Premium
Cinnamaldehyde and Nitric Oxide Attenuate Advanced Glycation End Products‐Induced the JAK/STAT Signaling in Human Renal Tubular Cells
Author(s) -
Huang JauShyang,
Lee YingHo,
Chuang LeaYea,
Guh JinnYuh,
Hwang JeanYu
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25058
Subject(s) - cinnamaldehyde , glycation , nitric oxide , chemistry , stat3 , pharmacology , stat1 , apoptosis , biochemistry , signal transduction , endocrinology , medicine , receptor , organic chemistry , catalysis
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. J. Cell. Biochem. 116: 1028–1038, 2015. © 2015 Wiley Periodicals, Inc.