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Apigenin-7-O-β-d-glucuronide inhibits LPS-induced inflammation through the inactivation of AP-1 and MAPK signaling pathways in RAW 264.7 macrophages and protects mice against endotoxin shock

HuThese authors equally contributed to this work., Weicheng, Wang, Xinfeng, Wu, Lei, Shen, Ting, Ji, Lilian, Zhao, Xihong, Si, Chuan-Ling, Jiang, Yunyao, Wang, Gongcheng
Food & function 2016 v.7 no.2 pp. 1002-1013
Juglans sigillata, agricultural wastes, aldehyde reductase, anti-inflammatory agents, antioxidants, cell viability, dose response, endotoxins, enzyme activity, enzyme inhibition, flavonoids, fruits, gene expression, health promotion, hulls, inducible nitric oxide synthase, inflammation, lipopolysaccharides, luciferase, macrophages, medicinal properties, messenger RNA, mice, mitogen-activated protein kinase, neoplasms, nitric oxide, phosphorylation, prostaglandin synthase, prostaglandins, signal transduction, tumor necrosis factor-alpha
Apigenin-7-O-β-d-glucuronide (AG), an active flavonoid derivative isolated from the agricultural residue of Juglans sigillata fruit husks, possesses multiple pharmacological activities, including anti-oxidant, anti-complement, and aldose reductase inhibitory activities. To date, no report has identified the anti-inflammatory mechanisms of AG. This study was therefore designed to characterize the molecular mechanisms of AG on lipopolysaccharide (LPS)-induced inflammatory cytokines in RAW 264.7 cells and on endotoxin-induced shock in mice. AG suppressed the release of nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumour necrosis factor-α (TNF-α) in LPS-stimulated RAW 264.7 macrophages in a dose-dependent manner without affecting cell viability. Additionally, AG suppressed LPS-induced mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α. AG treatment decreased the translocation of c-Jun into the nucleus, and decreased activator protein-1 (AP-1)-mediated luciferase activity through the inhibition of both p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) phosphorylation. Consistent with the in vitro observations, AG protected mice from LPS-induced endotoxin shock by inhibiting proinflammatory cytokine production. Taken together, these results suggest that AG may be used as a source of anti-inflammatory agents as well as a dietary complement for health promotion.