S. Chrubasik

Phytochemical composition and in vitro pharmacological activity of two rose hip (Rosa canina L.) preparations

The aim of the present study was to compare powdered rose hip with and without fruits (Rosae pseudofructus cum/sine fructibus, Rosa canina L., Rosaceae) with regard to their phytochemical profile and their in vitro anti-inflammatory and radical-scavenging properties. The two powders were subsequently extracted with solvents of increasing polarity and tested for inhibition of cyclooxygenase (COX-1, COX-2) and of 5-LOX-mediated leukotriene B(4) (LTB(4)) formation as well as for DPPH-radical-scavenging capacity. While the water and methanol extracts were inactive in the COX-1, COX-2 and LTB(4) inhibition assays, the n-hexane and the dichloromethane extracts inhibited all three enzymes. In the active extracts, the triterpenoic acids ursolic acid, oleanolic acid and betulinic acid were identified, although only in minute amounts. Furthermore, oleic, linoleic and alpha-linolenic acid were identified apart from several saturated fatty acids. Even though unsaturated fatty acids are known to be good inhibitors of COX-1, COX-2 and LT formation, no clear correlation between their concentration in the extracts and their activity was found. We suggest that other, yet unidentified, lipophilic constituents might play a more important role for the observed in vitro inhibitory activity on arachidonic acid metabolism. Some of the extracts also showed considerable DPPH radical scavenging activity, the methanolic extracts being most potent. The radical scavenging activity of the extracts correlated very well with their total phenolic content, while ascorbic acid contributes only little to the radical-scavenging activity due to its low concentration present in the extracts. In summary, extracts derived from powdered rose hip without fruits were more effective in all assays carried out compared with extracts derived from powdered rose hip with fruits.

Effects of an ethanolic salix extract on the release of selected inflammatory mediators in vitro.

Salix extracts are in current use for the treatment of pain and inflammation. In order to obtain an insight into the mechanism(s) of action of the ethanolic Salix extract 1520L--which is essentially similar to an extract for which clinical studies have demonstrated analgesic effectiveness--its effects were evaluated in an established in vitro assay test system using primary human monocytes. The IC50-values obtained for the inhibition of lipopolysaccharide (LPS)-induced release of prostaglandin E2 (PGE2) reflecting cyclooxygenase (COX)-2-mediated PGE2 release were 47 microg/ml and 0.6 microg/ml, for the Salix extract 1520L and rofecoxib-like research compound L745337, respectively. There was no effect on COX-1 and COX-2 activity. The Salix extract inhibited the LPS-induced release of tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 with IC50-values of 180.0, 33.0 and 86.0 microg/ml, respectively. Both, salicin and salicylate, had no effect in any of the parameters. Our results indicate that Salix extract 1520L inhibits COX-2-mediated PGE2 release through compounds other than salicin or salicylate. Our data further suggest that the proprietary Salix extract is a weak inhibitor of proinflammatory cytokines.

Comparison of outcome measures during treatment with the proprietary Harpagophytum extract doloteffin in patients with pain in the lower back, knee or hip.

Besides checking estimates of effectiveness and safety of using the proprietary Harpagophytum extract Doloteffin, this postmarketing surveillance compared various disease-specific* and generic** measures of effect. We enrolled 250 patients suffering from nonspecific low back pain (Back group: n = 104) or osteoarthritic pain in the knee (Knee group: n = 85) or hip (Hip group: n = 61). They took an 8-week course of Doloteffin at a dose providing 60 mg harpagoside per day. The measures of effect on pain and disability included the percentage changes from baseline of established instruments (Arhus low back pain index*, WOMAC index*, German version of the HAQ**) and unvalidated measures (total pain index*, three score index*, the patients global assessment** of the effectiveness of treatment). Patients also received a diary for the daily recording of their pain and any additional treatments for it. The three groups differed in age, weight and characteristics of initial pain. 227 patients completed the study. Multivariate analysis confirmed that several dimensions of effect were recorded by the several outcome measures but, in all groups, both the generic and disease-specific outcome measures improved by week 4 and further by 8. In multivariable analysis, the improvement tended to be more when the initial pain and disability score was more: older patients tended to improve less than younger, the hip group tended to improve convincingly more than the back group, whereas the improvement in the knee group was less readily differentiated from that in the back group. The subgroup of Back patients who required NSAIDs during the 8 weeks used significantly more per patient than patients in the other two groups, but that requirement also declined more with time. About 10% of the patients suffered from minor adverse events that could possibly have been attributable to Doloteffin. Between 50% and 70% of the patients benefitted from Doloteffin with few adverse effects. Thus, Doloteffin is well worth considering for osteoarthritic knee and hip pain and nonspecific low back pain.

