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鉴定石蒜中的石蒜裂碱及其对巨噬细胞 LPS 诱导的炎症反应的抑制作用。

Identification of narciclasine from Lycoris radiata (L'Her.) Herb. and its inhibitory effect on LPS-induced inflammatory responses in macrophages.

机构信息

College of Food and Bioengineering, South China University of Technology, Guangzhou, 510640, China.

College of Food and Bioengineering, South China University of Technology, Guangzhou, 510640, China.

出版信息

Food Chem Toxicol. 2019 Mar;125:605-613. doi: 10.1016/j.fct.2019.02.003. Epub 2019 Feb 7.

DOI:10.1016/j.fct.2019.02.003
PMID:30738987
Abstract

Lycoris radiata (L'Her.) Herb. (L. radiata) was traditionally used as a folk medicine in China for treatment of Alzheimer's disease. However, the specific component responsible for its considerable toxicity remained unclear thus restricting its clinical trials. Narciclasine (NCS) was isolated from L. radiata and treatment of NCS for 72 h exhibited significant antiproliferative effects against L02, Hep G2, HT-29 and RAW264.7 cells. However, what needs to be emphasized is that at safe working concentrations of 0.001-0.016 μM, administration of NCS for 24 h inhibited the mRNA expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-ɑ), interleukin-1beta (IL-1β) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced macrophages thereby suppressing production of nitric oxide (NO), IL-6, TNF-ɑ and IL-1β. NCS supplementation also inhibited nuclear factor-kappa B (NF-κB) activation by suppressing NF-κB P65 phosphorylation and nuclear translocation, IκBɑ degradation and phosphorylation, and IκKɑ/β phosphorylation. The phosphorylation of c-Jun N-terminal kinase (JNK) and P38, and expression of COX-2 was also attenuated by NCS. These results suggested that NCS might exert anti-inflammatory effects through inhibiting NF-κB and mitogen-activated protein kinase (MAPK) pathways even at very low doses.

摘要

石蒜(L'Her.)Herb.(L. radiata)在中国传统上被用作民间药物治疗阿尔茨海默病。然而,其显著毒性的确切成分仍不清楚,因此限制了其临床试验。石蒜碱(NCS)从石蒜中分离出来,NCS 治疗 72 h 对 L02、Hep G2、HT-29 和 RAW264.7 细胞表现出显著的抗增殖作用。然而,需要强调的是,在安全工作浓度 0.001-0.016 μM 下,NCS 给药 24 h 可抑制脂多糖(LPS)诱导的巨噬细胞中诱导型一氧化氮合酶(iNOS)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-ɑ)、白细胞介素-1β(IL-1β)和环氧化酶-2(COX-2)的 mRNA 表达,从而抑制一氧化氮(NO)、IL-6、TNF-ɑ和 IL-1β的产生。NCS 补充还通过抑制核因子-κB(NF-κB)P65 磷酸化和核易位、IκBɑ降解和磷酸化以及 IκKɑ/β磷酸化来抑制 NF-κB 激活。NCS 还抑制 c-Jun N 末端激酶(JNK)和 P38 的磷酸化以及 COX-2 的表达。这些结果表明,NCS 即使在非常低的剂量下,也可能通过抑制 NF-κB 和丝裂原活化蛋白激酶(MAPK)途径发挥抗炎作用。

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