甘草酸苷通过MAPK p38/NF-κB通路对炎症后色素沉着的抑制作用

Glycyrrhizic Acid Suppress Post-inflammatory Hyperpigmentation via MAPK p38/NF-κB Singalling Pathway

关键词:  甘草酸苷  角质形成细胞  炎症后色素沉着  COX-2  NF-κB  脂多糖

Key words:  glycyrrhizic acid  keratinocyte  post-inflammatory hyperpigmentation  COX-2  NF-κB  lipopolysaccharide(LPS)

摘要:

目的 探讨甘草酸苷对脂多糖（lipopolysaccharide，LPS）刺激后角质形成细胞分泌COX-2/PGE₂和对共培养黑素细胞合成黑素的影响，并探讨其可能的作用机制。方法 以人表皮角质形成细胞为对象，分为对照组、LPS组、甘草酸苷组（2，5，10 μmol·L^-1）。采用ELISA法检测PGE₂的含量，Western blot检测细胞COX-2、NF-κB p-p65、p-IKKα/β和MAPKp-p38蛋白的表达，比色法检测共培养黑素细胞的黑素含量。结果 与对照组比较，LPS显著增加角质形成细胞COX-2、NF-κB p-p65、p-IKKα/β、MAPK p-p38蛋白表达（P<0.01）和PGE₂的分泌（P<0.01），增加共培养黑素细胞黑素生成（P<0.01）。与LPS组比较，甘草酸苷呈剂量依赖性抑制COX-2、NF-κB p-p65、p-IKKα/β、MAPK p-p38蛋白表达（P<0.05）和PGE₂的分泌（P<0.05），减少共培养黑素细胞黑素生成（P<0.05）。结论 甘草酸苷通过抑制角质形成细胞MAPK p38/NF-κB通路，从而降低COX-2/PGE₂的表达，减少共培养黑素细胞合成黑素。

Abstract:

OBJECTIVE To investigate the inhibitory effect of glycyrrhizic acid(GA) on LPS-induced expression of COX-2/PGE₂ in keratinocytes and the melanin production in co-cultured melanocytes explore its possible mechanism. METHODS Human cutaneous keratinocytes were treated with GA of different concentration(0, 2, 5 and 10 μmol·L^-1) and LPS. The level of cytokine PGE₂ in the culture medium was determined using ELISA kit. The expression of COX-2, NF-κB p-p65, p-IKKα/β and MAPK p-p38 were studied by Western blotting. The melanin content in co-cultured melanocytes was measured by colorimetric method. RESULTS The expression of COX-2, NF-κB p-p65, p-IKKα/β and MAPK p-p38 in LPS-treated keratinocytes were significantly raised compared to that in control group. LPS also elevated PGE₂ levels in the culture medium. The melanin content in co-cultured melanocytes increased after LPS stimulation. GA decreased COX-2, NF-κB p-p65, p-IKKα/β and MAPK p-p38 expression in LPS-treated keratinocytes in a dose-dependent manner(P<0.05). GA decreased PGE₂ levels in the culture medium of keratinocytes dose-dependently (P<0.05). GA also decreased melanin production in co-cultured melanocytes dose-dependently(P<0.05). CONCLUSION GA decreases LPS-induced expression of COX-2/PGE₂ in keratinocytes and melanin production in co-cultured melanocytes through suppressing MAPK p38/NF-κB signal pathway.