Systematic review on the safety of Harpagophytum preparations for osteoarthritic and Low back pain

Harpagophytum products are a treatment option for osteoarthritic and low back pain. The aim of this study was to review the safety of treatment with Harpagophytum procumbens.

A one-year survey on the use of a powder from Rosa canina lito in acute exacerbations of chronic pain

This pilot surveillance included 152 patients with acute exacerbations of chronic pain, 124 (Back group) with non‐specific low back pain (NSLBP), 20 with NSLBP overridden by osteoarthritic pain (Knee‐Hip group), and eight with specific LBP (included in the safety analysis). Patients were recommended the rose hip and seed powder LitozinR at a dose providing up to 3 mg of galactolipid/day for up to 54 weeks. Clinical symptoms and well‐being were assessed every 6 weeks. The patients also kept a diary of their pain and the requirement for rescue medication. Data were analysed by intention to treat with last observation carried forward.

Willow Species and Aspirin: Different Mechanism of Actions

Many believe that willow is the natural source of aspirin. However, willow species contain only a low quantity of the prodrug salicin which is metabolized during absorption into various salicylate derivatives. If calculated as salicylic acid, the daily salicin dose is insufficient to produce analgesia. Salicylic acid concentrations following an analgesic dose of aspirin are an order of magnitude higher. Flavonoids and polyphenols contribute to the potent willow bark analgesic and anti‐inflammatory effect. The multi‐component active principle of willow bark provides a broader mechanism of action than aspirin and is devoid of serious adverse events. In contrast to synthetic aspirin, willow bark does not damage the gastrointestinal mucosa. An extract dose with 240 mg salicin had no major impact on blood clotting. In patients with known aspirin allergy willow bark products are contraindicated. Copyright

Listerine® Products: An Update on the Efficacy and Safety

In the 19th century, the mouthwash Listerine® was formulated from four essential oils. Later, the oils were replaced by their marker substances. To keep them in solution, 24–27% ethanol was added as a vehicle. This is an update of our previous review on the efficacy and safety of Listerine®. Method: PubMed was searched for clinical studies on the therapeutic benefits and safety of Listerine® from the end of 2011 to the end of October 2015. Results: Sixteen studies were found and extracted. Three of the four 6‐month studies were of sound confirmatory design. Two of these investigated Listerine® and one Listerine Zero®. The evidence of effectiveness for Listerine®, based on the bulk of three confirmatory studies and numerous exploratory studies carried out so far, is strong, but only moderate for Listerine® Zero and poor for Listerine® Cool Blue. In the three safety studies identified, we found methodological flaws that biased the results. Conclusions: Evidence is accumulating that Listerine® is effective in improving oral health, but the absence of systematic toxicological studies means that an accurate safety assessment cannot be made. Copyright

Mise à jour de la monographie allemande de la commission E sur Petasites hybridus (pétasite officinal)

RésuméCette monographie apporte une mise à jour de la monographie allemande de la Commission E sur la racine du pétasite officinal Petasites hybridus). Elle est fondée sur une recherche informatique de littérature en utilisant la même structure que la monographie: substance principale, utilisation clinique, contre-indications, effets secondaires, interactions, dosage, mode d’administration, actions activité in vitro et in vivo, actions activité et données de sécurité précliniques.AbstractThis monograph provides an update of the Commission E monograph on Petasites hybridus root, based on computerized literature research and using the same organisational structure: active principle, clinical use, contraindications, adverse events, interactions, dosage, mode of administration, in vitro and in vivo actions and preclinical safety data.

