Formononetin alleviates acute pancreatitis by reducing oxidative stress and modulating intestinal barrier.
Acute pancreatitis
Formononetin
Intestinal injury
Kelch like ECH Associated protein 1
Nuclear factor erythroid2-related factor 2
Reactive oxygen species
Journal
Chinese medicine
ISSN: 1749-8546
Titre abrégé: Chin Med
Pays: England
ID NLM: 101265109
Informations de publication
Date de publication:
27 Jun 2023
27 Jun 2023
Historique:
received:
13
02
2023
accepted:
19
05
2023
medline:
28
6
2023
pubmed:
28
6
2023
entrez:
27
6
2023
Statut:
epublish
Résumé
Acute pancreatitis (AP) is a recurrent inflammatory disease. Studies have shown that intestinal homeostasis is essential for the treatment of AP. Formononetin is a plant-derived isoflavone with antioxidant properties that can effectively treat a variety of inflammatory diseases. This study aims to investigate the role of formononetin in protecting against AP and underlying mechanism. Caerulein was used to induce AP. The inflammatory cytokines were detected using Quantitative real-time PCR and commercial kits. Histological examination was applied with hematoxylin and eosin staining. Western blot was conducted to detect expression of intestinal barrier protein and signaling molecular. Molecular docking was performed to assess protein-ligand interaction. In this study, we found formononetin administration significantly reduced pancreatic edema, the activities of serum amylase, lipase, myeloperoxidase, and serum endotoxin. The mRNA levels of inflammatory cytokines such as tumor necrosis factor α, monocyte chemoattractant protein-1, interleukin-6, and interleukin-1 beta (IL-1β) in pancreas were also significantly decreased by formononetin. The following data showed formononetin pretreatment up-regulated the expressions of tight junction proteins in the colon, and decreased Escherichia coli translocation in the pancreas. In addition, formononetin inhibited the activation of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing 3 in pancreatic and colonic tissues of AP mice. Moreover, formononetin activated Kelch Like ECH Associated Protein 1 (Keap1) / Nuclear factor erythroid2-related factor 2 (Nrf2) signaling pathway to reduce reactive oxygen species (ROS) levels. Docking results showed that formononetin interact with Keap1 through hydrogen bond. These findings demonstrate that formononetin administration significantly mitigate AP through reducing oxidative stress and restoring intestinal homeostasis, and provide insights into the new treatment for AP.
Sections du résumé
BACKGROUND
BACKGROUND
Acute pancreatitis (AP) is a recurrent inflammatory disease. Studies have shown that intestinal homeostasis is essential for the treatment of AP. Formononetin is a plant-derived isoflavone with antioxidant properties that can effectively treat a variety of inflammatory diseases. This study aims to investigate the role of formononetin in protecting against AP and underlying mechanism.
METHODS
METHODS
Caerulein was used to induce AP. The inflammatory cytokines were detected using Quantitative real-time PCR and commercial kits. Histological examination was applied with hematoxylin and eosin staining. Western blot was conducted to detect expression of intestinal barrier protein and signaling molecular. Molecular docking was performed to assess protein-ligand interaction.
RESULTS
RESULTS
In this study, we found formononetin administration significantly reduced pancreatic edema, the activities of serum amylase, lipase, myeloperoxidase, and serum endotoxin. The mRNA levels of inflammatory cytokines such as tumor necrosis factor α, monocyte chemoattractant protein-1, interleukin-6, and interleukin-1 beta (IL-1β) in pancreas were also significantly decreased by formononetin. The following data showed formononetin pretreatment up-regulated the expressions of tight junction proteins in the colon, and decreased Escherichia coli translocation in the pancreas. In addition, formononetin inhibited the activation of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing 3 in pancreatic and colonic tissues of AP mice. Moreover, formononetin activated Kelch Like ECH Associated Protein 1 (Keap1) / Nuclear factor erythroid2-related factor 2 (Nrf2) signaling pathway to reduce reactive oxygen species (ROS) levels. Docking results showed that formononetin interact with Keap1 through hydrogen bond.
CONCLUSIONS
CONCLUSIONS
These findings demonstrate that formononetin administration significantly mitigate AP through reducing oxidative stress and restoring intestinal homeostasis, and provide insights into the new treatment for AP.
Identifiants
pubmed: 37370098
doi: 10.1186/s13020-023-00773-1
pii: 10.1186/s13020-023-00773-1
pmc: PMC10304236
doi:
Types de publication
Journal Article
Langues
eng
Pagination
78Subventions
Organisme : National Natural Science Foundation of China
ID : 81902706
Organisme : Fundamental Research Funds for the Central Universities
ID : JUSRP122055
Informations de copyright
© 2023. The Author(s).
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