Preparation of Herbal Formulation for Inflammatory Bowel Disease Based on In Vitro Screening and In Vivo Evaluation in a Mouse Model of Experimental Colitis.

Jaemin Lee,Bon Am Koo,Myoung-Sook Shin,Ki Sung Kang,Sullim Lee,Sang-Back Kim,Gwi Seo Hwang,Han-Seok Choi,Jinkyung Lee,Jimin Park

doi:10.3390/molecules24030464

Jaemin Lee, Bon Am Koo + Show 8 more

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https://doi.org/10.3390/molecules24030464

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Abstract

Many medicinal plants have been used traditionally in East Asia for the treatment of gastrointestinal disease and inflammation. The aim of this study was to evaluate the anti-inflammatory activity of 350 extracts (175 water extracts and 175 ethanol extracts) from 71 single plants, 97 mixtures of two plants, and seven formulations based on traditional medicine, to find herbal formulations to treat inflammatory bowel disease (IBD). In the in vitro screening, nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels were determined in LPS-treated RAW264.7 cells and the TNF-α induced monocyte-epithelial cell adhesion assay was used for the evaluation of the anti-inflammatory activity of the compounds. Dextran sulfate sodium (DSS)-induced colitis model and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model were used to evaluate the therapeutic effect against IBD of the samples selected from the in vitro screening. KM1608, composed of Zingiber officinale, Terminalia chebula and Aucklandia lappa, was prepared based on the screening experiments. The oral administration of KM1608 significantly attenuated the severity of colitis symptoms, such as weight loss, diarrhea, and rectal bleeding, in TNBS-induced colitis. In addition, inflammatory mediators, such as myeloperoxidase, TNF-α, and IL-6 levels decreased in the lysate of colon tissues treated with KM1608. Collectively, KM1608 ameliorated colitis through the regulation of inflammatory responses within the colon, which indicated that KM1608 had potential for the treatment of IBD.

Highlights

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory condition of the gastrointestinal tract, comprising Crohn’s disease and ulcerative colitis
The samples that consisted of a mixture of two plants were mixed at a 1:1 (w/w) ratio, traditional medicine formulations were mixed at the ratios based on prescription, and KM1608 was mixed in a 1:2:2 ratio (Zingiber officinale: Terminalia chebula: Aucklandia lappa) before the extraction process
In the in vitro screening experiments, we tested the effects of 350 extracted samples on Nitric oxide (NO), tumor necrosis factor (TNF)-α, and IL-6 production in LPS-stimulated RAW264.7 cells and on TNF-α-induced monocyte (U937)-colonic epithelial (HT-29) adhesion ability

Summary

Introduction

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory condition of the gastrointestinal tract, comprising Crohn’s disease and ulcerative colitis. The symptoms of IBD are chronic diarrhea, abdominal pain, rectal bleeding, weight loss, and shortening of the colon. The present treatment regimen, including aminosalicylates, corticosteroids, biologics, and immunosuppressants, has therapeutic limits and leads to side effects [3]. Recent failures of drug targets in IBD, such as IL-17, IL-13, interferon (IFN)-γ, and chemokine receptor (CCR)-9, have indicated that single target therapy for IBD is difficult owing to pathogenic heterogeneity [4]. The discovery of alternative treatment options with multiple therapeutic targets is required. We expect that natural product formulations, such as medicinal plant extracts or traditional medicines, would offer excellent alternative therapies for IBD

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