Lee H S, Kim D H, Hong J E, Lee J-Y, Kim E J
Department of Food Science and Nutrition, Dongseo University, Busan, Republic of Korea.
Center for Efficacy Assessment and Development of Functional Food and Drugs, Hallym University, Chuncheon, Republic of Korea.
Hum Exp Toxicol. 2015 Aug;34(8):808-18. doi: 10.1177/0960327114559989. Epub 2014 Nov 25.
Excessive inflammation is considered a critical factor in many human diseases. Oxyresveratrol(trans-2,3',4,5'-tetrahydroxystilbene), a natural hydroxystilbene, has been shown to possess antioxidant and free radical-scavenging activity. In this study, we investigated the effects of oxyresveratrol (OxyR) on the lipopolysaccharide (LPS)-induced production of inflammatory cytokines and mediators and further explored the mechanism of action in RAW264.7 murine macrophage cell line. Production of nitric oxide (NO), prostaglandin E2 (PGE2), messenger RNA (mRNA) and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and granulocyte macrophage colony-stimulating factor (GM-CSF), phosphorylation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38), and the activation of nuclear factor κ-light chain enhancer of activated B cells (NFκB) with OxyR were assayed in LPS-stimulated RAW264.7 cells. OxyR inhibited the productions of NO, PGE2, IL-6, and GM-CSF significantly in LPS-stimulated RAW264.7 cells. OxyR suppressed mRNA and protein expressions of iNOS, COX-2, IL-6, and GM-CSF in LPS-stimulated RAW264.7 cells. OxyR suppressed the phosphorylation of Akt and JNK and p38 MAPKs and the translocation of NFκB p65 subunit into the nucleus. These results indicate that OxyR inhibits LPS-stimulated inflammatory responses though the blocking of MAPK and NFκB signaling pathway in macrophages, and suggest that OxyR possesses anti-inflammatory effects.
过度炎症被认为是许多人类疾病的关键因素。氧化白藜芦醇（反式 - 2,3',4,5'-四羟基二苯乙烯）是一种天然的羟基二苯乙烯，已被证明具有抗氧化和清除自由基的活性。在本研究中，我们研究了氧化白藜芦醇（OxyR）对脂多糖（LPS）诱导的炎性细胞因子和介质产生的影响，并进一步探讨了其在RAW264.7小鼠巨噬细胞系中的作用机制。检测了在LPS刺激的RAW264.7细胞中，氧化白藜芦醇对一氧化氮（NO）、前列腺素E2（PGE2）的产生、诱导型一氧化氮合酶（iNOS）、环氧化酶 - 2（COX - 2）、白细胞介素6（IL - 6）和粒细胞巨噬细胞集落刺激因子（GM - CSF）的信使核糖核酸（mRNA）和蛋白表达、丝裂原活化蛋白激酶（MAPKs；细胞外信号调节激酶（ERK）、c - Jun氨基末端激酶（JNK）、p38）的磷酸化以及活化B细胞核因子κ轻链增强子（NFκB）的激活的影响。氧化白藜芦醇在LPS刺激的RAW264.7细胞中显著抑制了NO、PGE2、IL - 6和GM - CSF的产生。氧化白藜芦醇在LPS刺激的RAW264.7细胞中抑制了iNOS、COX - 2、IL - 6和GM - CSF的mRNA和蛋白表达。氧化白藜芦醇抑制了Akt和JNK以及p38 MAPKs的磷酸化以及NFκB p65亚基向细胞核的转位。这些结果表明，氧化白藜芦醇通过阻断巨噬细胞中的MAPK和NFκB信号通路来抑制LPS刺激的炎症反应，并表明氧化白藜芦醇具有抗炎作用。
