Abstract

Chronic and excessive inflammation can destroy host organs and cause inflammatory diseases such as inflammatory bowel disease, asthma, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Alpinia katsumadai seed-derived 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (PHT) using lipopolysaccharide (LPS)-stimulated J774 cells and a formalin-induced chronic paw inflammation mouse model. The in vitro results showed that PHT exhibited no cytotoxicity and decreased LPS-induced NO secretion. Additionally, PHT inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. The quantitative real-time PCR results showed that PHT downregulated the gene expression of the proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). PHT inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). In a mouse model, oral administration of 50 mg/kg PHT significantly alleviated both mouse paw thickness and volume. These results indicate that PHT has potential anti-inflammatory effects and should be considered a possible functional material.

Highlights

  • The inflammatory response is a defense mechanism of the body against pathogenic factors such as bacterial and viral infection, irradiating substances and damaged cells [1]

  • TLR4 leads to the phosphorylation of c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK), p38 mitogen activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) [1,3]

  • We investigated the anti-inflammatory effects of PHT, an acyclic triterpenoid isolated from A. katsumadai seeds, on LPS-induced J774 cells and its therapeutic effects against chronic inflammatory disease in a formalin-induced mouse paw inflammation model

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Summary

Introduction

The inflammatory response is a defense mechanism of the body against pathogenic factors such as bacterial and viral infection, irradiating substances and damaged cells [1]. Detection of these factors by pattern recognition receptors (PRRs) initiates the inflammatory response [2]. We isolated four acyclic triterpenoids from A. katsumadai seeds and reported inhibitory effects on interleukin-6 (IL-6)-induced signal transducer and transcription. We investigated the anti-inflammatory effects of PHT, an acyclic triterpenoid isolated from A. katsumadai seeds, on LPS-induced J774 cells and its therapeutic effects against chronic inflammatory disease in a formalin-induced mouse paw inflammation model

PHT Decreases NO and PGE2 Production in LPS-Induced J774 Cells
Effect of PHT
PHT Alleviates Formalin-Induced Chronic Mouse Paw Inflammation
Methods
Procedure
Extraction and Isolation of PHT
NO Assay and MTT Assay
Quantitative Real-Time PCR
Immunoblot Analysis
Statistical Analysis
Conclusions
Full Text
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