophages [87,88,[94][95][96]. ...
Article
Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even though many of them have been proven effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarize the available scientific information on the following joint-friendly medicinal plants, which have been tested in human studies: Arnica montana, Boswellia spp., Curcuma spp., Equisetum arvense, Harpagophytum procumbens, Salix spp., Sesamum indicum, Symphytum officinalis, Zingiber officinalis, Panax notoginseng, and Whitania somnifera.
... Oni djeluju antioksidativno, najvjerojatnije sinergistički sa salicinom, te antiinfl amatorno i analgetski (64). Analgetsko djelovanje kore vrbe je vrlo izraženo, dok su nuspojave minimalne u usporedbi s onima tijekom uporabe acetilsalicilne kiseline (65). ...
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This article represents an overview of the most common used medicinal plant preparations in the self-treatment of viral warts. These plants (Chelidonium mains, Ficus carica, V.juja occidentalism Allium sativum, Melaleuca alternifolia, Melaleuca quinquenervia, Cinnamomum camphora cbemotype cineol, Ricinus communis, Salix alba, Citrus limon, Drosera rotundifolia and Taraxacum officinale) contain various chcmical compounds (flavonoids, phenolic acids, essential oils, tannins, alkaloids, coumarins, proteolytic enzymes, phenolic heterosides, vitamins, polysaccharides etc.) that contribute to their activity. Many of these herbs have a traditional medi-cinal use and some have even been tested in clinical trials. Some plants are shown to have proteolytic enzymes that soften the wart tissue, while others have antiviral substances.
... It is composed of Duhuo Jisheng decoction (a traditional herbal formula), nattokinase and the extraction of Salix alba cortex. All of these components have been shown to be effective in delaying degeneration in human intervertebral disc and potentiating thrombolysis and anti-coagulation profiles, [14][15][16] which may be effective in the management of cervical radiculopathy. Therefore, this study was aimed to evaluate the efficacy and safety of TD0019, a compound traditional Vietnamese herbal medicine, in the treatment of cervical radiculopathy. ...
Article
Introduction Cervical radiculopathy causes chronic pain and reduces patients’ quality of life. Oral analgesics are commonly used but only after careful consideration due to their complications. TD0019, a Vietnamese herbal medicine, composed of Duhuo Jisheng decoction, nattokinase and an extract of Salix alba cortex has shown evidence of some benefits for these patients in pre-clinical and phase-1 studies. This study aimed to evaluate the efficacy and safety of TD0019 in the treatment of cervical radiculopathy. Methods In this double-blind phase-2 trial, 180 patients with symptomatic cervical radiculopathy were randomized to either group 1 with intended dose of TD0019, group 2 with a higher dose (1.5 times the intended dose), or group 3, a placebo. The primary efficacy endpoint was the neck-specific disability score according to the Neck Disability Index (NDI) questionnaire. The safety endpoint included adverse events (AEs) and serious adverse events (SAEs). All patients received the drugs for 30 days and were followed for 60 days. Results Baseline characteristics were similar for the three groups. The reduction of NDI score from baseline to the end of study was greatest for group 2 (from 17.6 ± 7.2 to 4.8 ± 5.1), followed by group 1 (from 16.1 ± 6.9 to 5.4 ± 5.1) and placebo group (from 15.6 ± 6.2 to 7.8 ± 6.8), with a significant decrease for both groups compared to placebo. The percentage of AEs was comparable among three groups and no SAEs occurred. Conclusions TD0019 was superior to placebo for the reduction of symptoms with similar rates of side effects. The higher dose is more beneficial than the intended dose. This herbal medicine may be a potential alternative analgesic in the treatment of cervical radiculopathy.
... Salicin is β-glycoside that contains D-glucose. It is extracted from the bark of Salix alba and possesses an anti-inflammatory role [91]. Salicin generates its pharmacological response by modulating the inflammatory process and inhibition of activation of activation of NF-kB, and subsequent down regulating COX-2 expression [92]. ...
... Contrary to bark, leaves of many Salix species are mainly not studied and there is a general lack of data concerning their medicinal properties. While pharmacological effects of willow bark are mainly attributed to salicin as the major active constituent, newer studies suggest that these effects cannot be explained solely by the presence of salicin and its derivatives, but that other compounds such as flavonoids (flavan-3-ols) and simple phenols (phenolic acids) synergistically contribute to the therapeutic effects of willow bark [4][5][6][7]. Certain Salix species are known to exhibit strong antioxidant activity in many in vitro systems [8,9]. The anti-inflammatory effect of some phenolic acids has been associated with their antioxidant activity [10]. ...
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The genus Salix includes about 500 different, mainly woody species with potentially significant medicinal values. The aim of this study was to evaluate the chemical composition and antioxidant activity of little-studied bark and leaves extracts of seven different species of the genus Salix, and to examine the acetylcholinesterase (AChE) inhibitory potential of selected compounds. The extracts were characterized by High Pressure Liquid Chromatography (HPLC). Total phenolics and flavonoids content was determined spectrophotometrically and the antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and hydroxyl radical (•OH) scavenging assays. Molecular docking studies were conducted in order to elucidate the interaction and binding affinity between selected compounds of willow bark and leaves against AChE. The major components in bark and leaves of most of the species were rutin (1.26–22.09 mg/g), salicin (1.62–17.33 mg/g), chlorogenic acid (0.74–7.53 mg/g) and epicatechin (0.71–4.83 mg/g). The latter three compounds demonstrated significant inhibitory potential against AChE in docking studies. All extracts exhibited notable antioxidant activity as scavengers of both DPPH• and •OH. The obtained results indicate that willow species other than those in commercial use, and not only bark, but willow leaves as well, could be utilized as sources of valuable phytocompounds with antioxidant and neuroprotective properties.
... Salicin is usually described as the analgesic agent found in willow bark, responsible for its pharmacological effects. [1][2][3] However, it was suggested that many of these effects cannot be explained by the presence of salicylic derivatives only and that other compounds such as polyphenols (flavonoids, flavan-3-ols) and simple phenols (phenolic acids) can contribute to the therapeutic effects of willow bark. [4][5][6][7][8] On the other hand, leaves of many Salix species are mainly not studied and are considered as waste product after collection of bark. ...
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Contents of twelve selected bioactive substances and antioxidant potential of Salix caprea L. extracts were compared in its two vegetative organs (bark and leaves) and in terms of different ethanol/water mixtures used for extraction (30-70% aq, ethanol) and extraction time (30 min; 24, 48 and 72 h). The extracts were characterized by High Pressure Liquid Chromatography (HPLC), and total phenolics and flavonoids were determined spectrophotometrically. All secondary metabolites identified in Salix caprea L. extracts (gallic, chlorogenic and vanillic acid, epicatechin, rutin, quercetin and naringenin) were found more accumulated in bark. Salicin and p-hydroxybenzoic acid were detected in bark and ferulic, trans-cinnamic and p-coumaric acid in leaves extracts only. Rutin was most abundant bioactive compound both in bark (1.71 g/100 g of de) and leaves extracts (0.434 g/100 g of de). Bark extract with highest bioactive substances contents was obtained with 70% aq. ethanol as most suitable solvent during extraction time of 48 h. Molecular docking showed salicin to have similar affinity toward COX-2 as acetylsalicylic acid, but lower toward COX-1.
... The first active constituent of willow bark discovered in 1828 was salicin. Today we know that aqueous extracts of willow bark contain at least 11 related salicylate compounds, among them salicin and salicylic acid (reviewed in (Desborough and Keeling, 2017;Shara and Stohs, 2015)). It has previously been shown that salicylate is capable of directly activating AMPK in vivo and in vitro by binding to the beta subunit of the kinase (Hawley et al., 2012). ...
Article
Ethnopharmacological relevance: In different countries and areas of the world, traditional medicine has been and is still used for the treatment of various disorders, including chest pain or liver complaints, of which we now know that they can be linked with altered lipid and cholesterol homeostasis. As ATP-binding cassette transporter A1 (ABCA1) plays an essential in cholesterol metabolism, its modulation may be one of the molecular mechanisms responsible for the experienced benefit of traditional recipes. Intense research activity has been dedicated to the identification of natural products from traditional medicine that regulate ABCA1 expression. Aims of the review: This review surveys natural products, originating from ethnopharmacologically used plants, fungi or marine sources, which influence ABCA1 expression, providing a reference for future study. Materials and methods: Information on regulation of ABCA1 expression by natural compounds from traditional medicine was extracted from ancient and modern books, materia medica, and electronic databases (PubMed, Google Scholar, Science Direct, and ResearchGate). Results: More than 60 natural compounds from traditional medicine, especially traditional Chinese medicine (TCM), are reported to regulate ABCA1 expression in different in vitro and in vivo models (such as cholesterol efflux and atherosclerotic animal models). These active compounds belong to the classes of polyketides, terpenoids, phenylpropanoids, tannins, alkaloids, steroids, amino acids and others. Several compounds appear very promising in vivo, which need to be further investigated in animal models of diseases related to ABCA1 or in clinical studies. Conclusion: Natural products from traditional medicine constitute a large promising pool for compounds that regulate ABCA1 expression, and thus may prevent/treat diseases related to cholesterol metabolism, like atherosclerosis or Alzheimer's disease. In many cases, the molecular mechanisms of these natural products remain to be investigated.
