Evaluation of the anti-inflammatory action of curcumin analog (DM1): Effect on iNOS and COX-2 gene expression and autophagy pathways

• Published in: Bioorganic & medicinal chemistry 2016-04, Vol.24 (8), p.1927-1935
• Main Authors: Paulino, Niraldo, Paulino, Amarilis Scremin, Diniz, Susana N., de Mendonça, Sergio, Gonçalves, Ivair D., Faião Flores, Fernanda, Santos, Reginaldo Pereira, Rodrigues, Carina, Pardi, Paulo Celso, Quincoces Suarez, José Agustin
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Autophagy; Autophagy - drug effects; Carrageenan; Cells, Cultured; COX-2; Curcumin - analogs & derivatives; Curcumin - chemistry; Curcumin - pharmacology; Curcumin analog; Cyclooxygenase 2 - genetics; DM1; Dose-Response Relationship, Drug; Edema; Edema - chemically induced; Edema - drug therapy; Gene Expression Profiling; Gene Expression Regulation, Enzymologic - drug effects; Humans; iNOS; Male; Mice; Molecular Structure; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type II - genetics; Peritonitis; Structure-Activity Relationship
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2016.03.024

Transduction pathways that mediate the effect of DM-1 on sensitization of sensory neurons. Antioedematogenic and anti-inflammatory on edema and peritonitis induced by carregeenan, bradykinin and substance P. Cell damage increase the aracdonic acid and PGE2, activate G-protein-coupled receptors linked to the stimulatory G-protein, Gs. This results in an increase in adenylyl cyclase activity, enhanced production of cAMP, and activation of cAMPdependent protein kinase (PKA). Bradykinin receptors, B2 and NK1 are linked to G-proteins that activate PLC isozymes leading to an increase in IP3, and DAG. The former messenger increases calcium release from intracellular stores, whereas the latter activates PKC. Both PKA and PKC phosphorylate various proteins including ion channels and synaptic proteins that may contribute to hypersensitivity. These kinases also can increase gene transcription, which can augment the production of a number of proteins, including COX-2 and iNOS and other proteins that affect excitability and transmitter release. [Display omitted] This work describes the anti-inflammatory effect of the curcumin-analog compound, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate (DM1), and shows that DM1 modulates iNOS and COX-2 gene expression in cultured RAW 264.7 cells and induces autophagy on human melanoma cell line A375.