Article

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

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Abstract

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

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... Salix alba (SA), commonly known as white willow, is a plant that belongs to the Salicaceae family. Historically, this plant was used for therapeutic purposes, in particular for treatment of fever, skin diseases, infections, acute and chronic inflammatory diseases such as osteoarthritis, tendonitis, and in general, lumbar pain, joint pain, headaches, menstrual cramps, and flushing (Agnolet et al. 2012;Drummond et al. 2013;Qureshi, Khatoon, and Ahmed 2015;Shara and Stohs 2015). The analgesic, antipyretic, and anti-inflammatory properties may be related to salicin, the main component of Salix alba, an analogous precursor of the most widespread anti-inflammatory drug used, acetylsalicylic acid (Farinacci et al. 2008;Hedner and Everts 1998;Shara and Stohs 2015;Souza et al. 2009). ...
... Historically, this plant was used for therapeutic purposes, in particular for treatment of fever, skin diseases, infections, acute and chronic inflammatory diseases such as osteoarthritis, tendonitis, and in general, lumbar pain, joint pain, headaches, menstrual cramps, and flushing (Agnolet et al. 2012;Drummond et al. 2013;Qureshi, Khatoon, and Ahmed 2015;Shara and Stohs 2015). The analgesic, antipyretic, and anti-inflammatory properties may be related to salicin, the main component of Salix alba, an analogous precursor of the most widespread anti-inflammatory drug used, acetylsalicylic acid (Farinacci et al. 2008;Hedner and Everts 1998;Shara and Stohs 2015;Souza et al. 2009). Other substances also found in the extract of SA may also be related to the analgesic and anti-inflammatory effects of this extract, such as flavonoids and tannins (Agnolet et al. 2012;Drummond et al. 2013;Williamson 2001). ...
... In addition to the anti-inflammatory effects, SA bark extract demonstrated anti-oxidant activity in different test systems (Ishikado et al. 2012;Jukic et al. 2012;Katiki et al. 2013), and modulated the inhibitory activity of the enzyme acetylcholinesterase, an important step in the treatment of Alzheimer's disease (Jukic et al. 2012). Despite the long history of use willow bark extract, relatively few human and animal studies have been published that confirm anecdotal observations (Shara and Stohs 2015). ...
Article
Salix alba (SA), commonly known as white willow, is a plant used in folk medicine for the treatment of chronic and acute inflammation, infection, pain, and fever. The phytochemical characterization of the bark extract of this plant indicated that its main component is salicin, a precursor of the anti-inflammatory agent acetylsalicylic acid. Considering the lack of studies evaluating the genetic toxicity and cytotoxic action of SA bark extract on human cells, as well as the chemical characterization of its major phenolic compounds, the present study was designed to (1) investigate the cytotoxic and genotoxic potential of SA bark extract on human peripheral leukocyte cells and human hepatoma cell line HepG2, and (2) characterize its major phenolic constituents. The phenolic compounds found were salicylic acid, salicin, salidroside, saligenin, tremulodin, salicoylsalicin, salicortin, and tremulacin. The results using trypan blue staining test showed viability decreases (viability less than 70%) for concentrations of SA extract equal and higher to 200 µg/ml. Low genotoxic activity (comet assay) was exhibited for 50 and 100 µg/ml SA extract in human leukocytes. SA did not exert a marked clastogenic/aneugenic effect on leukocytes and HepG2 human cells. Data suggest that the genotoxic effects of SA bark extract occur when it is not metabolized by liver enzymes.
... Ancient Egyptians and Sumerians used willow bark and leaves against inflammatory conditions caused by injury and to relieve joint pain. Moreover, the Khoikhoi people of South Africa and the Indigenous peoples of North America, having discovered these properties completely independently, used the willow extracts to cure fever, osteoarthritis and headache (Al-Khalifa, 1993;Lichterman, 2004;Shara and Stohs, 2015;Volmink, 2008;Wood, 1993). ...
... The active agent that is responsible for analgesic, antipyretic and anti-inflammatory properties of willow is salicin. Salicin is metabolized by intestinal flora into saligenin, and then further metabolized by the liver into salicylic acida substance that differs from aspirin through a lack of an acetyl group (Shara and Stohs, 2015). ...
... Aspirin was then patented in the United States on February 27, 1900. Initially it was sold as a powder, however in 1904 aspirin became the first industrially produced drug available in tablet form worldwidea fact indicative of its wide commercial success (Lichterman, 2004;Shara and Stohs, 2015). ...
Article
Aspirin (acetylsalicylic acid), the oldest synthetic drug, was originally used as an anti-inflammatory medication. Being an irreversible inhibitor of COX (prostaglandin-endoperoxide synthase) enzymes that produce precursors for prostaglandins and thromboxanes, it has gradually found several other applications. Sometimes these applications are unrelated to its original purpose for example its use as an anticoagulant. Applications such as these have opened opportunities for new treatments. In this case, it has been tested in patients with cardiovascular disease to reduce the risk of myocardial infarct. Its function as an anticoagulant has also been explored in the prophylaxis and treatment of pre-eclampsia, where due to its anti-inflammatory properties, aspirin intake may be used to reduce the risk of colorectal cancer. It is important to always consider both the risks and benefits of aspirin's application. This is especially important for proposed use in the prevention and treatment of neurologic ailments like Alzheimer's disease, or in the prophylaxis of myocardial infarct. In such cases, the decision if aspirin should be applied, and at what dose may be guided by specific molecular markers. In this revived paper, the pleiotropic application of aspirin is summarized.
... alternaria, A. niger, M. hiemalis, P. notatum and S. commune) with remarkable effect [14]. Analysis of aqueous extracts of willow bark has shown the presence of at least 11 related salicylate compounds including salicin, saligenin, salicylic acid, isosalicin, salidroside, picein, triandrin, salicoylsalicin, salicortin, isosalipurpuroside and salipurpuroside (Scheme 2) [15]. ...
... alternaria, A. niger, M. hiemalis, P. notatum and S. commune) with remarkable effect [14]. Analysis of aqueous extracts of willow bark has shown the presence of at least 11 related salicylate compounds including salicin, saligenin, salicylic acid, isosalicin, salidroside, picein, triandrin, salicoylsalicin, salicortin, isosalipurpuroside and salipurpuroside (Scheme 2) [15]. Silver compounds are known antimicrobial agents [9,16]. ...
... Molecular formulae of the main components of willow bark extract[15]. Scheme 2. Molecular formulae of the main components of willow bark extract[15]. ...
Article
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Eucalyptus leaves (ELE) and willow bark (WBE) extracts were utilized towards the formation of silver nanoparticles (AgNPs(ELE), AgNPs(WBE)). AgNPs(ELE) and AgNPs(WBE) were dispersed in polymer hydrogels to create pHEMA@AgNPs(ELE)_2 and pHEMA@AgNPs(WBE)_2 using hydroxyethyl-methacrylate (HEMA). The materials were characterized in a solid state by X-ray fluorescence (XRF) spectroscopy, X-ray powder diffraction analysis (XRPD), thermogravimetric differential thermal analysis (TG-DTA), differential scanning calorimetry (DTG/DSC) and attenuated total reflection spectroscopy (ATR-FTIR) and ultraviolet visible (UV-vis) spectroscopy in solution. The antimicrobial potential of the materials was investigated against the Gram-negative bacterial strain Pseudomonas aeruginosa (P. aeruginosa) and the Gram-positive bacterial strain of the genus Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus), which are involved in microbial keratitis. The percentage of bacterial viability of P. aeruginosa and S. epidermidis upon their incubation over the pHEMA@AgNPs(ELE)_2 discs is interestingly low (28.3 and 6.8% respectively), while the inhibition zones (IZ) formed are 12.3 ± 1.7 and 13.2 ± 1.2 mm, respectively. No in vitro toxicity of this material towards human corneal epithelial cells (HCEC) was detected. Despite its low performance against S. aureus, pHEMA@AgNPs(ELE)_2 could be an efficient candidate towards the development of contact lenses that reduces microbial infection risk.
... The monographs specify the minimum and maximum salicin content in willow bark in the range of 1.5 -15 % and the maximum daily oral dose of salicin not exceeding 240 mg. [135,136] Salicylates show analgesic, antipyretic, anti-inflammatory, and anti-aggregation activities, which results from the inhibition of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2, respectively). Inhibition of COX-1 and COX-2 activity blocks the synthesis of prostanoids: prostaglandins, prostacyclin, and thromboxane. ...
... The most commonly reported adverse effects associated with the use of salicylates are gastrointestinal disorders and allergic reactions in people allergic to salicylates. [135,136] In early 1990, studies involving obese people were conducted, in which the effectiveness of the mixture of substances, namely 30-150 mg ephedrine, 150-200 mg caffeine, and 300-330 mg aspirin, in weight reduction was proven. [137 -139] Dietary supplements (fat burner) were introduced to the distribution and containing a combination of active substances: salicylates, ephedrine (or synephrine), and caffeine. ...
Article
This review focuses on four new product categories of food supplements: pre‐workout, fat burner/thermogenic, brain/cognitive booster, and hormone/testosterone booster. Many food supplements have been shown to be contaminated with unauthorized substances. In some cases, the ingredients in the new categories of dietary supplements were medicinal products or new synthetic compounds added without performing clinical trials. Some of the new ingredients in dietary supplements are plant materials that are registered in the pharmacopoeia as herbal medicines. In other cases, dietary supplements may contain plant materials that have no history of human use and are often used as materials to “camouflage” stimulants. In the European Union, new ingredients of dietary supplements, according to European Food Safety Authority or unauthorized novel food. Furthermore, selected ingredients in dietary supplements may be prohibited in sports and are recognized as doping agents by World Anti‐Doping Agency.
... It is obtained from the willow tree also known as Salix, and is generally standardized to salicin (Figure 9) but may contain other salicylates as well as flavonoids and polyphenols. It has been used for thousands of years for its antipyretic, analgesic, and anti-inflammatory effects [155,156]. The active agents of willow bark extract inhibit COX-2 mediated release of prostaglandins E2 and the release of interleukin 1ß and tumor necrosis factor-α [157]. ...
... It should be avoided in pregnant females as salicylates can cross the placenta and are eliminated slowly in newborns. There is an increased risk of bleeding and concomitant treatment with other salicylate-containing medication increases these risks and therapy should be monitored or modified [155,159]. NSAIDs also have the potential to interact with herbal supplements that are known to possess antiplatelet activity, such as willow bark [160]. Nonetheless, no relevant drug interactions were reported in a trial on the aqueous willow bark extract STW 33-I, in patients allowed to co-medicate with NSAIDs and opioids [161]. ...
Article
Full-text available
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.
... The resulting metabolites are reported to have a higher biological activity than their precursor structures [127]. Some authors [128] showed that phenolic compounds contained in willow bark extract are metabolized by the gut bacteria to small phenolic metabolites like hydroxyphenylpropionic acids, hydroxyphenylvaleric acids, and salicylic acid. The mechanisms by which polyphenols exert the antimicrobial effect in the intestine is by decreasing the abundance of harmful bacteria by inhibiting the adhesion to intestinal epithelial cells and by reducing intracellular invasion and colonization by harmful bacteria [129]. ...
... There are limited studies evaluating the impact of willow bark polyphenols on the gut intestinal microbiota. Some authors [128] evaluated the influence of willow bark extract on human fecal microbiota, incubating the feces with 0 mg/ ml (PBS and vehicle control), 2 mg/ ml and 10 mg/ ml of willow bark extract at 0.5, 4, and 24 h. The authors reported that constituents of willow bark extract were metabolized by fecal bacteria and influenced the microflora composition; the beneficial microorganisms such as Bacteroides sp., Parabacteroides populations have increased. ...
Preprint
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.
... So far, there are many in vivo and in vitro studies that have proved the antioxidant properties of willow extracts [7][8][9]. A good antibacterial activity of Salix alba was reported [10], positively correlated with its antioxidant potential [11]. ...
... Data on total phenolic content of Salix alba powder used in this study revealed a high level of TPC. There are many studies showing that Salix alba bark is a natural source of phenolic compounds with antioxidant activity [8,9,11]. Compared to data reported by [6] on total phenolic content of ethanolic extracts of S. alba bark, our results are 2.4 times higher. ...
