Aharoni Saar, Lati Yoni, Aviram Michael, Fuhrman Bianca
The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa, Israel.
Biofactors. 2015 Jan-Feb;41(1):44-51. doi: 10.1002/biof.1199. Epub 2015 Feb 4.
It was documented that pomegranate has anti-inflammatory effects. In this study, we investigated a direct effect of pomegranate juice (PJ) and its polyphenols on macrophage inflammatory phenotype. In vitro, PJ and its major polyphenols dose-dependently attenuated macrophage response to M1 proinflammatory activation in J774.A1 macrophage-like cell line. This was evidenced by a significant decrease in TNFα and IL-6 secretion in response to stimulation by IFNγ and Lipopolysaccharide. In addition, PJ and punicalagin dose-dependently promoted the macrophages toward a M2 anti-inflammatory phenotype, as determined by a significant increase in the spontaneous secretion of IL-10. In mice, supplementation with dietary PJ substantially inhibited the M2 to M1 macrophage phenotypic shift associated with age, toward a favorable anti-inflammatory M2 phenotype. This effect was also reflected in the mice atherosclerotic plaques, as evaluated by the distinct expression of arginase isoforms. PJ consumption inhibited the increment of arginase II (Arg II, M1) mRNA expression during aging, and maintained the levels of Arg I (M2) expression similar to those in young mice aorta. This study demonstrates, for the first time, that pomegranate polyphenols directly suppress macrophage inflammatory responses and promote M1 to M2 switch in macrophage phenotype. Furthermore, this study indicates that PJ consumption may inhibit the progressive proinflammatory state in the aorta along atherosclerosis development with aging, due to a switch in macrophage phenotype from proinflammatory M1 to anti-inflammatory M2.
据记载，石榴具有抗炎作用。在本研究中，我们调查了石榴汁（PJ）及其多酚对巨噬细胞炎症表型的直接影响。在体外，PJ及其主要多酚在J774.A1巨噬细胞样细胞系中剂量依赖性地减弱巨噬细胞对M1促炎激活的反应。这通过对IFNγ和脂多糖刺激的反应中TNFα和IL - 6分泌的显著减少得到证明。此外，PJ和石榴皮素剂量依赖性地促进巨噬细胞向M2抗炎表型转变，这通过IL - 10自发分泌的显著增加来确定。在小鼠中，饮食中补充PJ显著抑制了与年龄相关的M2到M1巨噬细胞表型转变，趋向于有利的抗炎M2表型。这种效应也反映在小鼠动脉粥样硬化斑块中，通过精氨酸酶同工型的不同表达来评估。食用PJ抑制了衰老过程中精氨酸酶II（Arg II，M1）mRNA表达的增加，并使Arg I（M2）表达水平维持在与年轻小鼠主动脉相似的水平。本研究首次证明，石榴多酚直接抑制巨噬细胞炎症反应并促进巨噬细胞表型从M1向M2转变。此外，本研究表明，由于巨噬细胞表型从促炎M1向抗炎M2转变，食用PJ可能抑制随着衰老和动脉粥样硬化发展在主动脉中逐渐出现的促炎状态。
