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Background and aim: Osteoarthritis (OA) is a chronic degenerative disease characterized by an inflammatory state and significant oxidative stress. As curcuma is known for its anti-inflammatory and antioxidant activities, it could be used as alternative therapy next to or together with the standard treatment. This treatment consists of analgesics, steroids or non-steroidal anti-inflammatory drugs (NSAIDs) to reduce pain and inflammation related symptoms. The current study investigates the effect of bio-optimized curcuma on genetic (SIRT1) and metabolic regulation of inflammation and associated symptomatology in patients with osteoarthritis.  Materials and methods: In the in vitro study, Hela human cells were seeded in 12-well plates, incubated with curcuma at different concentrations and incubated for 3, 6 and 24 hours. The targeted protein expression/phosphorylation was evaluated by immunoblotting, while cytotoxicity tests were performed by CellTiter-Blue Cell Viability Assay. In the in vivo study, a total of 33 patients were recruited and divided into 3 subgroups based on the treatment: standard treatment (ST), ST + curcuma and ST + curcuma + Vitamin D (2000UI). The health status (SF36) and osteoarthritis index (WOMAC score) were analyzed at 0; 1,5 and 3 months with blood sampling at 0 and 3 months for the evaluation of inflammation markers, 25 (OH) VitD and SIRT1.  Results: in vitro data showed no statistically significant decrease (p&gt;0.05) in the number of viable cells. The expression of SIRT1 and the activation of AMP activated protein kinase (AMPK) were significantly increased in all experimental groups compared with the control group (p&lt;0.001). A significant increase in 25(OH) VitD values in the ST + curcuma + VitD group (p &lt;0.007) and in SIRT1 in all groups taking curcuma (p &lt;0.001) was shown. Also for IL-1 (p=0.031), IL-6 (p=0.031) and IFN-γ (p=0.013), all groups taking curcuma showed significantly lower inflammatory markers with no added value of vitamin D.  Conclusions: Curcuma as an adjuvant to ST leads to a positive modulation of the SIRT1 pathway, a significant decline of blood inflammatory markers and a better osteoarthritis outcome.

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Bio-Optimized Curcuma as Adjuvant Therapy of Osteoarthritis and Its Influence on Gene Regulation (Sirt1), Metabolic Inflammation and Associated Symptoms