Article
Full-text available
The paper aimed to analyse the effect of dietary Salix alba L. bark powder (SAB) on broiler performance in terms of oxidative stress parameters in liver and gut microflora. One hundred and eighty Cobb 500 broiler chicks (14 days) were allotted to three homogeneous treatments (SAB 0%; SAB 0.025%; SAB 0.05%). The broilers were housed in an environmentally controlled space (10 replicates, six broilers/replicate). Compared to dietary control treatment (SAB 0%), the other treatments included 0.025% SAB (SAB 0.025%) and 0.05% SAB (SAB 0.05%). The results showed that SAB powder used in broiler diet had a high total phenolic content. Regarding the performance results, significant differences between experimental and control treatments were recorded only for average daily feed intake (35–42 days). The broilers fed with SAB powder had a significantly lower hepatic level of malondialdehide and glutathione, a higher total antioxidant capacity than those fed control treatment, and demonstrated a positive effect on the development of non-pathogenic bacteria (lactobacilli) but a decrease in the population of pathogenic ones (E. coli, staphylococci). Our findings suggested that dietary 0.05% SAB powder could be an effective solution to impede the oxidative stress in broiler liver and to improve gut microflora.
... The monographs specify the minimum and maximum salicin content in willow bark in the range of 1.5 -15 % and the maximum daily oral dose of salicin not exceeding 240 mg. [135,136] Salicylates show analgesic, antipyretic, anti-inflammatory, and anti-aggregation activities, which results from the inhibition of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2, respectively). Inhibition of COX-1 and COX-2 activity blocks the synthesis of prostanoids: prostaglandins, prostacyclin, and thromboxane. ...
... The most commonly reported adverse effects associated with the use of salicylates are gastrointestinal disorders and allergic reactions in people allergic to salicylates. [135,136] In early 1990, studies involving obese people were conducted, in which the effectiveness of the mixture of substances, namely 30-150 mg ephedrine, 150-200 mg caffeine, and 300-330 mg aspirin, in weight reduction was proven. [137 -139] Dietary supplements (fat burner) were introduced to the distribution and containing a combination of active substances: salicylates, ephedrine (or synephrine), and caffeine. ...
... Adverse effects of bark extracts appear to be minimal. The primary risk may relate to allergic reactions in salicylate-sensitive individuals [57,58]. ...
... Generally, the extracts of Salix bark have been regarded as being safe, although sensitive individuals may get allergic reactions due to salicylates. Studies have also shown that there are other salicin-related compounds that contribute to various effects, which may also concern cytotoxicity [57]. ...
Article
Full-text available
Biocolourants have been investigated as alternatives to synthetic dyes. However, natural origin per se is not a label of harmlessness and research is needed to obtain safe dyes. We studied the cytotoxicity of the extracts from fungal (Cortinarius semisanguineus, Tapinella atrotomentosa) and plant (Tanacetum vulgare, Salix phylicifolia) sources and the woollen fabrics dyed with the extracts. Cytotoxicity in vitro using hepa-1 mouse hepatoma cells for 24 h and 72 h exposure was observed as the highest tolerated dose. All biocolourants produced intensive colour on fabrics with fastness properties from moderate to good. The Salix and Cortinarius samples did not show any cytotoxic effects, whereas the Tanacetum and Tapinella samples had slightly higher test values but were not interpreted as being significantly toxic. Higher than zero values of the undyed fabrics showed the importance of examining their toxicity as well. It was found that the cytotoxicity of the samples dyed with the biocolourants did not differ significantly from the undyed wool fabric. The concentrations of dyes used in the assays were very low, imitating the dose of the user. In addition to colouring properties, natural dyes may have pharmaceutical and antibacterial properties which would enhance the interest in using them in products for added value. (This article belongs to the Special Issue Fungal Secondary Metabolites)
... Salix cortex is also used in dietary supplements, e.g., for weight reduction and to enhance performance in sports (Matyjaszczyk and Schumann, 2018). Despite its long history of use, so far only little data is available on the toxicity or potential adverse effects of Salix cortex preparations (Shara and Stohs, 2015). Based on a limited number of studies, one safety report by Shara and Stohs (2015) recommended that people who 1) are allergic to aspirin, 2) suffer from pathological conditions such as gastritis, stomach ulcers, diabetes, asthma, or hemophilia; or 3) are under anticoagulant-drug therapy, as well as beta-blockers, diuretics, and non-steroidal anti-inflammatory drugs (NSAIDs), may avoid Salix cortex. ...
... Despite its long history of use, so far only little data is available on the toxicity or potential adverse effects of Salix cortex preparations (Shara and Stohs, 2015). Based on a limited number of studies, one safety report by Shara and Stohs (2015) recommended that people who 1) are allergic to aspirin, 2) suffer from pathological conditions such as gastritis, stomach ulcers, diabetes, asthma, or hemophilia; or 3) are under anticoagulant-drug therapy, as well as beta-blockers, diuretics, and non-steroidal anti-inflammatory drugs (NSAIDs), may avoid Salix cortex. ...
Article
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Herbal preparations of willow bark (Salix cortex) are available in many countries as non-prescription medicines for pain and inflammation, and also as dietary supplements. Currently only little information on toxicity and drug interaction potential of the extracts is available. This study now evaluated the effects of two Salix cortex extracts on human hepatocyte-like HepaRG cells, in view of clinically relevant CYP450 enzyme activity modulation, cytotoxicity and production of reactive oxygen species (ROS). Drug metabolism via the CYP450 enzyme system is considered an important parameter for the occurrence of drug-drug interactions, which can lead to toxicity, decreased pharmacological activity, and adverse drug reactions. We evaluated two different bark extracts standardized to 10 mg/ml phenolic content. Herein, extract S6 (S. pentandra, containing 8.15 mg/ml total salicylates and 0.08 mg/ml salicin) and extract B (industrial reference, containing 5.35 mg/ml total salicylates and 2.26 mg/ml salicin) were tested. Both Salix cortex extracts showed no relevant reduction in cell viability or increase in ROS production in hepatocyte-like HepaRG cells. However, they reduced CYP1A2 and CYP3A4 enzyme activity after 48 h at ≥25 μg/ml, this was statistically significant only for S6. CYP2C19 activity inhibition (0.5 h) was also observed at ≥25 μg/ml, mRNA expression inhibition by 48 h treatment with S6 at 25 μg/ml. In conclusion, at higher concentrations, the tested Salix cortex extracts showed a drug interaction potential, but with different potency. Given the high prevalence of polypharmacy, particularly in the elderly with chronic pain, further systematic studies of Salix species of medical interest should be conducted in the future to more accurately determine the risk of potential drug interactions.
... (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). ...
... However, extracts containing a mixture of willow compounds could also have synergistic effects. Similar observations were made by Shara and Stohs (2015), who concluded that the typical effective dosage of aspirin is twice that of salicin needed in willow bark extract, probably because of the presence of beneficial polyphenols and flavonoids in the bark extract. ...
Article
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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.
... Ivanaga et al. (27) discussed that in patients with type 2 diabetes mellitus, the treatment of residual pockets (with PD ≥5 mm and BOP) with antimicrobial photodynamic therapy with 100 mg/L curcumin solution and LED irradiation as adjunctive therapy to scaling and root planing, may yield short-term (three months) clinical benefits regarding clinical attachment gain. 42 Sparabombe et al. (28) r eported that the use of a polyherbal mouthwash (Propolis resin extract, Plantago lanceolata, Salvia officinalis leaves extract, and 1.75% essential oil) in patients with moderate or severe periodontitis was safe and effective for BOP and PI after 3 months, in comparison with the control group; however, there was no significant difference between the two groups regarding PD and clinical attachment level. ...
... Microbial control in turn reduces the inflammatory response, which in turn decreases the plasma leakage in saliva through gingival crevicular fluid; this statement could be supported by the overall reduction in total salivary protein levels. (16) Further investigations: Several studies have reported anti-inflammatory effects of cocoa flavonoids,(36) thyme, (37) Artemisia annua, (38) Inonotus obliquus (chaga mushroom), (39) leaf extract of Ananas comosus, (40) Thykamine extracts from spinach (41) and White Willow Bark (Salix alba) (42) on different parts of the body. An analysis ...
Article
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Background and Aim: The most common etiology of gingivitis is accumulation of bacterial plaque. The complete removal of microbial plaques by mechanical procedures is not possible in some situations, for example the aged and disabled patients, might not be capable of removing the bacterial plaques properly. And also chemical mouthwashes have some adverse effects. Therefore, finding a new treatment approach would be helpful. Global focus on the use of herbal medicine in the treatment of different health conditions has been rising. Present study aimed at searching and gathering scientific evidence of medicinal herbs to treat gingivitis and periodontitis. Materials and Methods: This article is a review of an electronic search of the literature which was conducted mostly through PubMed, Scopus, Google Scholar, and Wiley online library databases. Studies were considered for inclusion if they evaluated medicinal herbs affecting gingival and periodontal inflammation or periodontal pathogens.197 full text article were evaluated and finally, based on the inclusion criteria 22 articles were selected. Results: There are various medical herbs with antibacterial and anti-inflammatory properties, which can significantly reduce gingival and periodontal inflammation, bleeding on probing (BOP), plaque index (PI), probing depth (PD) and levels of major periodontal pathogens and promote clinical attachment level (CAL) gain. Conclusion: Introduced herbal products could be an efficient and safe alternative to chemical products.
... Willow bark was included as part of the Materia Medica in the first volume of the U. S. Pharmacopeia published in 1820 [6]. Today, willow bark is used for the treatment of pain, particularly, LBP, osteoarthritis (OA), headaches, and inflammatory conditions such as tendinitis and bursitis [7]. ...
... Fig. 3Chemical structures of some salicylate derivatives found in willow bark: salicin (1); salicylaldehyde (2); salicylic acid (3); acetylsalicylic acid (4); salicortin (5); 2′-O-acetylsalicortin (6); (−)-tremulacin(7). ...
Article
Willow bark (Salix spp.) is an ingredient in some dietary supplements. No serious adverse effects were reported from trials of willow bark extracts delivering 120 – 240 mg salicin (the purported active constituent) daily for up to 8 weeks. All studies involved adults only; none involved special subpopulations such as pregnant or breastfeeding women, or children. The most common adverse effects associated with willow bark are gastrointestinal; a few allergic reactions were also reported. Some publications advise caution when taking willow bark. There is a risk of increased bleeding in vulnerable individuals, salicylates cross the placenta and are eliminated slowly in newborns, some persons are sensitive or allergic to aspirin, and children are at risk of Reye syndrome. Concurrent use with other salicylate-containing medicines increases these risks. Metabolism of 240 mg salicin from willow bark could yield 113 mg of salicylic acid, yet dietary supplement products are not required to be labeled with warnings. In contrast, over-the-counter low-dose aspirin (81 mg strength), which delivers 62 mg salicylic acid, is required by law to include cautions, warnings, and contraindications related to its use in pregnant and nursing women, children, and other vulnerable subpopulations, e.g., those using anticoagulants. In the interest of protecting public health, the United States Pharmacopeia has included a cautionary labeling statement in the United States Pharmacopeia Salix Species monograph as follows: “Dosage forms prepared with this article should bear the following statement: ‘Not for use in children, women who are pregnant or nursing, or by persons with known sensitivity to aspirin.’”
... The bark extract also contains phenolic and flavonoid compounds with antioxidant activity [20][21][22]. In addition to antioxidant and anti-inflammatory properties, willow bark extract is used in weight loss supplements [23], and for its hypocholesterolemic activity [24,25]. Few data are available on the use of Sa in poultry species, despite acetylsalicylic acid and sodium salicylate being considered safe for poultry and used in avian medicine [26]. ...
... Accordingly, Pozniak and a co-worker found that the BW gain decreased in broilers when the feed was supplemented with 0.04% of acetylsalicylic acid; this effect is presumably related to anti-inflammatory and analgesic activities of the phytocomplex [26]. However, a paucity of controlled clinical trials has been performed to evaluate the efficacy of willow bark extract and the use in association with other extracts hampers the evaluation of its direct efficacy on weight loss [23]. ...
