Date of Award

5-30-2023

Document Type

Doctoral Dissertation - Open Access

Degree Name

Doctor of Philosophy

Department

Microbiology and Immunology

First Advisor

Xiu-min Li, M.D., MSc

Abstract

Food allergy is a highly prevalent disease affecting about 30 million people in the U.S. It is managed primarily by food avoidance due to lack of promising treatment options. ASHMI (anti-asthma herbal intervention) which consists of three components, Sophorae flavescentis, Ganoderma lucidum, Glycyrrhiza uralensis has been shown to inhibit allergic lung inflammation in antigen sensitized and challenged mice. In this study we isolate and identify the active compound in Sophorae flavescentis, characterized the mechanism of IgE inhibitory effect, biomarkers and potential to prevent food anaphylaxis.

To separate and identify the compounds we used column chromatography, high-performance liquid chromatography, mass spectrometry and proton nuclear magnetic resonance. Using computational technology, we identified biological targets regulated by formononetin and finally we determined its effect in a peanut allergic mice model.

The IgE inhibitory compound isolated from Sophorae flavescentis was identified as formononetin. Formononetin decreased IgE production in a dose dependent fashion without cytotoxicity. Its inhibitory mechanism is specific to IgE production, as it did not inhibit IgG. Formononetin potentially regulates 25 targets in food allergy, 51 in IgE diseases and 19 in mast cell disease. Peanut allergic mice treated with formononetin but not vehicle was significantly protected from anaphylaxis to oral peanut challenges as indicated by lower symptom scores, better retention of body temperature and reduced plasma histamine.

Taken together, this study has shown that formononetin might be a potential treatment and preventive option for food anaphylaxis reaction seen in food allergy and a clinical trial is needed as next steps.

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