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A Systematic Review on the Effectiveness of Willow Bark for Musculoskeletal Pain
Abstract
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
... Notwendigkeit eines künstlichen Kniegelenkersatzes um mehr als 2,5 Jahre hinaus zu zögern. Dass die ins Gelenk verabreichte Hyaluronsäure-Injektion den Knorpel effektiv stärken und damit belastbarer machen kann, zeigen auch die Ergebnisse wissenschaftlicher Studien zur Anwendung dieser Therapieform bei anderen Erkrankungen, welchen eine nutritive Knorpeldegeneration als Ursache zugrunde liegt [10]. Aufgrund dieser Datenlage und klinischen Erfahrungen wurde inzwischen die Hyaluronsäure-Therapie von nationalen und internationalen Fachgesellschaften als wichtiger Bestandteil (1. ...
... Aufgrund dieser Datenlage und klinischen Erfahrungen wurde inzwischen die Hyaluronsäure-Therapie von nationalen und internationalen Fachgesellschaften als wichtiger Bestandteil (1. Therapiestufe) in die Therapieempfehlungen zur konservativen Arthrosebehandlung aufgenommen (DGOU, BVOU, DGOOC, Task-Force der EULAR) und auf die entsprechende aktuelle spezifische Fachliteratur verwiesen [8,9,10]. ...
... 2011 Aug;28(4):355-65. [10] Vas J, Ortega C, Olmo V, Perez-Fernandez F, Hernandez L, Medina I et al. Single-point acupuncture and physiotherapy for the treatment of painful shoulder: a multicentre randomized controlled trial. ...
... The terms 'Listerine' and 'essential oil mouthwash' were used to locate clinical studies published during the period from 31 December 2011 to 31 October 2015. The studies identified were extracted and classified systematically, as previously described (Chrubasik et al., 2004(Chrubasik et al., , 2006(Chrubasik et al., , 2007a(Chrubasik et al., , 2007b(Chrubasik et al., , 2008(Chrubasik et al., , 2010Vlachojannis et al., 2009Vlachojannis et al., , 2010aVlachojannis et al., , 2010b. In short, the Listerine® product investigated was listed as well as the number of the included patients, the study design [parallel or cross-over, randomized, and double-blind (single-blind)], any positive and/or negative controls, the study duration, the primary outcome measure(s), the statistical analysis (intention-to-treat or per protocol), the study hypothesis, and the result(s) of the study. ...
... Other systematic reviews have concluded that the anti-gingivitis and anti-plaque effectiveness of Listerine® is similar to that of the mouthwash CPC (Gunsolley, 2010) or other mouthwashes (Gunsolley, 2006) and that rinsing with Listerine® was superior to uncontrolled brushing of the teeth (Stoeken et al., 2007). The evidence of effectiveness for Listerine® as an anti-gingivitis and anti-plaque mouthwash can therefore be classified today as 'strong' on the basis of three confirmatory and numerous exploratory studies on efficacy (Chrubasik et al., 2004(Chrubasik et al., , 2006(Chrubasik et al., , 2007a(Chrubasik et al., , 2007b(Chrubasik et al., , 2008(Chrubasik et al., , 2010Vlachojannis et al., 2009Vlachojannis et al., , 2010aVlachojannis et al., , 2010b. The American Acceptance Program Guidelines concerning 'Adjunctive Dental Therapies for the Reduction of Plaque and Gingivitis' (ADA, 2011) require only two clinical studies for a product to enter the market, provided that the studies (i) include patients with (at least) mild gingivitis, (ii) are conducted over (at least) 4 weeks, (iii) that the test includes a placebo control, and (iv) demonstrates at least a 15% (estimated proportionate reduction) and 20% (arithmetic mean of the estimated proportionate reduction) improvement in the plaques and gingivitis indices. ...
... An earlier shorter exploratory study (Charles et al., 2012) came to the same result as the confirmatory 6-month study (Cortelli et al., 2013), but in another exploratory study (Pizzo et al., 2013) Listerine® Zero was no more effective than the control solution. The evidence of effectiveness can be classified as "moderate" which is defined as 'consistent findings from one confirmatory study with a clinically relevant effect or from multiple exploratory studies of high internal validity, or from both (provided that a clinically relevant effect was achieved)' (Chrubasik et al., 2010;Vlachojannis et al., 2009Vlachojannis et al., , 2010aVlachojannis et al., , 2010b. For Listerine® Cool Blue, the evidence of effectiveness is poor (one exploratory study). ...
Unlabelled:
In the 19th century, the mouthwash Listerine® was formulated from four essential oils. Later, the oils were replaced by their marker substances. To keep them in solution, 24-27% ethanol was added as a vehicle. This is an update of our previous review on the efficacy and safety of Listerine®.
Method:
PubMed was searched for clinical studies on the therapeutic benefits and safety of Listerine® from the end of 2011 to the end of October 2015.
Results:
Sixteen studies were found and extracted. Three of the four 6-month studies were of sound confirmatory design. Two of these investigated Listerine® and one Listerine Zero®. The evidence of effectiveness for Listerine®, based on the bulk of three confirmatory studies and numerous exploratory studies carried out so far, is strong, but only moderate for Listerine® Zero and poor for Listerine® Cool Blue. In the three safety studies identified, we found methodological flaws that biased the results.
Conclusions:
Evidence is accumulating that Listerine® is effective in improving oral health, but the absence of systematic toxicological studies means that an accurate safety assessment cannot be made.
... Willow bark is regarded as a successful example of a modern drug developed from an herbal remedy, which was first described 200 years ago. Salicin (SA) is the main chemically standardized willow bark extract; its chemical oxidation resulted in a new substance termed "salicylic acid", and the acetylated derivative was finally turned into the famous drug called "aspirin" 4,5 . SA is metabolized into salicylic acid after oral ingestion and plays roles in the treatment of pain, headaches, and inflammatory conditions 5,6 . ...
... Salicin (SA) is the main chemically standardized willow bark extract; its chemical oxidation resulted in a new substance termed "salicylic acid", and the acetylated derivative was finally turned into the famous drug called "aspirin" 4,5 . SA is metabolized into salicylic acid after oral ingestion and plays roles in the treatment of pain, headaches, and inflammatory conditions 5,6 . However, the formation of salicylic acid alone is unlikely to explain the analgesic or anti-rheumatic effects of willow bark 7 , which indicates potential mechanisms that need further clarification. ...
Despite the high prevalence of osteoarthritis (OA) in older populations, disease-modifying OA drugs (DMOADs) are still lacking. This study was performed to investigate the effects and mechanisms of the small molecular drug salicin (SA) on OA progression. Primary rat chondrocytes were stimulated with TNF-α and treated with or without SA. Inflammatory factors, cartilage matrix degeneration markers, and cell proliferation and apoptosis markers were detected at the mRNA and protein levels. Cell proliferation and apoptosis were evaluated by EdU assays or flow cytometric analysis. RNA sequencing, molecular docking and drug affinity-responsive target stability analyses were used to clarify the mechanisms. The rat OA model was used to evaluate the effect of intra-articular injection of SA on OA progression. We found that SA rescued TNF-α-induced degeneration of the cartilage matrix, inhibition of chondrocyte proliferation, and promotion of chondrocyte apoptosis. Mechanistically, SA directly binds to IRE1α and occupies the IRE1α phosphorylation site, preventing IRE1α phosphorylation and regulating IRE1α-mediated endoplasmic reticulum (ER) stress by IRE1α-IκBα-p65 signaling. Finally, intra-articular injection of SA-loaded lactic-co-glycolic acid (PLGA) ameliorated OA progression by inhibiting IRE1α-mediated ER stress in the OA model. In conclusion, SA alleviates OA by directly binding to the ER stress regulator IRE1α and inhibits IRE1α-mediated ER stress via IRE1α-IκBα-p65 signaling. Topical use of the small molecular drug SA shows potential to modify OA progression.
... Several studies have been performed on the chemical composition of willow bark. Many compounds such as saligenin and its derivative salicin, flavonoids and tannins have been identified in the willow bark [32,78,79]. Salicin is considered the main active ingredient as it is metabolized to salicylic acid. ...
... However, willow bark is an important bitter tonic with marked astringent properties in humans, making it useful in chronic hypersecretory states, such as mucus discharges, passive hemorrhage, leucorrhea, humid asthma, diarrhea, and dysentery [80]. The effects of willow bark attributed to the salicin compounds include analgesic [78], anti-inflammatory [32,81,82], antipyretic [83,84], and antiplatelet activity [80]. These activities are also well known for supporting the body's response to normal physiological stress [85]. ...
Over the last decade, there has been a growing interest in the use of a wide range of phytoadditives to counteract the harmful effects of heat stress in poultry. Willow (Salix spp.) is a tree with a long history. Among various forms, willow bark is an important natural source of salicin, β-O-glucoside of saligenin, but also of polyphenols (flavonoids and condensed tannins) with antioxidant, antimicrobial, and anti-inflammatory activity. In light of this, the current review presents some literature data aiming to: (1) describe the relationship between heat stress and oxidative stress in broilers, (2) present or summarize literature data on the chemical composition of Salix species, (3) summarize the mechanisms of action of willow bark in heat-stressed broilers, and (4) present different biological effects of the extract of Salix species in different experimental models.