... Zabihi et al. (2018) show that although salicin is the main active compound of the willow bark, its polyphenols and flavonoids must receive due attention. Other authors (Sulaiman et al., 2013;Shara & Stohs, 2015) showed that willow bark contains flavonoids and polyphenols that contribute synergistically to the beneficial effects of Salix alba and may be more important than those of synthetic salicylic acid. Salix alba extract has free radical scavenging activity and can be used as a radical inhibitor or scavenger, with the possibility of acting as a primary antioxidant (Sulaiman et al., 2013). ...
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A study was conducted to determine the effects of dietary hydroalcoholic willow bark extract powder (HWE) supplemented to broilers (14-42 days old) that were exposed to heat stress, on the performance, serum biochemical parameters, liver oxidative status and caecal microflora. The feeding trial was conducted on 120 Cobb 500 broilers (14 days old), assigned to three treatments (T0, T25, and T50), each treatment consisting of eight replicates (five chicks per replicate). The broilers were housed in an experimental hall at a 32 °C constant temperature and 23 hours light regimen. Unlike the dietary control treatment (T0), the experimental treatments were supplemented with 25 g HWE powder/100 kg diet (T25), and 50 g HWE powder 100 kg diet (T50), respectively. Dietary HWE powder did not affect the broilers' performance significantly (14-42 days). A significantly lower amount of malondialdehyde was noticed in the liver of broilers from T25 and T50 treatments in comparison with broilers from T0. Also, the serum cholesterol, triglycerides and alanine aminotransferase were significantly lower in broilers fed with T50, compared with those fed with T0. At 35 and at 42 days, the broilers from T25 and T50 recorded a significantly lower number of E. coli and staphylococci and a higher number of lactobacilli in the caecum than those of T0. It could be concluded that supplementation of dietary HWE powder reduced some of the adverse effects of heat stress, the most effective being the level of 50 g/100 kg diet. ______________________________________________________________________________________
... While dosage of EGCG varies widely based upon species of tea, steeping time, oxidizing time while being processed, a cup of green tea typically contains approximately 50 mg of EGCG while supplement forms may contain much higher concentrations. While green tea is noted to have no severe adverse effects, dosage greater than 10 mg/kg/day can cause hepatic injury in those who are predisposed [46,47]. ...
... In numerous in vitro and in vivo studies, anti-inflammatory effects have been shown for white willow extract, e.g. downregulation of several pro-inflammatory cytokines like TNF-α and inhibition of NF-κB translocation, which supports the data obtained by us [48][49][50]. The anti-inflammatory effects have been credited to salicin [48]. ...
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Herbal extracts represent an ample source of natural compounds, with potential to be used in improving human health. There is a growing interest in using natural extracts as possible new treatment strategies for inflammatory diseases. We therefore aimed at identifying herbal extracts that affect inflammatory signaling pathways through toll-like receptors (TLRs), TLR2 and TLR4. Ninety-nine ethanolic extracts were screened in THP-1 monocytes and HeLa-TLR4 transfected reporter cells for their effects on stimulated TLR2 and TLR4 signaling pathways. The 28 identified anti-inflammatory extracts were tested in comparative assays of stimulated HEK-TLR2 and HEK-TLR4 transfected reporter cells to differentiate between direct TLR4 antagonistic effects and interference with downstream signaling cascades. Furthermore, the ten most effective anti-inflammatory extracts were tested on their ability to inhibit nuclear factor-κB (NF-κB) translocation in HeLa-TLR4 transfected reporter cell lines and for their ability to repolarize M1-type macrophages. Ethanolic extracts which showed the highest anti-inflammatory potential, up to a complete inhibition of pro-inflammatory cytokine production were Castanea sativa leaves, Cinchona pubescens bark, Cinnamomum verum bark, Salix alba bark, Rheum palmatum root, Alchemilla vulgaris plant, Humulus lupulus cones, Vaccinium myrtillus berries, Curcuma longa root and Arctostaphylos uva-ursi leaves. Moreover, all tested extracts mitigated not only TLR4, but also TLR2 signaling pathways. Seven of them additionally inhibited translocation of NF-κB into the nucleus. Two of the extracts showed impact on repolarization of pro-inflammatory M1-type to anti-inflammatory M2-type macrophages. Several promising anti-inflammatory herbal extracts were identified in this study, including extracts with previously unknown influence on key TLR signaling pathways and macrophage repolarization, serving as a basis for novel lead compound identification.
... White willow bark has been employed since time immemorial as an herbal medication for the antiinflammatory, anti-pyretic and analgesics activity. Salicin is predominantly considered as the key constituent for the manifestation of the anti-inflammatory property along with relative salicylates, flavonoids and other polyphenols (Shara M et al., 2015, Setty AR et al., 2005. Anti-inflammation is achieved through the down-regulation of cyclo-oxygenase pathway and NF-kB with the suppression of TNF-α which is an approach equivalent to that of non-steroidal anti-inflammatory drugs particularly aspirin (Maroon JC et al., 2006, Graf J et al., 2000, Bonaterra GA et al., 2010. ...
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Inflammation is a natural strategy of the living body to restrain and overcome the numerous infections, and injuries any damages caused substantially by the external pathogenic invasions or other factors. Despite the beneficial aspects of acute inflammation for healing, prolonged persistence of the inflammatory response can result in redundant consequences like other diseases instigation. Therefore, the anti-inflammatory drugs implemented have the dual property of both healing and non-manifestation of undesirable pain, soreness and edema. Non-steroidal drugs are one of the most substantial and effective anti-inflammatory drugs but their use is limited due to their side effects inclusive of gastrointestinal tract damage and renal destruction. Substitution of these chemical and synthetic drugs is effectively accomplished by herbal and natural anti-inflammatory products. Naturally occurring products like citrus fruits, curcumin, white willow bark and green tea along with their corresponding anti-inflammatory properties are discussed. Apart from herbal sources, animal-derived products like fish oil also serve as a rich source of polyunsaturated fatty acids which extensively assists in the anti-inflammation
... Side effects include allergic reactions and gastrointestinal symp- toms [5]. The main constituents of willow bark with respect to the pharmacological action are phenolic glycosides (e.g., salicin, salicortin, 2′-O-acetylsalicortin, and/or tremulacin) [6,7] although the other secondary metabolites (e.g., polyphenolic compounds) may also participate in the total anti-inflammatory activity [8]. Phenolic glycosides are considered as prodrug compounds that are metabolized to salicylic acid in gastrointestinal tract and liver. ...
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Osteoarthritis (OA) is the most common form of arthritis, which represents a substantial economic burden for society and significantly affects patients' quality of life. Current conventional treatments of OA may be insufficiently effective and unsafe. In an attempt to overcome these limitations, many patients use herbal medicinal products (HMPs) and dietary supplements. A considerable number of herbal drugs and preparations (e.g., willow bark, Salicis cortex; devil's claw root, Harpagophyti radix; blackcurrant leaf, Ribis nigri folium; nettle leaf/herb, Urticae folium/herba; meadowsweet/meadowsweet flower, Filipendulae ulmariae herba/flos; rosemary leaf/oil, Rosmarini folium/aetheroleum; and juniper oil, Juniperi aetheroleum) are traditionally employed to relieve minor articular pain. Active constituents (e.g., sesquiterpene lactones, triterpenic acids, diarylheptanoids, iridoid glycosides, phenolic glycosides, procyanidins, and alkaloids) are not often fully known. Experimental studies suggest that herbal extracts/compounds are able to suppress inflammation, inhibit catabolic processes, and stimulate anabolic processes relevant to OA. Therapeutic benefit of most HMPs is expected solely from the experience of their long-standing traditional use. Efficacy and safety of several HMPs were assessed in clinical trials. The growing body of preclinical and clinical evidence provides rationale for the use of herbal products in the treatment of OA. However, at present, they cannot be recommended to patients with confidence.
... Also, various in vitro studies have shown antioxidant activity of willow extract (Bonaterra et al. 2010;Jukic et al. 2012). The willow bark extract has been used for thousands of years but, despite its long history, few studies on animals have been published, which to support these observations (Shara et al. 2015). ...
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A 28-day feeding trial was conducted on 60, Cobb 500 broilers (14 days), assigned to 2 groups (C, E) housed in an experimental hall (32° C, 23 h light regimen). Compared to the conventional diet C, the experimental diet (E) included 1% white willow bark extract (WBE). At 42 days of age, 6 blood samples /group were collected and 6 broilers/ group were slaughtered and caecal content was collected. The dietary WBE didn’t influence broiler performance. The serum concentrations of glycaemia, cholesterol and triglycerides were lower (P <0.05) in E group than in C group. E broilers had the lowest count (P<0.05) of Enterobacteriaceae, E. coli and staphylococci colony forming units in the caecal content. The inclusion of WBE (1%) in the diet of broilers reared at 32° C had an hypocholesterolemiant and hypoglycaemic effect and reduced the pathogenic bacteria in the caecum.
