Anti-inflammatory activity of flavonols via inhibiting MAPK and NF-κB signaling pathways in RAW264.7 macrophages

Ruting Zhong; Lingchao Miao; Haolin Zhang; Lihua Tan; Yuxin Zhao; Yanbei Tu; Miguel Angel Prieto; Jesus Simal-Gandara; Lei Chen; Chengwei He; Hui Cao

doi:10.1016/j.crfs.2022.07.007

Anti-inflammatory activity of flavonols via inhibiting MAPK and NF-κB signaling pathways in RAW264.7 macrophages

Curr Res Food Sci. 2022 Jul 20:5:1176-1184. doi: 10.1016/j.crfs.2022.07.007. eCollection 2022.

Authors

Ruting Zhong^{1

2}, Lingchao Miao¹, Haolin Zhang¹, Lihua Tan^{1

2}, Yuxin Zhao^{1

2}, Yanbei Tu^{1

2}, Miguel Angel Prieto³, Jesus Simal-Gandara³, Lei Chen⁴, Chengwei He^{1

2}, Hui Cao^{4

3}

Affiliations

¹ Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao Special Administrative Region of China.
² Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Taipa, Macao Special Administrative Region of China.
³ Universidade de Vigo, Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Sciences, 32004, Ourense, Spain.
⁴ College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Zhanjiang, 524088, China.

Abstract

Fisetin (Fis), quercetin (Que), and myricetin (Myr) are flavonols with similar structure but different number of hydroxyl groups. The present research focused on the anti-inflammatory effect of these three flavonols in lipopolysaccharide-stimulated RAW264.7 cells. The number and site of hydroxyl group in flavonols obviously affected their anti-inflammation activity. These flavonols suppressed the overproduction of nitric oxide. Fis showed the best activity with an inhibition rate of 52% at 20 μM. Moreover, the flavonols reduced the levels of ROS, TNF-α, and IL-6. The mechanistic study showed that they inhibited the activation of NF-κB and MAPK pathways by suppressing the phosphorylation of IκBα, p65, JNK, ERK, p38, MEK, and reducing the nuclear translocation of NF-κB p65. In addition, the metabolism of the flavonols was examined. The results indicated that Fis was both methylated and glucuronidated. Que and Myr were mainly transformed into methylated products. This study highlights the anti-inflammatory activity of flavonols, particularly Fis, which has the potential for the prevention or treatment of inflammation as an adjuvant medicine or food additive.

Keywords: Anti-inflammation; Fisetin; MAPK; Myricetin; NF-κB; Quercetin.