... Several studies have been performed on the chemical composition of willow bark. Many compounds such as saligenin and its derivative salicin, flavonoids and tannins have been identified in the willow bark [29,75,76]. Salicin is considered the main active ingredient as it is metabolized to salicylic acid. ...
... However, willow bark is an important bitter tonic with marked astringent properties in humans, making it useful in chronic hypersecretory states, such as mucus discharges, passive hemorrhage, leucorrhea, humid asthma, diarrhea and dysentery [77]. The effects of willow bark attributed to the salicin compounds include analgesic [75], anti-inflammatory [29,78,79], antipyretic [80,81] and antiplatelet activity [77]. These activities are also well known for supporting the body's response to normal physiological stress [82]. ...
Over the last decade, there has been a growing interest in the use of a wide range of phytoadditives to counteract the harmful effects of heat stress in poultry. Willow (Salix spp.) is a tree with a long history. Among various forms, willow bark is an important natural source of salicin, β-O-glucoside of saligenin, but also of polyphenols (flavonoids and condensed tannins) with antioxidant, antimicrobial and anti-inflammatory activity. In light of this, the current review presents some literature data aiming to: (1) describe the relationship between heat stress and oxidative stress in broilers, (2) present or summarize literature data on the chemical composition of Salix species, (3) summarize the mechanisms of action of willow bark in heat-stressed broilers, (4) present different biological effects of the extract of Salix species in different experimental models.
... Traditional knowledge. Various species from the genus Salix, or willow, were already in common use for pain relief in antiquity [63,64], being first mentioned in the Ebers papyrus (about 1550 BC) [65], and afterwards by all the great masters of medicine in antiquity, middle ages, and modern times [66]. ...
... A systematic review concluded that there is moderate evidence for the efficiency of WBE in low back pain, but insufficient data for OA and RA, suggesting that higher doses should be tested [64]. ...
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 an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved 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 summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.
... Traditional knowledge. Various species from the genus Salix, or willow, were already in common use for pain relief in antiquity [83,84], being first mentioned in the Ebers papyrus (about 1550 BC) [85], and afterwards by all the great masters of medicine in antiquity, middle ages, and modern times [86]. ...
... A systematic review concluded that there is moderate evidence for the efficiency of WBE in low back pain, but insufficient data for OA and RA, suggesting that higher doses should be tested [84]. ...
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.
... Various species from the genus Salix, or willow, were already in common use for pain relief in antiquity (Vlachojannis et al., 2009), The inflammation-suppressing effect of willow extract relies, at least partially, on its ability to antagonize the activated monocytes, by blocking the activity of pro-inflammatory cytokines (TNFα), enzymes (COX-2), and mediators (NF-κB) (Bonaterra et al., 2010). ...
... were found, they were used for their healing and recuperative properties (Gensler, 1981, Moerman, 2009, Mahdi, 2010 and, more recently, within dietary supplements, where the bioactive compounds present in willow may contribute to easing musculoskeletal pain. Phenolic glucosides, also known as salicylic glucosides, are now known to be responsible for this effect (Vlachojannis et al., 2009). A comparison of these supplements with typical doses of synthetically produced acetylsalicin (aspirin) revealed that while the quantity of salicin present in bark extracts was considerably lower, it nevertheless had an analgesic effect, which was partially attributed to polyphenols and flavonoids present in the extracts (Vlachojannis et al., 2011). ...
Throughout history, the genus Salix (willow) has been an incredibly useful temperate plant for humans, with widespread global distribution and species indigenous to all continents except Antarctica. Estimations of the number of species range from 450 to 520 worldwide, and there are still more natural hybrids and multi-hybrid combinations. Several biomass willow breeding programmes have been established across the globe. All of these attempt to produce fast-growing, high-yielding stems with a straight habit and minimal side branching that are highly adaptable to different sites and are also disease and pest resistant. Short rotation coppice (SRC) cultivation involves growing willow at close spacings with a stocking rate of around 15,000 per hectare with harvests every 2–4 years. The crop is mechanically harvested, typically using a forager, and material has recently been used for bioenergy applications. Trial plots have achieved yields of up to 20 odt/ha/yr, whilst well-tended commercial crops have yielded up to 14 odt/ha/yr. Global willow breeding programmes have produced a wide variety of commercial genotypes that have suitable properties for easy planting and harvesting and have the added benefit of elevated levels of bioactive compounds, including salicin, present in the bark, which can be used in medical and veterinary applications. These high-yielding willow varieties grow well in the wetter regions of the globe, including NW Europe, and afford multiple harvests before re-planting. Salix's versatility and adaptability and the SRC cultivation process make them an ideal candidate feedstock for use in an integrated biorefinery to produce a range of biobased materials, including pharmaceuticals, and biocomposites, fuels, energy and fertiliser.
... Salicin is one of active ingredients of the broad Salicaceae woody plant family [42]. This compound has anti-inflammatory properties [43,44]. Salicin was the original source of aspirin. ...
Phenolic compounds of natural origin have been valued for their beneficial effects on health since ancient times. During our study, we performed the extraction of phenolic compounds from balsam poplar buds using different concentrations of aqueous polyethylene glycol 400 solvents (10–30% PEG400). The aqueous 30% PEG400 extract showed the best phenolic yield. The stability of the extract during autoclave sterilization was evaluated. The extract remained stable under heat sterilization. Ophthalmic formulations are formed using different concentrations (8–15%) of poloxamer 407 (P407) together with hydroxypropyl methylcellulose (0.3%), sodium carboxymethyl cellulose (0.3%) or hyaluronic acid (0.1%). Physicochemical parameters of the formulations remained significantly unchanged after sterilization. Formulations based on 12% P407 exhibited properties characteristic of in situ gels, the gelation point of the formulations was close to the temperature of the cornea. After evaluating the amount of released compounds, it was found that, as the concentration of polymers increases, the amount of released compounds decreases. Formulations based on 15% P407 released the least biologically active compounds. Sterilized formulations remained stable for 30 days.
... (El-Shemy et al., 2007;Ward et al., 2020). Willow extracts can also be used to relieve pain, inflammation, and fever in a wide variety of conditions with minor adverse effects (Chrubasik et al., 2000;Vlachojannis et al., 2009;Shara and Stohs, 2015). As only mild cytotoxicity has been discovered in willow bark extracts, willows are a promising biomass for various health applications (Ramos et al., 2019). ...
Earlier studies have shown that the bark of Salix L. species (Salicaceae family) is rich in extractives, such as diverse bioactive phenolic compounds. However, we lack knowledge on the bioactive properties of the bark of willow species and clones adapted to the harsh climate conditions of the cool temperate zone. Therefore, the present study aimed to obtain information on the functional profiles of northern willow clones for the use of value-added bioactive solutions. Of the 16 willow clones studied here, 12 were examples of widely distributed native Finnish willow species, including dark-leaved willow ( S. myrsinifolia Salisb.) and tea-leaved willow ( S. phylicifolia L.) (3 + 4 clones, respectively) and their natural and artificial hybrids (3 + 2 clones, respectively). The four remaining clones were commercial willow varieties from the Swedish willow breeding program. Hot water extraction of bark under mild conditions was carried out. Bioactivity assays were used to screen antiviral, antibacterial, antifungal, yeasticidal, and antioxidant activities, as well as the total phenolic content of the extracts. Additionally, we introduce a fast and less labor-intensive steam-debarking method for Salix spp. feedstocks. Clonal variation was observed in the antioxidant properties of the bark extracts of the 16 Salix spp. clones. High antiviral activity against a non-enveloped enterovirus, coxsackievirus A9, was found, with no marked differences in efficacy between the native clones. All the clones also showed antibacterial activity against Staphylococcus aureus and Escherichia coli , whereas no antifungal ( Aspergillus brasiliensis ) or yeasticidal ( Candida albicans ) efficacy was detected. When grouping the clone extract results into Salix myrsinifolia , Salix phylicifolia , native hybrid, artificial hybrid, and commercial clones, there was a significant difference in the activities between S. phylicifolia clone extracts and commercial clone extracts in the favor of S. phylicifolia in the antibacterial and antioxidant tests. In some antioxidant tests, S. phylicifolia clone extracts were also significantly more active than artificial clone extracts. Additionally, S. myrsinifolia clone extracts showed significantly higher activities in some antioxidant tests than commercial clone extracts and artificial clone extracts. Nevertheless, the bark extracts of native Finnish willow clones showed high bioactivity. The obtained knowledge paves the way towards developing high value-added biochemicals and other functional solutions based on willow biorefinery approaches.
