title: Cinnamaldehyde and nitric oxide attenuate advanced glycation end products-induced the Jak/STAT signaling in human renal tubular cells.
abstract: Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. It possesses anti-diabetic properties in vitro and in vivo and has anti-inflammatory and anti-cancer effects. To explore whether cinnamaldehyde was linked to altered advanced glycation end products (AGE)-mediated diabetic nephropathy, the molecular mechanisms of cinnamaldehyde responsible for inhibition of AGE-reduced nitric oxide (NO) bioactivity in human renal proximal tubular cells were examined. We found that raising the ambient AGE concentration causes a dose-dependent decrease in NO generation. Cinnamaldehyde significantly reverses AGE-inhibited NO generation and induces high levels of cGMP synthesis and PKG activation. Treatments with cinnamaldehyde, the NO donor S-nitroso-N-acetylpenicillamine, and the JAK2 inhibitor AG490 markedly attenuated AGE-inhibited NOS protein levels and NO generation. Moreover, AGE-induced the JAK2-STAT1/STAT3 activation, RAGE/p27(Kip1) /collagen IV protein levels, and cellular hypertrophy were reversed by cinnamaldehyde. The ability of cinnamaldehyde to suppress STAT activation was also verified by the observation that it significantly increased SCOS-3 protein level. These findings indicate for the first time that in the presence of cinnamaldehyde, the suppression of AGE-induced biological responses is probably mediated by inactivating the JAK2-STAT1/STAT3 cascade or activating the NO pathway.
authors.affiliation: Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan.
authors.forename: Jau-Shyang
authors.initials: JS
authors.lastname: Huang
authors.forename: Ying-Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Lea-Yea
authors.initials: LY
authors.lastname: Chuang
authors.forename: Jinn-Yuh
authors.initials: JY
authors.lastname: Guh
authors.forename: Jean-Yu
authors.initials: JY
authors.lastname: Hwang
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017127:Glycation End Products, Advanced; D020030:Nitric Oxide Donors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; D009569:Nitric Oxide; D000171:Acrolein; D026423:S-Nitroso-N-Acetylpenicillamine; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C012843:cinnamaldehyde
keywords: ADVANCED GLYCATION END PRODUCTS; CINNAMALDEHYDE; DIABETIC NEPHROPATHY; HUMAN RENAL PROXIMAL TUBULAR CELLS; JANUS KINASE 2; NITRIC OXIDE