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Biflorin, Isolated from the Flower Buds of Syzygium aromaticum L., Suppresses LPS-Induced Inflammatory Mediators via STAT1 Inactivation in Macrophages and Protects Mice from Endotoxin Shock

Author:
Lee, Hwi-Ho, Shin, Ji-Sun, Lee, Woo-Seok, Ryu, Byeol, Jang, Dae Sik, Lee, Kyung-Tae
Source:
Journal of natural products 2016 v.79 no.4 pp. 711-720
ISSN:
1520-6025
Subject:
B-lymphocytes, Syzygium aromaticum, animal models, anti-inflammatory activity, buds, ears, edema, endotoxemia, endotoxins, gene expression, inducible nitric oxide synthase, inhibitory concentration 50, interleukins, lipopolysaccharides, macrophages, messenger RNA, mice, mitogen-activated protein kinase, nitric oxide, prostaglandin synthase, prostaglandins, protein synthesis, rats, signal transduction, survival rate, transactivators, transcription (genetics), transcription factor NF-kappa B, tumor necrosis factor-alpha
Abstract:
Two chromone C-glucosides, biflorin (1) and isobiflorin (2), were isolated from the flower buds of Syzygium aromaticum L. (Myrtaceae). Here, inhibitory effects of 1 and 2 on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin E₂ (PGE₂) in RAW 264.7 macrophages were evaluated, and 1 (IC₅₀ = 51.7 and 37.1 μM, respectively) was more potent than 2 (IC₅₀ > 60 and 46.0 μM). The suppression of NO and PGE₂ production by 1 correlated with inhibition of iNOS and COX-2 protein expression. Compound 1 reduced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression via inhibition of their promoter activities. Compound 1 inhibited the LPS-induced production and mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. Furthermore, 1 reduced p-STAT1 and p-p38 expression but did not affect the activity of nuclear factor κ light-chain enhancer of activated B cells (NF-κB) or activator protein 1 (AP-1). In a mouse model of LPS-induced endotoxemia, 1 reduced the mRNA levels of iNOS, COX-2, and TNF-α, and the phosphorylation-mediated activation of the signal transducer and activator of transcription 1 (STAT1), consequently improving the survival rates of mice. Compound 1 showed a significant anti-inflammatory effect on carrageenan-induced paw edema and croton-oil-induced ear edema in rats. The collective data indicate that the suppression of pro-inflammatory gene expression via p38 mitogen-activated protein kinase and STAT1 inactivation may be a mechanism for the anti-inflammatory activity of 1.
Agid:
5498430