... Willows (Salicaceae) have been an integral part of the human societies since the ancient times due to their multiple uses, such as the use of their bark to alleviate pain (Vlachojannis et al. 2009) and the utilization of their wood to create willow coracles, which dates back to Herodotus in the fifth century BC (Karp et al. 2011). Nowadays, fastgrowing willow (Salix spp.) clones are also cultivated in the framework of short-rotation forestry (Lumme and Tormala 1988), thus being important plants for cultivation as bioenergy crops throughout the world (Kopp et al. 2001;Adegbidi et al. 2001;Maruyama et al. 2002;Volk et al. 2006; Mola-Yudego and Pelkonen 2008; Mola-Yudego and González-Olabarria 2010; El Kasmioui and Ceulemans 2012; Guidi Nissim et al. 2013;Fabio et al. 2017;Nordborg et al. 2018;Kakuk et al. 2021). ...
Ground-level ozone (O3) is a widespread air pollutant causing extensive injuries in plants. However, its effects on perennial energy crops remain poorly understood due to technical difficulties in cultivating fast-growing shrubs for biomass production under O3 treatment on the field. Here we present the results of a two-year evaluation in the framework of which willow (Salix sachalinensis F. Schmid) shrubs were exposed to ambient (AOZ) or elevated (EOZ) O3 in two successive growing seasons (2014, 2015) and treated with 0 (EDU0) or 400 mg L−1 (EDU400) ethylenediurea spray in the second growing season. In 2014, EOZ altered the chemical composition of both top young and fallen leaves, and a novel mechanism of decreasing Mg in fallen leaves while highly enriching it in young top leaves was revealed in shrubs exposed to EOZ. In 2015, EDU400 alleviated EOZ-induced decreases in leaf fresh mass to dry mass ratio (FM/DM) and leaf mass per area (LMA). While EDU400 protected against EOZ-induced suppression of the maximum rate at which leaves can fix carbon (Amax) in O3-asymptomatic leaves, it did not alleviate EOZ-induced suppression of the maximum rates of carboxylation (VCmax) and electron transport (Jmax) and chlorophylls a, b, and a + b in the same type of leaves. In O3-symptomatic leaves, however, EDU400 alleviated EOZ-induced suppression of chlorophylls a and a + b, indicating different mode of action of EDU between O3-asymptomatic and O3-symptomatic leaves. Extensive herbivory occurred only in AOZ-exposed plants, leading to suppressed biomass production, while EOZ also led to a similar suppression of biomass production (EDU0 × EOZ vs. EDU400 × EOZ). In 2016, carry-over effects were also evaluated following cropping and transplantation into new ambient plots. Effects of EOZ in the preceding growing seasons extended to the third growing season in the form of suppressed ratoon biomass production, indicating carry-over effect of EOZ. Although EDU400 protected against EOZ-induced suppression of biomass production when applied in 2015, there was no carry-over effect of EDU in the absence of EDU treatment in 2016. The results of this study provide novel mechanistic understandings of O3 and EDU modes of action and can enlighten cultivation of willow as energy crop.
--This is an open-access paper, which can be downloaded for free at https://doi.org/10.1007/s11676-021-01400-1
... The effectiveness and safety profile of herbal medicines such as willow bark extract is of great interest. In this sense, the ethanolic extract showed to be effective and safe to treat low back pain [21,22], and it showed a moderate analgesic effect against osteoarthritis [17]. The action of willow bark extract as an anti-inflammatory agent was compared to celecoxib and acetylsalicylic acid, and it was found to be as effective as these drugs [23]. ...
In this review, a timeline starting at the willow bark and ending in the latest discoveries of analgesic and anti-inflammatory drugs will be discussed. Furthermore, the chemical features of the different small organic molecules that have been used in pain management will be studied. Then, the mechanism of different types of pain will be assessed, including neuropathic pain, inflammatory pain, and the relationship found between oxidative stress and pain. This will include obtaining insights into the cyclooxygenase action mechanism of nonsteroidal anti-inflammatory drugs (NSAID) such as ibuprofen and etoricoxib and the structural difference between the two cyclooxygenase isoforms leading to a selective inhibition, the action mechanism of pregabalin and its use in chronic neuropathic pain, new theories and studies on the analgesic action mechanism of paracetamol and how changes in its structure can lead to better characteristics of this drug, and cannabinoid action mechanism in managing pain through a cannabinoid receptor mechanism. Finally, an overview of the different approaches science is taking to develop more efficient molecules for pain treatment will be presented.
... The proper substances for incorporation into collagen can be several plant extracts, including willow bark extract which contains salicin. Willow bark extract is eminently efficient in the treatment of diseases like rheumatoid arthritis [22,23], painful mobility disorders [24], osteoarthritis [25][26][27], and other inflammatory afflictions. Anti-inflammatory properties of salicin and its derivatives in willow bark extract include natural pro-drugs of salicylates [24]. ...
Collagen films are widely used as adhesives in medicine and cosmetology. However, its properties require modification. In this work, the influence of salicin on the properties of collagen solution and films was studied. Collagen was extracted from silver carp skin. The rheological properties of collagen solutions with and without salicin were characterized by steady shear tests. Thin collagen films were prepared by solvent evaporation. The structure of films was researched using infrared spectroscopy. The surface properties of films were investigated using Atomic Force Microscopy (AFM). Mechanical properties were measured as well. It was found that the addition of salicin modified the roughness of collagen films and their mechanical and rheological properties. The above-mentioned parameters are very important in potential applications of collagen films containing salicin.
... Salicin is the main component of the willow bark extract, commonly used in traditional medicine for its anti-inflammatory and antipyretic effects [115]. Salicin is metabolized to salicylic acid in vivo; therefore, it is also known as "nature's aspirin". ...
High-mobility group box 1 (HMGB1) is a protein that is part of a larger family of non-histone nuclear proteins. HMGB1 is a ubiquitary protein with different isoforms, linked to numerous physiological and pathological pathways. HMGB1 is involved in cytokine and chemokine release, leukocyte activation and migration, tumorigenesis, neoangiogenesis, and the activation of several inflammatory pathways. HMGB1 is, in fact, responsible for the trigger, among others, of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), toll-like receptor-4 (TLR-4), and vascular endothelial growth factor (VEGF) pathways. Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) that is rapidly growing in number. DR is an inflammatory disease caused by hyperglycemia, which determines the accumulation of oxidative stress and cell damage, which ultimately leads to hypoxia and neovascularization. Recent evidence has shown that hyperglycemia is responsible for the hyperexpression of HMGB1. This protein activates numerous pathways that cause the development of DR, and HMGB1 levels are constantly increased in diabetic retinas in both proliferative and non-proliferative stages of the disease. Several molecules, such as glycyrrhizin (GA), have proven effective in reducing diabetic damage to the retina through the inhibition of HMGB1. The main focus of this review is the growing amount of evidence linking HMGB1 and DR as well as the new therapeutic strategies involving this protein.
... 6,7 as confirmed by in-vitro and animal studies from the past decades, this product is still in use nowadays for its antipyretic, analgesic, anti-inflammatory and anti-microbial activities. [8][9][10][11][12] W-mal contains not less than 1.5% of total salicylic alcohol derivatives, expressed as salicin. Upon ingestion, more than 80% of salicin contained in the extract is metabolized by the liver to salicylic acid, chemically similar to aspirin, and exerts crucial antiinflammatory role. ...
... Known for its alleviating effect on fever, pain, and inflammation, willow bark has been referred to as "nature's Aspirin." In preclinical and clinical studies, willow bark has been reported to be effective in pain management and anti-inflammation [8,9]. Salicin is the major component of willow bark extract. ...
Retinal endothelial cells (RECs) are involved in many ocular diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Salicin is the major ingredient of willow bark extract, and it has been shown to be a potent anti-inflammatory agent. We aim to explore whether salicin has a vascular protective effect in RECs. Our data indicate that the presence of salicin in RECs culture media ameliorates interleukin-1β (IL-1β)-induced cellular reactive oxygen species (ROS) production and NADPH oxidase 4 (NOX-4) expression. At the cellular level, salicin attenuates IL-1β-induced mitochondrial injury as revealed by its preservation on mitochondrial membrane potential (MMP). Furthermore, salicin inhibits IL-1β-induced production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), vascular adhesion molecules such as intercellular cell adhesion molecule-1 (iCAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and high-mobility group protein 1 (HMGB-1). On the other hand, salicin recovers IL-1β-induced reduction of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) release. The presence of salicin significantly reduces the IL-1β-induced release of lactate dehydrogenase (LDH), indicating that it mitigates cytokine caused cytotoxicity. Mechanistically, we show that salicin suppresses IL-1β-induced activation of the nuclear factor-kappa B (NF-κB) signaling as revealed by its suppression on nuclear p65 protein and transfected NF-κB promoter. Collectively, our study demonstrates by multiple facets of its mechanisms that salicin is a protective agent in retinal endothelial cells. These results imply its potential use in therapeutic usage of retinal disease.
... White willow (Salix alba) has been used traditionally, as a source of bioactive compounds including salicin, polyphenols, and flavonoids (Vlachojannis et al. 2009). Among these active compounds, salicin is known best for its support of the response of the organism to the normal physiological stress (Albrecht et al. 1990). ...
