Ulmus davidiana var. japonica Extracts Suppress Lipopolysaccharide-Induced Apoptosis Through Intracellular Calcium Modulation in U937 Macrophages

Jang-Hyuk Yun,Sun-Eun Choi,Chuanling Si,Jae-Hun Jeong,Hyun-Ouk Kim,Kwang-Hyun Park,Yerin Min

doi:10.3389/fenrg.2022.820330

Abstract

This study was aimed to examine the antiapoptotic effect of Ulmus davidiana extracts through regulation of the intracellular cation mobilization in U937 human monocytic cells. To investigate the modulatory effects on lipopolysaccharide-induced apoptosis and the Ca2+ signaling pathway, we measured the levels of intracellular Ca2+ and various protein markers such as Bax, Bcl-2, and PARP. To isolate biopotent molecules, the branches of U. davidiana were processed sequentially using 60% ethanol, supercritical fluid extraction, and ethyl acetate extraction of the remaining samples to obtain single fractions and catechin-glycoside, which is one of the known bioeffector molecules of U. davidiana. Lipopolysaccharide increased intracellular Ca2+ mobilization in U937 cells by inducing transient oscillations and markedly increased Bax and PARP protein expression and decreased Bcl-2 expression. All U. davidiana and catechin-glycoside significantly reduced lipopolysaccharide-induced intracellular Ca2+ mobilization and downregulated apoptosis-related molecules. These results suggest that U. davidiana and catechin-glycoside may be useful for improving immune system function.

Highlights

The branches of Ulmus davidiana var. japonica (ULDA) has been used as a traditional Korean medicine for the treatment of inflammatory disorders (Lee, 1966; Hong et al, 1990; Kim et al, 2010)
We assessed whether LPS would increase intracellular Ca2+ mobilization in U937 cells, mimicking cell exposure to Gramnegative bacteria, and whether ULDA extracts and catechinglycoside could protect cells from LPS exposure (Figure 5)
We determined whether ULDA extracts and catechin-glycoside reduced Ca2+ mobilization in response to LPS treatment (Figures 5C,F,I,L)

Summary

Introduction

The branches of Ulmus davidiana var. japonica (ULDA) has been used as a traditional Korean medicine for the treatment of inflammatory disorders (Lee, 1966; Hong et al, 1990; Kim et al, 2010). Japonica (ULDA) has been used as a traditional Korean medicine for the treatment of inflammatory disorders (Lee, 1966; Hong et al, 1990; Kim et al, 2010). Previous pharmacological studies have reported that ULDA possesses antioxidant, anti-angiogenic, anticancer, and neuroprotective effects (Kim et al, 2005; Si et al, 2013a). Recent studies indicate that ULDA extracts have various ameliorative effects on acute inflammatory responses in rats (Lee et al, 2013a; 2013b; Si et al, 2013b; Park et al, 2020), osteopenia (Zhuang et al, 2016), and in vitro models (Kim et al, 2019). The supercritical fluid of ULDA has anti-inflammatory, anti-angiogenic (Jung and Park, 2006; Si et al, 2009b), and antimelanin effects (Jeon et al, 2020; Xiong et al, 2021a; Xiong et al, 2021b)

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