Kaempferol Suppresses Carbon Tetrachloride-Induced Liver Damage in Rats via the MAPKs/NF-κB and AMPK/Nrf2 Signaling Pathways.

Content Provider	Europe PMC
Author	Lee, Changyong Yoon, Sik Moon, Jeon-Ok
Editor	Herranz-López, María
Copyright Year	2023
Abstract	Oxidative stress plays a critical role in the development of liver disease, making antioxidants a promising therapeutic approach for the prevention and management of liver injuries. The aim of this study was to investigate the hepatoprotective effects of kaempferol, an antioxidant flavonoid found in various edible vegetables, and its underlying mechanism in male Sprague-Dawley rats with carbon tetrachloride (CCl4)-induced acute liver damage. Oral administration of kaempferol at doses of 5 and 10 mg/kg body weight resulted in the amelioration of CCl4-induced abnormalities in hepatic histology and serum parameters. Additionally, kaempferol decreased the levels of pro-inflammatory mediators, TNF-α and IL-1β, as well as COX-2 and iNOS. Furthermore, kaempferol suppressed nuclear factor-kappa B (NF-κB) p65 activation, as well as the phosphorylation of Akt and mitogen-activated protein kinase members (MAPKs), including extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 in CCl4-intoxicated rats. In addition, kaempferol improved the imbalanced oxidative status, as evidenced by the reduction in reactive oxygen species levels and lipid peroxidation, along with increased glutathione content in the CCl4-treated rat liver. Administering kaempferol also enhanced the activation of nuclear factor-E2-related factor (Nrf2) and heme oxygenase-1 protein, as well as the phosphorylation of AMP-activated protein kinase (AMPK). Overall, these findings suggest that kaempferol exhibits antioxidative, anti-inflammatory, and hepatoprotective effects through inhibiting the MAPK/NF-κB signaling pathway and activating the AMPK/Nrf2 signaling pathway in CCl4-intoxicated rats.
Journal	International Journal of Molecular Sciences [Int J Mol Sci]
Volume Number	24
DOI	10.3390/ijms24086900
PubMed Central reference number	PMC10138912
Issue Number	8
PubMed reference number	37108064
e-ISSN	14220067
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2023-04-07
Access Restriction	Open
Subject Keyword	kaempferol antioxidative anti-inflammatory hepatoprotective NF-κB MAPK Nrf2 AMPK
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry Molecular Biology Spectroscopy Catalysis Computer Science Applications Medicine Inorganic Chemistry Organic Chemistry