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.
... The anti-inflammatory and analgesic effects of the inner bark of the willow tree (Salix species), the original source of acetylsalicylic acid in aspirin, are supported by a systematic review concluding that oral willow bark extract in daily doses of up to 240 mg (60 mg capsules TID or QID) has evidence of effectiveness for low back pain and osteoarthritis. 11 In the review, 3 well-designed studies were noted to demonstrate a dose-dependent analgesic effect similar to the nonsteroidal anti-inflammatory rofecoxib in patients with low back pain and osteoarthritis. ...
... Salix extract (willow bark extract) has been shown to be a potent antioxidant in vitro and slowed the development of OA using an animal model by reducing inflammatory cytokines (e.g., tumor necrosis factor [TNF]-α, IL-1β, and IL-6) and nitric oxide [NO] production [67]. A systematic review conducted by Vlachojannis et al. [68] reported that willow bark extract alleviated lower back pain, and in the Liu et al. [29] meta-analysis, the ES on pain across two studies was − 0.29 (95% CI − 0.62, 0.04) and − 0.24 (95% CI − 0.55, 0.07) on improving physical functioning, with a low quality of evidence. Willow bark extract contains a bioactive compound related to aspirin (i.e., salicin; a prodrug that is metabolized to salicylate derivatives), which is thought to be responsible for its analgesic and anti-inflammatory properties [69,70]. ...
Purpose of Review
Osteoarthritis, the most common joint disease, is associated with substantial medical costs, lost productivity, and reduced quality of life. However, available pharmaceutical treatments have limitations in terms of efficacy and long-term safety.
Recent Findings
In vitro evidence suggests that some natural products may possess anti-inflammatory and anti-oxidative properties and may inhibit the release of key osteoarthritis-related cytokines. There is, therefore, ongoing interest in identifying natural products that safely promote joint health and treat osteoarthritis. Numerous plant extracts, including curcumin, Boswellia extract, and pycnogenol, have shown effect sizes (ES) for reducing pain and functional disability larger than those observed with analgesics and products such as glucosamine and chondroitin. The ES for methylsulfonylmethane and avocado/soybean unsaponifiables are also considered to be clinically relevant.
Summary
Data from a small number of studies using natural products for treating osteoarthritis are promising but require confirmation in further well-designed clinical trials.
... Several studies identified many compounds in the willow bark, which contribute to its biological activity. Among these active com pounds, salicin is known most for its support of the organism answer to normal physiological stress, having antiinflammatory properties (Fiebich and Chrubasik, 2004;Nahrstedt et al., 2007;Vlachojannis et al., 2009). According to the European Pharmacopoeia (04/2008: 2312), the willow bark extract contains at least 5.0% of the total salicylic derivates, expressed as salicin (C 13 H 18 O 7 ). ...
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.
... The active ingredient, salicin, which was used to develop aspirin in the 1800s, is responsible for the claimed anti-inflammatory effects [50]. Vlachojannis et al. [51] conducted a systematic review on the efficacy of willow bark for musculoskeletal pain that demonstrated conflicting results in patients with OA. A subsequent systematic review identified two RCTs of willow bark extract in a dose corresponding to 240 mg salicin per day, including 162 participants in a period of 2 or 6 weeks, and suggested no significant effect for symptomatic improvement when compared with placebo. ...
OA is a chronic and disabling joint disease with limited evidence-based pharmacological treatment options available that improve outcomes for patients safely. Faced with few effective pharmacological treatments , the use has grown of dietary supplements and complementary medicines for symptomatic relief among people living with OA. The aim of this review is to provide a summary of existing evidence and recommendations supporting the use of supplements for OA. Systematic reviews and randomized controlled trials investigating oral supplements for treating OA were identified. Limited research evidence supports recommendations for the oral use of Boswellia serrata extract and Pycnogenol, curcumin and methylsulfonylmethane in people with OA despite the poor quality of the available studies. Few studies adequately reported possible adverse effects related to supplementation, although the products were generally recognized as safe. Further high quality trials are needed to improve the strength of evidence to support this recommendation and better guide optimal treatment of people living with OA.
... 6,7 as confirmed by in-vitro and animal studies from the past decades, this product is still in use nowadays for its antipyretic, analgesic, anti-inflammatory and anti-microbial activities. [8][9][10][11][12] W-mal contains not less than 1.5% of total salicylic alcohol derivatives, expressed as salicin. Upon ingestion, more than 80% of salicin contained in the extract is metabolized by the liver to salicylic acid, chemically similar to aspirin, and exerts crucial antiinflammatory role. ...
Background:
The 1,2-decanediol (S-Mal) is an organic compound belonging to the 1,2- alkanediol family, with two hydroxyl groups located on the first and second carbon of the alkane chain, probably responsible for the enhanced anti-bacterial efficacy. The willow bark total extract (W-Mal) has been used since thousands of years as an herbal remedy for its antipyretic, analgesic, anti-inflammatory and anti-microbial activities. S-Mal is used in cosmetic preparations, whether W- Mal can be topically or systemically administered. Aim of our study was to evaluate in vitro the anti-inflammatory and antioxidant properties of S-Mal and W-Mal, singularly or in combination, in LPS-stimulated keratinocytes.
Methods:
The possible toxic effect of S-Mal and W-Mal was assessed through analysis of cell viability 24h after treatment. The anti-inflammatory and antioxidant activities were evaluated by measuring IL-8, TNF-α and IL-1β production as well as cellular antioxidants (GSH and NADPH) consumption, respectively, 24 and 48h after LPS stimulation.
Results:
Both substances resulted able to: i) increase cell viability (P < 0.05), ii) decrease the release of inflammatory mediators (IL-8, TNF-α and IL-1β) (P < 0.05- P < 0.001), and iii) limit the depletion of cellular antioxidants (GSH and NADPH) (P < 0.001).
Conclusions:
S-Mal and W-Mal have shown a potential cytoprotective activity when used together, and good anti-inflammatory and antioxidant effects when used either singularly or in combination. In light of our results, S-Mal and W-Mal could represent effective and safe options in the management of bacterial-induced or aggravated skin conditions.
... A systematic review of seven clinical trials related to the use of willow bark for musculoskeletal pain indicated that willow bark extract inhibited COX-2, showed an antioxidant effect in animal models, and reduced infl ammation and pain. 23 An open-label observational study with willow bark extract STW33-I provided Level 3 evidence of the effectiveness of willow bark. The authors used a willow bark dose equivalent to 240 mg salicylic alcohol in 436 outpatients. ...
This is part 2 of a three-part series designed to provide clinicians with a working knowledge of the use of herbal supplements for health and disease states. Part 2 of the series focuses on the efficacy of herbal supplements used in the treatment of common chronic conditions.
... These were compared with those used in the meta-analyses of the reviews. The individual studies were classified as 'confirmatory' (an adequately controlled and appropriately sized trial where hypotheses were stated in advance) or 'exploratory' (all other studies) in order to evaluate the evidence of effectiveness for the outcomes as previously reported (Chrubasik-Hausmann et al., 2014a, 2014bVlachojannis et al., 2009Vlachojannis et al., , 2010aVlachojannis et al., , 2010bVlachojannis et al., , 2013Vlachojannis et al., , 2015aVlachojannis et al., , 2015bVlachojannis et al., , 2016. ...
The aim of the study was to review the effect of cocoa flavanols on cardiovascular health, with emphasis on the doses ingested, and to analyze a range of cocoa products for content of these compounds. PubMed was searched from 2010 to locate systematic reviews (SR) on clinical effects of chocolate consumption. Thirteen SRs were identified and reviewed, and provided strong evidence that dark chocolate did not reduce blood pressure. The evidence was however strong for an association with increased flow-mediated vasodilatation (FMD) and moderate for an improvement in blood glucose and lipid metabolism. Our analysis showed that cocoa products with around 100 mg epicatechin can reliably increase FMD, and that cocoa flavanol doses of around 900 mg or above may decrease blood pressure in specific individuals and/or if consumed over longer periods. Out of 32 cocoa product samples analyzed, the two food supplements delivered 900 mg of total flavanols and 100 mg epicatechin in doses of 7 g and 20 g and 3 and 8 g, respectively. To achieve these doses with chocolate, around 100 to 500 g (for 900 mg flavanols) and 50 to 200 g (for 100 mg epicatechin) would need to be consumed. Chocolate products marketed for their purported health benefits should therefore declare the amounts of total flavanols and epicatechin. Copyright © 2016 John Wiley & Sons, Ltd.