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Treating patients with osteoarthritis requires careful individualization in order to achieve patient-specific goals, which may vary from obtaining short-term pain relief to achieving long-term maintenance of function or even preservation of cartilage. In response to specific patient goals, the provider makes use of a toolbox of physical, adjunctive, alternative, pharmacologic, and operative interventions. Among the alternative category are the nutraceuticals, which will be reviewed here with particular attention given to those agents with randomized control trial (RCT) data showing statistically significant benefits. Some of these can be used to minimize patient symptoms with very low risks. The safety of these agents is particularly important in treating patients with osteoarthritis as many of the patients are older with significant comorbidities. Further, it is very likely that it will be necessary for the patients to continue treatment for many years.
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This chapter discusses the ethnopharmacological properties, phytochemistry, and culture conditions of the Salix species. Salix aegyptiaca L. (Fam. – Salicaceae) is a deciduous shrub or small tree, and the decoction of leaves or bark infusion of this species is used to cure rheumatic pains in old age people. The leaf decoction mixed with sugar is used by Iranian and Turkish population in depression, neuropathic pain, and rheumatic arthritis. Similarly, S. babylonica infusion of leaves is used to cure rheumatic problems. The other species of Salix possess anti‐inflammatory, anti‐leishmanial, analgesic, astringent, antiviral, and antipyretic activities. The leaves of S. cinerea and S. viminalis have been cultured on Murashige and Skoog culture medium with supplementation of glutamine, casein hydrolysate, benzyl adenine, indole‐3‐butyric acid, and sucrose for induction of callus, and maximum cell biomass has been obtained.
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From the past decades, carbon dioxide emissions have been dramatically increased and concentrate in atmosphere mainly due to human activities. This disastrous situation was a huge concern on the increasing the atmospheric carbon dioxide emissions inside urban areas and it became a challenge to the public health worldwide, as well as, its main cause of rising climate changes. Hence, the present project study tempted to address the important role of the urban vegetation for air quality. Here, we report the carbon dioxide capture by two urban tree species frequently planted (Morus nigra L.) and/or naturally occurred (Salix alba L.)in Duhok governorate areas and almost in all towns and cities of the Kurdistan Region.The results of this study showed a variation between Salix alba and M. nigra trees species in term of ratio dry/wet biomass, the carbon sequestration net and the annual CO 2 sequestration capacity. The main findings of this research were the annual carbon content quantification for common tree species grown in Duhok city: for white willow was (23 kg) and for black mulberry was (15 kg). Compare with, for some other trees that been done in previous studies for Pinus brutia, Eucalyptus camaldulesnsis, Quercus aegilops, and Cupressuss empervirens were 44.95, 38, 33.93 and 17.2 respectively. These results can be considered as an initial step to decrease the level of carbon dioxide emissions by planting the native treespecies. For the first time, a site-species-specific allometric equation has been developed based on the relationship between tree volume-wood biomass extracted from true values "destructive method" of biomass quantification. Consequently, thanks to this new volume-weight equation, we can assess the important roles of urban trees in the carbon sequestration process in urban areas of the Kurdistan Region without cutting the trees can be assessed.
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Salix alba (SA), commonly known as white willow, is a plant used in folk medicine for the treatment of chronic and acute inflammation, infection, pain, and fever. The phytochemical characterization of the bark extract of this plant indicated that its main component is salicin, a precursor of the anti-inflammatory agent acetylsalicylic acid. Considering the lack of studies evaluating the genetic toxicity and cytotoxic action of SA bark extract on human cells, as well as the chemical characterization of its major phenolic compounds, the present study was designed to (1) investigate the cytotoxic and genotoxic potential of SA bark extract on human peripheral leukocyte cells and human hepatoma cell line HepG2, and (2) characterize its major phenolic constituents. The phenolic compounds found were salicylic acid, salicin, salidroside, saligenin, tremulodin, salicoylsalicin, salicortin, and tremulacin. The results using trypan blue staining test showed viability decreases (viability less than 70%) for concentrations of SA extract equal and higher to 200 µg/ml. Low genotoxic activity (comet assay) was exhibited for 50 and 100 µg/ml SA extract in human leukocytes. SA did not exert a marked clastogenic/aneugenic effect on leukocytes and HepG2 human cells. Data suggest that the genotoxic effects of SA bark extract occur when it is not metabolized by liver enzymes.
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It is believed that 40–60% of Americans use complementary and alternative medicine to treat a variety of medical conditions. Of these Americans, 30% cite pain as the primary condition being treated. The clinical use of nutritional modulators as a treatment of pain has been widely studied. Pain states such as myalgias from statin use, rheumatoid arthritis, menstrual pain, and osteoarthritis, just to name a few, have been investigated. Strong evidence supports the use of probiotics, omega-3 fatty acids, magnesium, glucosamine/chondroitin, and vitamin D in a variety of pain states. Other modulators including turmeric, devil’s claw, methylsulfonylmethane (MSM), Boswellia, white willow bark, and green tea have contradictory or minimal evidence to support their use for pain relief. Despite the medical evidence or lack thereof, passionate consumers continue to utilize these modulators as supplements or alternatives to traditional pharmacotherapy.
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Exercise is a stressor that is known to in some cases suppress antimicrobial protein levels, particularly secretory immunoglobulin type A (IgA). Athletes in the midst of in-season training often demonstrate declining levels of sIgA as well as increased risk for ailments such as upper respiratory tract infections. Therefore, it is important to investigate natural supplements that may enhance post exercise mucosal immune function. Methods: Twenty healthy college-aged males volunteered to participate in the present single blind, repeated measures study. Three treatments were administered (botanical spray, botanical drops, placebo) at the onset of 30 minutes of 80% VO2 max cycle ergometer exercise. Secretory IgA and Human Alpha Defensin were quantified in saliva samples 30 minutes and 90 minutes post exercise. Results: Analysis via repeated measures Anova revealed a significant treatment effect at 30 min (p=0.030) with post hoc testing revealing a difference between the botanical spray and placebo (p=0.027), but by 90 minutes there was no differences by treatment (p=0.758). There was no difference by treatment observed at either 30 or 90 minutes for human alpha defensin concentrations. Conclusions: Based upon these preliminary data, it appears that a single dose of the tested botanical blend delivered via mouth spray can increase sIgA, one of the primary anti-microbial proteins in the oral cavity, for a short time post exercise.
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Background Elevated levels of skin sebum are associated with the growth of Propionibacterium acnes. Intensive degreasing of the skin reduces Propionibacterium acnes but also may cause skin irritation. Aims We assessed the degreasing effect and skin tolerability of a botanical face cleanser with hops and willow bark extract and disodium cocoyl glutamate as mild cleansing agent compared to a standard face cleanser with sodium laureth sulfate (SLES). Materials and Methods A total of 21 healthy volunteers with normal to oily skin were enrolled in this study. Both cleansers were applied twice a day on the left or right side of the forehead for 15 days in a standardized manner. Bioengineering measurements were performed on day 8 and 15 and on day 17 after an application break of 48 hours. The sebum level was determined using a Sebumeter®, and skin redness was measured using a Mexameter®. Results The botanical face cleanser significantly reduced the sebum level (P < .01) in the test area on day 17. The SLES containing cleanser showed a statistically relevant degreasing effect already on day 15, but after the application break the sebum level increased again on day 17. None of the cleansers caused skin irritation as determined by skin redness measurements. Conclusions In contrast to the SLES containing cleanser, the botanical skin cleanser with hops and willow bark extract had a continuous degreasing effect without reactive seborrhoe after the treatment break. Skin cleansing without SLES might be advantageous for sensitive skin.
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Mung bean is a legume crop which has a various health-promoting effects. Although rich flavonoids are reported to be responsible for its biological activities, little is known about other nutrients that may potentiate the activities. To obtain information on mung bean nutritional properties, gel-free/label-free proteomic analysis and metabolomic profiling were combined. Pathway reconstruction detected that amino acid metabolism is more active in flesh. Coat contained wider variety of lipids and phenolic acids/flavonoids than flesh. Among the compounds detected in coat, sphingolipids, arachidonic acid, and prostaglandin E2 are compounds which are related to immune response induction. Furthermore, identification of prostaglandin F2α added scientific support to empirical validity of mung bean usage. The abundance of bioactive compounds such as naringenin, which can be metabolized into vitexin, varied among cultivars. These results suggest that lipids together with flavonoids might be potential responsible compounds for biological activity of mung bean coat and flesh.
