ReferenceID 2866
Metabolic mechanism and anti-inflammation effects of sinomenine and its major metabolites N-demethylsinomenine and sinomenine-N-oxide
Life Sci
AIMS: Sinomenine (SIN) is clinically used as an anti-rheumatic drug. However, the metabolic and pharmacological mechanisms of SIN combined with its metabolites are unclear. This study aims to explore the cyclic metabolic
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Record Fields
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- Reference Id
- 2866
- Evidence Id
- 19456
- Core Evidence Id
- 19456
- Source Reference Id
- 5719
- Herb2 Reference Id
- HBREF006516
- Subject Paper Key
- HBIN044111_32950572
- Pubmed Id
- 32950572
- Doi
- 10.1016/j.lfs.2020.118433
- Paper Title
- Metabolic mechanism and anti-inflammation effects of sinomenine and its major metabolites N-demethylsinomenine and sinomenine-N-oxide
- Paper Abstract
- AIMS: Sinomenine (SIN) is clinically used as an anti-rheumatic drug. However, the metabolic and pharmacological mechanisms of SIN combined with its metabolites are unclear. This study aims to explore the cyclic metabolic mechanism of SIN, the anti-inflammation effects of SIN and its major metabolites (N-demethylsinomenine (DS) and sinomenine-N-oxide (SNO)), and the oxidation property of SNO. MATERIALS AND METHODS: SIN was administrated to rats via gavage. Qishe pills (a SIN-containing drug) were orally administrated to humans. The bio-samples were collected to identify SIN's metabolites. Enzymatic and non-enzymatic incubations were used to reveal SIN's metabolic mechanism. Impacts of SIN, SNO and DS on the inflammation-related cytokine's levels and nuclear translocation of NF-kappaB were evaluated in LPS-induced Raw264.7 cells. ROS induced by SNO (10 muM) was also assessed. KEY FINDINGS: CYP3A4 and ROS predominantly mediated the formation of SNO, and CYP3A4 and CYP2C19 primarily mediated the formation of DS. Noteworthily, SNO underwent N-oxide reduction both enzymatically, by xanthine oxidase (XOD), and non-enzymatically, by ferrous ion and heme moiety. The levels of IL-6 and TNF-alpha and nuclear translocation of NF-kappaB were ameliorated after pretreatment of SIN in LPS-induced Raw264.7 cells, while limited attenuations were observed after pretreatment of DS (SNO) even at 200 muM. In contrast, SNO induced ROS production. SIGNIFICANCE: This study elucidated that SIN underwent both enzymatic and non-enzymatic cyclic metabolism and worked as the predominant anti-inflammation compound, while SNO induced ROS production, suggesting more studies of SIN combined with SNO and DS are necessary in case of DDI and potential toxicities.
- Journal
- Life Sci
- Publish Year
- 2020
- Experiment Subject
- rat; human; raw264.7 cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Metabolic mechanism and anti-inflammation effects of sinomenine and its major metabolites N-demethylsinomenine and sinomenine-N-oxide
- Bilingual Status
- semi_complete