Salicin is a notable phenolic glycoside derived from plants including Salix and Populus genus and has multiple biological activities such as anti-inflammatory and antiarthritic, anticancer, and antiaging effects. In this work, we engineered production of salicin from cheap renewable carbon resources in Escherichia coli (E. coli) by extending the shikimate pathway. We first investigated enzymes synthesizing salicylate from chorismate. Subsequently, carboxylic acid reductases (CARs) from different resources were screened to achieve efficient reduction of salicylate. Third, glucosyltransferases from different sources were selected for constructing cell factories of salicin. The enzymes including salicylate synthase AmS from Amycolatopsis methanolica, carboxylic acid reductase CARse from Segniliparus rotundus, and glucosyltransferase UGT71L1 from Populous trichocarpa were overexpressed in a modified E. coli strain MG1655-U7. The engineered strain produced 912.3 ± 12.7 mg/L salicin in 72 h of fermentation. These results demonstrated the production of salicin in a microorganism and laid significant foundation for its commercialization for pharmaceutical and nutraceutical applications.
Resolvins and lipoxins endue a novel way of approaching aspirin mechanism of action by developing models. Recent advances in research of aspirin from starting point Willow bark (Salix alba) to resolvins and lipoxins along with their repurposing network. Therefore, aspirin have a big impact on most interesting areas of research. Aspirin and there interaction with several targets molecules (Magic shotguns) give the option in the uses of various disorder but there MOA based uses in all cases not limited to COX rather than newer ones like resolvins, lipoxins, protectins and maresins, In particular, resolvin and lipoxins will play a central part while research aspirin and their rescheduling in different human diseases that's are better emphasize by novel MOA of aspirin.
Therapeutics against breast cancer is a major research field, due to inefficiency or partial efficiency of existing therapeutics. An urge to discover better therapeutics always persists. Our objective is to study salicin against breast cancer cells, in order to find its therapeutic properties. To study the effect of salicin on breast cancer cells, we performed MTT assay on MCF-7 (hormone positive) and MDA-MB-231 (triple negative) breast cancer cell lines, we did brine shrimp lethality test (BSLT) assay to see the lethal effects of salicin. By the help of bioinformatics we tried to locate the targets that delineate salicin activity. Salicin was docked with estrogen receptor (ER), progesterone receptor (PR) and Human epidermal growth factor receptor 2 (HER2) to study its binding efficiency and possible targets of salicin. Salicin remarkably reduces cell viability both in MCF-7 and MDA-MB-231, along with being lethal to brine shrimps. These results together opine that salicin can be an effective therapeutics against breast cancer cells. The mechanism of action of salicin is probably through ER, PR and HER2 receptors because it can efficiently bind these receptors with minimum energy required for binding. This explains that salicin can easily bind to these receptors. These results together opine that salicin can be an effective therapeutics against breast cancer cells. The mechanism of action of salicin is probably through ER, PR and HER2 receptors because it can efficiently bind these receptors with minimum binding energy. ER, PR and HER2 are major reasons behind the disease pathogenicity depending on the type of breast cancer. According to our results salicin may either induce apoptosis or reduce cellular mitosis both via P53 dependent and independent pathway, which makes salicin a good choice of both hormone positive and negative breast cancer cells.
Complementary and alternative medicines such as herbal medicines are not currently part of the conventional medical system. As the popularity of and global market for herbal medicine grows among all age groups, with supporting scientific data and clinical trials, specific alternative treatments such as herbal medicine can be reclassified as a practice of conventional medicine. One of the most common conditions for which adults use herbal medicine is pain. However, herbal medicines carry safety concerns and may impact the efficacy of conventional therapies. Unfortunately, mechanisms of action are poorly understood, and their use is unregulated and often underreported to medical professionals. This review aims to compile common and available herbal medicines which can be used as an alternative to or in combination with conventional pain management approaches. Efficacy and safety are assessed through clinical studies on pain relief. Ensuing herb–drug interactions such as cytochrome modulation, additive and synergistic effects, and contraindications are discussed. While self-management has been recognized as part of the overall treatment strategy for patients suffering from chronic pain, it is important for practitioners to be able to also optimize and integrate herbal medicine and, if warranted, other complementary and alternative medicines into their care.
Willow (Salix spp.) is well known as a source of medicinal compounds, the most famous being salicin, the progenitor of aspirin. Here we describe the isolation, structure determination, and anti-cancer activity of a cyclodimeric salicinoid (miyabeacin) from S. miyabeana and S. dasyclados. We also show that the capability to produce such dimers is a heritable trait and how variation in structures of natural miyabeacin analogues is derived via cross-over Diels-Alder reactions from pools of ortho-quinol precursors. These transient ortho-quinols have a role in the, as yet uncharacterised, biosynthetic pathways around salicortin, the major salicinoid of many willow genotypes.
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.
This study attempts a systematic evaluation of the clinical evidence for the use of odourless garlic prepared by ageing or fermentation. By PubMed, CENTRAL, and handsearching, 59 clinical studies were identified for potential extraction, of which 24 fulfilled the inclusion criteria. The quality of the studies and evidence of effectiveness were assessed by an established set of conventional criteria. Even the 12 best clinical trials (50%) had fundamental flaws that prevented to grade them as confirmatory. On the basis of a subsample of 19 exploratory studies (79%), an impressive reduction of cardiovascular risk was found for odourless garlic (evidence of effectiveness, “moderate” and for other indications, “poor”). Evidence of effectiveness is further limited by the fact that most studies used aged garlic produced by one pharmaceutical company and that products differed in composition and dose of the marker substance S‐allyl‐cysteine. In case odourless garlic is potentially an effective remedy in particular for cardiovascular diseases, we discern an urgent need for long‐term confirmatory studies. The ultimate cardiovascular endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques or blood markers of cardiovascular risk would be useful surrogates. Sample sizes for various assumptions are provided.
Eine komplette Darstellung aller komplementärmedizinischen Verfahren unter dem Gesichtspunkt „Schmerz“ würde den Umfang dieses Buches sprengen. Es darf aber keineswegs übersehen werden, dass insbesondere bei Patienten mit chronischen Schmerzen seit Jahrzehnten großes Interesse an einer alternativen oder ergänzenden Behandlung mit anderen, vermeintlich nebenwirkungsärmeren Heilmethoden besteht. Die Inanspruchnahme von komplementärmedizinischen „Therapeuten“ und entsprechende Selbstbehandlungen wird eher selten den behandelnden Ärzten mitgeteilt. Zunächst folgt ein kurzer Überblick über den komplexen Bereich der Komplementärmedizin einschließlich einem allgemeinen Überblick über den Stand der klinischen Evidenz von komplementärmedizinischen Methoden bei Schmerz. Anschließend werden – quasi beispielhaft – drei ausgesuchte und für die Schmerztherapie besonders relevante Methoden ausführlich und für die praktische Anwendung dargestellt: Phytotherapie, Akupunktur und Neuraltherapie.
This chapter presents indications, clinical evidence, pre-clinical evidence, mechanisms of action, interactions, and contraindications of willow (bark) (Salix alba). The main constituents are the phenolic glycosides salicin, acetylsalicin, salicortin, salireposide, picein, triandrin. Esters of salicylic acid, salicyl alcohol, flavonoids including ampelopsin, taxifolin and derivatives, catechin and tannins are also present. The bark of various willow species has been used for treating a wide range of ailments, including fever, headache, influenza, rheumatism, gout and arthritis and is sold in products throughout Europe. Adverse effects, dosage, and general plant information are included in the chapter. Willow preparations have been used throughout the world as antipyretics and analgesics. The origin of aspirin can be traced back to willow bark and its traditional uses, evolving from salicin to salicylic acid and then to the more effective and less toxic acetylsalicylic acid.
Opinion statement
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.
The present study aimed to some of hematological and biochemical parameters in the female alnbino rats of exposing to different concentration of ethanolic extract of Salix acmophylla.
Thus (30) animals of mature female rats were divided into six groups, the rats were proven fertile after checking their estrus cycle through daily raginal smearing for two cycles, the represented control group which intraperitonial injection with physiological solution (0.9 %/ Nacl), the first represented (G1) which injected with ethanolic extract concentration (0.85 mg/ kg) of the body weight, the second represented (G2) which injected with ethanolic extract concentration (1.7 mg/ kg) of the body weight , The third represented (G3) which injected with ethanolic extract concentration (3.4 mg/ kg), the four represented (G4) which injected with concentration (6.8 mg / kg) of the body weight, and the five concentration (13.6 mg / kg) of the body weight.
After finishing the period of the experiment. Samples of blood were collected to determine some hematological and biochemical parameters ,hematological parameters which included the haemoglobin concentration (Hb), packed cells volume (P. C. V. ), total and differential white blood cells (W.B.C.) w biochemical parameters included measurement of the total protein concentration, triglyceride (TG), concentration of the high density lipoprotein cholesterol (HDL-C) and concentration of low density lipoprotein cholesterol (LDL-C) ,The increasing concentration of alcoholic extract resulted to :
1- Significant decrease (p<0.05) of Hb concentration and packed cells volume (PCV).
2- Significant decrease (p<0.05) of total WBC count, neutrophils and monocytes count, besides significant increase (p<0.05) of Lymphocytes, and eosinophil count.
