title: Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.
abstract: Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I.
authors.affiliation: Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio, United States of America.
authors.forename: Bina
authors.initials: B
authors.lastname: Joe
authors.affiliation: Department of Lipid Science and Traditional Foods, Central Food Technological Research Institute, Mysore, Karnataka, India.
authors.forename: Anitha
authors.initials: A
authors.lastname: Nagaraju
authors.affiliation: Department of Protein Chemistry and Technology, Central Food Technological Research Institute, Mysore, Karnataka, India.
authors.forename: Lalitha R
authors.initials: LR
authors.lastname: Gowda
authors.affiliation: Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio, United States of America; Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Venkatesha
authors.initials: V
authors.lastname: Basrur
authors.affiliation: Department of Lipid Science and Traditional Foods, Central Food Technological Research Institute, Mysore, Karnataka, India.
authors.forename: Belur R
authors.initials: BR
authors.lastname: Lokesh
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D004032:Diet / Q000379:methods; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007704:Kininogens / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D006023:Glycoproteins; D007704:Kininogens; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D003474:Curcumin; D002211:Capsaicin