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The competition and cooperation between weak intermolecular interactions are important in determining the conformational preferences of molecules. Understanding the relative strengths of these effects in the context of potential drug candidates is therefore essential. We use a combination of gas-phase spectroscopy and quantum-chemical calculations to elucidate the nature of such interactions for the analgesic salicin [2-(hydroxymethyl)phenyl β-D-glucopyranoside], an analog of aspirin found in willow bark. Of several possible conformers, only three are observed experimentally, and these are found to correspond with the three lowest energy conformers obtained from density functional theory calculations and simulated Franck-Condon spectra. Natural bond orbital analyses show that these are characterized by a subtle interplay between weak n→* interaction and conventional strong hydrogen bond, with additional insights into this interaction provided by analysis of quantum theory of atoms in molecules and symmetry-adapted perturbation theory calculations. In contrast, the higher energy conformers, which are not observed experimentally, are mostly stabilized by the hydrogen bond with negligible contribution of n→* interaction. The n→* interaction results in a preference for the benzylic alcohol group to adopt a gauche conformation, a characteristic also found when salicin is bound to the β-gluocosidase enzyme. As such, understanding the interplay between these weak interactions has significance in the rationalization of protein structures.
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Greek islands of the North Aegean Region are a group of 9 inhabited islands (Lemnos, Agios Efstratios, Lesvos, Chios, Psara, Oinousses, Samos, Ikaria and Fourni) in the northern part of the Aegean Sea, close to Asia Minor. Each island of this region can be considered as an autonomous unit in terms of culture and biodiversity. Therefore, we tried to evaluate the status of the traditional uses of medicinal plants in this remote Greek region. Endemic and endangered species such as Sideritis sipylea Boiss., Origanum sipyleum L., Thymus sipyleus Boiss., Pistacia lentiscus L., Verbascum ikaricum Murb., are still used by natives to treat different ailments. Moreover, the use of some species for the ailment of specific diseases has been reported for the first time. About 109 wild plant species of medicinal importance from 52 families, their uses for therapeutic purposes and galenic preparations by local medical doctors and pharmacists are reported. Information included comes primarily by informants and from literature sources. The information was collected through semi-structured interviews with 200 informants (100 men and 100 women). In addition, informant consensus factor (FIC) and UV value were calculated for the medicinal plants of the current study related with the diseases treated. This research confirms the importance of the medicinal plants and their use in traditional medicine for this region. This ethnopharmacological survey is a fundamental step for the preservation of the local knowledge both for further scientific research and for the protection of endangered and endemic medicinal plants
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Forword Sports injuries are common, and vary from minor toe injuries to major complex trauma. Usually, only soft tissue is damaged, but there can also be fracturing of bone. Soft tissue injuries include sprains, strains and bruising. A sprain is a partial or complete rupture of a ligament, a strain is a partial tear of muscles and a bruise is a rupture of tissue leading to a haematoma. Any soft-tissue injury can lead to a tenderness, swelling, haematoma, scarring, fibrosis and loss of function. After a sports injury or sprain, immediate first aid is very important. The acronym RICE summarizes the approach: • Rest the injured part as soon as it is hurt to avoid further injury. • Ice the area of pain to decrease swelling and bleeding. • Compress the area with an elastic bandage to limit swelling and bleeding. • Elevate the injured part above the level of the heart to increase drainage of fluids out of the injured area. But that's not all you can do. In the next few days after injury, you can greatly improve recovery time by taking nutrients that decrease inflammation and speed healing. Here are four especially good strategies: Most commonly, sports injuries affect the lower limb, particularly the ankle (e.g. Achilles tendinopathy, sprains) and knee (e.g. patellofemoral pain syndrome, ligament injuries). Other common sporting injuries include those of the shoulder (e.g. dislocations, acromioclavicular joint injuries, rotator cuff injuries); elbow (e.g. tennis, golfer's); wrist (e.g. strains, sprains, breaks); leg (e.g. shin splints, stress fractures, hamstring injuries); foot (e.g. plantar fasciitis); groin (strain); and back (e.g. acute lumbar sprain). Injuries can be caused by trauma as a result of a sudden impact or awkward movement, or can develop over time often due to continual use of the same joints or muscle groups. Contributing factors can be not warming, using inadequate equipment or training too hard for current level of fitness. The aims of therapy are to relieve pain, control inflammation, hasten resolution of a haematoma, and accelerate repair. Also, there should be restoration of function and recovery of muscle power. Conventional approaches to sports injuries include RICE, anti-inflammatory drugs and analgesics, immobilisation, corticosteroid injections, physiotherapy and surgery. Injured sport men no longer have to rely on the standard sports medicine regimen of anti-inflammatories, rest, and even surgery to bounce back. Recent clinical studies have endorsed an array of alternatives—everything from innovative massage techniques to injection treatments to laser therapies. Even ancient remedies, like acupuncture, are being fused with new technology for sports medicine purposes. Anyone who has suffered a sports injury should consult a doctor as soon as possible. However, once the injury is stabilized, patient should take the time to consult an expert in alternative treatments for sports injuries. Alternative medicine methods for pain management treatment varied widely. One holistic practitioners take a comprehensive approach to identity the root causes the pain. Athletes have always been progressive in finding therapies or treatments thought to increase power, speed, and overall performance. There are a variety of choices available which can provide specific and individualized results with the guidance of a qualified practitioner. As you can see, complementary and alternative medicine has found its way not only into the healthcare arena of the general public, but also onto the practice fields and into the equipment bags of both amateur and professional athletes. We must find a way to guide and educate those active and athletic patients who are trying to navigate this maze of healthcare options. Integration of complementary and alternative medicine into the sport arena is only going to increase in the future, which calls for more collaboration and discussion between healthcare practitioners of both conventional and complementary medicine. This education has purpose to promote integrative medicine methods for sport prevention and treatment of injuries, and increasing sport men performances. This publication is consist of personal experience and consulting studies. Ramova and Angelovska
White willow bark (Salix alba). The Longwood Herbal Task Force
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  • Kemper KJ
Willow bark extract increases antioxidant exzymes and reduces oxidative stress through activation of Nrf2 in vascular endothelial cells and Caenorhabditis elegans
  • Ishikado A
  • Sono Y
  • Matsumoto M
Analytical and biological studies on Salicaceae substances, especially salacin. II. Biological study
  • Steinegger E
  • Hovel H
White willow bark ( Salix alba ) The Longwood Herbal Task Force 1 12 http
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Coffee and willow are known as valuable sources of biologically active phytochemicals such as chlorogenic acid, caffeine, and salicin. The aim of the study was to determine the interactions between the active compounds contained in water extracts from coffee and bark of willow (Salix purpurea and Salix myrsinifolia). Raw materials and their mixtures were characterized by multidirectional antioxidant activities; however, bioactive constituents interacted with each other. Synergism was observed for ability of inhibition of lipid peroxidation and reducing power, whereas compounds able to scavenge ABTS radical cation acted antagonistically. Additionally, phytochemicals from willow bark possessed hydrophilic character and thermostability which justifies their potential use as an ingredient in coffee beverages. Proposed mixtures may be used in the prophylaxis or treatment of some civilization diseases linked with oxidative stress. Most importantly, strong synergism observed for phytochemicals able to prevent lipids against oxidation may suggest protective effect for cell membrane phospholipids. Obtained results indicate that extracts from bark tested Salix genotypes as an ingredient in coffee beverages can provide health promoting benefits to the consumers; however, this issue requires further study.
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The purpose of this study was to assess the effect of 8-weeks ingestion of a commercialized joint pain dietary supplement (InstaflexTM Joint Support, Direct Digital, Charlotte, NC) compared to placebo on joint pain, stiffness, and function in adults with self-reported joint pain. InstaflexTM is a joint pain supplement containing glucosamine sulfate, methylsufonlylmethane (MSM), white willow bark extract (15% salicin), ginger root concentrate, boswella serrata extract (65% boswellic acid), turmeric root extract, cayenne, and hyaluronic acid. Subjects included 100 men and women, ages 50-75 years, with a history (>3 months) of joint pain, and were randomized to InstaflexTM or placebo (3 colored gel capsules per day for 8 weeks, double-blind administration). Subjects agreed to avoid the use of non-steroidal anti-inflammatory drugs (NSAID) and all other medications and supplements targeted for joint pain. Primary outcome measures were obtained pre- and post-study and included joint pain severity, stiffness, and function (Western Ontario and McMaster Universities [WOMAC]), and secondary outcome measures included health-related quality of life (Short Form 36 or SF-36), systemic inflammation (serum C-reactive protein and 9 plasma cytokines), and physical function (6-minute walk test). Joint pain symptom severity was assessed bi-weekly using a 12-point Likert visual scale (12-VS). Joint pain severity was significantly reduced in InstaflexTM compared to placebo (8-week WOMAC, [downwards arrow]37% versus [downwards arrow]16%, respectively, interaction effect P = 0.025), with group differences using the 12-VS emerging by week 4 of the study (interaction effect, P = 0.0125). Improvements in ability to perform daily activities and stiffness scores in InstaflexTM compared to placebo were most evident for the 74% of subjects reporting knee pain (8-week WOMAC function score, [downwards arrow]39% versus [downwards arrow]14%, respectively, interaction effect P = 0.027; stiffness score, [downwards arrow]30% versus [downwards arrow]12%, respectively, interaction effect P = 0.081). Patterns of change in SF-36, systemic inflammation biomarkers, and the 6-minute walk test did not differ significantly between groups during the 8-week study CONCLUSIONS: Results from this randomized, double blind, placebo-controlled community trial support the use of the InstaflexTM dietary supplement in alleviating joint pain severity in middle-aged and older adults, with mitigation of difficulty performing daily activities most apparent in subjects with knee pain.Trial registration: ClinicalTrials.gov Identifier: NCT01956500.