3- Significant decrease (p<0.05) of serum total protein, significant increase (p<0.05) of cholesterol concentration , Triglyceride, and HDL-C, LDL-C in serum of the high concentration of alcoholic extract.
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
It is widely accepted that elevated levels of surface ozone (O3) negatively affect plants. Ethylenediurea (EDU) is a synthetic substance which effectively protects plants against O3-caused phytotoxicity. Among other questions, the one still open is: which EDU application method is more appropriate for treating fast-growing tree species. The main aims of this study were: (i) to test if chronic exposure of Salix sachalinensis plants to 200–400 mg EDU L−1, the usually applied range for protection against O3 phytotoxicity, is beneficial to plants; (ii) to evaluate the effects of chronic exposure to elevated O3 on S. sachalinensis; (iii) to assess the efficacy of two methods (i.e. soil drench and foliar spray) of EDU application to plants; (iv) to investigate the appropriate concentration of EDU to protect against elevated O3-induced damage in S. sachalinensis; and (v) to compare the two methods of EDU application in terms of effectiveness and EDU consumption. Current-year cuttings grown in infertile soil free from organic matter were exposed either to low ambient O3 (AOZ, 10-h ≈ 28.3 nmol mol−1) or to elevated O3 (EOZ, 10-h ≈ 65.8 nmol mol−1) levels during daylight hours. Over the growing season, plants were treated every nine days with 200 mL soil drench of 0, 200 or 400 mg EDU L−1 or with foliar spray of 0, 200 or 400 mg EDU L−1 (in two separate experiments). We found that EDU per se had no effects on plants exposed to AOZ. EOZ practically significantly injured S. sachalinensis plants, and the impact was indifferent between the experiments. EDU did not protect plants against EOZ impact when applied as soil drench but it did protect them when applied as 200–400 mg L−1 foliar spray. We conclude that EDU may be more effective against O3 phytotoxicity to fast-growing species when applied as a spray than when applied as a drench.
The article can be found at:
http://www.sciencedirect.com/science/article/pii/S0048969716318861
Since ancient times until the era when chemotherapy was introduced, phytomedicines were the only treatment available for inflammatory conditions and pain. The most popular treatment was the oral use of the leaf or bark of Salix species or of the aspen tree, the herb of meadowsweet, goldenrod, or wintergreen. Research has shed light into the mechanism(s) of action of the phyto-anti-inflammatory drugs (PAIDs), and many clinical studies have investigated their efficacy. Animal studies indicate a chondroprotective effect for some of the PAIDs (e.g., avocado-soybean unsaponifiables, Devil's claw, boswellia); however, clinical studies so far have not proven a demonstrable chondroprotective effect. Topical PAIDs may, in addition to the conventional pathways, have a skin-irritating component or may contain toxic compounds so they cannot be applied orally. Tripterygium wilfordii Hook F (TWHF) is part of the Traditional Chinese Medicine that recommends crude water extracts from the root to treat inflammatory conditions.
Phytotherapie ist die Behandlung mit ausgesuchten pflanzlichen Arzneimitteln, die das natürliche Vielstoffgemisch der Pflanze noch weitgehend enthalten. Demnach gehören isolierte Pflanzenstoffe, z. B. das Menthol aus dem (Pfeffer-)- Minzöl, streng genommen nicht mehr zur Phytotherapie, sie sollen hier in Einzelfällen aber dennoch besprochen werden. In der modernen Phytotherapie werden keine Pflanzen mit einer geringen therapeutischen Breite (Giftpflanzen) verwendet, sondern – im Gegensatz zu den traditionellen Medizinsystemen (z. B. Traditionelle Chinesische Medizin, Traditionelle Europäische Medizin) – ausschließlich sog. mild wirksame Arzneipflanzen mit großer therapeutischer Breite und einer guten Verträglichkeit.
In der Phytotherapie wird das in der Pflanze enthaltene Vielstoffgemisch formal als ein Wirkstoff betrachtet und begründet als ein dogmatisches Charakteristikum die entsprechende »besondere Therapierichtung«. Im Zuge des Arzneimittelgesetzes haben Phytotherapie, Homöopathie und Anthroposophische Arzneimittel als »besondere Therapierichtungen« eigene (Nach-)Zulassungskommissionen erhalten. Für die Phytotherapie ist dies die Kommission E, die für über 300 Pflanzen/-teile) aus dem gesammelten Erkenntnismaterial Monografien erstellt hat.
The rheumatologic diseases like osteoarthritis, rheumatoid arthritis, lowback pain and fibromyalgia are very common. The synthetic drugs available for treatment of these diseases have low efficacy and considerable adverse effects. Numerous approaches are used as alternatives and complementary to synthetic drugs to treat these diseases. One of the approaches is use of herbal medications. Here, the effects of medicinal plants and herbal active constituents used in treatment of these diseases including gammalinolenic acid, glucosamine, devil's claw (Harpagophytum procumbens), Ocimum species, Salix species, feverfew (Tanacetum parthenium), Tripterygium wilfordii, Uncaria species, nettle (Urtica dioica), ginger (Zingiber officinale), turmeric (Curcuma longa), chicory (Cichorium intybus), dog rose (Rosa canina) and avocado/soybean unsaponifiables obtained from search for english articles published in the databases PubMed and SCOPUS from 1966 to the end of 2011 using the keywords including the scientific, common and traditional names of plants are reviewed. Limited research has been conducted on the antirheumatic effects of these plants and active constituents so far. Thus it seems that further research to determine the mechanisms of action, drug interactions, efficacy and safety of medicinal plants and herbal active constituents potentially useful in treatment of these diseases are warranted.
Reactive oxygen species such as OH, peroxynitrite and the non-radical, hypochlorous acid, play outstanding roles in many disease. The formation of OH (Fenton)-type radicals is catalyzed by enzymes such as xanthine oxidase (XOD) via one-electron reduction of molecular oxygen producing superoxide radical anions (O2). Subsequent transfer of one electron to hydrogen peroxide by Fe2+ or Cu+ -ions yields OH-radicals measurable as ethene release from 1-keto-4-methylthiobutyrate (KMB). Xanthine oxidase or activated neutrophils are prominent sources of this strong oxidant produced at inflammatory sites. Many natural compounds such as salicylates or flavonoids interfere either with the production of these activated oxygen species or function as radical scavengers and thus as antioxidants. Extracts from willow-bark (Salix spec.) and also other species such as ash-tree (Fraxinus spec.) or poplar (Populus spec.) have been used as antiinflammatory drugs since a long time. In this communication we wish to report on model reactions to demonstrate a) the radical scavenging activities of such plant extracts inhibiting ethene release from KMB induced by Fenton-type oxidants and b) the inhibition of the formation of nitrogen monoxide (NO) from hydroxylamine including XOD either in the presence or absence of myoglobin (MYO) measurable as nitrite formation: In the absence of MYO, superoxide dismutase is an excellent inhibitor of nitrite formation but is inactive in its presence. Extracts from the willow-bark or the drug Phytodolar however, are inhibitory both in the presence and absence of MYO. As active principle, the flavonoid rutin included in these extracts is likely to function as one inhibitor of the XOD-mediated reaction.
To evaluate the pharmacokinetics of salicin and its major metabolites in humans after oral administration of a chemically standardised willow bark extract.
Willow bark extract corresponding to 240 mg salicin (1,360 mg, 838 micromol) was ingested by ten healthy volunteers in two equal doses at times 0 h and 3 h. Over a period of 24 h, urine and serum levels of salicylic acid and its metabolites, i.e. gentisic acid and salicyluric acid, were determined using reverse-phase high-performance liquid chromatography. Renal excretion rate, elimination half-life and total bioavailability of salicylates were calculated.
Salicylic acid was the major metabolite of salicin detected in the serum (86% of total salicylates), besides salicyluric acid (10%) and gentisic acid (4%). Peak levels were reached within less than 2 h after oral administration. Renal elimination occurred predominantly in the form of salicyluric acid. Peak serum levels of salicylic acid were on average 1.2 mg/l, and the observed area under the serum concentration time curve (AUC) of salicylic acid was equivalent to that expected from an intake of 87 mg acetylsalicylic acid.
Willow bark extract in the current therapeutic dose leads to much lower serum salicylate levels than observed after analgesic doses of synthetic salicylates. The formation of salicylic acid alone is therefore unlikely to explain analgesic or anti-rheumatic effects of willow bark.
The objective of this review is to determine the effectiveness of Harpagophytum procumbens preparations in the treatment of various forms of musculoskeletal pain.
Several databases and other sources were searched to identify randomized controlled trials, quasi-randomized controlled trials, and controlled clinical trials testing Harpagophytum preparations in adults suffering from pain due to osteoarthritis or low back pain.
Given the clinical heterogeneity and insufficient data for statistical pooling, trials were described in a narrative way, taking into consideration methodological quality scores. Twelve trials were included with six investigating osteoarthritis (two were identical trials), four low back pain, and three mixed-pain conditions.
