RESUMEN
Background: Postoperative pain has well defined and is perceived by patients as one of the most obnoxious aspects of surgical pain. The aim of this study was to determine whether the combination of Therapeutic ultrasound (TUS) and Curcumin (CUR) resulted in an enhancement of their pain relieving activities in a rat model of postoperative pain. Methods: We explored the effect of these treatment and their interaction with signal transduction pathways involved in inflammatory. In this study, TUS and CUR alone or in combination were administered prior to or simultaneously with or after the incisional surgery. Results: At the start time of administration, we observed that the TUS plus CUR treatment reduced the mean paw withdrawal threshold more efficiently than CUR alone. Then we demonstrated that TUS potentiates the antinociceptive effect of CUR in a rat model of chronic postoperative pain and that the combination could facilitate the recovery of surgical pain. However, preventive value was not statistically significant when the treatments were given prior to the incisional surgery. We provide evidence that TUS plus CUR administrations were safe and significantly reduced the ED50 compared to treatment with the single CUR treatment in rats. TUS plus CUR administrations decreases incisional surgery induced activation of inflammatory cells and down-regulation of chemokines and proinflammatory cytokines, MCP-1, MIP-1α, IL-1ß, and TNF-α through regulating Sirt1/NF-κB signaling pathway. Conclusions: Taken together, our results indicate that the combinations of TUS and CUR can be more effective in the anti-nociceptive effects than the treatment with CUR alone.
RESUMEN
SIRT1 is one of seven mammalian homologs of Sir2 that catalyzes NAD(+)-dependent protein deacetylation. The aim of the present study is to explore the effect of SIRT1 small molecule activator on the anticancer activity and the underlying mechanism. We examined the anticancer activity of a novel oral agent, curcumin, which is the principal active ingredient of the traditional Chinese herb Curcuma Longa. Treatment of FaDu and Cal27 cells with curcumin inhibited growth and induced apoptosis. Mechanistic studies showed that anticancer activity of curcumin is associated with decrease in migration of HNSCC and associated angiogenesis through activating of intrinsic apoptotic pathway (caspase-9) and extrinsic apoptotic pathway (caspase-8). Our data demonstrating that anticancer activity of curcumin is linked to the activation of the ATM/CHK2 pathway and the inhibition of nuclear factor-κB. Finally, increasing SIRT1 through small molecule activator curcumin has shown beneficial effects in xenograft mouse model, indicating that SIRT1 may represent an attractive therapeutic target. Our studies provide the preclinical rationale for novel therapeutics targeting SIRT1 in HNSCC.