Structure–Activity Relationship (SAR) of Flavones on Their Anti-Inflammatory Activity in Murine Macrophages in Culture through the NF-κB Pathway and c-Src Kinase Receptor
2022
Wang, Xiang | Cao, Yujia | Chen, Siyu | Lin, Jiachen | Yang, Xin | Huang, Dejian
Flavones benefit human health through their anti-inflammatory activity; however, their structure–activity relationship is unclear. Herein, we selected 15 flavones with the same backbone but different substituents and systematically assessed their anti-inflammatory activities in RAW 264.7 regarding cellular-Src kinase (c-Src) affinity, suppression of IκBα phosphorylation, inhibition of nitric oxide (NO) and inducible nitric oxidase (iNOS) production, and downregulation of genes of proinflammatory cytokines interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α). Overall, our results showed that the double bond between C2-C3 and C3′- and C4′-OH promoted anti-inflammatory activity, while C8- and C5′-OH and the methoxy group on C4′ attenuated the overall anti-inflammatory and antioxidant activities. The hydroxyl groups at other positions exhibited more complicated functions. The two most effective flavones are 3′,4′-dihydroxyflavone and luteolin with inhibitory concentration (IC₅₀) values for inhibiting the LPS-induced nitric oxide level are 9.61 ± 1.36 and 16.90 ± 0.74 μM, respectively. Furthermore, they suppressed the production of iNOS by approximately 90% and inhibited IL-1β and IL-6 by more than 95%. Taken together, our results established a relationship between the flavone structure and anti-inflammatory activity in vitro.
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