# A Small Molecule Compound, Berberine Reduces IgE but Not IgG Production via Promoting miRNA-34a-p53 Axis

## TL;DR

Berberine, a natural compound, reduces IgE production without affecting IgG, possibly through the miR-34a-p53 pathway in IgE-producing cells.

## Contribution

This study identifies a novel mechanism by which berberine specifically suppresses IgE via the miR-34a-p53 axis.

## Key findings

- Berberine reduces IgE production in human tonsil cells and IgE plasma cells without affecting IgG levels.
- Berberine increases miR-34a and p53 expression, and modulates cell cycle genes in IgE plasma cells.
- The miR-34a-p53 axis is implicated in the specific suppression of IgE by berberine.

## Abstract

Current therapeutic strategies for IgE-mediated diseases are limited. The drawbacks include adverse reactions, ineffectiveness, and relapses. Natural compound berberine (BBR) may combat this therapeutic gap through sustained transcriptional regulation of IgE. Human tonsil cells were cultured in the presence or absence of BBR to establish dose-dependent effects on IgE, IgG, and cell viability. IgE-producing plasma cells (U266, IgE plasma cells) and IgG-producing plasma cells (ARH-77, IgG plasma cells) were used as surrogate cells to validate dose-dependent effects on IgE and IgG production, respectively. At 10 μg/mL BBR, cell viability and proliferation were determined, and cells were harvested for protein, RNA, and miRNA and analyzed by Western blot and qPCR. BBR treatment of human tonsil samples resulted in reduced IgE production (p < 0.001) with no effect on IgG levels or cell viability. BBR demonstrated sustained, dose-dependent inhibition of IgE production by IgE plasma cells (p < 0.001), without affecting IgG production by IgG plasma cells. There was no significant reduction in cell viability of either cell type. Proliferation was reduced in IgE plasma cells (p = 0.02), but not IgG plasma cells. Assessment of IgE regulation and cell cycle at the RNA level revealed that BBR reduced IgE heavy chain expression and CCND1 (p < 0.01), with increased the GADD45A expression of IgE plasma cells, only (p = 0.016). At the protein level, BBR increased p53 (p = 0.02) and CDKN1C (p = 0.03), and decreased CDK2 (p = 0.01) expression of IgE plasma cells, only. Investigation of miRNAs implicated in B cell and p53 regulation demonstrated increased p53 and GADD45A activator, miR-34a (p = 0.04). miRNAs that are present in IgE plasma cells allow for specific effects on B cells and cell cycle genes by BBR, that are not present in IgG plasma cells. A novel mechanism for specific suppression of IgE by BBR highlights miR-34a, involved in the p53 pathway and B cell development, and may be crucial to pathological IgE production.