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Objective: This study was undertaken to determine the effects of an ephedrine- and synephrine-based compound on body mass, body composition, metabolic variables, and mood states in healthy overweight adults.Methods: Thirty subjects with a body mass index > 27 kg/m2 were assigned randomly to the experimental group or the placebo group. The experimental group received a capsule containing ephedrine alkaloids 20 mg, synephrine 5 mg, caffeine 200 mg, and salicin 15 mg twice daily for 8 weeks, whereas the other group received a matching placebo. A registered dietitian instructed all patients about a 22-kcal/kg National Cholesterol Education Program Step One diet. In addition, all patients performed a cross-training exercise program 3 days per week under the guidance of an exercise physiologist. During the exercise sessions, patients achieved ∼70% of age-predicted maximum heart rate.Results: The experimental group had a significantly greater weight loss compared with the placebo group (3.14 kg vs 2.05 kg, respectively; P < 0.05). The experimental group experienced a 16% decrease in body fat compared with a 1% increase for the placebo group. The between-group difference was significant (P = 0.005). Both groups achieved a significant reduction in fat-free mass; however, the reduction in the placebo group was greater than that of the experimental group. This suggests a muscle-sparing effect in the experimental group. No significant changes in blood pressure, serial electrocardiograms, pulse rate, serum chemistry, or caloric intake were noted.Conclusions: These findings indicate the apparent safety and efficacy of the ephedrine- and synephrine-based compound within the confines of this study.
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Dear Editor, A 61-year-old female with the past medical history of hypertension and osteoarthritis presented to Emergency Department with sudden onset of shortness of breath and non-productive cough 30 min, after taking white willow bark supplement. The patient denied any history of the drug or supplement allergy. Pulse oximetry demonstrated oxygen desaturation; SpO2 of 75% on ambient air and 94% on nasal cannula with the flow of oxygen 20 L/min. Arterial blood gas although on FiO2 of 100% showed severe hypoxemia with the high A-a gradient, metabolic acidosis with respiratory compensation (pH 7.28, PCO2 36 mmHg, PaO2 75 mmHg, and HCO3 19 mmol/L). Blood tests demonstrated evidence of wide anion gap (AG) metabolic acidosis (AG 14 mmol/L) from lactic acidosis (lactic acid 4.9 mmol/L) with the normal gap metabolic acidosis (∆AG/∆Bicarb = 0.4) and the patient had no osmolal gap. Furthermore, serum ketone and salicylate levels were undetectable and her chest X-ray showed bilateral interstitial infiltrates [Figure 1]. Transthoracic echocardiogram revealed normal systolic and diastolic function. The diagnosis of acute hypoxic respiratory failure secondary to severe acute respiratory distress syndrome (ARDS) from reaction to white willow bark was made; the PaO2/FiO2 of 75 mmHg. The patient was promptly started on intravenous venous methylprednisolone and oral antihistamines including diphenhydramine and ranitidine. The patient responded well with our treatment and her oxygen requirement gradually improved from 94% on FiO2 of 100% to 95% on room air. Lactic acidosis also subsided after maintaining adequate oxygenation. Figure 1 Chest X-ray demonstrated bilateral interstitial infiltrates The use of white willow bark supplement was first reported back to the time of Hippocrates (400 BC) when patients were advised to chew on the bark for pain relief and fever reduction. Willow bark is also included in weight-loss products.[1] There have been a remarkably small number of reported cases of adverse reactions to willow bark extract. These adverse drug reactions are usually mild (maculopapular rashes). White willow bark induced anaphylaxis is rare; however, a few cases have been reported.[2,3] To our knowledge, this is the first report of white willow bark induced ARDS. People who are allergic or sensitive to salicylates (such as aspirin) should not use willow bark.
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Diabetic retinopathy is a complex condition where inflammation and oxidative stress represent crucial pathways in the pathogenesis of the disease. Aim of the study was to investigate the effects of a fortified extract of red berries, Ginkgo biloba and white willow bark containing carnosine and α-lipoic acid in early retinal and plasma changes of streptozotocin-induced diabetic rats. Diabetes was induced by a single streptozotocin injection in Sprague Dawley rats. Diabetics and nondiabetic (control) rats were treated daily with the fortified extract for the ten days. Retina samples were collected and analyzed for their TNF-α and VEGF content. Moreover, plasma oxidative stress was evaluated by thiobarbituric acid reacting substances (TBARS). Increased TNF-α and VEGF levels were observed in the retina of diabetic rats. Treatment with the fortified extract significantly lowered retinal cytokine levels and suppressed diabetes-related lipid peroxidation. These data demonstrate that the fortified extract attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the retina in early diabetic rats.
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JEPonline. 2001;4(2):28-34. The purpose was to determine the effects of an herbal preparation containing ma huang, bitter orange and guarana on resting energy expenditure (REE), blood chemistries, and body composition in obese adults. Five males and 15 females (age=31±6.6 yr, height=168.1 ±8.4 cm, weight=93.4±17.1 kg, %fat=43.8 ±6.5%) were matched, randomly assigned to either the supplement (N=12) or placebo (N=8) group, and participated in a 44 d aerobic exercise program (3 d/wk). REE was determined by open-circuit spirometry, and serum samples were analyzed for glucose, cholesterol, triglycerides, HDL, and LDL. Changes in body mass (BM), %fat, fat mass (FM), and fat-free mass (FFM) were determined using DEXA. Due to limited compliance, pre-and post-treatment diet recalls were analyzed for only 14 subjects (supplement=9, placebo=5). Analysis included doubly MANOVA repeated measures (diet recalls and blood chemistries) and independent t-tests (REE and body composition) at á<0.05. The only significant difference was in FM (p=0.033). When a more liberal alpha (á<0.10) is considered, %fat and BM were significant (p=0.096 and 0.087). The supplement, thus, may result in reductions in FM, %fat and BM, but has little effect on energy expenditure, diet or blood chemistries following a six-week period of supplementation and training.
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The aim of this study was to characterize the anti-inflammatory mode of action of botanical extracts from rosehip (Rosa canina), willow bark (Salix alba), and nettle leaf (Urtica dioica) in an in vitro model of primary canine articular chondrocytes. Methods. The biological effects of the botanical extracts were studied in chondrocytes treated with IL-1β for up to 72 h. Expression of collagen type II, cartilage-specific proteoglycan (CSPG), β1-integrin, SOX-9, COX-2, and MMP-9 and MMP-13 was examined by western blotting. Results. The botanical extracts suppressed IL-1β-induced NF-κB activation by inhibition of IκBα phosphorylation, IκBα degradation, p65 phosphorylation, and p65 nuclear translocation. These events correlated with downregulation of NF-κB targets including COX-2 and MMPs. The extracts also reversed the IL-1β-induced downregulation of collagen type II, CSPG, β1-integrin, and cartilage-specific transcription factor SOX-9 protein expression. In high-density cultures botanical extracts stimulated new cartilage formation even in the presence of IL-1β. Conclusions. Botanical extracts exerted anti-inflammatory and anabolic effects on chondrocytes. The observed reduction of IL-1β-induced NF-κB activation suggests that further studies are warranted to demonstrate the effectiveness of plant extracts in the treatment of OA and other conditions in which NF-κB plays pathophysiological roles.
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To establish whether acetaminophen improves performance of self-paced exercise through the reduction of perceived pain, 13 trained male cyclists performed a self-paced 10-mile (16.1 km) cycle time trial (TT) following the ingestion of either acetaminophen (ACT) or a placebo (PLA), administered in randomized double-blind design. TT were completed in a significantly faster time (t(12) = 2.55, P < 0.05) under the ACT condition (26 min 15 s +/- 1 min 36 s vs. 26 min 45 s +/- 2 min 2 s). Power output (PO) was higher during the middle section of the TT in the ACT condition, resulting in a higher mean PO (P < 0.05) (265 +/- 12 vs. 255 +/- 15 W). Blood lactate concentration (B[La]) and heart rate (HR) were higher in the ACT condition (B[La] = 6.1 +/- 2.9 mmol/l; HR = 87 +/- 7%max) than in the PLA condition (B[La] = 5.1 +/- 2.6 mmol/l; HR = 84 +/- 9%max) (P < 0.05). No significant difference in rating of perceived exertion (ACT = 15.5 +/- 0.2; PLA = 15.7 +/- 0.2) or perceived pain (ACT = 5.6 +/- 0.2; PLA = 5.5 +/- 0.2) (P > 0.05) was observed. Using acetaminophen, participants cycled at a higher mean PO, with an increased HR and B[La], but without changes in perceived pain or exertion. Consequently, completion time was significantly faster. These findings support the notion that exercise is regulated by pain perception, and increased pain tolerance can improve exercise capacity.
