In Vitro Anti-Inflammatory Activity in Arthritic Synoviocytes of A. brachypoda Root Extracts and Its Unusual Dimeric Flavonoids.

Carlota Salgado,Nayara Coriolano De Aquino,Laurence Marcourt,Emerson Ferreira Queiroz,Hugo Morin,Eric Allémann,Laurence Neff,Wagner Vilegas,Cláudia Quintino Da Rocha,Jean-Luc Wolfender,Olivier Jordan

doi:10.3390/molecules25215219

Abstract

Arrabidaea brachypoda is a plant commonly used for the treatment of kidney stones, arthritis and pain in traditional Brazilian medicine. Different in vitro and in vivo activities, ranging from antinociceptive to anti-Trypanosoma cruzi, have been reported for the dichloromethane root extract of Arrabidaea brachypoda (DCMAB) and isolated compounds. This work aimed to assess the in vitro anti-inflammatory activity in arthritic synoviocytes of the DCMAB, the hydroethanolic extract (HEAB) and three dimeric flavonoids isolated from the DCMAB. These compounds, brachydin A (1), B (2) and C (3), were isolated both by medium pressure liquid and high-speed counter current chromatography. Their quantification was performed by mass spectrometry on both DCMAB and HEAB. IL-1β activated human fibroblast-like synoviocytes were incubated with both extracts and isolated compounds to determine the levels of pro-inflammatory cytokine IL-6 by enzyme-linked immunosorbent assay (ELISA). DCMAB inhibited 30% of IL-6 release at 25 µg/mL, when compared with controls while HEAB was inactive. IC50 values determined for 2 and 3 were 3-fold higher than 1. The DCMAB activity seems to be linked to higher proportions of compounds 2 and 3 in this extract. These observations could thus explain the traditional use of A. brachypoda roots in the treatment of osteoarthritis.

Highlights

Arrabidaea brachypoda (D.C.) is a shrub native to the Brazilian region of Cerrado
Analysis revealed three major compounds (Figure 1) which were previously characterized as three unusual dimeric flavonoids named brachydin A (1), brachydin B (2), and brachydin C (3) [8]
Separation conditions were optimized at HPLC-PDA analytical scale (Figure S1, Supplementary Material) and transferred to medium pressure liquid chromatography (MPLC) at a semi-preparative scale, using a gradient transfer method

Summary

Introduction

Arrabidaea brachypoda (D.C.) is a shrub native to the Brazilian region of Cerrado (neotropical savanna). Antinociceptive, anti-inflammatory, anti-Trypanosoma cruzi, gastroprotective, antileishmanial, and antimicrobial activities have been recently reported in different in vitro and in vivo assays from both root extracts and isolated compounds [8,9,10,11,12,13,14,15]. In these previous studies, different oral and/or topical administration setups were explored. We aimed to test the in vitro anti-inflammatory activity of A. brachypoda root extracts and three isolated dimeric flavonoids in the context of osteoarthritis (OA)

Objectives

Methods

Results

Conclusion