Article
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This study was conducted to evaluate the safety and the beneficial effects of dietary supplementation with Boswellia serrata (Bs) and Salix alba (Sa) in Leghorn hens during the critical pre-laying and laying phases. A total of 120 pullets, 17 weeks of age, were assigned to two groups (Control—C; Treated—T, n = 60 each). For 12 weeks, the T group received a diet supplemented with 0.3% of dry extracts of Bs (5%) and Sa (5%). The study lasted 19 weeks. Productive performance, serum analytes, H/L ratio, IgA and anti-IBV antibodies were investigated. Water intake was significantly higher, while body and egg weight was significantly lower for the T group (p < 0.05). No other differences were detected in performance parameters, serum analytes, IgA and H/L ratio excluding t0, with a significantly (p < 0.05) higher H/R ratio and higher titers of anti-IBV antibody for the T group. Overall, the data obtained in this study show that the supplementation with Bs and Sa was safe and resulted in an increase in water consumption, a decrease in egg weight, and a sedative effect in the hens. In the future, it would be interesting to test this supplement in hens reared on intensive farms.
... It is generally standardized to salicin. However, other salicylates, polyphenols, and flavonoids may also play important roles in therapeutic actions (Shara and Stohs, 2015). Some components: (+)-catechin, syringin, triandrin, ampelopsin, ethyl-1-hydroxy-6-oxocyclohex-2-enecarboxylate taxifolin, 3-O-methyltaxifolin, 7-O-methyltaxifolin-3-Oglucoside; p-coumaric, benzoic, p-hydroxybenzoic, p-methoxy benzoic, cinnamic, trans-p-methoxycinnamic, and cis-pmethoxy cinnamic acids (Agnolet et al., 2012). ...
Article
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Method: The plant selection is primarily based on species 32 listed by the WHO and EMA, but some other herbal remedies are considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. Target population: adults with early flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown. Results: A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix and Sambucus nigra), promising in 10 cases (Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Pelargonium sidoides, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine. Conclusions: Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their opportunity as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches
... Quercitrin, morusin, salicin, and cinnamaldehyde possess known biological activities [26][27][28][29]. The latter three substances are transferred from their respective host trees and accumulate within TH. ...
Preprint
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Background: Taxilli Herba (TH) is a commonly used Chinese medicinal herb that parasitizes different tree types, but objective methods to determine its quality and detect contamination from host substances have not been reported. Thus, we aimed to establish methods to improve the safety and quality of TH. Methods: We collected 10 samples each of TH hosted by mulberry, willow, and cinnamon trees from different regions and batches, along with twigs of the corresponding host trees. Samples were prepared by ultrasonic extraction with methanol as a solvent. HPLC was used to measure the content of quercitrin, the intrinsic component of TH, as well as of morusin, salicin, and cinnamaldehyde, characteristic of mulberry, willow, and cinnamon, respectively. Results: Quercitrin was detected in all host trees but not in host twigs. However, the accumulation of the characteristic components of the hosts in TH substantially varied among the three hosts. The contents of morusin, salicin, and cinnamaldehyde in mulberry, willow, and cinnamon twigs were 134.78-437.60, 1787.91-2564.65 and 7219.36-10783.21 µg/g respectively, and the corresponding values in TH obtained from mulberry, willow, and cinnamon were 0.27-4.27、102.62-545.83 and 11.33-120.97 µg/g, respectively. Conclusions: The host influences TH quality to varying degrees via the transfer of characteristic components. In this study, we successfully detailed a potentially generalizable, accurate, and reproducible dual-component measurement method to identify the TH host.
... Active phytochemicals. Although traditionally salicin was considered as the active principle, there are opinions that this substance cannot explain the whole range of effects of WBE, and that other phytochemicals might be involved, such as polyphenols and flavonoids [67,68,[74][75][76]. ...
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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.
... It is generally standardized to salicin. However, other salicylates, polyphenols, and flavonoids may also play important roles in therapeutic actions (Shara and Stohs, 2015). Some components: (+)-catechin, syringin, triandrin, ampelopsin, ethyl-1-hydroxy-6-oxocyclohex-2-enecarboxylate taxifolin, 3-O-methyltaxifolin, 7-O-methyltaxifolin-3-Oglucoside; p-coumaric, benzoic, p-hydroxybenzoic, p-methoxy benzoic, cinnamic, trans-p-methoxycinnamic, and cis-pmethoxy cinnamic acids (Agnolet et al., 2012). ...
Article
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Background: Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines. Aims: To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for “respiratory diseases” within the current frame of the COVID-19 pandemic as an adjuvant treatment. Method: The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown. Results: A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases (Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine. Conclusions: Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches.
... It is composed of Duhuo Jisheng decoction (a traditional herbal formula), nattokinase and the extraction of Salix alba cortex. All of these components have been shown to be effective in delaying degeneration in human intervertebral disc and potentiating thrombolysis and anti-coagulation profiles, [14][15][16] which may be effective in the management of cervical radiculopathy. Therefore, this study was aimed to evaluate the efficacy and safety of TD0019, a compound traditional Vietnamese herbal medicine, in the treatment of cervical radiculopathy. ...
Article
Introduction Cervical radiculopathy causes chronic pain and reduces patients’ quality of life. Oral analgesics are commonly used but only after careful consideration due to their complications. TD0019, a Vietnamese herbal medicine, composed of Duhuo Jisheng decoction, nattokinase and an extract of Salix alba cortex has shown evidence of some benefits for these patients in pre-clinical and phase-1 studies. This study aimed to evaluate the efficacy and safety of TD0019 in the treatment of cervical radiculopathy. Methods In this double-blind phase-2 trial, 180 patients with symptomatic cervical radiculopathy were randomized to either group 1 with intended dose of TD0019, group 2 with a higher dose (1.5 times the intended dose), or group 3, a placebo. The primary efficacy endpoint was the neck-specific disability score according to the Neck Disability Index (NDI) questionnaire. The safety endpoint included adverse events (AEs) and serious adverse events (SAEs). All patients received the drugs for 30 days and were followed for 60 days. Results Baseline characteristics were similar for the three groups. The reduction of NDI score from baseline to the end of study was greatest for group 2 (from 17.6 ± 7.2 to 4.8 ± 5.1), followed by group 1 (from 16.1 ± 6.9 to 5.4 ± 5.1) and placebo group (from 15.6 ± 6.2 to 7.8 ± 6.8), with a significant decrease for both groups compared to placebo. The percentage of AEs was comparable among three groups and no SAEs occurred. Conclusions TD0019 was superior to placebo for the reduction of symptoms with similar rates of side effects. The higher dose is more beneficial than the intended dose. This herbal medicine may be a potential alternative analgesic in the treatment of cervical radiculopathy.
... It is generally standardized to salicin. However, other salicylates, polyphenols, and flavonoids may also play important roles in therapeutic actions (Shara and Stohs, 2015). Some components: (+)-catechin, syringin, triandrin, ampelopsin, ethyl-1-hydroxy-6-oxocyclohex-2-enecarboxylate taxifolin, 3-O-methyltaxifolin, 7-O-methyltaxifolin-3-Oglucoside; p-coumaric, benzoic, p-hydroxybenzoic, p-methoxy benzoic, cinnamic, trans-p-methoxycinnamic, and cis-pmethoxy cinnamic acids (Agnolet et al., 2012). ...
Article
Full-text available
Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines. To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for “respiratory diseases” within the current frame of the COVID-19 pandemic as an adjuvant treatment. The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown. A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases (Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine. Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches.
... Salicin is usually described as the analgesic agent found in willow bark, responsible for its pharmacological effects. [1][2][3] However, it was suggested that many of these effects cannot be explained by the presence of salicylic derivatives only and that other compounds such as polyphenols (flavonoids, flavan-3-ols) and simple phenols (phenolic acids) can contribute to the therapeutic effects of willow bark. [4][5][6][7][8] On the other hand, leaves of many Salix species are mainly not studied and are considered as waste product after collection of bark. ...
Article
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Contents of twelve selected bioactive substances and antioxidant potential of Salix caprea L. extracts were compared in its two vegetative organs (bark and leaves) and in terms of different ethanol/water mixtures used for extraction (30-70% aq, ethanol) and extraction time (30 min; 24, 48 and 72 h). The extracts were characterized by High Pressure Liquid Chromatography (HPLC), and total phenolics and flavonoids were determined spectrophotometrically. All secondary metabolites identified in Salix caprea L. extracts (gallic, chlorogenic and vanillic acid, epicatechin, rutin, quercetin and naringenin) were found more accumulated in bark. Salicin and p-hydroxybenzoic acid were detected in bark and ferulic, trans-cinnamic and p-coumaric acid in leaves extracts only. Rutin was most abundant bioactive compound both in bark (1.71 g/100 g of de) and leaves extracts (0.434 g/100 g of de). Bark extract with highest bioactive substances contents was obtained with 70% aq. ethanol as most suitable solvent during extraction time of 48 h. Molecular docking showed salicin to have similar affinity toward COX-2 as acetylsalicylic acid, but lower toward COX-1.
... However, with a variety of analgesic ingredients, Pain Bloc-R matched the efficacy of acetaminophen potentially by targeting multiple pain pathways with its ingredients. Vitamin D [15], white willow bark [16], and Angelica root extract [17] serve as anti-inflammatory agents. The antioxidant properties of acetyl L-carnitine and Benfotiamine can potentially reduce neuroinflammation and alleviate pain caused by peripheral neuropathy [41]. ...
Article
Full-text available
The lack of effective treatment for chronic discomfort without negative side effects highlights the need for alternative treatments. Pain Bloc-R is a natural health product composed of vitamins B6, B12, D, white willow bark extract, Angelica root extract, acetyl L-carnitine HCl, caffeine, L-theanine, Benfotiamine, and L-tetrahydropalmatine. The objective of this study was to compare the effects of Pain Bloc-R, acetaminophen, and placebo on unresolved aches and discomfort as assessed by the brief pain inventory (BPI) and modified Cornell musculoskeletal discomfort questionnaires. This randomized, double-blind, placebo-controlled, crossover study consisted of three 7-day periods with Pain Bloc-R, acetaminophen, or placebo, each separated by a 7-day washout. Twenty-seven healthy adults (ages 22–63 years) were randomized to receive the three interventions in different sequences. The BPI “pain at its worst” scores were significantly lower when participants took Pain Bloc-R than when they took acetaminophen (21.8% vs. 9.8% decrease, p = 0.026) after seven days of supplementation. Pain Bloc-R achieved a significant improvement in the “pain at its least” score, significantly decreased the interference of discomfort in walking, and significantly decreased musculoskeletal discomfort total scores (34%, p = 0.040) after seven days. In a post hoc subgroup analysis based on age and gender, male participants ≤45 years taking Pain Bloc-R reported significant reductions in pain severity and pain interference vs. acetaminophen. Pain Bloc-R performed as well as acetaminophen in managing unresolved non-pathological pain in otherwise healthy individuals.
... Nonetheless, pharmacological quality of the willow does not only arise from all out salicin portion in the willow bark. It is thought that antioxidant active ingredients such as polyphenol and flavonoid in willow bark contribute to the anti-inflammatory activity (Nahrstedt et al., 2007;Freischmidt et al., 2015;Shara and Stohs, 2015). Therefore, comprehending inflammation and antioxidant activity is crucial to interpret the pharmacological strength of the willow genus. ...
Conference Paper
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Willow is a rich genus that spreads with 500 species in the world. 27 species are found naturally in Turkey and 4 of them are endemic. Salicylates (salicylic acid and acetylsalicylic acid) extracted from willow species have been used for centuries because of their analgesic, antipyretic and anti-inflammatory properties and especially after the discovery of aspirin, interest in this genus has increased dramatically. However, studies have shown that the total salicin fraction in the willow bark is not sufficient to explain the pharmacological strength of the willow bark. Therefore, it is believed that the anti-inflammatory potential in willow bark can be explained by additional mechanisms, such as antioxidant activity provided by other phytochemical components, especially polyphenols and flavonoids. The previous studies on the antioxidant and anti-inflammatory effects of willow species also found in Turkey (S. purpurea, S. alba, S. amplexicaulis, S.babylonica, S.elaeagnos, S.fragilis, S.triandra, S.caprea, S.aegyptiaca) have shown potential in a great extend. According to recently published molecular and morphological data; S.acmophylla, S.purpurea subsp. leucodermis (endemic), S.myrsinifolia and S.caucasica were determined as the closest relatives to Salix species used in the previous phytochemical and bioactivity studies. In the current review study, it is strongly suggested that these species have potential to be utilized in pharmacological studies in the long run. When considering the richness of Turkey’s willow species, selected Turkish Salix appears to have potential both in obtaining medicinal and food-related products and in preventing oxidative stress-related diseases. The potential is important to be evaluated for contributing the public health and the national economy.
