Divalent cations of magnesium, iron and copper regulate oxidative responses and inflammatory cytokines in RAW 264.7 macrophages

The metal ions play a decisive role in regulating the redox balance of cells and subsequentially alter cellular functions. The pacifying (“cold”) or irritating (“hot”) effects of food on the human body have been traditionally recognized and utilized by Chinese for hundreds of years. The principal components of fruits and vegetables corresponding to these effects have been identified to be magnesium, iron, and copper cations in combination. This study aims to elucidate the regulatory effects of the three cations on the oxidative responses and inflammatory cytokines production in RAW264.7 macrophages. Two “cold” solutions and two “hot” solutions were prepared with MgSO4, FeSO4, and CuSO4. The contents of three cations were calculated with a previously established regression equation and set to the physiologically meaningful levels (at ppm). It was found that the “cold” solution exhibited antioxidant and anti-inflammatory effects in the macrophages. They reduced the intracellular ROS level and restored the mitochondrial respiratory of the AAPH-insulted macrophages, while suppressing the LPS-induced expression of TNF-α, IL-1β, and IL-6 in the cells. Conversely, the “hot” solutions exhibited pro-oxidative and pro-inflammatory effects as they increased the intracellular ROS and expression of inflammatory cytokines in normal cells. It demonstrates the bidirectional regulation of the Mg2+, Cu2+, and Fe2+ cocktails on oxidative and inflammatory responses of murine macrophages. Inspired by the traditional Chinese food concept, the outcome of this study provides a new perspective and useful tool for future research and innovations in healthy and sustainable food.