Inhibitory effects of nodakenin on inflammation and cell death in lipopolysaccharide-induced liver injury mice.

Abstract

BACKGROUND:

Nodakenin, a coumarin glucoside isolated from the roots of Angelica biserrata, has been reported to have anti-inflammatory, antibacterial, anticancer effects. However, despite these studies, the potential liver protective effects of nodakenin in inflammatory liver injury models have not been reported.

METHODS:

A mouse model of inflammatory liver injury was induced by injection of lipopolysaccharide (LPS) (15 mg/kg, intraperitoneally (i.p)). Liver tissue AST, ALT, ROS, T-GSH and T-SOD were analyzed by ELISA. The concentrations of TNF-α, IL-6, and IL-1β in serum of LPS-induced inflammatory liver injury mice were analyzed. The mRNA expression levels of GPx1, catalase, SOD1, SOD2, TNF-α, IL-6, IL-1β, iNOS and COX-2 were analyzed using real-time PCR. The expressions of MAPK, IRF3, NF-κB, Nrf2, HO-1, caspase-3 and caspase-7 were analyzed using western blotting. Liver tissue was stained with IHC to confirm NF-κB, Nrf-2, HO-1, caspase-3, Bax, and Bcl2. Tunnel analysis was performed to confirm the fragmented nuclear DNA characteristics of apoptosis.

RESULTS:

The administration of nodakenin (10 and 30 mg/kg) reduced serum aminotransferase levels compared to LPS-induced liver damage and significantly improved the oxidative state of liver tissue and pathological damage. Moreover, inhibited the phosphorylation of transforming growth factor beta (TGF-β)-activated kinase (TAK)-1 in LPS-induced inflammatory liver injury model, and significantly inhibited the transcriptional of nuclear factor-kappa B (NF-kB) and the secretion of pro-inflammatory mediators. In addition nodakenin pre-treatment also attenuated hepatocyte death by regulating apoptosis-related mitochondrial proteins, such as cysteinyl aspartate specific proteinase 3 (caspase 3), poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax).

CONCLUSION:

Our findings suggest that nodakenin has anti-inflammatory, anti-oxidant and anti-apoptotic activity and may be an adjunctive prevention agent for liver injury.

• Authors: Ji-Ye Lim, Ji-Hyun Lee, Dae-Ho Yun, Young-Mi Lee, Dae-Ki Kim
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 81 Pg. 153411 (Jan 2021) ISSN: 1618-095X [Electronic] Germany
• PMID: 33310307 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier GmbH.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Coumarins
• Cytokines
• Enzymes
• Glucosides
• Lipopolysaccharides
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, mouse
• Protective Agents
• nodakenin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Antioxidants (metabolism, pharmacology)
• Apoptosis (drug effects)
• Chemical and Drug Induced Liver Injury (drug therapy, metabolism, pathology)
• Coumarins (pharmacology)
• Cytokines (blood, genetics)
• Enzymes (metabolism)
• Glucosides (pharmacology)
• Hepatitis, Animal (drug therapy, metabolism, pathology)
• Lipopolysaccharides (toxicity)
• Male
• Mice, Inbred ICR
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Protective Agents (pharmacology)