... Zabihi et al. (2018) show that although salicin is the main active compound of the willow bark, its polyphenols and flavonoids must receive due attention. Other authors (Sulaiman et al., 2013;Shara & Stohs, 2015) showed that willow bark contains flavonoids and polyphenols that contribute synergistically to the beneficial effects of Salix alba and may be more important than those of synthetic salicylic acid. Salix alba extract has free radical scavenging activity and can be used as a radical inhibitor or scavenger, with the possibility of acting as a primary antioxidant (Sulaiman et al., 2013). ...
Article
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A study was conducted to determine the effects of dietary hydroalcoholic willow bark extract powder (HWE) supplemented to broilers (14-42 days old) that were exposed to heat stress, on the performance, serum biochemical parameters, liver oxidative status and caecal microflora. The feeding trial was conducted on 120 Cobb 500 broilers (14 days old), assigned to three treatments (T0, T25, and T50), each treatment consisting of eight replicates (five chicks per replicate). The broilers were housed in an experimental hall at a 32 °C constant temperature and 23 hours light regimen. Unlike the dietary control treatment (T0), the experimental treatments were supplemented with 25 g HWE powder/100 kg diet (T25), and 50 g HWE powder 100 kg diet (T50), respectively. Dietary HWE powder did not affect the broilers' performance significantly (14-42 days). A significantly lower amount of malondialdehyde was noticed in the liver of broilers from T25 and T50 treatments in comparison with broilers from T0. Also, the serum cholesterol, triglycerides and alanine aminotransferase were significantly lower in broilers fed with T50, compared with those fed with T0. At 35 and at 42 days, the broilers from T25 and T50 recorded a significantly lower number of E. coli and staphylococci and a higher number of lactobacilli in the caecum than those of T0. It could be concluded that supplementation of dietary HWE powder reduced some of the adverse effects of heat stress, the most effective being the level of 50 g/100 kg diet. ______________________________________________________________________________________
... The first active constituent of willow bark discovered in 1828 was salicin. Today we know that aqueous extracts of willow bark contain at least 11 related salicylate compounds, among them salicin and salicylic acid (reviewed in (Desborough and Keeling, 2017;Shara and Stohs, 2015)). It has previously been shown that salicylate is capable of directly activating AMPK in vivo and in vitro by binding to the beta subunit of the kinase (Hawley et al., 2012). ...
Article
Ethnopharmacological relevance: In different countries and areas of the world, traditional medicine has been and is still used for the treatment of various disorders, including chest pain or liver complaints, of which we now know that they can be linked with altered lipid and cholesterol homeostasis. As ATP-binding cassette transporter A1 (ABCA1) plays an essential in cholesterol metabolism, its modulation may be one of the molecular mechanisms responsible for the experienced benefit of traditional recipes. Intense research activity has been dedicated to the identification of natural products from traditional medicine that regulate ABCA1 expression. Aims of the review: This review surveys natural products, originating from ethnopharmacologically used plants, fungi or marine sources, which influence ABCA1 expression, providing a reference for future study. Materials and methods: Information on regulation of ABCA1 expression by natural compounds from traditional medicine was extracted from ancient and modern books, materia medica, and electronic databases (PubMed, Google Scholar, Science Direct, and ResearchGate). Results: More than 60 natural compounds from traditional medicine, especially traditional Chinese medicine (TCM), are reported to regulate ABCA1 expression in different in vitro and in vivo models (such as cholesterol efflux and atherosclerotic animal models). These active compounds belong to the classes of polyketides, terpenoids, phenylpropanoids, tannins, alkaloids, steroids, amino acids and others. Several compounds appear very promising in vivo, which need to be further investigated in animal models of diseases related to ABCA1 or in clinical studies. Conclusion: Natural products from traditional medicine constitute a large promising pool for compounds that regulate ABCA1 expression, and thus may prevent/treat diseases related to cholesterol metabolism, like atherosclerosis or Alzheimer's disease. In many cases, the molecular mechanisms of these natural products remain to be investigated.
... While dosage of EGCG varies widely based upon species of tea, steeping time, oxidizing time while being processed, a cup of green tea typically contains approximately 50 mg of EGCG while supplement forms may contain much higher concentrations. While green tea is noted to have no severe adverse effects, dosage greater than 10 mg/kg/day can cause hepatic injury in those who are predisposed [46,47]. ...
... The plant-based knowledge present in India's and China's traditional texts led to the discovery of anti-hyperlipidemic guggulsterone from Commiphora mukul, anti-malarial molecule artemisinin from Artemesia alba and bacosides from Bacopa monnieri for enhancing memory (Katiyar et al., 2012). Another such common example is salicylic acid popularly known as Aspirin (a most commonly used antipyretic molecule) that originated from Salix alba and is now produced synthetically (Shara and Stohs, 2015). Similarly, Paclitaxel (anti-cancer molecule) and Silymarin (liver treating drug) originated from Taxus brevifolia and Silybum marianum respectively (Wani et al., 1971;Hadaruga and Hadaruga, 2009). ...
Article
The covid -19 pandemic has wreaked havoc on the global healthcare system and the economy. At present, no specific antiviral vaccine is available to combat this contagious virus. Traditional medicine has a long history of playing a significant role in managing several infectious diseases. In this context, scientists around the globe are also exploring various traditional medical interventions to prevent the covid -19 pandemic. In the present work, we summarize available scientific data advocating the use of traditional medicine for preventing covid -19. A robust literature review was conducted using scientific platforms such as Science Direct, National Center for Biotechnology Information ( ncbi ), Pubmed, Google Scholar, and online database like The Plant List (The Plant List 2013) version 1.1. Special emphasis was given to potential natural antiviral, immuno-modulator plants, and traditional medicines to highlight their possible roles in reducing the disease burden. Immuno-modulator such as Withania somnifera and other natural compounds especially glycyrrhizin, kaempferol, ginsenoside, and lycorine can be leading candidates against sars -CoV-2. Besides the need for rigorous scientific validation of potential herbs and related formulations, their use can be beneficial for the preventive as well as symptomatic treatment of covid -19 infected patients. This work provides a run-through of the experimental therapeutics, preventive and treatment options for covid -19.
... Natural products, including compounds derived from plants, have been used for the development of new drugs, one of the main examples being acetylsalicylic acid (Aspirin), extracted from the bark of the plant Salix alba L. Antioxidant substances based on natural compounds play a preventive role in protecting against the generation of free radicals and, therefore, are one of the most valuable therapeutic agents for reducing the various associated in ammatory diseases (Shara and Stohs 2015). For example, in addition to having antioxidant activities, avonoids and phenolic compounds also play an effective role as antiin ammatory factors, blocking two main signaling pathways, such as NF-κB and MAPKs, which have the main role in the production of several mediators proin ammatory (Arulselvan et al. 2016). ...
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Myrciaria plinioides D. Legrand (Myrtaceae) is a native plant of Southern Brazil, which have potential in the food industry due to its edible fruits. Many plants belonging to this genus have been used for a variety of illnesses, including inflammatory disorders due to antioxidant properties. However, therapeutic uses of M. plinioides have been poorly studied. The aim of study was to assess the anti-inflammatory and anticoagulant activities of the ethanol leaf extract of M. plinioides . In M. plinioides extract-treated RAW 264.7 cells, assessments of cell viability, TNF-α release and p38 MAPK pathway-dependent protein expression were detected. In addition, rat paw edema models were used to analyze the anti-inflammatory effect of the extract. Macrophages cell line treated with M. plinioides extract showed a slight decrease in cell viability. In LPS-stimulated macrophages treated with different concentrations of the extract for 24 h, TNF-α release was inhibited, while modulation of p38 signaling pathway and inhibition of NF-κB p65 protein expression were dose-dependent. In rats, the extract inhibited the formation of paw edema, while an inhibitory effect on trypsin-like enzymes derived from mast cells was seen. Furthermore, the extract presented anticoagulant activity via extrinsic pathway, being able to block specifically factor Xa and thrombin. The study suggests that extract possess potent anti-inflammatory and anticoagulant effects. M. plinioides present great biological potential as a source for the development of anti-inflammatory and anticoagulant drugs. Additional studies can be proposed to better elucidate the mechanism by which M. plinioides exerts its effects.
... Obtaining digoxin from Digitalis purpurea L. allowed for an effective treatment of atrial fibrillation and heart failure 5 . Salicylic acid, which is found, among others, in Salix alba L., after esterification forms acetylsalicylic acid, used in pain and thrombotic diseases 6 . The isolated artimizin from Artemisia annua L. is used in the treatment of a resistant form of malaria 7 . ...
... Perhaps mixing some of these herbs in specific proportions could exert greater effects than even modern drugs. Additionally, it is very important to remember that even some of the modern-day drugs have been derived from plants, i.e., salicylic acid (aspirin) from willow bark (Shara and Stohs, 2015). ...
Article
Full-text available
This experiment examined the separate and combined effects of daidzein (Da) and Chinese herbs (CH) on laying performance and egg quality of post-peak laying hens. Additionally, we explored potential mechanisms of action for these 2 additives by examining plasma hormone levels. After 4 wk of acclimation to caging, sixty-week-old Hyline Brown hens (360) were selected and randomly divided into 4 groups with 6 replicates and 15 chickens per replicate. The following 4 dietary groups were utilized: 1) control group (basal diet); 2) Da group (basal diet + 0.03 kg/t DA); 3) CH group (basal diet +0.6 kg/t CH); 4) Da + CH group (basal diet + 0.03 kg/t Da + 0.6 kg/t CH). Data were analyzed in a completely randomized design with a 2×2 factorial arrangement of treatments. Egg production and FCR treatment averages were analyzed in the following 3 phases: Weeks 1-4, 5-8, and 1-8 of treatment administration. Results revealed that Da increased egg production but decreased FCR (P<0.05) for Weeks 1-8 and especially during Weeks 5-8 (P<0.05). CH decreased FCR in Weeks 1-4 and 5-8 (P<0.05), but increased egg production only during Weeks 5-8 (P<0.05). Da increased Haugh units (P<0.05) on Weeks 4 and 8; CH increased Haugh units (P<0.05) but decreased yolk ratio (P<0.05) on Weeks 4 and 8. Da increased the plasma levels of T3, PROG, FSH, LH and E2 (P<0.05); CH increased the plasma level of T3 (P<0.05). Additionally, Da x CH interactions existed for albumen height, Haugh units, albumen ratio and the level of T3 on Week 8 (P<0.05), indicating that the combination of Da and CH was more effective than administration of either of these dietary components independently. In conclusion, Da and CH, both independently and in combination, increase laying performance, egg quality and plasma hormones levels in post-peak laying hens. Therefore, these treatments may be able to provide prolonged economic benefits to aged laying hens.
... The genus Salix L. (willows) belongs to the Salicaceae family and includes 330-500 species of trees and shrubs with simple, stipulate leaves alternately arranged on woody stems [20]. The medicinal and economic value of willows are exploited in traditional medicine as well as in pharmacy, and willow-originated metabolites are known to be used in the food industry as natural additives and as ingredients in cosmetic products, including sunscreen and anti-aging cream formulations [21][22][23]. Willows are mostly known for their high levels of salicylates, becoming a major object of research after the discovery of aspirin. The pharmacological value of willows does not only arise from the salicin portion in the willow bark but from other components as well such as polyphenolics. ...
Article
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This study presents the first report on phenolic composition and bioactivity of ethanolic extracts of three plant species that grow in the western Balkan mountains and are used in traditional folk medicine: Valeriana montana, Salix retusa, and Campanula hercegovina. Phenolics were extracted from different aerial plant parts using 80% ethanol to assess the possibility of sustainable use of these plants as a source of bioactive compounds without disruption to the roots (for V. montana) or destruction of whole habitats (for S. retusa and C. hercegovina). The ethanolic extract of V. montana flower contained noticeable levels of apigenin and quercetin. The branches and bark of S. retusa were significantly rich in catechin, while rutin was the major phenolic found in the leaf extract of C. hercegovina. Furthermore, the flower extract of V. montana revealed the best antioxidant activity, which was comparable to 4-hydroxybenzoic acid and quercetin. Considering antimicrobial activity, the leaf extracts of V. montana and C. hercegovina demonstrated potent activity against all microbes tested, while the extracts of S. retusa were moderately effective. The presented results emphasize the potential of these plants as novel sources of bioactive compounds.
... The bark and shoots are used as antiinflammatory and analgesic medications [53,54]. Apart from their content of salicylic acid, willows contain a range of other compounds, like other salicylates, flavonoids and polyphenols [55], and preparations made from ground parts of plants have exhibited antioxidant and inhibitory activity against acetylcholinesterase [56]. The results of our study show that the most beneficial anti-proliferative effect was achieved with extract E2, obtained from a willow. ...
