# Buckwheat Flavonoids Modulate Inflammation in RAW 264.7 Macrophages at Physiologically Relevant Concentrations via the LPS/COX‑2 Pathway

## TL;DR

This study identifies how buckwheat flavonoids reduce inflammation in macrophages by targeting specific pathways, offering potential for treating inflammation-related diseases.

## Contribution

The study reveals distinct molecular mechanisms by which buckwheat flavonoids modulate the LPS/COX-2 pathway at physiological concentrations.

## Key findings

- Luteolin, apigenin, and kaempferol reduce COX-2 levels, while quercetin increases them.
- Luteolin and kaempferol inhibit Ikkβ phosphorylation and target TLR4.
- Luteolin and quercetin reduce PGE2 and PGD2 by inhibiting hPGDS, independent of COX-2 modulation.

## Abstract

Buckwheat (BW) is
recognized as a functional food with antioxidant
and anti-inflammatory properties. BW (poly)­phenols are important bioactive
compounds associated with these benefits, although their therapeutic
role remains elusive. We used a multidisciplinary approach to identify
the bioactive flavonoids of BW and their molecular mechanisms. Physiologically
relevant concentrations of luteolin (Lute), quercetin (Quer), apigenin
(Api), and kaempferol (Kaem) were effective in reducing prostaglandin
(PG)­E2 and PGD2 biosynthesis in LPS-activated
macrophages by acting at distinct branch points of the LPS/COX-2 pathway.
Lute, Api, and Kaem reduced COX-2 levels, whereas Quer exerted the
opposite effect. Lute and Kaem inhibited Ikkβ phosphorylation,
while TLR4 was identified as a flavonoid's target. PGE2 and PGD2 reductions were independent of COX-2 modulation
and correlated with hematopoietic prostaglandin D synthase (hPGDS)
inhibition (exerted by Lute and Quer). These findings offer a new
perspective on the LPS/COX-2 pathway as a target of BW-derived products
to address inflammation-related diseases.