Formononetin Isolated From Inhibits B Cell-Ige Production by Regulating ER-Stress Transcription Factor XBP-1

Authors

Nan Yang, General Nutraceutical Technology LLC, Elmsford, NY, United States.
Ibrahim Musa, Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, United States.
Anish R. Maskey, Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, United States.
Ke Li, Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, United States.
Zhenzhen Wang, Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, United States.
Banghao Liang, Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, United States.
Shuwei Zhang, Department of Biological Engineering, Utah State University, Logan, UT, United States.
Jixun Zhan, Department of Biological Engineering, Utah State University, Logan, UT, United States.
Xiu-Min Li, Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, United States.

Author Type(s)

Faculty

Journal Title

Frontiers in Allergy

First Page

1056203

Document Type

Article

Publication Date

1-1-2022

Department

Pathology, Microbiology and Immunology

Abstract

RATIONALE: IgE plays an important pathologic role in most, if not all, allergic conditions. We previously showed that ASHMI (anti-asthma herbal medicine intervention) suppressed IgE production in murine models of asthma and in asthma subjects. However, the active compounds in ASHMI responsible for the IgE suppression are still unknown. OBJECTIVE: We sought to identify the compound(s) in ASHMI that are responsible for IgE inhibition as well as investigate the mechanisms by which the identified compound(s) decreases IgE production. METHODS: The compounds in were separated using Column chromatography and preparative-HPLC. The separated compounds were identified using LC-MS and H-NMR. U266 cells, an IgE-producing plasma cell line, were cultured with various concentrations of identified compounds. The levels of IgE production by the U266 cell were measured by ELISA. Trypan blue exclusion was used to determine the cell viability. The gene expression of XBP-1 and IgE-heavy chain was determined by RT-PCR. RESULTS: A single compound identified as formononetin was isolated from . Formononetin significantly and dose dependently decreased the IgE production in U266 cells across a concentration range of 2-20 µg/ml ( < 0.05-0.001 vs. untreated cells) with an IC50 value of 3.43 μg/ml. There was no cytotoxicity at any tested concentration. Formononetin significantly decreased XBP-1, and IgE-heavy chain gene expression compared with untreated cells ( < 0.001). CONCLUSION: Formononetin decreased IgE production in human B cell line U266 cells in a dose-dependent fashion through the regulation of XBP-1 ER transcription. Formononetin may be a potential therapy for allergic asthma and other IgE-mediated diseases.

Recommended Citation

Yang, N., Musa, I., Maskey, A. R., Li, K., Wang, Z., Liang, B., Zhang, S., Zhan, J., & Li, X. (2022). Formononetin Isolated From Inhibits B Cell-Ige Production by Regulating ER-Stress Transcription Factor XBP-1. Frontiers in Allergy, 3, 1056203. https://doi.org/10.3389/falgy.2022.1056203