Article
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Six new water extracts (E1–E6) were obtained from nest carton produced by jet black ants Lasius fuliginosus and tested for their biochemical and bioactive properties, including antioxidative and anticancer effects. The present study demonstrated significant qualitative and quantitative differences in the content of individual biochemical constituents, as well as bioactive properties between the investigated samples. All tested extracts demonstrated antioxidant properties (determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods), and the highest antioxidative potential was recorded in extracts E1 and E2 (188.96 and 313.67 μg/mL of ascorbic acid equivalent for ABTS and 176.42 and 202.66 μg/mL for DPPH reagent). Furthermore the six extracts exhibited strong inhibitory activity towards human melanoma cells of the A-375 CRL-1619 line in a dose-dependent manner. The most interesting chemopreventive activity was exhibited by extract E2, which inhibited the proliferation of A-375 cells to the greatest extent, while having a minimal effect on Vero cells. The effect on cancer cells has been confirmed using the Electric Cell-substrate Impedance Sensing (ECIS) technique. Significant impedance changes have been detected in A-375 and Vero cells following the administration of extract E2. The obtained results are really promising and constitute the basis for further research on the nest carton of jet black ant.
... Salicylic acid inhibits cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), the same enzymes targeted by synthetic non-steroidal anti-inflammatory drugs (NSAIDs) to alleviate pain and inflammation [137]. Because of this conversion process, white willow generally takes longer to act than aspirin, but the effects last for an extended period of time [96]. ...
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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.
... Other value-added bioproducts in willow have been explored alongside lignocellulosic bioenergy potential to only a limited degree (Brereton et al., 2017;Budzianowski and Reviews, 2017;Devappa et al., 2015aDevappa et al., , 2015bTyśkiewicz et al., 2019), even though willow bark extract is already marketed for its medicinal properties (Beer and Wegener, 2008;Chrubasik et al., 2000;Nahrstedt et al., 2007;Shara and Stohs, 2015). Extractable phytochemicals have potential as bioproducts due to antioxidant, anticancer, anti-inflammatory and antimicrobial functions (Devappa et al., 2015a) with high social, environmental and economic value within the medical (pharmaceuticals), agricultural (biopesticides and biostimulants), commercial (cosmetics, nutraceuticals and household chemicals) and industrial (lubricants and resins) sectors. ...
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The use of willow plantations can be a sustainable approach for treating primary municipal wastewater, potentially reducing both the environmental and economic burdens associated with conventional treatment. However, the impact of wastewater irrigation upon the willow biorefinery potential has not yet been established. To investigate this effect, three-year-old field grown willows were harvested from plots kept as either controls or irrigated with primary municipal wastewater effluent at 29.5 million L ha⁻¹ yr⁻¹. Biomass compositional analysis, ionic liquid pretreatment and enzymatic saccharification were assessed and differential abundance of persistent extractable phytochemicals was evaluated using untargeted metabolite profiling. Glucan significantly increased by 8% in wastewater treated trees, arabinose and galactose were significantly decreased by 8 and 29%, respectively, while xylose, mannose and lignin content were unaltered. Ionic liquid pretreatment and enzymatic saccharification efficiencies did not vary significantly, releasing >95% of the cell wall glucose and recovering 35% of the lignin. From a total of 213 phytochemical features, 83 were significantly depleted and 14 were significantly enriched due to wastewater irrigation, including flavonoids and lignan derivatives. Considered alongside increased biomass yield from wastewater irrigation (+200%), lignocellulosic bioenergy yields increased to 8.87 t glucose ha⁻¹ yr⁻¹ and 1.89 t ha⁻¹ yr⁻¹ recovered lignin, while net extractives yields increased to 1.48 t ha⁻¹ yr⁻¹, including phytochemicals of interest. The maintenance of glucose accessibility after low-cost ionic liquid pretreatment is promising evidence that sustainable lignocellulose bioenergy production can complement wastewater treatment. Untargeted metabolite assessment revealed some of the phytochemical toolkit employed by wastewater irrigated willows, including accumulation of flooding and salinity tolerance associated flavonoids glabraoside A and glabrene. The extractable phytochemicals underpin a novel high biomass phenotype in willow and, alongside lignocellulosic yields, could help enhance the economic feasibility of this clean wastewater treatment biotechnology through integration with sustainable biorefinery.
... The timing of treatment may present a critical factor here and this might also be true for herbal medicines. There is an arising voice that herbal medicines, which have been used to prevent respiratory viral infection for years, currently present promising candidates as adjuvants during COVID-19 [61]. ...
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The usefulness of anti-inflammatory drugs as an adjunct therapy to improve outcomes in COVID-19 patients is intensely discussed in this paper. Willow bark (Salix cortex) has been used for centuries to relieve pain, inflammation, and fever. Its main active ingredient, salicin, is metabolized in the human body into salicylic acid, the precursor of the commonly used pain drug acetylsalicylic acid (ASA). Here, we report on the in vitro anti-inflammatory efficacy of two methanolic Salix extracts, standardized to phenolic compounds, in comparison to ASA in the context of a SARS-CoV-2 peptide challenge. Using SARS-CoV-2 peptide/IL-1β-or LPS-activated human PBMCs and an inflammatory intestinal Caco-2/HT29-MTX co-culture, Salix extracts, and ASA concentration-dependently suppressed prostaglandin E2 (PGE2), a principal mediator of inflammation. The inhibition of COX-2 enzyme activity, but not protein expression was observed for ASA and one Salix extract. In activated PBMCs, the suppression of relevant cytokines (i.e., IL-6, IL-1β, and IL-10) was seen for both Salix extracts. The anti-inflammatory capacity of Salix extracts was still retained after transepithelial passage and liver cell metabolism in an advanced co-culture model system consisting of intestinal Caco-2/HT29-MTX cells and differentiated hepatocyte-like HepaRG cells. Taken together, our in vitro data suggest that Salix extracts might present an additional an-ti-inflammatory treatment option in the context of SARS-CoV-2 peptides challenge; however, more confirmatory data are needed.
... 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]. The extract contains only 24% salicin, which suggests other components of the extract such as flavonoids are helping to increase its effectiveness [20]. ...
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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 active extract of the willow's bark, called salicin, was isolated to its crystalline form (aspirin) as a non-steroidal antiinflammatory drug [15]. Also, other active substances (other salicylates, polyphenols, and flavonoids) are important for the therapeutic purposes of willow bark [40]. Sweet chestnut (Castanea sativa Mill.) is a known source of condensed and hydrolysable tannins [41]. ...
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Traditional knowledge of plants and their preparations used for the treatment of animal diseases was passed down orally from generation to generation, so there are no written records or they are very rare. This study is based on the first documentation of ethnoveterinary knowledge for indigestion or diarrhoea treatment in cattle on the Bilogora hills in northwestern Croatia. Data collection was conducted from 2008 until 2018, in eighteen villages of four municipalities in the Koprivničko-križevačka county, Croatia. Plant specimens were well known, in addition they were confirmed and identified by the skilled botanist. Nine plant species: flax (Linum usitatissimum L.), chamomile (Matricaria recutita L.), hazelwort (Asarum europaeum L.), broad-leaved dock (Rumex obtusifolius L.), sweet chestnut (Castanea sativa Mill.), common oak (Quercus robur L.), white willow (Salix alba L.), common mallow (Malva sylvestris L.), yarrow (Achillea millefolium L.) from 7 botanical families were documented. Decoction and herbal tea were the most common preparation methods. The most often used plants to treat mild diarrhea in cattle were chamomile and broad-leaved dock, and for hard, watery diarrhoea bark of sweet chestnut and sessile oak. The most often used plants to treat indigestion in cattle were hazelwort, chamomille, and flaxseed. Farmers used mostly leaves (about 57%), flowers and stems (more than 25%), bark (about 13%), branches, and seeds (5%) for herbal preparations. Thus the aim of the present study is to document that ethnoveterinary tradition for the next generations.
... In addition, modulation of specific signaling pathways, such as mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB), which can be induced by oxidative stress, are important targets in the discovery of new drugs for the treatment of a wide range of inflammatory disorders (Laufer et al. 2002). Natural products, including compounds derived from plants, have been used for the development of new drugs, one of the main examples being acetylsalicylic acid (Aspirin), extracted from the bark of the plant Salix alba L. Antioxidant substances based on natural compounds play a preventive role in protecting against the generation of free radicals and, therefore, are one of the most valuable therapeutic agents for reducing the various associated inflammatory diseases (Shara and Stohs 2015). For example, in addition to having antioxidant activities, flavonoids and phenolic compounds also play an effective role as anti-inflammatory factors, blocking two main signaling pathways, such as NF-κB and MAPKs, which have the main role in the production of several mediators proinflammatory (Arulselvan et al. 2016). ...
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Myrciaria plinioides D. Legrand (Myrtaceae) is a native plant of Southern Brazil, which have potential in the food industry due to its edible fruits. Many plants belonging to this genus have been used for a variety of illnesses, including inflammatory disorders due to antioxidant properties. However, therapeutic uses of M. plinioides have been poorly studied. The aim of study was to assess the anti-inflammatory and anticoagulant activities of the ethanol leaf extract of M. plinioides . In M. plinioides extract-treated RAW 264.7 cells, assessments of cell viability, TNF-α release and p38 MAPK pathway-dependent protein expression were detected. In addition, rat paw edema models were used to analyze the anti-inflammatory effect of the extract. Macrophages cell line treated with M. plinioides extract showed a slight decrease in cell viability. In LPS-stimulated macrophages treated with different concentrations of the extract for 24 h, TNF-α release was inhibited, while modulation of p38 signaling pathway and inhibition of NF-κB p65 protein expression were dose-dependent. In rats, the extract inhibited the formation of paw edema, while an inhibitory effect on trypsin-like enzymes derived from mast cells was seen. Furthermore, the extract presented anticoagulant activity via extrinsic pathway, being able to block specifically factor Xa and thrombin. The study suggests that extract possess potent anti-inflammatory and anticoagulant effects. M. plinioides present great biological potential as a source for the development of anti-inflammatory and anticoagulant drugs. Additional studies can be proposed to better elucidate the mechanism by which M. plinioides exerts its effects.
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Objectives Colorectal cancer continues to have one of the highest incidents of occurrence with a rising rate of diagnosis among people under the age of 50. Chemotherapy with irinotecan results in severe gastrointestinal dose-limiting toxicity that is caused by the glucuronidated form of the active metabolite (SN-38G). This study evaluates herbal compounds and analogs to biomodulate the metabolism of IR to decrease dose-limiting toxicity while increasing the amount of the active metabolite. Methods In vitro metabolism using human liver microsomes was conducted with white willow bark (WWB) extract, select specific components of WWB, and analogues to evaluate biomodulation of the IR metabolism. Samples were analyzed using liquid chromatography-tandem mass spectrometry to measure metabolites between reactions with and without herbals components. Results WWB showed an optimal decrease (>80%) in SN-38G and a corresponding increase in SN-38 levels (128%) at a concentration of near 200 μg/mL. Tannic acid produced a 75% decrease in SN-38G with a 130% increase in SN-38 at 10 μg/mL, whereas the treatment with beta-pentagalloyl glucose and various analogues decreased SN-38G by 70% and increased SN-38 by 20% at 10 μg/mL. Conclusions These results suggest naturally occurring compounds from WWB may have the potential to increase potency by increasing the conversion of IR to SN-38 and decrease dose-limiting toxicity of IR chemotherapy by reducing glucuronidation of SN-38.
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Salix alba (white willow) bark extract is widely used for conditions associated with inflammation, fever, microbial infection or pain. Exposure of human cultured leukocytes to S. alba in vitro noted a genotoxic response. However, data regarding the influence of this bark extract on DNA damage in vivo are lacking. The main goal of this study was to examine the potential of S.alba bark extract to induce DNA damage and chromosome aberrations in an in vivo model using cells obtained from male Swiss albino mice administered the compound orally. The extract was administered by oral gavage daily for 7 days at doses of 500, 1000, or 2000 mg/kg b.w. Genotoxicity analysis was performed using the comet assay on peripheral blood leukocytes, as well as liver, bone marrow, heart, and testicular cells collected 4 hr after the last treatment and the micronucleus (MN) test on bone marrow cells. In essence cells were collected 28 hr after the penultimate treatment Data demonstrated that S. alba bark extract did not induce significant DNA damage in any cell types examined, or clastogenic/aneugenic effects as detected by the MN test at the three tested doses. Under these experimental conditions, evidence indicates that S.alba bark extract did not initiate genotoxic or chromosome aberrations in various mouse cells investigated.
