Caffeic Acid, One of the Major Phenolic Acids of the Medicinal Plant Antirhea borbonica, Reduces Renal Tubulointerstitial Fibrosis

Abstract

The renal fibrotic process is characterized by a chronic inflammatory state and oxidative stress. Antirhea borbonica (A. borbonica) is a French medicinal plant found in Reunion Island and known for its antioxidant and anti-inflammatory activities mostly related to its high polyphenols content. We investigated whether oral administration of polyphenol-rich extract from A. borbonica could exert in vivo a curative anti-renal fibrosis effect. To this aim, three days after unilateral ureteral obstruction (UUO), mice were daily orally treated either with a non-toxic dose of polyphenol-rich extract from A. borbonica or with caffeic acid (CA) for 5 days. The polyphenol-rich extract from A. borbonica, as well as CA, the predominant phenolic acid of this medicinal plant, exerted a nephroprotective effect through the reduction in the three phases of the fibrotic process: (i) macrophage infiltration, (ii) myofibroblast appearance and (iii) extracellular matrix accumulation. These effects were associated with the mRNA down-regulation of Tgf-β, Tnf-α, Mcp1 and NfkB, as well as the upregulation of Nrf2. Importantly, we observed an increased antioxidant enzyme activity for GPX and Cu/ZnSOD. Last but not least, desorption electrospray ionization-high resolution/mass spectrometry (DESI-HR/MS) imaging allowed us to visualize, for the first time, CA in the kidney tissue. The present study demonstrates that polyphenol-rich extract from A. borbonica significantly improves, in a curative way, renal tubulointerstitial fibrosis progression in the UUO mouse model.

Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

“…Additionally, we observed an increase of NF-κB staining both in dressed as well as undressed wounds, but immunosignal up-regulation was lower in the latter. Verren et al [ 60 ] showed the connection between the reduction of macrophage infiltrates and down-regulation of NF-κB. We postulate that NF-κB increases in the infiltration of the dressed area by macrophages.…”

Myofibroblasts: Function, Formation, and Scope of Molecular Therapies for Skin Fibrosis

“…Natural compounds have a long history of use in wound healing, and the cellular mechanisms of action are beginning to be delineated as active components are extracted and assessed [280][281][282]. The exploitation of the aromatic nature and antioxidant capabilities of various naturally sourced polyphenolic compounds and their extracts have been demonstrated in numerous in vitro and in vivo systems, with desirable biocompatible and anti-fibrotic effects in models of pulmonary [283][284][285]; renal [286,287]; myocardial [288,289]; and skin fibrosis [290,291]. The clinical potential of natural compound-based therapies is often restricted by the lack of clarity in their multifaceted bioactivities.…”

Special Issue: Anti-Inflammatory Activity of Plant Polyphenols 2.0

“…Vereen B. et al evaluated the anti-renal fibrosis effect of an extract from Antirhea borbonica , a French medicinal plant found in Reunion Island, in comparison to caffeic acid, one of the major phenolic acids of the extract, in mice subjected to unilateral ureteral obstruction [ 16 ]. Mice were treated daily with an oral dose of 25 mg/kg of Antirhea borbonica or 25 mg/kg of caffeic acid by gavage.…”