Micro‐Morphometrical Assessment of the Effect of Harpagophytum procumbens Extract on Articular Cartilage in Rabbits with Experimental Osteoarthritis using Magnetic Resonance Imaging

In vitro effects indicate a putative beneficial effect of Harpagophytum procumbens on cartilage turnover, however, in vivo protective effects on cartilage have yet to be demonstrated. A 7.1T MRI scanner was used to derive measurements of thickness, surface area and volume of the tibial condylar cartilage and to assess their precision (in the case of volume also accuracy) against the volumes of dissected cartilage measured by water displacement. Quantitative measurements were made in 16 rabbits, 6 months after unilateral medial meniscectomy and transection of the anterior cruciate ligament, after which eight of these were given a proprietary extract of Harpagophytum procumbens (HP). A semiquantitative MRI‐based grading of the tibial cartilage was also compared with a ‘macroscopic’ grading based on direct visual inspection of dissected joints. The test–retest precision for MRI‐based measurement was ≤6.4%. MRI‐based measurements correlated well with volumes of surgically resected cartilage (r = 0.97, pair‐wise random difference 4.2%). The medial tibial cartilage thickness and volume were about 35% smaller in the operated knees than in the non‐operated contralateral knees (p < 0.05). The findings suggest that MRI is a precise and accurate tool for evaluating cartilage in a rabbit model of OA. The difference between the intact and operated knee in thickness and volume of the medial tibial cartilage was slightly but not significantly smaller in the HP‐treated group than in the non‐treated group. Copyright

Expressing treatment-associated changes.

SummaryThe Osteoarthritis Research Society International is attempting to establish a consensus on outcome measures, so as to facilitate comparability between different clinical studies in this area of research. There are no general recommendations on how changes in outcome measure (effect size) should be expressed. We therefore used data froma recently published study to express change as: a) the mean of the change from baseline divided by the individual baseline, b) the median of the change from baseline divided by the individual baseline, c) the mean of the change from baseline divided by the SD of baseline and d) the median of change from baseline divided by the SD of baseline.The results show that the correlations between different ways of expressing effect sizes were poor and the perceived relative magnitudes of various effects depended on how they were expressed. Organisations aiming at consensus ought to recommend the way in which change ought to be expressed. Until they do, authors should justify their choice of expression, particularly if it critically influences their conclusion, and/or present their data as fully as possible on a website.ZusammenfassungDie Organisation „Osteoarthritis Research Society International“ ist um ein Konsens bei der Nutzung von Messinstrumenten innerhalb der Rheumatologie bemüht, um die Vergleichbarkeit zwischen Studien auf diesem Gebiet zu erleichtern. Es gibt keine allgemeinen Empfehlungen, wie die Änderungen der Messergebnisse (Therapieeffekte) dargestellt werden sollen. Wir haben deshalb die Daten einer kürzlich veröffentlichten Studie dazu genutzt, die Ergebnisse wie folgt zu berechnen: a) als Mittelwert der Veränderung vom Basalwert dividiert durch den individuellen Basalwert, b) als Median der Veränderung vom Basalwert dividiert durch den individuellen Basalwert, c) als Mittelwert der Veränderung vom Basalwert dividiert durch die Standardabweichung des Basalwerts und d) als Median der Veränderung vom Basalwert dividiert durch die Standardabweichung des Basalwerts.Das Ergebnis zeigt, dass die unterschiedlichen Darstellungsweisen schlecht korrelierten und dass das Ausmaß der Therapieeffekte von der Art der Darstellung abhing. Die Organisationen, die sich um einen Konsens bemühen, sollten daher Empfehlungen formulieren, wie die Befundänderungen auszudrücken sind. Bis dahin sollten die Autoren die Wahl ihrer Darstellung begründen, besonders wenn die Schlussfolgerungen dadurch beeinflusst werden; außerdem sollten die Daten möglichst umfassend auf einer Website platziert werden.