There is limited evidence for an ethanolic Harpagophytum extract containing less than <30 mg harpagoside per day in the treatment of knee and hip osteoarthritis. There is moderate evidence of effectiveness for (1) the use of a Harpagophytum powder at 60 mg harpagoside in the treatment of osteoarthritis of the spine, hip and knee; (2) the use of an aqueous Harpagophytum extract at a daily dose of 100 mg harpagoside in the treatment of acute exacerbations of chronic non-specific low back pain; and (3) the use of an aqueous extract of Harpagophytum procumbens at 60 mg harpagoside being non-inferior to 12.5 mg rofecoxib per day for chronic non-specific low-back pain (NSLBP) in the short term. Strong evidence exists for the use of an aqueous Harpagophytum extract at a daily dose equivalent of 50 mg harpagoside in the treatment of acute exacerbations of chronic NSLBP.
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.
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.
Essential oils and their volatile constituents are used widely to prevent and treat human disease. The possible role and mode of action of these natural products is discussed with regard to the prevention and treatment of cancer, cardiovascular diseases including atherosclerosis and thrombosis, as well as their bioactivity as antibacterial, antiviral, antioxidants and antidiabetic agents. Their application as natural skin penetration enhancers for transdermal drug delivery and the therapeutic properties of essential oils in aroma and massage therapy will also be outlined.
Objectives. To compare the effects of a proprietary extract of willow bark (Assalix) and a selective inhibitor (rofecoxib) of the enzyme cyclo-oxygenase-2 (COX-2). Methods. An open, randomized, post-marketing study was carried out in an out-patients clinic on two groups of patients aged 18 to 80 yr presenting over a 6-month period with acute exacerbations of low back pain. Using computer-generated random list, 114 patients were allocated to receive a daily dose of herbal extract containing 240 mg of salicin wPAID ( phyto-anti-inflammatory drug) groupx and 114 were allocated to receive 12.5 mg of the synthetic COX-2 inhibitor rofecoxib wNSAID (non-steroidal anti-inflammatory drug) groupx. The doses were chosen according to existing recommendations. All patients were free to use whatever additional conventional treatments were thought necessary. The outcome measures were a modified Arhus index, its pain component and the Total Pain Index. Results. Groups were well matched. After 4 weeks of treatment, the Arhus index had improved by about 20%, its pain component by about 30% and the Total Pain Index by about 35%. The number of pain-free patients (visual analogue scale score <2) was about 20 in each group. About 60% of the patients in each group responded well to the treatment (as judged by an improvement of 030% in the Total Pain Index relative to its baseline). The improvement was also reflected reasonably well in the physicians’ and patients’ judgements of the effectiveness of treatment, which were largely concordant. Few patients of either group resorted to the additional conventional treatment options. The incidence of adverse events was similar in the two groups. Treatment with rofecoxib was about 40% more expensive than that with Assalix. Conclusion. There was no significant difference in effectiveness between the two treatments at the doses chosen. Treatment with Assalix was less expensive.
Various preparations from Harpagophytum procumbens are used for the treatment of pain in the joints and lower back. Studies published in peer reviewed journals were examined for their clinical evidence. The studies offering preparations with 50–60 mg harpagoside in the daily dosage are of better quality and provide more reliable evidence on efficacy than a proprietary ethanol extract with half the amount of harpagoside per day. However, confirmatory studies are required for all extracts before they can gain a place in treatment guidelines. Copyright © 2004 John Wiley & Sons, Ltd.
Objective: To assess the clinical efficacy of a chemically standardized willow bark extract in the treatment of osteoarthritis. Methods: Willow bark extract, in a dose corresponding to 240mg salicin/day, was compared to 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 assessment by both patients and investigators. Results: 78 patients (39 willow bark extract, 39 placebo) participated in the trial. A statistically significant difference between active treatment and placebo group was observed in the WOMAC pain dimension (d=6.5mm, 95%¶C.I.=0.2–12.7mm, p=0.047); the WOMAC pain score was reduced by 14% from baseline level after two weeks of active treatment, compared to an increase of 2% in the placebo group. Patient diary VAS confirmed this result, and likewise the final overall assessments showed superiority of willow bark extract over placebo ¶(patients assessment, p=0.0002; investigators assessment, p=0.0073). Conclusion: Willow bark extract shows a moderate analgesic effect in osteoarthritis.
The order of decreasing potency for five most potent flavonoids as inhibitors of hyaluronidase was found to be: condensed tannin less than luteolin less than apigenin less than kaempferol less than silybin. Kinetic studies of these inhibitors showed that their mode of inhibition was competitive. Aglycones were stronger inhibitors than their corresponding glycosides. The following flavonoid structure conferred potent inhibitory effect: a double bond between carbons 2 and 3; unsubstituted hydroxyl groups at positions 5, 7 and 4' and a ketone group at position 4.
The antioxidative activity of a total of 92 phenolic extracts from edible and nonedible plant materials (berries, fruits, vegetables, herbs, cereals, tree materials, plant sprouts, and seeds) was examined by autoxidation of methyl linoleate. The content of total phenolics in the extracts was determined spectrometrically according to the Folin-Ciocalteu procedure and calculated as gallic acid equivalents (GAE). Among edible plant materials, remarkable high antioxidant activity and high total phenolic content (GAE > 20 mg/g) were found in berries, especially aronia and crowberry. Apple extracts (two varieties) showed also strong antioxidant activity even though the total phenolic contents were low (GAE < 12.1 mg/g). Among nonedible plant materials, high activities were found in tree materials, especially in willow bark, spruce needles, pine bark and cork, and birch phloem, and in some medicinal plants including heather, bog-rosemary, willow herb, and meadowsweet. In addition, potato peel and beetroot peel extracts showed strong antioxidant effects. To utilize these significant sources of natural antioxidants, further characterization of the phenolic composition is needed.
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.
To assess 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 to 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 assessment by both patients and investigators.
78 patients (39 willow bark extract, 39 placebo) participated in the trial. A statistically significant difference between active treatment and 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 baseline level after two weeks of active treatment, compared to an increase of 2% in the placebo group. Patient diary VAS confirmed this result, and likewise the final overall assessments showed superiority of willow bark extract over placebo (patients assessment, p = 0.0002; investigators assessment, p = 0.0073).
Willow bark extract shows a moderate analgesic effect in osteoarthritis.
The bark of Salix species contains several prodrugs of salicylate, mainly salicin. The aim of this study was to investigate if during pain treatment with Salicis cortex extract platelet aggregation was affected. A total of 51 patients were enrolled in the study. Thirty-five patients suffering from acute exacerbations of chronic low back pain received randomly and double-blind either Salicis cortex extract with 240 mg salicin/day (n = 19) or placebo (n = 16). Further sixteen patients with stable chronic ischemic heart disease were given 100 mg acetylsalicylate per day. Platelet aggregation was studied using an aggregometer. As aggregating agents, arachidonic acid (500 micrograms/ml), adenosine di-phosphate (2 x 10(-5) M) and collagen (0.18 microgram/ml) were used. The mean maximal arachidonic acid induced platelet aggregation was 61%, 78% and 13% in the Salicis cortex extract, placebo and acetylsalicylate groups. Acetylsalicylate had a significant inhibitory effect on platelet aggregation compared to Salicis cortex extract (p = 0.001) and placebo (p = 0.001). There was also a significant difference between the placebo and the willow bark-treated groups in the maximal platelet aggregation induced by arachidonic acid (p = 0.04) and ADP (p = 0.01). No statistical difference was found between the groups when collagen was applied to the human platelets. Daily consumption of Salicis cortex extract with 240 mg salicin per day affects platelet aggregation to a far lesser extent than acetylsalicylate. Further investigation needs to clarify if this finding is of clinical relevance in patients with impaired thrombocyte function.
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.
An open, non-randomised, study (postmarketing surveillance) was carried out on three groups of patients aged 18 to 80 presenting over an 18 month period with acute exacerbations of low back pain. The objective was to assess the possible economic impact of including a regular dose of proprietary willow bark extract (Assalix) in the treatment provided. A first group of 115 patients, presenting to 3 general practitioners in the first 3 months, was prescribed a daily dose of extract containing 120 mg of salicin (group W120). They also had access, if necessary, to the range of conventional treatments allowed for in the general practitioners' budgets. A second group of 112 patients presenting to the same general practitioners over the next 15 months, was prescribed extract equivalent to 240 mg salicin per day (group W240). A third "control" or "comparator" group of 224 patients, presenting to 3 orthopedists (specialists in physical medicine) over the whole 18 month period, received only the conventional therapeutic options allowed in the orthopedists' budgets (Group C). In the group C patients, the exacerbations had been shorter but the pain had been more intense as judged by Arhus Index and Total Pain Index. After 4 weeks of treatment, about 40% of group W240 patients were free of pain whether or not they had to resort to supplementary treatments. In group W120 as a whole, about 19% of patients were pain-free at 4 weeks, but only 8% of those who did not resort to supplementary treatment. In group C, 18% of patients were painfree. These findings were reflected reasonably well in the changes in the Arhus Index and Total Pain Index, and the findings in group W240 were consistent with those in a previous randomised controlled trial. Multivariable modelling to examine for possible confounding effects tended to identify membership of group W240 as an independent explanator of better pain relief than membership of group C. Though the measures of effect tended to be similar in group W120 as a whole and group C, the avoidance of more expensive conventional treatments in group W120 meant that the average cost per patient of treatment was reduced by about 35-50% (health service and private costings respectively). The better pain relief in group W240 was accompanied by an even smaller reliance on supplementary conventional treatments than in group W120 but the extra savings on these were outweighed by the extra cost of the additional Assalix so that the average cost per patient was reduced by 14-40% of the costs in group C. The possibility is discussed that, if orthopedists had relied more on regular full dosing with NSAIDs, they might have increased the effectiveness and reduced the cost of their treatment, though with the possibility of more side effects. Substituting established NSAIDs with COX-2 inhibitors might reduce the side effects, but at greater cost than with the Assalix.
