Natural phenylethanoid glycosides isolated from Callicarpa kwangtungensis suppressed lipopolysaccharide-mediated inflammatory response via activating Keap1/Nrf2/HO-1 pathway in RAW 264.7 macrophages cell.

Published on Aug 10, 2020in Journal of Ethnopharmacology3.69
· DOI :10.1016/J.JEP.2020.112857
Ai-Zhi Wu5
Estimated H-index: 5
(Guangzhou University of Chinese Medicine),
Aizhi Wu1
Estimated H-index: 1
(Guangzhou University of Chinese Medicine)
+ 6 AuthorsChen-Chen Zhu11
Estimated H-index: 11
(Guangzhou University of Chinese Medicine)
Abstract Callicarpa kwangtungensis, as a characteristic traditional herb in China, has been widely used as indigenous medicine for thousands of years in the treatment of gynecological inflammatory disease in China. Phenylethanoid glycosides (PhGs), as natural polyphenols, are especially abundant in this herb and can be regarded as the representative active ingredients in C. kwangtungensis. This study was performed to investigate the anti-inflammatory pharmacodynamic basis of six PhGs (acteoside, forsythoside B, poliumoside, alyssonoside, Parvifloroside A, and syringalide A 3′-α-L-rhanmnopyranoside) isolated from C. kwangtungensis from the perspective of antioxidation. Compared with the model group, six PhGs revealed obviously inhibitory effects on inflammatory factors TNF-α, IL-6, NO and the generation of ROS in RAW 264.7 macrophages. Further, the effective anti-inflammatory mechanism of two PhGs (forsythoside B and alyssonoside) via Keap1/Nrf2/OH-1 signaling pathway was explored. The experiments confirmed forsythoside B and alyssonoside could act as the inhibitors of Keap1-Nrf2 interaction, then activated the nuclear translocation of Nrf2 and promoted the upregulated protein expression of heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1), finally suppressed LPS-induced inflammatory response in RAW 264.7 cells. Molecular modeling exhibited potential interaction between PhGs and the Nrf2 binding site in Kelch-like ECH-association protein 1 (Keap1), and hydrogen bonds played a crucial role for the binding of PhGs with Keap1. These results provided experimental and theoretical basis for the deeper use of C. Kwangtungensis in the treatment and prevention of diseases related to inflammation and oxidative stress.
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