Suppression of Inflammatory Responses by Dihydromyricetin, a Flavonoid from Ampelopsis grossedentata, via Inhibiting the Activation of NF-κB and MAPK Signaling Pathways
Suppression of Inflammatory Responses by Dihydromyricetin, a Flavonoid from Ampelopsis grossedentata, via Inhibiting the Activation of NF-κB and MAPK Signaling Pathways
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DOI：
10.1021/acs.jnatprod.5b00275
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发表时间：
2015-07-01
影响因子：
5.1
通讯作者：
Fang, J. G.
中科院分区：
文献类型：
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作者：
Hou, X. L.;Tong, Q.;Fang, J. G.
显齿蛇葡萄是我国南方的一种乡土植物，在中医中用于治疗咽炎已有数百年的历史。在这项研究中，我们探讨了二氢杨梅素（1），其主要生物活性成分的抗炎活性，以及这种作用的潜在机制。我们证明，1抑制促炎细胞因子，如肿瘤坏死因子-α（TNF-α），白细胞介素-1 β（IL-1 β），白细胞介素-6（IL-6）的水平，以及增加水平的抗炎细胞因子白细胞介素-10（IL-10）在脂多糖（LPS）处理的小鼠。此外，发现1显著抑制一氧化氮（NO）的产生以及TNF-α、IL-1 β和IL-6的水平，而它增加LPS诱导的RAW 264.7巨噬细胞中IL-10的水平。化合物1还降低巨噬细胞中诱导型一氧化氮合酶（iNOS）、TNF-α和环氧合酶-2（考克斯-2）的蛋白质表达。此外，1还抑制了脂多糖刺激的巨噬细胞中NF-κ B（NF-κ B）和I-κ B α的磷酸化以及p38和JNK的磷酸化，但不抑制ERK 1/2的磷酸化。综上所述，本研究结果表明，1通过抑制NF-κ B的活化和p38和JNK的磷酸化来发挥其局部抗炎作用。因此，1可能是一个潜在的有用的治疗剂，炎症相关疾病。
Ampelopsis grossedentata, an indigenous plant in southern China, has been used for treating pharyngitis in traditional Chinese medicine for hundreds of years. In this study, we explored the anti-inflammatory activity of dihydromyricetin (1), its major bioactive component, and the underlying mechanism of this action. We demonstrated that 1 suppressed the levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) as well as increased the level of the anti-inflammatory cytokine interleuldn-10 (IL-10) in lipopolysaccharide (LPS)-treated mice. Moreover, 1 was found to markedly inhibit the production of nitric oxide (NO) and the levels of TNF-alpha, IL-1 beta, and IL-6, whereas it increased the level of IL-10 in LPS-induced RAW 264.7 macrophage cells. Compound 1 also reduced the protein expression of inducible nitric oxide synthase (iNOS), TNF-alpha, and cyclooxygenase-2 (COX-2) in macrophage cells. Furthermore, 1 suppressed the phosphorylation of NF-kappa B (NF-kappa B) and I kappa B alpha as well as the phosphorylation of p38 and JNK but not ERK1/2 in LPS-stimulated macrophages. Taken together, the present results suggest that 1 exerts its topical anti-inflammatory action through suppressing the activation of NF-kappa B and the phosphorylation of p38 and JNK. Thus, 1 may be a potentially useful therapeutic agent for inflammatory-related diseases.