Chapter
Conventional treatment of complex regional pain syndrome (CRPS) involves a pharmacologic regimen that supplements intensive physical and cognitive-behavioral therapy. Pharmacotherapies available for CRPS are at times insufficient for pain control or carry with them intolerable side effects. Frequently, patients and practitioners then turn to adjuvant therapies to facilitate treatment and symptom relief and reduce prescription pain medication use. This chapter offers an overview of adjuvant treatments, their proposed mechanisms of action, and a review of existing literature. Overall, there was a paucity of literature investigating the use of nonconventional therapies for CRPS, suggesting the need for further evidence-based research in this area.
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From the past decades, carbon dioxide emissions have been dramatically increased and concentrate in atmosphere mainly due to human activities. This disastrous situation was a huge concern on the increasing the atmospheric carbon dioxide emissions inside urban areas and it became a challenge to the public health worldwide, as well as, its main cause of rising climate changes. Hence, the present project study tempted to address the important role of the urban vegetation for air quality. Here, we report the carbon dioxide capture by two urban tree species frequently planted (Morus nigra L.) and/or naturally occurred (Salix alba L.)in Duhok governorate areas and almost in all towns and cities of the Kurdistan Region.The results of this study showed a variation between Salix alba and M. nigra trees species in term of ratio dry/wet biomass, the carbon sequestration net and the annual CO 2 sequestration capacity. The main findings of this research were the annual carbon content quantification for common tree species grown in Duhok city: for white willow was (23 kg) and for black mulberry was (15 kg). Compare with, for some other trees that been done in previous studies for Pinus brutia, Eucalyptus camaldulesnsis, Quercus aegilops, and Cupressuss empervirens were 44.95, 38, 33.93 and 17.2 respectively. These results can be considered as an initial step to decrease the level of carbon dioxide emissions by planting the native treespecies. For the first time, a site-species-specific allometric equation has been developed based on the relationship between tree volume-wood biomass extracted from true values "destructive method" of biomass quantification. Consequently, thanks to this new volume-weight equation, we can assess the important roles of urban trees in the carbon sequestration process in urban areas of the Kurdistan Region without cutting the trees can be assessed.
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This chapter discusses the ethnopharmacological properties, phytochemistry, and culture conditions of the Salix species. Salix aegyptiaca L. (Fam. – Salicaceae) is a deciduous shrub or small tree, and the decoction of leaves or bark infusion of this species is used to cure rheumatic pains in old age people. The leaf decoction mixed with sugar is used by Iranian and Turkish population in depression, neuropathic pain, and rheumatic arthritis. Similarly, S. babylonica infusion of leaves is used to cure rheumatic problems. The other species of Salix possess anti‐inflammatory, anti‐leishmanial, analgesic, astringent, antiviral, and antipyretic activities. The leaves of S. cinerea and S. viminalis have been cultured on Murashige and Skoog culture medium with supplementation of glutamine, casein hydrolysate, benzyl adenine, indole‐3‐butyric acid, and sucrose for induction of callus, and maximum cell biomass has been obtained.
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Clinical application of small-diameter artificial vascular grafts has been hampered by intimal blockages owing to the lack of an endothelial layer and the formation of thrombosis. In this study, an expanded polytetrafluoroethylene (ePTFE) vascular graft was fabricated using a biofriendly ethanol/water mixture as a lubricant and drug carrier. Natural silk fibroin (SF) hydrogel and white willow extract salicin were embedded into ePTFE graft successfully via the ethanol/water lubricant and drug carrier as verified by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The ePTFE graft functionalized by SF hydrogel improved the proliferation of human umbilical vein endothelial cell (HUVEC) due to SF’s hydrophilia and cytocompatibility as measured by the live/dead and cell counting kit-8 (CCK-8) assays. The rapid endothelialization of ePTFE graft helped reduced intimal blockages in vitro. Furthermore, the salicin-modified ePTFE graft exhibited an anticoagulation property as demonstrated by platelet adhesion and activated partial thromboplastin time (APTT) tests. These results suggest that ePTFE graft fabricated with silk fibroin and salicin can be an attractive candidate for vascular grafts.
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Debarking has the potential to make short rotation woody crops more economically attractive by both improving the quality of woody material and creating a new product stream from separated bark. Thus, in this research the ultimate strength of the wood-bark interface was studied relative to the development and optimisation of debarking systems and strategies. Four genetically different cultivars of shrub willow, three harvest times and different moisture levels were tested at a quasi-static extension rate of 0.5 mm min⁻¹. Regression models show that moisture content has a negative correlation with wood-bark bond strength, which is similar to observations made on other species. Harvesting time had a significant effect on wood-bark strength of shrub willow (p < 0.01). Shrub willow harvested during the winter had significantly (p < 0.01) higher wood-bark bond strength compared to early-growing with a mean increase of 90% and 108% compared to mid-year. This is thought to be due to seasonal changes in cambium layer morphology. Moreover, wood-bark bond strength was significantly different (p < 0.05) for genetically different cultivars of shrub willow. Cultivar ‘Millbrook’ had higher wood-bark bond strength than ‘Fabius’. Preliminary indications suggest it is possible that cross-linkages of calcium ions, and arabinan and galactan side chains of pectins play a role in cultivars that have high wood-bark bond strength.
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Efficient utilization, treatment, and disposal of agricultural wastewater and sewage sludge are important environmental risks. In our research, effluent water from intensive aquaculture was evaluated for the irrigation of short rotation energy willow in a lysimeter experiment. Two different water types and their combinations were applied with weekly doses of 15, 30, and 60 mm, respectively. Our results revealed that implementing effluent water instead of fresh water could potentially increase the yield of the willow due to its higher nitrogen content (29 N mg/l). The biomass of irrigated short rotation coppice (SRC) willow plants were between 493–864 g/plant, 226–482 g/plant, and 268–553 g/plant dry weight during experiment period (2015–2017), respectively. However, due to the chemical properties (Na concentration, SAR value) of effluent water, the increase of the soil exchangeable sodium percentage (ESP) was significant and it can lead to soil degradation in the long term. The current study also investigated the relationship between chemical composition of the plant tissue and the irrigation water. In the case of K-levels of willow clones, an increasing trend was observed year-by-year. In terms of N and Na content was localized in leaf parts, especially in samples irrigated with effluent. Less N and Na values were detected in the stem and in the samples irrigated with surface water. In SRC willow plants, phosphorus was mostly localized in the stem, to a lower extent in the leaf part. The difference is mostly observed in the case of the amount of irrigation water, where the P content of the examined plant parts decreased with the increase of the amount of irrigation water. In the case of phenological observations, higher values of plant height were measured during diluted and effluent irrigation. Moreover, the SPAD of the plants irrigated with effluent water exceeded the irrigated ones with surface water.
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The mechanical behavior of the wood-bark interface of shrub willow was tested to investigate the influence of key factors: harvest season, moisture content, and cultivars. The mechanical properties enable the design and optimization of the performance of debarking equipment for short-rotation woody stems and can help improve understanding of the mechanical performance of the wood-bark interface. Results show that the low moisture content samples have a significantly higher shear modulus, G (Mean =0.34 GPa) and modulus of toughness Ut (Mean = 12.84 kPa). However, the degree of ductility (0.02) and the ratio of ultimate strain εu to strain ε50 (2.18) are lower for low moisture content samples. Different willow cultivars have no significant influence on the mechanical properties of the wood-bark interface tested. Results also reveal that the values of ultimate strain εu (0.11), modulus of toughness Ut (16.09 kPa), and degree of ductility (0.031) are significantly higher for samples collected in the dormant season compared to the growing season. Covariance analysis reveals that aspect ratio of the sample has a significant effect on shear modulus, G (p = 0.041), ultimate strain, εu (p = 0.008), modulus of toughness (p = 0.012) and degree of ductility (p = 0.001). Identifying the combination of these desirable properties provides a framework to achieve the maximum debarking efficiency and effectiveness for short-rotation woody crops.
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The environment is being continuously deteriorated by air pollution and global warming, increased pressure of work or family on life, and changes in lifestyle; these factors have contributed to an increase in the proportion of both females and males with sensitive skin. To this end, the cosmetics market has focused on developing hypoallergenic or skin-soothing and make-up products. Here, we summarize the definition and causes of sensitive skin, list the mechanisms underlying the development of this condition, and review the natural plant products and purified active components that have potential for use in anti-allergic cosmetics. A review of studies that evaluated the anti-allergic properties of natural products was conducted. There has been a progressive increase in the number of natural products identified as potential anti-allergic raw materials in cosmetics. Finally, we suggest strategies for developing anti-allergic cosmetics in the future.
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Coffee and willow are known as valuable sources of biologically active phytochemicals such as chlorogenic acid, caffeine, and salicin. The aim of the study was to determine the interactions between the active compounds contained in water extracts from coffee and bark of willow (Salix purpurea and Salix myrsinifolia). Raw materials and their mixtures were characterized by multidirectional antioxidant activities; however, bioactive constituents interacted with each other. Synergism was observed for ability of inhibition of lipid peroxidation and reducing power, whereas compounds able to scavenge ABTS radical cation acted antagonistically. Additionally, phytochemicals from willow bark possessed hydrophilic character and thermostability which justifies their potential use as an ingredient in coffee beverages. Proposed mixtures may be used in the prophylaxis or treatment of some civilization diseases linked with oxidative stress. Most importantly, strong synergism observed for phytochemicals able to prevent lipids against oxidation may suggest protective effect for cell membrane phospholipids. Obtained results indicate that extracts from bark tested Salix genotypes as an ingredient in coffee beverages can provide health promoting benefits to the consumers; however, this issue requires further study.
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The purpose of this study was to assess the effect of 8-weeks ingestion of a commercialized joint pain dietary supplement (InstaflexTM Joint Support, Direct Digital, Charlotte, NC) compared to placebo on joint pain, stiffness, and function in adults with self-reported joint pain. InstaflexTM is a joint pain supplement containing glucosamine sulfate, methylsufonlylmethane (MSM), white willow bark extract (15% salicin), ginger root concentrate, boswella serrata extract (65% boswellic acid), turmeric root extract, cayenne, and hyaluronic acid. Subjects included 100 men and women, ages 50-75 years, with a history (>3 months) of joint pain, and were randomized to InstaflexTM or placebo (3 colored gel capsules per day for 8 weeks, double-blind administration). Subjects agreed to avoid the use of non-steroidal anti-inflammatory drugs (NSAID) and all other medications and supplements targeted for joint pain. Primary outcome measures were obtained pre- and post-study and included joint pain severity, stiffness, and function (Western Ontario and McMaster Universities [WOMAC]), and secondary outcome measures included health-related quality of life (Short Form 36 or SF-36), systemic inflammation (serum C-reactive protein and 9 plasma cytokines), and physical function (6-minute walk test). Joint pain symptom severity was assessed bi-weekly using a 12-point Likert visual scale (12-VS). Joint pain severity was significantly reduced in InstaflexTM compared to placebo (8-week WOMAC, [downwards arrow]37% versus [downwards arrow]16%, respectively, interaction effect P = 0.025), with group differences using the 12-VS emerging by week 4 of the study (interaction effect, P = 0.0125). Improvements in ability to perform daily activities and stiffness scores in InstaflexTM compared to placebo were most evident for the 74% of subjects reporting knee pain (8-week WOMAC function score, [downwards arrow]39% versus [downwards arrow]14%, respectively, interaction effect P = 0.027; stiffness score, [downwards arrow]30% versus [downwards arrow]12%, respectively, interaction effect P = 0.081). Patterns of change in SF-36, systemic inflammation biomarkers, and the 6-minute walk test did not differ significantly between groups during the 8-week study CONCLUSIONS: Results from this randomized, double blind, placebo-controlled community trial support the use of the InstaflexTM dietary supplement in alleviating joint pain severity in middle-aged and older adults, with mitigation of difficulty performing daily activities most apparent in subjects with knee pain.Trial registration: ClinicalTrials.gov Identifier: NCT01956500.
