Artepillin C Reduces Allergic Airway Inflammation by Induction of Monocytic Myeloid-Derived Suppressor Cells

Núbia Sabrina Martins,Vânia Luiza Deperon Bonato,Giseli Furlan Correa,Jairo Kenupp Bastos,Juliana Issa Hori,Leandra Naira Zambelli Ramalho,Thais Fernanda de Campos Fraga-Silva,Débora Munhoz Rodrigues,Diego Luis Costa,Mèdéton Mahoussi Michaël Boko

doi:10.3390/pharmaceutics13111763

Núbia Sabrina Martins, Vânia Luiza Deperon Bonato + Show 8 more

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https://doi.org/10.3390/pharmaceutics13111763

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Journal: Pharmaceutics	Publication Date: Oct 22, 2021
Citations: 6	License type: CC BY 4.0

Affiliation: Universidade de São Paulo, Apis Flora (Brazil)

Abstract

Propolis is a natural product produced by bees that is primarily used in complementary and alternative medicine and has anti-inflammatory, antibacterial, antiviral, and antitumoral biological properties. Some studies have reported the beneficial effects of propolis in models of allergic asthma. In a previous study, our group showed that green propolis treatment reduced airway inflammation and mucus secretion in an ovalbumin (OVA)-induced asthma model and resulted in increased regulatory T cells (Treg) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) frequencies in the lungs, two leukocyte populations that have immunosuppressive functions. In this study, we evaluated the anti-inflammatory effects of artepillin C (ArtC), the major compound of green propolis, in the context of allergic airway inflammation. Our results show that ArtC induces in vitro differentiation of Treg cells and monocytic MDSC (M-MDSC). Furthermore, in an OVA-induced asthma model, ArtC treatment reduced pulmonary inflammation, eosinophil influx to the airways, mucus and IL-5 secretion along with increased frequency of M-MDSC, but not Treg cells, in the lungs. Using an adoptive transfer model, we confirmed that the effect of ArtC in the reduction in airway inflammation was dependent on M-MDSC. Altogether, our data show that ArtC exhibits an anti-inflammatory effect and might be an adjuvant therapy for allergic asthma.

Highlights

Propolis is a resin made by working Apis mellifera Linnaeus, 1758 bees from exudates and new buds of different plant species, which is traditionally used in alternative and complementary medicine
The chromatographic processes used to obtain pure Artepillin C (ArtC) were previously reported by Rodrigues and colleagues [24] and yielded approximately 68 mg of purified compound, which was used for running the biological assays
Because we previously reported that propolis increases the differentiation of regulatory (Treg) T cells [10], we first investigated whether purified ArtC would induce treated animals of regulatory (Treg) cells in vitro

Summary

Introduction

Propolis is a resin made by working Apis mellifera Linnaeus, 1758 bees from exudates and new buds of different plant species, which is traditionally used in alternative and complementary medicine. DC as its primary botanical source and is rich in prenylated derivative compounds. It has gained notoriety for displaying anti-inflammatory, immunomodulatory, antitumoral, antibacterial, and antiviral proprieties [1,2,3,4]. Experimental evidence of anti-inflammatory actions of propolis was demonstrated in several murine models of inflammatory diseases. Those actions include the reduction in neutrophils and the levels of pro-inflammatory cytokines IL-6 and TNF-α in the bronchoalveolar lavage fluid (BALF) during LPS-induced pulmonary inflammation [5]; reduction in neutrophil infiltration and serum levels of IL-6, Pharmaceutics 2021, 13, 1763. In the type 2 inflammation induced by inhaled allergen, the treatment with propolis during the sensitization phase resulted in reduction in allergen-specific IgE, airway inflammation, and hyper-reactivity [8]

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