麻醉椒苦素

中文名称:

麻醉椒苦素

中文同义词:

麻醉椒苫素;5,6-二氢-4-甲氧基-6-(3,4-(亚甲基二氧基)苯乙烯基)-2H-吡喃-2-酮;麻醉椒苦素

英文名称:

METHYSTICIN

英文同义词:

5,6-Dihydro-4-methoxy-6-(3,4-(methylenedioxy)styryl)-2H-pyran-2-one;METHYSTICIN;KAVAHIN;KAVATIN;(±)-Methystici);Methysticin (DL-Methysticin;2H-Pyran-2-one, 6-[(1E)-2-(1,3-benzodioxol-5-yl)ethenyl]-5,6-dihydro-4-methoxy-;METHYSTICIN USP/EP/BP

CAS号:

20697-20-5

分子式:

C15H14O5

分子量:

274.27

EINECS号:

相关类别:

中药对照品;标准品;植物提取物;标准品 -中药标准品

Mol文件:

20697-20-5.mol

熔点 

129-131 °C

沸点 

496.5±45.0 °C(Predicted)

密度 

1.31±0.1 g/cm3(Predicted)

概述

麻醉椒苫素即麻醉椒苦素，其为卡法根植物，为一种还被称为醉椒的胡椒植物，通常可在波利尼西亚、美拉尼西亚和密克罗尼西亚找到。

用途

麻醉椒苦素具有诱导细胞色素亚酶 CYP1A1 活性的作用，能够影响以 CYP1A1 作为代谢酶的药物利用；还是 1个低毒性的 NF-κB 抑制剂，对肿瘤、 艾滋病、哮喘、糖尿病、关节炎等多种与NF-κB 调控异常相关的疾病的防治具有潜在疗效。

生物活性

Methysticin 是存在于卡瓦提取物中的一种主要的卡瓦内酯，可用于诱导 CYP1A1。

靶点

CYP1A1

CYP1A1

体外研究

Methysticin triggers the most profound inducing effect on CYP1A1. Consistent with the experimental results, in silico molecular docking studies based on the aryl hydrocarbon receptor (AhR)-ligand binding domain homology model also reveals favorable binding to AhR for Methysticin compared with the remaining kavalactones. Additionally, results from a luciferase gene reporter assay suggested that kava extract, Methysticin is able to activate the AhR signaling pathway. Kava extract induces the expression of CYP1A1 via an AhR-dependent mechanism and that Methysticin contributes to CYP1A1 induction. The induction of CYP1A1 indicates a potential interaction between kava or kavalactones and CYP1A1-mediated chemical carcinogenesis. The MTS cell viability assay is used to determine the effects of kava extract and kavalactones on cell viability in mouse hepatic cells. Hepa1c1c7 cells are treated with various concentrations of kava extract (0-50 µg/mL) and six kavalactones (0-100 µM) for 24 h. The results indicate that kava extract at concentrations up to 50 µg/mL and kavalactones up to 100 µM do not induce cell death. For the following studies, kava extract at 0.78-6.25 µg/mL and kavalactones at 0.78-25 µM, concentrations that cause no damage to cells, are used.

体内研究

The kavalactone Methysticin (6 mg/kg) is administered once a week for a period of 6 months to 6 month old transgenic APP/Psen1 mice by oral gavage. Methysticin treatment activates the Nrf2 pathway in the hippocampus and cortex of mice. The Aβ deposition in brains of Methysticin-treated APP/Psen1 mice is not altered compared to untreated mice. However, Methysticin treatment significantly reduces microgliosis, astrogliosis and secretion of the pro-inflammatory cytokines TNF-α and IL-17A. Methysticin treatment results in a significant activation of the Nrf2/ARE pathway in hippocampus and the cortex but not in the midbrain and cerebellum of ARE-luciferase reporter gene mice. Methysticin treatment significantly increases the expression of both genes compared to untreated animals.