Modulation of the age-related nuclear factor-kappaB (NF-kappaB) pathway by hesperetin.
Nuclear factor-kappaB (NF-kappaB), a redox-sensitive transcription factor, plays an important role in the aging process. Thus, developing and identifying specific components that modulate NF-kappaB without adverse side-effects would be of major importance. Hesperetin, a flavanone abundant in citrus fruits, has a variety of pharmacological properties being antioxidant, cholesterol-lowering, and anti-inflammatory. In this study, we investigated how hesperetin fed to 6- and 24-month-old rats modulates NF-kappaB in their kidneys. Results showed that hesperetin suppressed NF-kappaB activation and related gene expressions. An even more interesting finding is that hesperetin suppressed NF-kappaB through four signal transduction pathways, NIK/IKK, ERK, p38, and JNK. Further evidence showed the remarkable efficacy of hesperetin to suppress the translocation of Trx/Ref-1, indicating its beneficial effect on the redox status. The most significant findings of the current study report new information on the use of hesperetin as a potential anti-aging agent.
Kim
Ji Young
JY
College of Pharmacy, Pusan National University, Busan, Korea.
Jung
Kyung Jin
KJ
Choi
Jae Sue
JS
Chung
Hae Young
HY
D000375:Aging / Q000502:physiology*; D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006569:Hesperidin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D006569:Hesperidin; D008156:Luciferases; C013015:hesperetin