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This study compared independent effects of caffeine and aspirin on muscular endurance (repetitions), heart rate (HR), perceived exertion (RPE), and perceived pain index (PPI) during light resistance training bouts performed to volitional failure. It was hypothesized that the hypoalgesic properties of these ergogenic aids would decrease pain perception and potentially result in enhanced performance. College-aged men (n = 15) participated in a within-subjects, double-blind study with three independent, counterbalanced sessions wherein aspirin (10 mg x kg(-1)), caffeine (6 mg x kg(-1)), or matched placebo were ingested 1 hour before exercise, and RPE, HR, PPI, and repetitions (per set and total per exercise) were recorded at 100% of individual, predetermined, 12-repetition maximum for leg extensions (LE) and seated arm curls (AC). Repeated-measures analyses of variance were used for between-trial comparisons. Caffeine resulted in significantly greater (p < 0.05) HR (LE and AC), total repetitions (LE), and repetitions in set 1 (LE and AC) compared with aspirin and placebo. Aspirin resulted in significantly higher PPI in set 1 (LE). In LE, 47% of participants' performance exceeded the predetermined effect size (>or= 5 repetitions) for total repetitions, with 53% exceeding the effect size (>or= 2 repetitions) for repetitions in set 1 with caffeine (vs. placebo). In AC, 53% (total repetitions) and 47% (set 1 repetitions) of participants exceeded effect sizes with caffeine (vs. placebo), with only 13% experiencing decrements in performance (total repetitions). Aspirin also produced a higher PPI and RPE overall and in set 1 (vs. placebo). This study demonstrates that caffeine significantly enhanced resistance training performance in LE and AC, whereas aspirin did not. Athletes may improve their resistance training performance by acute ingestion of caffeine. As with most ergogenic aids, our analyses indicate that individual responses vary greatly.
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The influence of a submaximal exercise on urinary 2,3-dinor-6-ketoprostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha), 2,3-dinor-thromboxane B2 (2,3-dinor-TxB2), and prostaglandin E2 excretion and on platelet aggregation was compared in untrained and trained subjects before and after low-dose aspirin administration (50 mg/day, 7 days). 2,3-Dinor-TxB2 excretion was significantly higher in the athletes at rest (P < 0.05). Submaximal exercise selectively increased 2,3-dinor-6-keto-PGF1 alpha excretion without affecting 2,3-dinor-TxB2 or prostaglandin E2 excretion rates or platelet aggregation. Low-dose aspirin inhibited platelet aggregation and 2,3-dinor-TxB2 excretion but reduced 2,3-dinor-6-keto-PGF1 alpha by only 24% in the untrained and by 51% in the trained subjects (P < 0.05). After low-dose aspirin administration, the selective stimulatory effect of submaximal exercise on urinary 2,3-dinor-6-keto-PGF1 alpha excretion was even more pronounced than before. The ratio of 2,3-dinor-6-keto-PGF1 alpha to 2,3-dinor-TxB2 was increased by exercise; this effect was significantly enhanced by low-dose aspirin (P < 0.05). Our results suggest that the stimulatory effect of submaximal exercise on prostacyclin production is mostly due to an activation of prostacyclin synthesis from endogenous precursors rather than the result of an enhanced endoperoxide shift from activated platelets to the endothelium. This effect is potentiated by low-dose aspirin pretreatment, indicating that 50 mg/day of aspirin do not impair exercise-induced endothelial prostacyclin production.
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To investigate the efficacy and safety of a standardized willow bark extract in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). We studied 127 outpatients with hip or knee OA and a WOMAC pain score of at least 30 mm and 26 outpatients with active RA in 2 randomized, controlled, double-blind trials with followup for 6 weeks. OA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg of salicin/day, diclofenac 100 mg/day, or placebo (n = 43, 43, and 41, respectively). Main outcome measure was the pain subscore of the WOMAC OA Index. RA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg salicin/day (n = 13) or placebo (n = 13). Main outcome measure was the patient's assessment of pain rated on a 100 mm visual analog scale (VAS). OA trial: WOMAC pain scores decreased by 8 mm (17%) in the willow bark group and by 23 mm (47%) in the diclofenac group, compared with 5 mm (10%) in the placebo group. The difference between willow bark extract and placebo was not statistically significant (-2.8 mm; 95% CI -12.1 to 6.4 mm; p = 0.55, ANCOVA), but the difference between diclofenac and placebo was highly significant (-18.0 mm; 95% CI -27.2 to -8.8 mm; p = 0.0002, ANCOVA). RA trial: The mean reduction of pain on the VAS was -8 mm (15%) in the willow bark group compared with -2 mm (4%) in the placebo group. The difference was not statistically significant (estimated difference -0.8 mm; 95% CI -20.9 to 19.3 mm; p = 0.93, ANCOVA). The OA study suggested that the willow bark extract showed no relevant efficacy in patients with OA. Similarly, the RA trial did not indicate efficacy of this extract in patients with RA.
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To report a case of anaphylaxis resulting from the use of a willow bark-containing dietary supplement in a patient with a history of an aspirin allergy. A 25-year-old white woman presented to the emergency department of a community teaching hospital with anaphylaxis requiring epinephrine, diphenhydramine, methylprednisolone, and volume resuscitation to which she responded favorably. Medication history revealed that she had ingested 2 capsules of Stacker 2 (NVE Pharmaceuticals, Newton, NJ), a dietary supplement promoted for weight loss, prior to experiencing her initial symptoms. Among other active ingredients, this product contains willow bark. Of significance is that this patient also reported a history of allergy to acetylsalicylic acid. No other causes for anaphylaxis were identified. She continued to receive routine supportive care and the remaining hospital course was uncomplicated. Dietary supplements, including herbal products, are used by many individuals who consider them to be inherently safe despite limited regulatory oversight by the Food and Drug Administration. While there may be value to specific botanical ingredients, a potential for adverse effects also exists. The popular product consumed by our patient is used for weight loss and contains willow bark, a source of salicylates. Based on the Naranjo probability scale, it is probable that this case of anaphylaxis was due to this dietary supplement. The use of any willow bark-containing dietary supplement may present a risk of anaphylactic reaction to patients with a history of allergy to salicylates. Clinicians need to recognize the potential for adverse effects from dietary supplements.
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Many higher plants contain novel metabolites with antimicrobial, antifungal and antiviral properties. However, in the developed world almost all clinically used chemotherapeutics have been produced by in vitro chemical synthesis. Exceptions, like taxol and vincristine, were structurally complex metabolites that were difficult to synthesize in vitro. Many non-natural, synthetic drugs cause severe side effects that were not acceptable except as treatments of last resort for terminal diseases such as cancer. The metabolites discovered in medicinal plants may avoid the side effect of synthetic drugs, because they must accumulate within living cells. The aim here was to test an aqueous extract from the young developing leaves of willow (Salix safsaf, Salicaceae) trees for activity against human carcinoma cells in vivo and in vitro. In vivo Ehrlich Ascites Carcinoma Cells (EACC) were injected into the intraperitoneal cavity of mice. The willow extract was fed via stomach tube. The (EACC) derived tumor growth was reduced by the willow extract and death was delayed (for 35 days). In vitro the willow extract could kill the majority (75%-80%) of abnormal cells among primary cells harvested from seven patients with acute lymphoblastic leukemia (ALL) and 13 with AML (acute myeloid leukemia). DNA fragmentation patterns within treated cells inferred targeted cell death by apoptosis had occurred. The metabolites within the willow extract may act as tumor inhibitors that promote apoptosis, cause DNA damage, and affect cell membranes and/or denature proteins.
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The efficacy of willow bark extract in the treatment of painful mobility disorders, such as back pain and arthritis, has been attributed to the content of salicin and its derivatives as pro-drugs of salicylates. However, based on clinical experience and the evidence of experimental pharmacological studies, the fraction of total salicin cannot satisfactorily explain the clinical efficacy of willow bark. In addition, salicins and their metabolites lack the acetylating potential of ASA and must therefore possess a different mechanism of action. A detailed pharmacological screening of the aqueous willow bark extract STW 33-I addressed the question of the identification of fractions contributing to the overall effect. All in vivo and in vitro models studied pointed to relevant contributions of the fraction of polyphenols and flavonoids. The single compounds or their combinations responsible for the effect remain to be elucidated.
