| dc.description.abstract | The endogenous compound palmitoylethanolamide (PEA), has significant anti-inflammatory and immune modulating properties. As a nutraceutical, PEA assists in prevention and treatment of chronic inflammatory diseases, acting at several molecular targets. This study hypothesized a potential synergistic interaction between PEA, quercetin and curcuminoids in mitigating the inflammatory response. The interactive effects of their combination against inflammation in RAW264.7 macrophages were investigated and combinations demonstrated ability to reduce the expression of proinflammatory markers related to the NF-kB pathway, such as IL-1b, TNF-α and IL-10. The synergistic nature of the interactions was demonstrated in mRNA expression of IL-1b. Simulated CI values identified, for the first time, a range of effect levels in which combinations are synergistic. PEA reduced IL-1b and TNF-α expression via activation of the peroxisome proliferator-activated receptor (PPAR-α), whereas quercetin and curcuminoids effects were not affected by PPAR-α blockage. LPS-stimulation decreased expression of PEA-degrading enzymes, while treatment with PEA increased enzyme expression. PEA exhibited good stability under cell culture conditions, as 82% and 78% of added PEA and d4-PEA, respectively, were found in the supernatant after 12h. Presence of quercetin and curcuminoids did not change d4-PEA cellular uptake. Additional studies are recommended to understand the role of polyphenols in the PEA uptake process.
A combined formulation containing the three agents (PCQ) reduced in vitro expression of pro-inflammatory markers, as well as reactive oxygen species and nitric oxide release in RAW264.7 cells. When given as a dietary supplement for 8-weeks to family-owned osteoarthritic dogs, PCQ reduced concentration of disease associated pro-inflammatory markers in some patients. Improvement in pain scores from Canine Brief Pain Inventory (CBPI was seen in 3 out of 6 dogs and force plate analysis indicated that 4 dogs exhibited improvement in both peak vertical force (PVF) and vertical impulse (VI). Outcomes from this pilot study provided insight on the potential benefits of this combination in an already established disease and how the supplementation can help in pain management, activity and improved gait, as well as in reduction of OA-associated inflammation. The novel formulation exhibits high applicability as a dietary supplement to be used alone or as an adjuvant to standard of care in chronic inflammatory conditions. | |