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Objective: This study was undertaken to determine the effects of an ephedrine- and synephrine-based compound on body mass, body composition, metabolic variables, and mood states in healthy overweight adults.Methods: Thirty subjects with a body mass index > 27 kg/m2 were assigned randomly to the experimental group or the placebo group. The experimental group received a capsule containing ephedrine alkaloids 20 mg, synephrine 5 mg, caffeine 200 mg, and salicin 15 mg twice daily for 8 weeks, whereas the other group received a matching placebo. A registered dietitian instructed all patients about a 22-kcal/kg National Cholesterol Education Program Step One diet. In addition, all patients performed a cross-training exercise program 3 days per week under the guidance of an exercise physiologist. During the exercise sessions, patients achieved ∼70% of age-predicted maximum heart rate.Results: The experimental group had a significantly greater weight loss compared with the placebo group (3.14 kg vs 2.05 kg, respectively; P < 0.05). The experimental group experienced a 16% decrease in body fat compared with a 1% increase for the placebo group. The between-group difference was significant (P = 0.005). Both groups achieved a significant reduction in fat-free mass; however, the reduction in the placebo group was greater than that of the experimental group. This suggests a muscle-sparing effect in the experimental group. No significant changes in blood pressure, serial electrocardiograms, pulse rate, serum chemistry, or caloric intake were noted.Conclusions: These findings indicate the apparent safety and efficacy of the ephedrine- and synephrine-based compound within the confines of this study.
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Dear Editor, A 61-year-old female with the past medical history of hypertension and osteoarthritis presented to Emergency Department with sudden onset of shortness of breath and non-productive cough 30 min, after taking white willow bark supplement. The patient denied any history of the drug or supplement allergy. Pulse oximetry demonstrated oxygen desaturation; SpO2 of 75% on ambient air and 94% on nasal cannula with the flow of oxygen 20 L/min. Arterial blood gas although on FiO2 of 100% showed severe hypoxemia with the high A-a gradient, metabolic acidosis with respiratory compensation (pH 7.28, PCO2 36 mmHg, PaO2 75 mmHg, and HCO3 19 mmol/L). Blood tests demonstrated evidence of wide anion gap (AG) metabolic acidosis (AG 14 mmol/L) from lactic acidosis (lactic acid 4.9 mmol/L) with the normal gap metabolic acidosis (∆AG/∆Bicarb = 0.4) and the patient had no osmolal gap. Furthermore, serum ketone and salicylate levels were undetectable and her chest X-ray showed bilateral interstitial infiltrates [Figure 1]. Transthoracic echocardiogram revealed normal systolic and diastolic function. The diagnosis of acute hypoxic respiratory failure secondary to severe acute respiratory distress syndrome (ARDS) from reaction to white willow bark was made; the PaO2/FiO2 of 75 mmHg. The patient was promptly started on intravenous venous methylprednisolone and oral antihistamines including diphenhydramine and ranitidine. The patient responded well with our treatment and her oxygen requirement gradually improved from 94% on FiO2 of 100% to 95% on room air. Lactic acidosis also subsided after maintaining adequate oxygenation. Figure 1 Chest X-ray demonstrated bilateral interstitial infiltrates The use of white willow bark supplement was first reported back to the time of Hippocrates (400 BC) when patients were advised to chew on the bark for pain relief and fever reduction. Willow bark is also included in weight-loss products.[1] There have been a remarkably small number of reported cases of adverse reactions to willow bark extract. These adverse drug reactions are usually mild (maculopapular rashes). White willow bark induced anaphylaxis is rare; however, a few cases have been reported.[2,3] To our knowledge, this is the first report of white willow bark induced ARDS. People who are allergic or sensitive to salicylates (such as aspirin) should not use willow bark.
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Diabetic retinopathy is a complex condition where inflammation and oxidative stress represent crucial pathways in the pathogenesis of the disease. Aim of the study was to investigate the effects of a fortified extract of red berries, Ginkgo biloba and white willow bark containing carnosine and α-lipoic acid in early retinal and plasma changes of streptozotocin-induced diabetic rats. Diabetes was induced by a single streptozotocin injection in Sprague Dawley rats. Diabetics and nondiabetic (control) rats were treated daily with the fortified extract for the ten days. Retina samples were collected and analyzed for their TNF-α and VEGF content. Moreover, plasma oxidative stress was evaluated by thiobarbituric acid reacting substances (TBARS). Increased TNF-α and VEGF levels were observed in the retina of diabetic rats. Treatment with the fortified extract significantly lowered retinal cytokine levels and suppressed diabetes-related lipid peroxidation. These data demonstrate that the fortified extract attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the retina in early diabetic rats.
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JEPonline. 2001;4(2):28-34. The purpose was to determine the effects of an herbal preparation containing ma huang, bitter orange and guarana on resting energy expenditure (REE), blood chemistries, and body composition in obese adults. Five males and 15 females (age=31±6.6 yr, height=168.1 ±8.4 cm, weight=93.4±17.1 kg, %fat=43.8 ±6.5%) were matched, randomly assigned to either the supplement (N=12) or placebo (N=8) group, and participated in a 44 d aerobic exercise program (3 d/wk). REE was determined by open-circuit spirometry, and serum samples were analyzed for glucose, cholesterol, triglycerides, HDL, and LDL. Changes in body mass (BM), %fat, fat mass (FM), and fat-free mass (FFM) were determined using DEXA. Due to limited compliance, pre-and post-treatment diet recalls were analyzed for only 14 subjects (supplement=9, placebo=5). Analysis included doubly MANOVA repeated measures (diet recalls and blood chemistries) and independent t-tests (REE and body composition) at á<0.05. The only significant difference was in FM (p=0.033). When a more liberal alpha (á<0.10) is considered, %fat and BM were significant (p=0.096 and 0.087). The supplement, thus, may result in reductions in FM, %fat and BM, but has little effect on energy expenditure, diet or blood chemistries following a six-week period of supplementation and training.
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To report a case of anaphylaxis resulting from the use of a willow bark-containing dietary supplement in a patient with a history of an aspirin allergy. A 25-year-old white woman presented to the emergency department of a community teaching hospital with anaphylaxis requiring epinephrine, diphenhydramine, methylprednisolone, and volume resuscitation to which she responded favorably. Medication history revealed that she had ingested 2 capsules of Stacker 2 (NVE Pharmaceuticals, Newton, NJ), a dietary supplement promoted for weight loss, prior to experiencing her initial symptoms. Among other active ingredients, this product contains willow bark. Of significance is that this patient also reported a history of allergy to acetylsalicylic acid. No other causes for anaphylaxis were identified. She continued to receive routine supportive care and the remaining hospital course was uncomplicated. Dietary supplements, including herbal products, are used by many individuals who consider them to be inherently safe despite limited regulatory oversight by the Food and Drug Administration. While there may be value to specific botanical ingredients, a potential for adverse effects also exists. The popular product consumed by our patient is used for weight loss and contains willow bark, a source of salicylates. Based on the Naranjo probability scale, it is probable that this case of anaphylaxis was due to this dietary supplement. The use of any willow bark-containing dietary supplement may present a risk of anaphylactic reaction to patients with a history of allergy to salicylates. Clinicians need to recognize the potential for adverse effects from dietary supplements.
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Many higher plants contain novel metabolites with antimicrobial, antifungal and antiviral properties. However, in the developed world almost all clinically used chemotherapeutics have been produced by in vitro chemical synthesis. Exceptions, like taxol and vincristine, were structurally complex metabolites that were difficult to synthesize in vitro. Many non-natural, synthetic drugs cause severe side effects that were not acceptable except as treatments of last resort for terminal diseases such as cancer. The metabolites discovered in medicinal plants may avoid the side effect of synthetic drugs, because they must accumulate within living cells. The aim here was to test an aqueous extract from the young developing leaves of willow (Salix safsaf, Salicaceae) trees for activity against human carcinoma cells in vivo and in vitro. In vivo Ehrlich Ascites Carcinoma Cells (EACC) were injected into the intraperitoneal cavity of mice. The willow extract was fed via stomach tube. The (EACC) derived tumor growth was reduced by the willow extract and death was delayed (for 35 days). In vitro the willow extract could kill the majority (75%-80%) of abnormal cells among primary cells harvested from seven patients with acute lymphoblastic leukemia (ALL) and 13 with AML (acute myeloid leukemia). DNA fragmentation patterns within treated cells inferred targeted cell death by apoptosis had occurred. The metabolites within the willow extract may act as tumor inhibitors that promote apoptosis, cause DNA damage, and affect cell membranes and/or denature proteins.
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The efficacy of willow bark extract in the treatment of painful mobility disorders, such as back pain and arthritis, has been attributed to the content of salicin and its derivatives as pro-drugs of salicylates. However, based on clinical experience and the evidence of experimental pharmacological studies, the fraction of total salicin cannot satisfactorily explain the clinical efficacy of willow bark. In addition, salicins and their metabolites lack the acetylating potential of ASA and must therefore possess a different mechanism of action. A detailed pharmacological screening of the aqueous willow bark extract STW 33-I addressed the question of the identification of fractions contributing to the overall effect. All in vivo and in vitro models studied pointed to relevant contributions of the fraction of polyphenols and flavonoids. The single compounds or their combinations responsible for the effect remain to be elucidated.
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What is already known about this subject: Performance-enhancing dietary supplements have not been clinically tested for safety or efficacy. In clinical trials performed under resting conditions, performance-enhancing supplements raise blood pressure and affect glucose homeostasis. The effect of exercise on the pharmacokinetics and pharmacodynamics of stimulant herbals is unknown. What this study adds: Supplement-induced effects on blood pressure and glucose levels are not ameliorated by exercise. Exercise does not affect the kinetics of stimulant ingredients, caffeine and synephrine. Performance-enhancing supplement use modestly improves exercise tolerance. AIMS Dietary supplements (DS) promoted to enhance athletic performance often contain herbal sympathomimetics such as Citrus aurantium (synephrine) and caffeine. We aimed to characterize the pharmacology of a performance-enhancing DS in the setting of exercise. Methods: Ten healthy adults (three women) aged 20-31 years participated in a three-arm, double-blind, placebo-controlled, crossover study. Subjects ingested one dose of DS (Ripped Fuel Extreme Cut(R) with 21 mg synephrine and 304 mg caffeine by analysis) under resting conditions and 1 h prior to moderately intense exercise (30 min on cycle ergometer at 75-80% HR(max)), with a placebo (PLC)/exercise control. Plasma synephrine and caffeine concentrations were measured over 12 h, and vital signs, serum electrolytes, oxygen consumption and perceived exercise exertion were monitored. Results: No significant adverse events occurred. Synephrine and caffeine pharmacokinetics were unaffected by exercise. Post-exercise diastolic blood pressure was higher after DS (peak mean 71.7 +/- 8.7 mmHg) than PLC (63.0 +/- 4.9 mmHg) (p = 0.007). There were no substantial treatment-related differences in post-exercise HR, systolic blood pressure, or temperature. Postprandial plasma glucose increased to 121.0 +/- 31.6 mg dl(-1) with DS and exercise vs. 103.7 +/- 25.5 mg dl(-1) with PLC and exercise (P = 0.004). No treatment differences in exercise-related oxygen consumption, serum lactate, or insulin were observed. Exercise was rated less difficult with DS than PLC (P = 0.001). Conclusions: Blood pressure and plasma glucose increased post-exercise with DS use, which could be detrimental in some people. Exercise was perceived as less strenuous after DS, presumably due to the stimulant effects of caffeine.
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Objective. To investigate the efficacy and safety of a standardized willow bark extract in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. We studied 127 outpatients with hip or knee OA and a WOMAC pain score of at least 30 mm and 26 outpatients with active RA in 2 randomized, controlled, double-blind trials with followup for 6 weeks. OA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg of salicin/day, diclofenac 100 mg/day, or placebo (n = 43, 43, and 41, respectively). Main outcome measure was the pain subscore of the WOMAC OA Index. RA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg salicin/day (n = 13) or placebo (n = 13). Main outcome measure was the patient's assessment of pain rated on a 100 mm visual analog scale (VAS). Results. OA trial: WOMAC pain scores decreased by 8 mm (17%) in the willow bark group and by 23 turn (47%) in the diclofenac group, compared with 5 mm (10%) in the placebo group. The difference between willow bark extract and placebo was not statistically significant (-2.8 mm; 95% CI -12.1 to 6.4 mm; p = 0.55, ANCOVA), but the difference between diclofenac and placebo was highly significant (-18.0 mm; 95% CI -27.2 to -8.8 mm; p = 0.0002, ANCOVA). RA trial: The mean reduction of pain on the VAS was -8 turn (15%) in the willow bark group compared with -2 mm (4%) in the placebo group. The difference was not statistically significant (estimated difference -0.8 mm; 95% CI -20.9 to 19.3 mm; p = 0.93, ANCOVA). Conclusion. The OA study suggested that the willow bark extract showed no relevant efficacy in patients with OA. Similarly, the RA trial did not indicate efficacy of this extract in patients with RA.
