# Delphinidin Exerts Immunomodulatory Effects in Canine Neutrophils and Peripheral Blood Mononuclear Cells by Limiting Tissue Damaging Mechanisms and Regulating Cytokine Responses

## TL;DR

Delphinidin, a compound from maqui berries, modulates the immune system in dogs by reducing inflammation and tissue damage without harming cells.

## Contribution

This study is the first to demonstrate delphinidin's immunomodulatory effects in canine neutrophils and PBMCs, highlighting its potential as a natural anti-inflammatory supplement.

## Key findings

- Delphinidin reduces reactive oxygen species and extracellular trap formation in canine neutrophils.
- It modulates cytokine production by decreasing pro-inflammatory cytokines and increasing interferon-γ.
- Delphinidin promotes chemotaxis and reduces matrix metalloproteinase 9 activity in canine immune cells.

## Abstract

Diseases that cause chronic inflammation severely affect the quality of life of dogs by damaging their tissues and causing premature aging. Currently, natural alternatives are being sought to treat these problems without the side effects of traditional medications. In this context, delphinidin, a bioactive compound present in maqui berries, is emerging as a promising candidate for treating these conditions in dogs, although there is still limited scientific evidence regarding its efficacy. This study aimed to evaluate whether delphinidin regulates the canine immune system. When tested on canine blood cells, the results showed that this compound does not affect cell viability, increases cell migration, and acts by reducing mechanisms that cause tissue damage, as it decreases the production of reactive oxygen species, formation of extracellular traps, and activity of the enzyme metalloproteinase 9. Simultaneously, it regulated the production of inflammatory cytokines, decreasing the production of interleukin 1β, tumor necrosis factor α, and interleukin 6, and increasing the production of interferon-γ. In conclusion, delphinidin effectively balanced the immune response in dogs. These findings support the study and development of new naturally occurring compounds that can be used as supplements to prevent and treat inflammatory diseases in dogs.

Dogs can develop chronic inflammatory diseases that induce progressive tissue damage and illness. Delphinidin is a component of maqui (Aristotelia chilensis) and has anti-inflammatory and antioxidant effects. This study evaluated the immunomodulatory effects of delphinidin chloride (DC) and delphinidin-3-glucoside (D3G) on neutrophils and peripheral blood mononuclear cells (PBMCs) in dogs. Leukocytes were isolated from 20 clinically healthy dogs and treated with DC and D3G at concentrations of 50, 100, and 150 µM. The cells were then stimulated with lipopolysaccharide (LPS), platelet-activating factor (PAF), or phorbol 12-myristate 13-acetate (PMA) to evaluate cell viability, reactive oxygen species (ROS) production, neutrophil extracellular trap (NET) formation, phagocytosis, chemotaxis, matrix metalloproteinase 9 (MMP-9) activity, and cytokine production. The results showed that both compounds preserved cell viability, significantly reducing ROS production and NET formation. DC significantly increased chemotaxis and D3G significantly reduced MMP-9 activity. Both compounds reduced the secretion of interleukin (IL) 1β (IL-1β) and tumor necrosis factor α (TNF-α) in neutrophils. In PBMCs, they decreased the production of IL-4 and IL-6 and modulated the production of interferon γ (IFN)-γ. In conclusion, delphinidin exerts selective anti-inflammatory activities in canine leukocytes, promoting inflammation resolution, suggesting its potential role as a nutraceutical for managing inflammatory pathologies in dogs.