To compare the effects of a proprietary extract of willow bark (Assalix) and a selective inhibitor (rofecoxib) of the enzyme cyclo-oxygenase-2 (COX-2).
An open, randomized, post-marketing study was carried out in an out-patients clinic on two groups of patients aged 18 to 80 yr presenting over a 6-month period with acute exacerbations of low back pain. Using computer-generated random list, 114 patients were allocated to receive a daily dose of herbal extract containing 240 mg of salicin [PAID (phyto-anti-inflammatory drug) group] and 114 were allocated to receive 12.5 mg of the synthetic COX-2 inhibitor rofecoxib [NSAID (non-steroidal anti-inflammatory drug) group]. The doses were chosen according to existing recommendations. All patients were free to use whatever additional conventional treatments were thought necessary. The outcome measures were a modified Arhus index, its pain component and the Total Pain Index.
Groups were well matched. After 4 weeks of treatment, the Arhus index had improved by about 20%, its pain component by about 30% and the Total Pain Index by about 35%. The number of pain-free patients (visual analogue scale score <2) was about 20 in each group. About 60% of the patients in each group responded well to the treatment (as judged by an improvement of >/=30% in the Total Pain Index relative to its baseline). The improvement was also reflected reasonably well in the physicians' and patients' judgements of the effectiveness of treatment, which were largely concordant. Few patients of either group resorted to the additional conventional treatment options. The incidence of adverse events was similar in the two groups. Treatment with rofecoxib was about 40% more expensive than that with Assalix.
There was no significant difference in effectiveness between the two treatments at the doses chosen. Treatment with Assalix was less expensive.
Salix extracts are in current use for the treatment of pain and inflammation. In order to obtain an insight into the mechanism(s) of action of the ethanolic Salix extract 1520L--which is essentially similar to an extract for which clinical studies have demonstrated analgesic effectiveness--its effects were evaluated in an established in vitro assay test system using primary human monocytes. The IC50-values obtained for the inhibition of lipopolysaccharide (LPS)-induced release of prostaglandin E2 (PGE2) reflecting cyclooxygenase (COX)-2-mediated PGE2 release were 47 microg/ml and 0.6 microg/ml, for the Salix extract 1520L and rofecoxib-like research compound L745337, respectively. There was no effect on COX-1 and COX-2 activity. The Salix extract inhibited the LPS-induced release of tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 with IC50-values of 180.0, 33.0 and 86.0 microg/ml, respectively. Both, salicin and salicylate, had no effect in any of the parameters. Our results indicate that Salix extract 1520L inhibits COX-2-mediated PGE2 release through compounds other than salicin or salicylate. Our data further suggest that the proprietary Salix extract is a weak inhibitor of proinflammatory cytokines.
Mechanismen der entzündungshemmenden Wirkung eines standardisierten Wei-denrindenextraktes
Um mögliche Mechanismen seiner entzündungshemmenden Wirkung aufzuklären, wurde ein standardisierter Wei-denrindenextrakt (STW 33-I) in zwei Entzündungsmodellen untersucht, dem 6-Tage air pouch-Modell bei der Ratte als einem Modell der akuten Entzündung und dem Modell der Adjuvans-induzierten Arthritis als einem Modell der chronischen Entzündung. Die untersuchten Parameter umfaβten die Leukozyten-Infiltration, die Blutspiegel von Zytokinen und Prostanoiden, die Wirkung auf Cyclooxygenase (COX)-1 und/oder COX-2 sowie die Wirkung auf die Produktion freier Radikale. Die Wirkung des Extraktes in zwei unterschiedlichen Dosen wurde mit entzündungshemmenden Dosen von Acetylsalicylsäure (CAS 50-78-2, ASS) als nicht-selektivem COX-Hemmer und Celecoxib (CAS 169590-42-5) als selektivem COX-2-Hemmer verglichen. Bezogen auf die Dosis in mg/kg war der Extrakt mindestens ebenso wirksam wie ASA, was die Verringerung der Menge an entzündlichem Exsudat und die Hemmung der Leukozyten-Infiltration und des Anstieges der Cytokine betrifft. Er hemmte die Leukotrien-Bildung und COX-2 stärker als ASS, die Prostaglandin-Bildung vergleichbar wie dieses. Die vorliegenden Daten zeigen zudem, daß STW 33-I die Spiegel von reduziertem Glutathion (GSH) signifikant erhöhte, was der Bildung von Lipidperoxiden entgegen wirken kann. Der Extrakt war hierbei wirksamer als ASS oder Celecoxib. Höhere Dosen des Extraktes verringerten zudem die Malondialdehyd-Spiegel und erhöhten die Superoxiddismutase-Aktivität.
STW 33-I ist demnach sowohl ASS als auch Celecoxib in seiner Schutzwirkung gegen oxidativen Streß überlegen.
Bezogen auf eine vergleichbare Dosis in mg/kg wirkt STW 33-I also offensichtlich mindestens ebenso stark auf alle gemessenen Entzündungsparameter wie ASA. Der Extrakt enthält aber nur 24 % Salicin, woraus folgt, daβ er, berechnet in Mol, nur ein Sechstel der Menge an Salicylaten enthält wie ASA, was zu der Vermutung Anlaβ gibt, daß weitere Bestandteile an seiner Aktivität beteiligt sind. Für seine Radikalfängereigenschaften dürften insbesondere die enthaltenen Polyphenole verantwortlich sein. Die Überlegenheit gegenüber einer, auf das Gewicht bezogen, gleichen Dosis ASS läßt auf eine bessere entzündungshemmende Wirkung bei gleichzeitig geringerem Nebenwirkungspotential schließen.
The objective of this review is to evaluate whether clinical research has gained any evidence of effectiveness of Rosa canina preparations.
Several databases and other sources were searched to identify randomized controlled trials of Rosa canina preparations.
Trials were described in a narrative way, taking into consideration methodological quality scores. Four trials were included in this review and two were identified as subgroup analyses.
Moderate evidence exists for the use of a powder of the seeds and husks of a Rosa canina subspecies in patients suffering from osteoarthritis.
The objective of this review was to evaluate the strength of evidence of effectiveness for Petasites hybridus in the prophylaxis of migraine. Several databases and other sources were searched to identify randomised-controlled trials investigating P. hybridus preparations. Two trials totalling 293 patients (60 and 233 patients) were included in this review. Both trials investigated the proprietary Petasites root extract Petadolex. The trials were described in narrative way, taking into consideration methodological quality scores. Pooling of data was not carried out due to the heterogeneity of the results. The extract at higher dose (150 mg) showed a greater decreased frequency of migraine attacks and a greater number of responders (improvement>50%) after treatment over 3-4 months than the extract at lower dose (100 mg) and placebo. Moderate evidence of effectiveness is, thus, available for a higher than the recommended dose of the proprietary Petasites root extract Petadolex in the prophylaxis of migraine. Further rigorous studies are required to confirm effectiveness and safety in long-term use before treatment with Petasites root extract can be recommended as an alternative option in the treatment schedule for the prophylaxis of migraine.
Pharmacological properties of a standardized extract from Willow Bark (Cortex salicis) Chair of Pharma-cology and Toxicology. Pomeranian Academy of Medicine
- A Glinko
Glinko A. 1998. Pharmacological properties of a standardized extract from Willow Bark (Cortex salicis). Chair of Pharma-cology and Toxicology. Pomeranian Academy of Medicine: Szczecin.
Behandlung von Cox- und Gonarthrosen mit einem Trockenextrakt aus Salix purpurea + daphnoides
- B Schmid
Schmid B. 1998. Behandlung von Cox-und Gonarthrosen mit einem Trockenextrakt aus Salix purpurea + daphnoides.
Salicis cortex. In ESCOP monographs Ed European Scientific Cooperative on Phytotherapy
- Anonymous
Anonymous. 2003. Salicis cortex. In ESCOP monographs. Ed European Scientific Cooperative on Phytotherapy. Thieme Press: Stuttgart; 445–451.
A Pharmacometric Evaluation of nine Bio-Strath Herbal Remedies
- Leslie