Costunolide inhibits inflammation in LPS-induced RAW264.7 cells and ameliorates gastric acid reflux-induced esophageal injury in rat model

Li Nan,Byung-Kil Choo,Hyeon-Hwa Nam

doi:10.1186/s13765-020-00514-0

Abstract

As one of the gastroesophageal reflux disease (GERD), reflux esophagitis (RE) severely affects patients’ daily lives. Costunolide (Cos), pertains to a sesquiterpene lactone, performs multiple pharmacological activities including inhibited acute liver injury, anti-inflammation and anti-oxidant. We carried out our study to investigate the anti-inflammatory effect and protective effects of Cos against esophageal tissue damage caused by gastric acid refluxing. The determination of anti-inflammatory effects of Cos were conducted using lipopolysaccharide (LPS)-induced RAW 264.7 cell inflammatory model. The ameliorative effects of Cos on RE were confirmed on RE controlled rats model. The results indicated that Cos reduced nitrite production and inhibited cellular inflammation via regulating the activation of NF-κB. In addition, gastric acid reflux increased expression levels of inflammatory proteins (COX-2, TNF-α and IL-1β) in esophageal tissues, while Cos treatment significantly downregulated the expression of these proteins by inhibiting activation of NF-κB. Furthermore, through observing histological stain, Cos significantly improved esophageal damage caused by gastric acid reflux. Therefore, we suggested that Cos has the potential to be a material of natural drug for the treatment of reflux esophagitis caused by acid reflux.

Highlights

According to the American Society of Gastroenterology, the definition of gastroesophageal reflux disease (GERD) refers to some symptoms and complications that resulted in the contents of stomach refluxing into the esophagus or other parts [1]
We found that oral administration of Cos‐ tunolide (Cos) significantly ameliorated the esophageal mucosal damage caused by gastric acid reflux, increased the pH of gastric content and inhibited the expression of COX-2, Tumor necro‐ sis factor (TNF-α) and IL-1β in reflux esophagitis (RE) rat esophageal tissue, by regulating the Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway
Cos inhibited the Nitric oxide (NO) production and no effect on cell viability in LPS‐induced RAW 264.7 cells To evaluate the cytotoxicity of Cos and its inhibitory effect on NO production, cells were plated in 96-well plates at a density of 1 × 106 cells/ml

Summary

Introduction

According to the American Society of Gastroenterology, the definition of gastroesophageal reflux disease (GERD) refers to some symptoms and complications that resulted in the contents of stomach refluxing into the esophagus or other parts (oral or lung) [1]. Population-based studies from 2005 to 2014 have shown that the increase of the incidence of symptomatic GERD in the world including the area of Australia, North America, East Asia, Europe, Middle East, and South America. The incidence rate in East Asia has increased by about 3 times in 10 years (2.5–7.8%) [2, 3]. Proton pump inhibitors (e.g., omeprazole) and histamine type 2 receptor antagonists (e.g., ranitidine) are the main drugs for the treatment of this disease while one-third of the patients have not shown a reduction in symptoms when taking drugs [5, 6]

Methods

Results

Conclusion