Anti-inflammatory effects of the willow bark extract STW 33-I (Proaktiv®) in LPS-activated human monocytes and differentiated macrophages
ABSTRACT 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.
- SourceAvailable from: H P Vasantha Rupasinghe
[Show abstract] [Hide abstract]
- "DHA has been reported to significantly reduce the expression of p65 and its nuclear binding . Bonaterra et al.  explained similar effects on NF-κB translocation using willow bark extract, aspirin and diclofenac. The studies with various pharmaceutical medicines have indicated that therapeutics blocking NF-κB translocation might be an effective treatment for inflammatory disease . "
ABSTRACT: Phloridzin or phlorizin (PZ) is a predominant phenolic compound found in apple and also used in various natural health products. Phloridzin shows poor absorption and cellular uptake due to its hydrophilic nature. The aim was to investigate and compare the effect of docosahexaenoic acid (DHA) ester of PZ (PZ-DHA) and its parent compounds (phloridzin and DHA), phloretin (the aglycone of PZ) and cyclooxygenase inhibitory drugs (diclofenac and nimesulide) on production of pro-inflammatory biomarkers in inflammation-induced macrophages by lipopolysaccharide (LPS)-stimulation. Human THP-1 monocytes were seeded in 24-well plates (5×10(5)/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1μg/mL) for 48h to induce macrophage differentiation. After 48h, the differentiated macrophages were washed with Hank's buffer and treated with various concentrations of test compounds for 4h, followed by the LPS-stimulation (18h). Pre-exposure of PZ-DHA ester was more effective in reducing tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) protein levels compared to DHA and nimesulide. However, diclofenac was the most effective in reducing prostaglandin (PGE2) level by depicting a dose-dependent response. However, PZ-DHA ester and DHA were the most effective in inhibiting the activation of nuclear factor-kappa B (NF-κB) among other test compounds. Our results suggest that PZ-DHA ester might possess potential therapeutic activity to treat inflammation related disorders such as type 2 diabetes, asthma, atherosclerosis and inflammatory bowel disease. Copyright © 2015. Published by Elsevier B.V.
[Show abstract] [Hide abstract]
- "Therefore, COX-inhibition was first regarded the main mechanism of the anti-inflammatory activity of WB. In the meanwhile it was shown that WB can also modulate relevant pro-and anti-inflammatory cytokines like TNF-␣, IL-6, IL-1, IL-10, and IL-8 (Bonaterra et al. 2009; Fiebich et al. 2005; Fiebich and Chrubasik 2004) and that not only salicyl alcohol derivatives, but also the polyphenols of WB contribute to this modulation (Khayyal et al. 2005; Nahrstedt et al. 2007). In addition, polyphenols are known to possess antioxidant and neuroprotective effects which can also interfere with inflammatory events (Kannappan et al. 2011). "
ABSTRACT: Inflammatory processes are increasingly recognised to contribute to neurological and neuropsychatric disorders such as depression. Thus we investigated whether a standardized willow bark preparation (WB) which contains among other constituents salicin, the forerunner of non-steroidal antiphlogistic drugs, would have an effect in a standard model of depression, the forced swimming test (FST), compared to the antidepressant imipramine. Studies were accompanied by gene expression analyses. In order to allocate potential effects to the different constituents of WB, fractions of the extract with different compositions of salicyl alcohol derivative and polyphenols were also investigated.Phytomedicine: international journal of phytotherapy and phytopharmacology 06/2012; 19(10):930-9. DOI:10.1016/j.phymed.2012.05.004 · 2.88 Impact Factor
[Show abstract] [Hide abstract]
- "Due to the low achievable salicylic acid plasma concentration, which is equivalent to only ∼100 mg of acetylsalicylic acid after oral application of 240 mg Willow bark extract (Schmid et al. 2001), recent work concentrated on the additional contribution of polyphenolic compounds on the anti-inflammatory and analgesic effect. Standardised extracts rich in polyphenols showed significant clinical effects (for review Vlachojannis et al. 2009) and extracts as well as fractions containing polyphenols also showed inhibitory activity in vitro on several molecular targets like transcription factors, proinflammatory cytokines (Bonaterra et al. 2010), cyclooxygenases and radical production (Khayyal et al. 2005). Consequently, the overall effect of Willow bark extracts can be most likely explained by different effects of various phenolic compounds on distinct targets (Nahrstedt et al. 2007). "
ABSTRACT: 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.Phytomedicine: international journal of phytotherapy and phytopharmacology 02/2012; 19(3-4):245-52. DOI:10.1016/j.phymed.2011.08.065 · 2.88 Impact Factor