Chen Huajiao, Shi Daohua, Niu Peiguang, Zhu Yanting, Zhou Jintuo
Department of Pharmacy, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
Planta Med. 2018 Nov;84(16):1183-1190. doi: 10.1055/a-0626-7426. Epub 2018 May 17.
Cardamonin exhibits a variety of pharmacological activities including anti-inflammatory and antitumor, which are correlated with the inhibition of nuclear factor-kappaB and the mammalian target of rapamycin, respectively. However, whether the anti-inflammatory effects of cardamonin are mediated by the mammalian target of rapamycin remains unknown. In this study, ovarian cancer SKOV3 cells were cultured with lipopolysaccharide to induce inflammation, and the inhibitory effects and underlying molecular mechanisms of cardamonin were investigated using specific inhibitors of the mammalian target of rapamycin and the nuclear factor-kappaB pathway (rapamycin and pyrrolidine dithiocarbamate, respectively). Our results indicated that cardamonin inhibited the viability of normal and lipopolysaccharide-pretreated SKOV3 cells in a concentration-dependent manner. In accordance with rapamycin, the activation of the mammalian target of rapamycin and its downstream target, ribosomal protein S6 kinase 1, was inhibited by cardamonin, while pyrrolidine dithiocarbamate substantially blocked nuclear factor-kappaB activation and mildly inhibited the phosphorylation of the mammalian target of rapamycin and ribosomal protein S6 kinase 1. Pretreated with pyrrolidine dithiocarbamate, the effect of cardamonin on the mammalian target of rapamycin signalling was not affected, but the expression of inflammatory factors was further reduced. In cells pretreated with rapamycin, the inhibitory effects of cardamonin were completely suppressed with regards to the phosphorylation of the mammalian target of rapamycin, ribosomal protein S6 kinase 1, TNF-, and interleukin-6, and nuclear factor-kappaB p65 protein expression was decreased. In conclusion, our findings indicate that the anti-inflammatory effects of cardamonin are correlated with mammalian target of rapamycin inhibition.
小豆蔻明具有多种药理活性，包括抗炎和抗肿瘤，分别与抑制核因子-κB和雷帕霉素靶蛋白相关。然而，小豆蔻明的抗炎作用是否由雷帕霉素靶蛋白介导仍不清楚。在本研究中，用脂多糖培养卵巢癌SKOV3细胞以诱导炎症，并使用雷帕霉素靶蛋白和核因子-κB途径的特异性抑制剂（分别为雷帕霉素和吡咯烷二硫代氨基甲酸盐）研究小豆蔻明的抑制作用及其潜在的分子机制。我们的结果表明，小豆蔻明以浓度依赖的方式抑制正常和脂多糖预处理的SKOV3细胞的活力。与雷帕霉素一致，小豆蔻明抑制雷帕霉素靶蛋白及其下游靶点核糖体蛋白S6激酶1的激活，而吡咯烷二硫代氨基甲酸盐显著阻断核因子-κB的激活，并轻度抑制雷帕霉素靶蛋白和核糖体蛋白S6激酶1的磷酸化。用吡咯烷二硫代氨基甲酸盐预处理后，小豆蔻明对雷帕霉素靶蛋白信号通路的作用不受影响，但炎症因子的表达进一步降低。在用雷帕霉素预处理的细胞中，小豆蔻明对雷帕霉素靶蛋白、核糖体蛋白S6激酶1、肿瘤坏死因子-α和白细胞介素-6的磷酸化的抑制作用被完全抑制，核因子-κB p65蛋白表达降低。总之，我们的研究结果表明，小豆蔻明的抗炎作用与雷帕霉素靶蛋白抑制相关。
