Modulation of age-related NF-kappaB activation by dietary zingerone via MAPK pathway.
Zingerone, a major component found in ginger root, has been known as anti-mutagenic and anti-carcinogenic activities that are often associated with its anti-oxidative and anti-inflammatory activities. In recent studies, we examined molecular mechanism of zingerone treatment on pro-inflammatory NF-kappaB activation via the redox-related NIK/IKK and MAPK pathways. Action mechanism of zingerone on NF-kappaB signaling was investigated in aged rat kidney and endothelial cells. The results showed that zingerone had not only the antioxidant effect by constitutive suppression of ROS, but also anti-inflammatory effects by suppression of nuclear factor (NF)-kappaB activation in aged rat. In addition, zingerone treatment suppressed gene activation of pro-inflammatory enzymes, COX-2 and iNOS, which were upregulated with aging through NF-kappaB activation and IKK/MAPK signaling pathway. These experiments strongly indicate that zingerone treatment exerts a beneficial efficacy by suppressing both oxidative stress and age-related inflammation through the modulation of several key pro-inflammatory genes and transcription factors. Thus, the significance of our findings is that the zingerone treatment may provide some preventive measure against chronic inflammatory conditions that underlie many age-related inflammatory diseases, such as metabolic syndrome, cardiovascular disease, dementia, arthritis, diabetes, osteoprosis, and cancers.
Kim
Mi Kyung
MK
Department of Pharmacy, Pusan National University, Busan, South Korea.
Chung
Sang Woon
SW
Kim
Dae Hyun
DH
Kim
Ji Min
JM
Lee
Eun Kyeong
EK
Kim
Ji Young
JY
Ha
Young Mi
YM
Kim
Yun Hee
YH
No
Jae-Kyung
JK
Chung
Hye Sun
HS
Park
Kun-Young
KY
Rhee
Sook Hee
SH
Choi
Jae Sue
JS
Yu
Byung Pal
BP
Yokozawa
Takako
T
Kim
Young Jin
YJ
Chung
Hae Young
HY
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D031204:Caloric Restriction; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism* / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C013738:zingerone; D006139:Guaiacol; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases