Scientists from the Tokyo University of Science say they have identified a polyphenolic compound found in blueberries called pterostilbene (PSB) with strong immunosuppressive properties. They believe it can provide a potential therapeutic option for chronic inflammatory diseases, including inflammatory bowel disease (IBD).

The team, led by Chiharu Nishiyama, PhD, published its study “Pterostilbene reduces colonic inflammation by suppressing dendritic cell activation and promoting regulatory T cell development” in The FASEB Journal.

The compound is similar to another phytocompound known to have important medicinal effects, called resveratrol (RSV), which was known to have pronounced immunomodulatory and anti-inflammatory effects on animal models of colitis ulcer. The researchers investigated the possibility of other compounds structurally similar to RSV as a new type of treatment for IBD.

In patients with IBD, the gastrointestinal tract lining contains long-lasting ulcers caused by chronic inflammation due to an elevated immune response in the body. This involves the excessive production cytokines. Moreover, dendritic cells (DCs) and T cells, are also involved. At the onset of an immune response, DCs produce inflammatory cytokines and activate T cells to initiate a defense response. These processes together form a complex pathway that result in a hyper immune response.

Thus, to find an effective compound that can suppress the immune system, it was crucial to test it on this population of immune cells.

“The effect of pterostilbene (PSB) (3′,5′‐dimethoxy‐resveratrol), a resveratrol‐related polyphenol found in blueberries, on immune regulation was evaluated. Using an in vitro co‐culture system, PSB was found to exert the strongest inhibitory effect among all tested resveratrol derivatives on DC‐mediated T cell proliferation; moreover, PSB treatment decreased the Th1 and Th17 populations and increased the regulatory T cell (Treg) population,”  write the investigators.

“Upon co‐stimulation with anti‐CD3 and anti‐CD28 antibodies, PSB inhibited CD4+ T cell proliferation and differentiation into Th1 cells. Additionally, PSB acted on DCs to suppress the lipopolysaccharide‐induced transactivation of genes encoding antigen presentation‐related molecules and inflammatory cytokines by attenuating the DNA‐binding ability of the transcription factor PU.1.”

“Furthermore, PSB promoted DC‐mediated Foxp3+ Treg differentiation, and PU.1 knockdown increased DC‐induced Treg activity. Oral administration of PSB alleviated the symptoms of dextran sulfate sodium‐induced colitis and decreased tumor necrosis factor‐α expression in mice. Thus, PSB treatment ameliorates colonic inflammation.”

To begin, the scientists studied the effects of a range of plant-derived compounds on DC-mediated T cell proliferation. Their initial research led them to PSB, which showed stronger immunosuppressive activity than the other candidates. When they dug deeper, they found that PSB treatment prevents T cells from differentiating into Th1 and Th17 (subtypes of T cells that elevate the immune response) while increasing their differentiation into regulatory T cells (another subtype known to inhibit inflammation).

The researchers also revealed that PSB treatment inhibits inflammatory cytokine production from DCs by attenuating the DNA-binding activity of a crucial transcription factor PU.1. When they further tested PSB in mice with IBD, they found that oral intake of PSB improved symptoms of IBD. Thus, the study confirmed that PSB is a promising anti-inflammatory agent to fight IBD. It is also easily absorbed by the body, they add.

Through these findings, the scientists are confident that they opened the door to new therapeutic possibilities for the treatment of not just IBD but also other inflammatory disorders.

“For disease prevention, it is important to identify the beneficial components in foods and to understand the underlying mechanism by which immune responses and homeostasis are modulated in body,” says Takuya Yashiro, PhD,  also from the Tokyo University of Science and a corresponding author on the study. “Our findings showed that PSB possesses a strong immunosuppressive property, paving the way for a new, natural treatment for IBD.”

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