NYMC Student Theses and Dissertations

Date of Award

3-31-2023

Document Type

Doctoral Dissertation - Open Access

Degree Name

Doctor of Philosophy

Department

Basic Medical Sciences

First Advisor

Xiu-Min Li

Abstract

Eosinophilic Esophagitis (EoE), a chronic inflammatory condition of the esophagus, characterized by esophageal dysfunction and eosinophilic inflammation. Current treatments for EoE include dietary elimination and swallowed steroids. Recently, Dupixent was approved for the treatment of EoE, but it has side effects such as eye inflammation and eczema. Traditional Chinese Medicine (TCM) practice has been used to improve GI symptoms in EoE patients. Two key active ingredients of a TCM formula, 7,4’-Dihydroxyflavone (DHF) and Berberine (BBR), have shown remarkable results in treating EoE.

To understand the role of two active ingredients in EoE, different experimental models were used. First, a computational model to test the effect of DHF on EoE targets. 29 common targets including TNF-α, IL6, IL1β, IL-8, CCND, and MAPK1 were found, and these targets were validated ex-vivo on cultured human esophagus biopsy specimens from EoE patients. In another approach, we used a peanut-induced murine model of EoE to understand the underlying mechanisms associated with BBR-N protection in developing EoE. BBR-N treatment showed a reduction in the number of eosinophils in the esophagus, decreased epithelial thickening, and reduced fibrosis and fibronectin as compared to sham mice. BBR-N treatment led to the inhibition of peanut-specific IgE and prevented mast cell degranulation and modulated gut microbiome.

Our results conclude the potential of small molecule compounds, DHF and BBR-N, derived from a TCM formula in treating EoE. This study provides insight into the molecular mechanisms underlying multi-targeted benefits of DHF and BBR-N in treating EoE and further facilitate more effective clinical trials.

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