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

Author:
Shen, Chun-Yan, Xu, Xi-Lin, Yang, Lin-Jiang, Jiang, Jian-Guo
Source:
Food and chemical toxicology 2019 v.125 pp. 605-613
ISSN:
0278-6915
Subject:
Alzheimer disease, Lycoris radiata, anti-inflammatory activity, clinical trials, gene expression, inducible nitric oxide synthase, inflammation, interleukin-1beta, interleukin-6, lipopolysaccharides, macrophages, messenger RNA, mitogen-activated protein kinase, nitric oxide, phosphorylation, prostaglandin synthase, toxicity, toxicology, traditional medicine, transcription factor NF-kappa B, tumor necrosis factor-alpha, China
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.
Agid:
6309567