Evaluation ofIn VitroAnti-Inflammatory Activities and Protective Effect of Fermented Preparations of Rhizoma Atractylodis Macrocephalae on Intestinal Barrier Function against Lipopolysaccharide Insult

Shambhunath Bose,Hojun Kim

doi:10.1155/2013/363076

Abstract

Lipopolysaccharide (LPS), a potent inducer of systemic inflammatory responses, is known to cause impairment of intestinal barrier function. Here, we evaluated the in vitro protective effect of an unfermented formulation of Rhizoma Atractylodis Macrocephalae (RAM), a traditional Chinese herbal medicine widely used in the treatment of many digestive and gastrointestinal disorders, and two fermented preparations of RAM, designated as FRAM-1 (prepared in Luria-Bertani broth) and FRAM-2 (prepared in glucose), on intestinal epithelial cells (IECs) against LPS insult. In general, fermented formulations, especially FRAM-2, but not unfermented RAM, exerted an appreciable protective effect on IECs against LPS-induced perturbation of membrane resistance and permeability. Both fermented formulations exhibited appreciable anti-inflammatory activities in terms of their ability to inhibit LPS-induced gene expression and induced production of a number of key inflammatory mediators and cytokines in RAW 264.7 macrophage cells. However, in most cases, FRAM-2 exhibited stronger anti-inflammatory effects than FRAM-1. Our findings also suggest that suppression of nuclear factor-κ β (NF-κ β) activity might be one of the possible mechanisms by which the fermented RAM exerts its anti-inflammatory effects. Collectively, our results highlight the benefits of using fermented products of RAM to protect against LPS-induced inflammatory insult and impairment in intestinal barrier function.

Highlights

The intestinal epithelium, which is composed of a single layer of cells, functions as a selectively permeable barrier, allowing the absorption of nutrients, electrolytes, and water while preventing passage of larger, potentially toxic, compounds and/or enteric flora from the lumen [1]
Anti-Inflammatory Activities of the Fermented Herbal Formulation: Impact on Gene Expression and Production of Key Inflammatory Mediators and Production of nitric oxide (NO) and Prostaglandin E2 (PGE2). Because both fermented RAM-1 (FRAM-1) and fermented RAM-2 (FRAM-2) exerted stronger protection of intestinal epithelial cells (IECs) against LPS insult and exhibited greater antioxidant activity and polyphenol content, compared to Rhizoma Atractylodis Macrocephalae (RAM), we evaluated the anti-inflammatory activity of the two above-mentioned FRAMs using a RAW264.7 cell line as a model and LPS as the inflammation-inducing agent
Because nuclear factor-κβ (NF-κβ) plays a central role in inflammation [21, 22], which is mediated through an increase in nuclear translocation of p65 protein and depletion of cytosolic Iκβ [70], we evaluated the question of whether the anti-inflammatory impact of the fermented RAM on LPS-treated cells is driven through the inhibition of NF-κβ activation

Summary

Introduction

The intestinal epithelium, which is composed of a single layer of cells, functions as a selectively permeable barrier, allowing the absorption of nutrients, electrolytes, and water while preventing passage of larger, potentially toxic, compounds and/or enteric flora from the lumen [1]. It has been found that LPS or endotoxin, an integral component of the outer membrane of Gram-negative bacteria and one of the most abundant proinflammatory stimuli on the gastrointestinal tract, could cause impairment of intestinal barrier function [3]. This event may, in turn, result in augmentation of intestinal permeability, facilitating bacterial translocation from the gut lumen to mesenteric lymph nodes or other organs [4,5,6]. This process leads to the development of systemic sepsis and multipleorgan dysfunction syndrome (MODS) [7]

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