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What is already known about this subject: Performance-enhancing dietary supplements have not been clinically tested for safety or efficacy. In clinical trials performed under resting conditions, performance-enhancing supplements raise blood pressure and affect glucose homeostasis. The effect of exercise on the pharmacokinetics and pharmacodynamics of stimulant herbals is unknown. What this study adds: Supplement-induced effects on blood pressure and glucose levels are not ameliorated by exercise. Exercise does not affect the kinetics of stimulant ingredients, caffeine and synephrine. Performance-enhancing supplement use modestly improves exercise tolerance. AIMS Dietary supplements (DS) promoted to enhance athletic performance often contain herbal sympathomimetics such as Citrus aurantium (synephrine) and caffeine. We aimed to characterize the pharmacology of a performance-enhancing DS in the setting of exercise. Methods: Ten healthy adults (three women) aged 20-31 years participated in a three-arm, double-blind, placebo-controlled, crossover study. Subjects ingested one dose of DS (Ripped Fuel Extreme Cut(R) with 21 mg synephrine and 304 mg caffeine by analysis) under resting conditions and 1 h prior to moderately intense exercise (30 min on cycle ergometer at 75-80% HR(max)), with a placebo (PLC)/exercise control. Plasma synephrine and caffeine concentrations were measured over 12 h, and vital signs, serum electrolytes, oxygen consumption and perceived exercise exertion were monitored. Results: No significant adverse events occurred. Synephrine and caffeine pharmacokinetics were unaffected by exercise. Post-exercise diastolic blood pressure was higher after DS (peak mean 71.7 +/- 8.7 mmHg) than PLC (63.0 +/- 4.9 mmHg) (p = 0.007). There were no substantial treatment-related differences in post-exercise HR, systolic blood pressure, or temperature. Postprandial plasma glucose increased to 121.0 +/- 31.6 mg dl(-1) with DS and exercise vs. 103.7 +/- 25.5 mg dl(-1) with PLC and exercise (P = 0.004). No treatment differences in exercise-related oxygen consumption, serum lactate, or insulin were observed. Exercise was rated less difficult with DS than PLC (P = 0.001). Conclusions: Blood pressure and plasma glucose increased post-exercise with DS use, which could be detrimental in some people. Exercise was perceived as less strenuous after DS, presumably due to the stimulant effects of caffeine.
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Objective. To investigate the efficacy and safety of a standardized willow bark extract in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. We studied 127 outpatients with hip or knee OA and a WOMAC pain score of at least 30 mm and 26 outpatients with active RA in 2 randomized, controlled, double-blind trials with followup for 6 weeks. OA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg of salicin/day, diclofenac 100 mg/day, or placebo (n = 43, 43, and 41, respectively). Main outcome measure was the pain subscore of the WOMAC OA Index. RA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg salicin/day (n = 13) or placebo (n = 13). Main outcome measure was the patient's assessment of pain rated on a 100 mm visual analog scale (VAS). Results. OA trial: WOMAC pain scores decreased by 8 mm (17%) in the willow bark group and by 23 turn (47%) in the diclofenac group, compared with 5 mm (10%) in the placebo group. The difference between willow bark extract and placebo was not statistically significant (-2.8 mm; 95% CI -12.1 to 6.4 mm; p = 0.55, ANCOVA), but the difference between diclofenac and placebo was highly significant (-18.0 mm; 95% CI -27.2 to -8.8 mm; p = 0.0002, ANCOVA). RA trial: The mean reduction of pain on the VAS was -8 turn (15%) in the willow bark group compared with -2 mm (4%) in the placebo group. The difference was not statistically significant (estimated difference -0.8 mm; 95% CI -20.9 to 19.3 mm; p = 0.93, ANCOVA). Conclusion. The OA study suggested that the willow bark extract showed no relevant efficacy in patients with OA. Similarly, the RA trial did not indicate efficacy of this extract in patients with RA.
Article
Study objective: Efficacy and safety of willow bark extract for pain reduction in patients suffering from musculoskeletal disorders (MSD) has been shown in clinical short term trials. Therefore this observational study over 6 months should evaluate patterns of treatments like mono- or combinations therapy, dosage and safety during long-term treatment under pragmatic conditions with the aqueous willow bark extract STW 33-I, (Proaktiv(®); drug-extract-ratio 16-23:1). Patients and methods: The patients were treated with STW 33-I; comedication with other NSAIDs and opioids was allowed. An extensive case report form including pain questionnaires and patient diary was used for outcome evaluation. Results: Four hundred and thirty-six patients with rheumatic pain mainly due to osteoarthritis (56.2%) and back pain (59.9%) were included. During the study the mean reductions from baseline value 58.4±22.6-31.8±22.5 after 24 weeks in the pain intensity scale (VAS 0-100mm) were significant even after 3 weeks with a reduction by 26 mm (45.6% of the baseline value) at the end of the study. The relative reductions of the weekly means of the daily patient self-rated scores of the pain (6-point Likert-scales) were between 33% and 44% of the baseline values during the course of the study. We present results of subgroups according their analgetic/antiphlogistic comedication. The distribution and specification of the main adverse events and the ratings of the treatment showed a good tolerability. No relevant drug interactions were reported. Conclusion: These data suggest that STW 33-I can be used as a basic treatment in the long-term therapy of painful musculoskeletal disorders and that it can be combined with NSAIDs and opioids if necessary.
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Willow bark extract (WBE) is listed in the European Pharmacopoeia and has been traditionally used for treating fever, pain and inflammation. Recent studies have demonstrated its clinical usefulness. This study investigated the antioxidative effects of WBE in human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans. WBE prevented oxidative-stress-induced cytotoxicity of HUVECs and death of C. elegans. WBE dose-dependently increased mRNA and protein expression levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) target genes, heme oxygenase-1, γ-glutamyl-cysteine ligase modifier and catalytic subunits, and p62, and intracellular glutathione (GSH) in HUVECs. In the nematode C. elegans, WBE increased the expression of the gcs-1::green fluorescent protein (GFP) reporter, a well-characterized target of the Nrf2 ortholog SKN-1, in a manner that was SKN-1-dependent. WBE increased intranuclear expression and DNA binding of Nrf2, and activity of an antioxidant response element (ARE) reporter plasmid in HUVECs. WBE-induced expression of Nrf2-regulated genes, and increased GSH levels in HUVECs were reduced by Nrf2 and p38 small interfering (si)RNAs, and by the p38-specific inhibitor SB203580. Nrf2 siRNA reduced the cytoprotective effect of WBE against oxidative stress in HUVECs. Salicin, a major anti-inflammatory ingredient of WBE, failed to activate ARE-luciferase activity, while a salicin-free WBE fraction showed intensive activity. WBE induced antioxidant enzymes and prevented oxidative stress through activation of Nrf2 independently of salicin, providing a new potential explanation for the clinical usefulness of WBE.
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Here, proof-of-concept of a new analytical platform used for the comprehensive analysis of a small set of commercial willow bark products is presented, and compared with a traditional standardization solely based on analysis of salicin and salicin derivatives. The platform combines principal component analysis (PCA) of two chemical fingerprints, i.e., HPLC and (1)H NMR data, and a pharmacological fingerprint, i.e., high-resolution 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS(+)) reduction profile, with targeted identification of constituents of interest by hyphenated HPLC-solid-phase extraction-tube transfer NMR, i.e., HPLC-SPE-ttNMR. Score plots from PCA of HPLC and (1)H NMR fingerprints showed the same distinct grouping of preparations formulated as capsules of Salix alba bark and separation of S. alba cortex. Loading plots revealed this to be due to high amount of salicin in capsules and ampelopsin, taxifolin, 7-O-methyltaxifolin-3'-O-glucoside, and 7-O-methyltaxifolin in S. alba cortex, respectively. PCA of high-resolution radical scavenging profiles revealed clear separation of preparations along principal component 1 due to the major radical scavengers (+)-catechin and ampelopsin. The new analytical platform allowed identification of 16 compounds in commercial willow bark extracts, and identification of ampelopsin, taxifolin, 7-O-methyltaxifolin-3'-O-glucoside, and 7-O-methyltaxifolin in S. alba bark extract is reported for the first time. The detection of the novel compound, ethyl 1-hydroxy-6-oxocyclohex-2-enecarboxylate, is also described.
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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-α) 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-α significantly ( p < 0.05). Amongst the herbal extracts, willow bark had the greatest antiinflammatory activity at reducing IL-6 and TNF-α 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. Copyright © 2012 John Wiley & Sons, Ltd.
Article
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. 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. 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.
Article
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. 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). 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.
