Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Republic of Korea.
Eur J Pharm Sci. 2013 Oct 9;50(2):198-207. doi: 10.1016/j.ejps.2013.07.001. Epub 2013 Jul 12.
Histamine, a potent inflammatory mediator, has been known to cause the pathogenesis of atherosclerosis. In this sense, two bioactive peptides P1 (LDAVNR; 686Da) and P2 (MMLDF; 655Da) purified from gastric enzymatic hydrolysate of Spirulina maxima were examined for their protective effects against early atherosclerotic responses induced by histamine in EA.hy926 endothelial cells. Interestingly, both P1 and P2 exhibited inhibitory activities on the production and expression of IL-6 and MCP-1. Furthermore, P1 and P2 inhibited the production of adhesion molecules including P-selectin and E-selectin, and thus reducing in vitro cell adhesion of monocyte onto endothelial cells. In addition, the production of intracellular reactive oxygen species was observed to reduce in the presence of P1 or P2. Notably, the inhibitory activities of P1 and P2 were found due to down-regulating Egr-1 expression via histamine receptor and PKCδ-dependent MAPKs activation pathway. These results suggest that peptides P1 and P2 from S. maxima are effective to suppress histamine-induced endothelial cell activation that may contribute to the prevention of early atherosclerosis.
组胺是一种有效的炎症介质，已知它会导致动脉粥样硬化的发病机制。从这个意义上说，从螺旋藻胃蛋白酶水解产物中纯化得到的两种生物活性肽 P1（LDAVNR；686Da）和 P2（MMLDF；655Da），被检测其对组胺诱导的 EA.hy926 内皮细胞早期动脉粥样硬化反应的保护作用。有趣的是，P1 和 P2 均表现出抑制 IL-6 和 MCP-1 产生和表达的活性。此外，P1 和 P2 抑制包括 P-选择素和 E-选择素在内的粘附分子的产生，从而减少单核细胞在内皮细胞上的体外粘附。此外，在存在 P1 或 P2 的情况下，观察到细胞内活性氧物质的产生减少。值得注意的是，P1 和 P2 的抑制活性是由于通过组胺受体和 PKCδ依赖性 MAPKs 激活途径下调 Egr-1 表达而产生的。这些结果表明，螺旋藻的肽 P1 和 P2 可有效抑制组胺诱导的内皮细胞激活，这可能有助于预防早期动脉粥样硬化。
