Cellular pharmacodynamic effects of Pycnogenol® in patients with severe osteoarthritis: a randomized controlled pilot study

Abstract

BackgroundThe standardized maritime pine bark extract (Pycnogenol®) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol® and its in vivo mechanism of action in OA patients.MethodsThirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol® twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients’ chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples.ResultsThe oral intake of Pycnogenol® downregulated the gene expression of various cartilage degradation markers in the patients’ chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤ 0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p ≤ 0.05) after three weeks intake of the pine bark extract.ConclusionsThis is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol® on symptom scores of patients suffering from OA.Trial registration ISRCTN10754119. Retrospectively registered 08/10/2015.

Curcumin Inhibits Proliferation of Synovial Cells by Downregulating Expression of Matrix Metalloproteinase‐3 in Osteoarthritis

“…Jessberger et al . found that Pycnogenol can reduce the expression of MMP3 , MMP13 , and the pro‐inflammatory cytokine IL1β, so it has some effect on severe bone and joint inflammation. In our study, MMP3 was found to be overexpressed in osteoarthritis synovial cells.…”

“…Wang et al found that MMP3 expression was significantly increased after transfection of HS6ST2-specific interfering RNA (siRNA) into C28/12 cells, indicating that HS6ST2 may be involved in the pathogenesis of osteoarthritis and Kashin-Beck disease by affecting aggrecan metabolism 23 . Jessberger et al found that Pycnogenol can reduce the expression of MMP3, MMP13, and the pro-inflammatory cytokine IL1β, so it has some effect on severe bone and joint inflammation 24 . In our study, MMP3 was found to be overexpressed in osteoarthritis synovial cells.…”

Pleiotropic Effects of French Maritime Pine Bark Extract to Promote Healthy Aging

“…Constituents and metabolites of Pycnogenol were able to inhibit the activity of inflammatory mediators within the joint. 60,61 Three double-blind, placebo-controlled studies in 293 patients demonstrated a better physical function, less joint stiffness, and less pain. A mean improvement of 40% of these symptoms was observed in all studies.…”

Herbal Medicinal Products in the Treatment of Osteoarthritis

“…Its affinity to accumulate in macrophages, monocytes, and endothelial cells were demonstrated [42]. Investigation conducted in patients with severe OA showed that expression of matrix metalloproteinases (MMP-3 and MMP-13) and IL-1β in chondrocytes was decreased after intake of Pycnogenol ® , as well as level of ADAMTS-5 in serum [43]. Plasma obtained from volunteers taking Pycnogenol ® orally for 5 days decreased activation of transcription factor NF-κB in macrophages and inhibited COX-1 and COX-2 [44,45].…”