Article
The present study examined the skeletal muscle expression of several genes related to the inflammatory process before and after a bout of downhill running. Twenty-nine males between the ages of 18 and 35 years performed a 45-min downhill (-17.5%) treadmill protocol at 60% of maximal oxygen consumption. Venous bloods samples and muscle biopsy samples from the vastus lateralis were donated prior to and at 3-h and 24-h postexercise, along with ratings of perceived muscle soreness. Serum creatine kinase (CK) was determined, as was skeletal muscle gene expression of interleukin (IL)-6, IL-8, IL-12 (p35), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, cyclooxygenase 2 (COX2), and nuclear factor kappa B (NFkB) (p105/p50). Gene expression was analyzed using RT-PCR and compared with a standard housekeeping gene (beta-actin). Data were analyzed for statistical differences using multivariate analysis of variance with univariate follow-up. In addition, Pearson correlations were conducted to determine if any significant relationship exists between any of these transcripts and both CK and muscle soreness. Significant (p < 0.05) up-regulations in IL-6, IL-8, and COX2 mRNA expression were observed compared with baseline, whereas no significant changes for IL-12, IL-1beta, TNF-alpha, or NFkB were noted. Significant increases in IL-6 mRNA were observed at 3 h (p < 0.001) and 24 h (p = 0.043), whereas significant increases in IL-8 (p = 0.001) and COX2 (p = 0.046) mRNA were observed at 3-h postexercise. In addition, muscle soreness was significantly correlated with IL-8 at 24 h (r = -0.370; p = 0.048), whereas CK was significantly related to NFkB at baseline (r = -0.460; p = 0.012). These data indicate that increases in the mRNA expression of IL-6, IL-8, and COX2 occur in the vastus lateralis as a result of damaging eccentric exercise in young, recreationally trained males. Further, it appears that IL-8 transcription may play some role in inhibiting postexercise muscle soreness, possibly through regulation of angiogenesis.
Article
Since ancient times preparations from Salix species have been used to alleviate pain. The aim of this study was to update the evidence of the effectiveness of willow bark products in the treatment of musculoskeletal pain. OVID(MEDLINE), PUBMED, Silverplatter, and CENTRAL and manual searches were used to identify clinical trials investigating Salix preparations. Authors SC and JEV extracted the data independently and discussed disagreements. Seven manuscripts were identified, reporting four trials with confirmatory and four with exploratory study designs. Three manuscripts presented the same trial data: repetitious reports were excluded. One confirmatory and two exploratory studies indicate a dose-dependent analgesic effect not inferior to rofecoxib in patients with low back pain. In one exploratory and one confirmatory study conflicting results were achieved in participants with osteoarthritis. No significant effect was seen in a confirmatory study in patients with rheumatoid arthritis, but this study was grossly underpowered. All studies investigated ethanolic extracts with daily doses up to 240 mg salicin over periods of up to six weeks. Minor adverse events occurred during treatment. The review provides moderate evidence of effectiveness for the use of ethanolic willow bark extract in low back pain. Further studies are required to find out if treatment of osteoarthritis and rheumatoid arthritis requires extract with higher doses than 240 mg salicin per day. Copyright
Article
The enzymatic catalysis of the decomposition of Salicaceae phenolic glucosides was tested using almond beta-glucosidase and rabbit and porcine liver esterases. The beta-glucosidase catalyzed the complete hydrolysis of salicin and salicortin, yielding saligenin and glucose. Salicortin also produced (+)-6-hydroxycyclohexen-2-one (6-HCH). The acylglucosides were not decomposed by the beta-glucosidase. Both esterases catalyzed the decomposition of tremulacin, salicortin, and 2'-O-acetylsalicortin, releasing tremuloidin, salicin, and 2'-O-acetylsalicin as the main products, accompanied by 6-HCH and catechol. Tremuloidin and 2'-O-acetylsalicin were quite stable under the esterase hydrolysis, and salicin was not decomposed at all.
Article
Leiocarposide (1; 3-beta-D-glucopyranosyloxy-2-methoxy-6-hydroxy-benzoic acid -2'-beta-D-glucopyranosyloxybenzyl ester) is a phenolic glycoside from Solidago virgaurea L. After oral administration to rats it will be only poorly absorbed and mostly unchanged fecaly excreted. In the urine were found less than 10% as metabolites: leiocarpic acid (3; 3,6-dihydroxy-2-methoxy-benzoic acid, 2% of the administered dose), 3-conjugates (2%), salicylic acid (5; 0.5%), 5-conjugates (0.1%) and salicyluric acid (6; 0.5%). On the other hand salicin (2), structural part of 1, is good absorbed. In the urine were excreted 15% of the unchanged drug and the following metabolites: 0.1% saligenin (4), 30% 5, 5% 5-conjugates, 0.1% 6, 2% gentisic acid (7) and 0.1% 2,3-dihydroxy-benzoic acid (8). The different metabolic rates are explicable by the high stability of the ester bond of 1. It is hydrolyzed in artificial intestinal fluid only very slowly (t1/2 = 41.7 h).
Article
Herbal medicines are widely used for the treatment of pain, although there is not much information on their effectiveness. This study was designed to evaluate the effectiveness of willow (Salix) bark extract, which is widely used in Europe, for the treatment of low back pain. We enrolled 210 patients with an exacerbation of chronic low back pain who reported current pain of 5 or more (out of 10) on a visual analog scale. They were randomly assigned to receive an oral willow bark extract with either 120 mg (low dose) or 240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue medication, in a 4-week blinded trial. The principal outcome measure was the proportion of patients who were pain-free without tramadol for at least 5 days during the final week of the study. The treatment and placebo groups were similar at baseline in 114 of 120 clinical features. A total of 191 patients completed the study. The numbers of pain-free patients in the last week of treatment were 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%) of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo group (P <0.001). The response in the high-dose group was evident after only 1 week of treatment. Significantly more patients in the placebo group required tramadol (P <0.001) during each week of the study. One patient suffered a severe allergic reaction, perhaps to the extract. Willow bark extract may be a useful and safe treatment for low back pain.
Article
This study assessed the clinical efficacy of a chemically standardized willow bark extract in the treatment of osteoarthritis. Willow bark extract, in a dose corresponding to 240 mg salicin/day, was compared with placebo in a 2-week, double-blind, randomized controlled trial. The primary outcome measure was the pain dimension of the WOMAC Osteoarthritis Index. Secondary outcome measures included the stiffness and physical function dimensions of the WOMAC, daily visual analogue scales (VAS) on pain and physical function, and final overall assessments by both patients and investigators. A total of 78 patients (39 willow bark extract, 39 placebo) participated in the trial. A statistically significant difference between the active treatment and the placebo group was observed in the WOMAC pain dimension (d = 6.5 mm, 95% C.I. = 0.2-12.7 mm, p = 0.047); the WOMAC pain score was reduced by 14% from the baseline level after 2 weeks of active treatment, compared with an increase of 2% in the placebo group. The patient diary VAS confirmed this result, and likewise the final overall assessments showed superiority of the willow bark extract over the placebo (patients' assessment, p = 0.0002; investigators' assessment, p = 0.0073). It is concluded that the willow bark extract showed a moderate analgesic effect in osteoarthritis and appeared to be well tolerated.
Article
We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IκB kinase β (IKKβ) attenuated insulin signaling in cultured cells, whereas IKKβ inhibition reversed insulin resistance. Thus, IKKβ, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikkβ +/−) protected against the development of insulin resistance during high-fat feeding and in obese Lepob/ob mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKβ pathway as a target for insulin sensitization.
Article
Preparations containing willow bark extract are popular herbal remedies, but they are mostly standardised with respect to only one compound (usually salicin). RP-HPLC using a C18-column eluted with water:methanol:tetrahydrofuran and coupled to electrospray triple-quadrupole MS and MS/MS was used for the characterisation of dried extracts of Salix spp. and for the identification of their constituents. Comparison with reference substances led to the identification of 13 compounds (saligenin, salicylic acid, salicin, isosalicin, picein, salidroside, triandrin, salicoylsalicin, salicortin, isosalipurposide, salipurposide, naringenin-7-O-glucoside and tremulacin). Two pharmaceutical preparations containing willow bark extract, used in clinical trials and labelled Salix daphnoides and S. purpurea x daphnoides extracts, were compared using the described method and exhibited several clear differences, the most prominent of which was the possible presence of picein in the former preparation. The described method may be utilised for the characterisation of herbal medicines in order to ensure comparability of medication in further clinical trials.
Article
Recently, there have been extensive efforts to evaluate the chemopreventive role of substances present in natural products. The aim of this study was to examine the effects of the main groups of compounds (salicylalcohol derivates, flavonoids, proanthocyanidins), and salicin isolated from willow bark extract BNO 1455 on proliferation and apoptosis in human colon and cancer cells. We used human colon cyclooxygenase-2 (COX-2)-positive HT 29 and (COX-2)-negative HCT 116 or lung COX-2 proficient A 549 and low COX-2 expressing SW2 cells. After treatment for 72 h with various concentrations of single substances and acetylsalicylic acid (ASA) as control, inhibition of cell growth and cytotoxicity were measured by colorimetric WST-1 assay and propidium iodide uptake by flow cytometry, respectively. Apoptotic cells were identified by annexin V adhesion using flow cytometry. Studies on dose-dependent effects of BNO 1455 and its fractions showed anti-proliferative activity of all compounds with 50% maximal growth inhibitory concentrations (GI(50)) between 33.3 and 103.3 microg/ml for flavonoids and proanthocyanidins fractions and 50.0-243.0 microg/ml for salicylalcohol derivates and extract. Apoptosis induction was confirmed by annexin V adherence and analysis of cell morphology based on light scattering characteristics using flow cytometry in all cell lines at GI(50). We showed that willow bark extract BNO 1455 an its fractions inhibit the cell growth and promote apoptosis in human colon and lung cancer cell lines irrespective of their COX-selectivity.