Plantago Lanceolate L. Extract Protects Esophageal Mucosal Damages by Regulating Oxidative Stress and Inflammation in Reflux Esophagitis Induced Rat Model

Abstract

Ethnopharmacological relevance Plantago lanceolata L. is native to Europe and is distributed in many countries and it has been used as a folk medicine for various diseases. In addition, several studies have demonstrated antioxidant, anti-inflammatory and analgesic effects, and is actually used as a medicinal herb related to intestinal health.

Aim of the study Reflux esophagitis (RE) is a common gastrointestinal disease in which gastric acid refluxes into the esophagus, causing inflammation. The purpose of this study was to verify the protective effect of P. lanceolata on esophageal tissue in rats, against inflammation induced by acute RE. Antioxidant activities were assessed by measuring absorbance changes following treatment with P. lanceolata extract (PLE).

Methods Antioxidant activities were assessed by measuring absorbance changes following treatment with P. lanceolata extract (PLE). Reactive oxygen species (ROS) and anti-inflammatory activities were analyzed in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Esophageal protective effects were evaluated by assessing tissue damage, inflammatory protein levels, and expression of claudins (tight junction proteins) in Sprague Dawley rat models with reflux esophagitis. The bioactive compound of PLE was quantified using high-performance liquid chromatography analysis.

Results The antioxidant activity of P. lanceolata extract (PLE) tended to increase in a concentration-dependent manner, and the production of ROS decreased by about 50% upon treatment with 400 μg/mL PLE. In LPS-induced RAW 264.7 cells, PLE inhibited NF-κB phosphorylation and downregulated the expression of inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2) and decreased nitric oxide levels. In RE-induced rats, PLE treatment inhibited pro-inflammatory cytokines (tumor necrosis factor α and interleukin-1β) by regulating the inflammatory response associated with the NF-κB and mitogen-activated protein kinase pathway. In addition, the expression level of claudin increased, which protected the physical barrier function of the esophagus. In conclusion, the folk medicinal plant P. lanceolata is an excellent source for anti-inflammatory agents against RE.

Keywords: Plantago lanceolata, anti-inflammatory, folk medicinal plants, NF-κB, Pro-inflammatory cytokines, reflux esophagitis