Anti-inflammatory effects behind fruit and veg compound uncovered

4 February 2021

A common compound found in fruits and vegetables interacts with cells lining blood vessels in a way that may protect them from damage caused by high glucose spikes.

The biggest contributions to quercetin intakes in the UK are onions, apples and tea, but it is present in many fruits and several vegetables including broccoli

Quercetin, found in onions, apples, tea and other leafy vegetables, alters metabolic processes in vascular cells in a way that would protect against inflammation. Inflammation is a natural process used by the body to protect itself against immediate harm, but if it is prolonged over time it can have long term, chronic effects.

High blood glucose levels that can occur after eating a carbohydrate-rich meal or because of diabetes are an inflammation trigger for endothelial cells. These are the cells that line the blood vessels. Unchecked over time this inflammation may develop into atherosclerosis, a major contributor to cardiovascular disease, so this research may start to explain why diets rich in quercetin tend to reduce the risk of heart disease.

The findings come from a study using cultured endothelial cells collected from blood vessels in donated umbilical tissue. Human umbilical vein endothelial cells (HUVECs) can be grown in the lab to provide a useful model of the way endothelial cells in blood vessels behave. This model system has been used extensively in the study of diabetes and cardiovascular disease.

Previous studies with HUVECs showed how endothelial cells react to inflammation triggers, as well as elevated glucose concentrations. The aim of the new study was to understand the effects of quercetin on HUVECs, and also to see if it could mitigate the pro-inflammatory triggers.

The research team, led by Dr Paul Kroon from the Quadram Institute, used metabolomics to look at a wide range of HUVEC metabolites under pro-inflammatory and high glucose conditions. They then compared these results with the metabolite profile in the presence of quercetin. Differences between these datasets can indicate the metabolic processes and signals within the endothelial cells that quercetin affects. The research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UKRI.

The strength of this metabolomics approach is that it is untargeted, rather than concentrating on one gene, metabolite or process. This gives a wider picture of the systemic response. It can also take into account how quercetin itself once taken up is modified by the cells into different forms.

Publishing in the journal Molecular Nutrition & Food Research, they show that high glucose concentrations and pro-inflammatory treatments affect the way the cells generate and use energy. If these changes in cellular metabolism were seen in the human body, they would be regarded as being an unhealthy metabolic state. However, the changes were ameliorated by quercetin and its modified forms. These led to more anti-inflammatory and fewer pro-inflammatory metabolites.

The search for how quercetin promotes this shift to a more anti-inflammatory status centres on its role in purine metabolism. Further experiments showed that quercetin and the modified forms inhibit certain enzymes involved in purine processing.

Purines are key compounds, across all forms of life, involved in signalling and metabolic processes, and are part of the way cells use and store energy. This study provides powerful evidence for how quercetin in the diet, once taken up and modified by cells, can help fine tune central cellular processes in a way that reduces inflammation, and so would be expected to promote health.

“This research provides evidence of a mechanism which may explain why people who consume the highest quantities of quercetin in their diets have lower risk of developing cardiovascular diseases” said Dr Kroon. “To increase your consumption of quercetin you should eat more fruits and vegetables, and in particular onions, apples, broccoli and berries, and drink tea.”

Reference: Ozyel, B., Le, G., Needs, P. W., Kroon, P. A., Anti‐Inflammatory Effects of Quercetin on High‐Glucose and Pro‐Inflammatory Cytokine Challenged Vascular Endothelial Cell Metabolism. Mol. Nutr. Food Res. 2021, 2000777. https://doi.org/10.1002/mnfr.202000777