Article
Study objective: Efficacy and safety of willow bark extract for pain reduction in patients suffering from musculoskeletal disorders (MSD) has been shown in clinical short term trials. Therefore this observational study over 6 months should evaluate patterns of treatments like mono- or combinations therapy, dosage and safety during long-term treatment under pragmatic conditions with the aqueous willow bark extract STW 33-I, (Proaktiv(®); drug-extract-ratio 16-23:1). Patients and methods: The patients were treated with STW 33-I; comedication with other NSAIDs and opioids was allowed. An extensive case report form including pain questionnaires and patient diary was used for outcome evaluation. Results: Four hundred and thirty-six patients with rheumatic pain mainly due to osteoarthritis (56.2%) and back pain (59.9%) were included. During the study the mean reductions from baseline value 58.4±22.6-31.8±22.5 after 24 weeks in the pain intensity scale (VAS 0-100mm) were significant even after 3 weeks with a reduction by 26 mm (45.6% of the baseline value) at the end of the study. The relative reductions of the weekly means of the daily patient self-rated scores of the pain (6-point Likert-scales) were between 33% and 44% of the baseline values during the course of the study. We present results of subgroups according their analgetic/antiphlogistic comedication. The distribution and specification of the main adverse events and the ratings of the treatment showed a good tolerability. No relevant drug interactions were reported. Conclusion: These data suggest that STW 33-I can be used as a basic treatment in the long-term therapy of painful musculoskeletal disorders and that it can be combined with NSAIDs and opioids if necessary.
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Willow bark extract (WBE) is listed in the European Pharmacopoeia and has been traditionally used for treating fever, pain and inflammation. Recent studies have demonstrated its clinical usefulness. This study investigated the antioxidative effects of WBE in human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans. WBE prevented oxidative-stress-induced cytotoxicity of HUVECs and death of C. elegans. WBE dose-dependently increased mRNA and protein expression levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) target genes, heme oxygenase-1, γ-glutamyl-cysteine ligase modifier and catalytic subunits, and p62, and intracellular glutathione (GSH) in HUVECs. In the nematode C. elegans, WBE increased the expression of the gcs-1::green fluorescent protein (GFP) reporter, a well-characterized target of the Nrf2 ortholog SKN-1, in a manner that was SKN-1-dependent. WBE increased intranuclear expression and DNA binding of Nrf2, and activity of an antioxidant response element (ARE) reporter plasmid in HUVECs. WBE-induced expression of Nrf2-regulated genes, and increased GSH levels in HUVECs were reduced by Nrf2 and p38 small interfering (si)RNAs, and by the p38-specific inhibitor SB203580. Nrf2 siRNA reduced the cytoprotective effect of WBE against oxidative stress in HUVECs. Salicin, a major anti-inflammatory ingredient of WBE, failed to activate ARE-luciferase activity, while a salicin-free WBE fraction showed intensive activity. WBE induced antioxidant enzymes and prevented oxidative stress through activation of Nrf2 independently of salicin, providing a new potential explanation for the clinical usefulness of WBE.
Article
Here, proof-of-concept of a new analytical platform used for the comprehensive analysis of a small set of commercial willow bark products is presented, and compared with a traditional standardization solely based on analysis of salicin and salicin derivatives. The platform combines principal component analysis (PCA) of two chemical fingerprints, i.e., HPLC and (1)H NMR data, and a pharmacological fingerprint, i.e., high-resolution 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS(+)) reduction profile, with targeted identification of constituents of interest by hyphenated HPLC-solid-phase extraction-tube transfer NMR, i.e., HPLC-SPE-ttNMR. Score plots from PCA of HPLC and (1)H NMR fingerprints showed the same distinct grouping of preparations formulated as capsules of Salix alba bark and separation of S. alba cortex. Loading plots revealed this to be due to high amount of salicin in capsules and ampelopsin, taxifolin, 7-O-methyltaxifolin-3'-O-glucoside, and 7-O-methyltaxifolin in S. alba cortex, respectively. PCA of high-resolution radical scavenging profiles revealed clear separation of preparations along principal component 1 due to the major radical scavengers (+)-catechin and ampelopsin. The new analytical platform allowed identification of 16 compounds in commercial willow bark extracts, and identification of ampelopsin, taxifolin, 7-O-methyltaxifolin-3'-O-glucoside, and 7-O-methyltaxifolin in S. alba bark extract is reported for the first time. The detection of the novel compound, ethyl 1-hydroxy-6-oxocyclohex-2-enecarboxylate, is also described.
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Antiinflammatory compounds in the diet can alleviate excessive inflammation, a factor in the pathogenesis of common diseases such as rheumatoid arthritis, atherosclerosis and diabetes. This study examined three European herbs, chamomile (Matricaria chamomilla), meadowsweet (Filipendula ulmaria L.) and willow bark (Salix alba L.), which have been traditionally used to treat inflammation and their potential for use as antiinflammatory agents. Aqueous herbal extracts and isolated polyphenolic compounds (apigenin, quercetin and salicylic acid, 0-100 μM) were incubated with THP1 macrophages, and interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α) were measured. At concentrations of 10 μM, both apigenin and quercetin reduced IL-6 significantly ( p < 0.05). Apigenin at 10 μM and quercetin at 25 μM reduced TNF-α significantly ( p < 0.05). Amongst the herbal extracts, willow bark had the greatest antiinflammatory activity at reducing IL-6 and TNF-α production. This was followed by meadowsweet and then chamomile. The lowest effective antiinflammatory concentrations were noncytotoxic (MTT mitochondrial activity assay). The Comet assay, which was used to study the protective effect of the isolated phenols against oxidative damage, showed positive results for all three polyphenols. These are the first findings that demonstrate the antiinflammatory capacity of these herbal extracts. Copyright © 2012 John Wiley & Sons, Ltd.
Article
A quantified aqueous Willow bark extract (STW 33-I) was tested concerning its inhibitory activity on TNF-α induced ICAM-1 expression in human microvascular endothelial cells (HMEC-1) and further fractionated to isolate the active compounds. At 50 μg/ml the extract, which had been prepared from Salix purpurea L., decreased ICAM-1 expression to 40% compared to control cells without showing cytotoxic effects. Further liquid-liquid partition revealed an ethyl acetate phase with potent reduction of ICAM-1 expression to 40% at 8 μg/ml. This fraction was comprehensively characterised by the isolation of flavanone aglyca and their corresponding glycosides, chalcone glycosides, salicin derivatives, cyclohexane-1,2-diol glycosides, catechol and trans-p-coumaric acid. All compounds were investigated for their activity on TNF-α induced ICAM-1 expression. The flavonoid and chalcone glycosides were not active up to 50 μM, whereas catechol and eriodictyol at the same concentration showed a significant reduction of ICAM-1 expression to 50% of control. Interestingly, other isolated flavanone aglyca like taxifolin, dihydrokaempferol and naringenin showed only weak or moderate inhibitory activity. Eriodictyol was a minor compound in the extract, whereas the catechol content in the extract (without excipients) reached 2.3%, determined by HPLC. One of the isolated cyclohexan-1,2-diol glucosides, 6'-O-4-hydroxybenzoyl-grandidentin, is a new natural compound. As catechol is quantitatively important in Willow bark extracts it can be concluded from the in vitro data that not only flavonoids and salicin derivatives, but also catechol can probably contribute to the anti-inflammatory activity of Willow bark extracts.
Article
Willow bark extract is frequently used in the treatment of painful rheumatological diseases, such as arthritis and back pain. Its effect has been attributed to its main component salicin, but pharmacological studies have shown that the clinical efficacy of the willow bark extract cannot be explained by its salicin content alone. Therefore different modes of action have been suggested for the anti-inflammatory effect of willow bark extract. Here, we report in vitro data revelling the effect and mode of action of the aqueous willow bark extract STW 33-I as well as a water-soluble fraction (fraction E [Fr E]) in comparison with well-known non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin (ASA) and diclofenac (Diclo) on pro-inflammatorily activated human monocytes and differentiated macrophages. STW 33-I and the water-soluble Fr E showed concentration-dependent and significant anti-inflammatory effects in lipopolysaccharide-activated monocytes. Both inhibited the intracellular protein expression of tumour necrosis factor-alpha (TNFα) as well as the mRNA expression of TNFα and cyclooxygenase 2 (COX-2), and the release of nitric oxide (NO). In addition, apoptosis of pro-inflammatorily activated monocytes was induced. Furthermore, treatment of activated macrophages with STW 33-I inhibited the nuclear translocation of the p65 subunit of the nuclear transcription factor-kappa B (NF-κB p65). The present in vitro investigations suggest a significant anti-inflammatory activity of willow bark water extract STW 33-1 and of its water-soluble fraction by inhibiting pro-inflammatory cytokines (TNFα), COX-2 and nuclear translocation of the transcription factor NF-κB in pro-inflammatorily activated monocytes. Our results provide further evidence for the therapeutic use of STW 33-I in inflammation-related disorders.
Article
The present study examined the skeletal muscle expression of several genes related to the inflammatory process before and after a bout of downhill running. Twenty-nine males between the ages of 18 and 35 years performed a 45-min downhill (-17.5%) treadmill protocol at 60% of maximal oxygen consumption. Venous bloods samples and muscle biopsy samples from the vastus lateralis were donated prior to and at 3-h and 24-h postexercise, along with ratings of perceived muscle soreness. Serum creatine kinase (CK) was determined, as was skeletal muscle gene expression of interleukin (IL)-6, IL-8, IL-12 (p35), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, cyclooxygenase 2 (COX2), and nuclear factor kappa B (NFkB) (p105/p50). Gene expression was analyzed using RT-PCR and compared with a standard housekeeping gene (beta-actin). Data were analyzed for statistical differences using multivariate analysis of variance with univariate follow-up. In addition, Pearson correlations were conducted to determine if any significant relationship exists between any of these transcripts and both CK and muscle soreness. Significant (p < 0.05) up-regulations in IL-6, IL-8, and COX2 mRNA expression were observed compared with baseline, whereas no significant changes for IL-12, IL-1beta, TNF-alpha, or NFkB were noted. Significant increases in IL-6 mRNA were observed at 3 h (p < 0.001) and 24 h (p = 0.043), whereas significant increases in IL-8 (p = 0.001) and COX2 (p = 0.046) mRNA were observed at 3-h postexercise. In addition, muscle soreness was significantly correlated with IL-8 at 24 h (r = -0.370; p = 0.048), whereas CK was significantly related to NFkB at baseline (r = -0.460; p = 0.012). These data indicate that increases in the mRNA expression of IL-6, IL-8, and COX2 occur in the vastus lateralis as a result of damaging eccentric exercise in young, recreationally trained males. Further, it appears that IL-8 transcription may play some role in inhibiting postexercise muscle soreness, possibly through regulation of angiogenesis.
Article
Since ancient times preparations from Salix species have been used to alleviate pain. The aim of this study was to update the evidence of the effectiveness of willow bark products in the treatment of musculoskeletal pain. OVID(MEDLINE), PUBMED, Silverplatter, and CENTRAL and manual searches were used to identify clinical trials investigating Salix preparations. Authors SC and JEV extracted the data independently and discussed disagreements. Seven manuscripts were identified, reporting four trials with confirmatory and four with exploratory study designs. Three manuscripts presented the same trial data: repetitious reports were excluded. One confirmatory and two exploratory studies indicate a dose-dependent analgesic effect not inferior to rofecoxib in patients with low back pain. In one exploratory and one confirmatory study conflicting results were achieved in participants with osteoarthritis. No significant effect was seen in a confirmatory study in patients with rheumatoid arthritis, but this study was grossly underpowered. All studies investigated ethanolic extracts with daily doses up to 240 mg salicin over periods of up to six weeks. Minor adverse events occurred during treatment. The review provides moderate evidence of effectiveness for the use of ethanolic willow bark extract in low back pain. Further studies are required to find out if treatment of osteoarthritis and rheumatoid arthritis requires extract with higher doses than 240 mg salicin per day. Copyright