Elucidating Korean meadowsweet (Filipendula glaberrima Nakai)-derived arabinogalactan protein-induced macrophage activation and its associated mechanism of action

Abstract

This study aimed to confirm macrophage-stimulatory component from Korean meadowsweet (Filipendula glaberrima; FG) and characterize its compositional and structural properties. FG-CWH, prepared via cool-water extraction and ethanol precipitation, induced the highest secretion of NO (6.0–8.0 μM), TNF-α (8.7–9.5 ng/mL), and IL-6 (1.0–5.7 ng/mL) compared to other samples at 0.4–10 μg/mL in RAW 264.7 cells. Analytical results revealed that FG-CWH is a high-molecular-weight component with an average molecular weight of 220 kDa, constituting a polysaccharide-protein mixture. Chemical and enzymatic treatment of FG-CWH indicated its primary composition as arabinogalactan protein (AGP)-rich glycoprotein, with activity likely associated with the chemical and structural characteristics of AGP. FG-CWH treatment resulted in significant and concentration-dependent increases in iNOS (20.0–29.6 folds), TNFα (10.6–18.6 folds) and IL6 (10.9–155.6 folds) gene expression, as well as the secretion of NO (5.3–6.3 μM), TNF-α (35.4–44.3 ng/mL), and IL-6 (4.1–8.4 ng/mL) secretion, even at a reduced concentration range of 125–500 ng/mL, compared to the negative control group. Immunoblotting analysis indicated FG-CWH-induced macrophage stimulation significantly associated with the activation of MAPK (ERK, JNK, and p38) and NF-κB (p65 and IκBα). These findings can serve as valuable groundwork for developing FG-derived AGP as novel functional ingredients to enhance human immunity. © 2024 Elsevier B.V.