White crystalline powder
Piper methysticum Forst
2H-Pyran-2-one, 6-[(E)-2-(1,3-benzodioxol-5-yl)ethenyl]-5,6-dihydro-4-methoxy-, (6S)-/(E)-6-[2-(benzo[d][1,3]dioxol-5-yl)vinyl]-4-methoxy-5,6-dihydropyran-2-one/2H-Pyran-2-one, 6-[(E)-2-(1,3-benzodioxol-5-yl)ethenyl]-5,6-dihydro-4-methoxy-, (6R)-/(+-)-Methysticin/(R-(E))-6-(2-(1,3-Benzodioxol-5-yl)ethenyl)-5,6-dihydro-4-methoxy-2H-pyran-2-one/[R-(E)]-6-[2-(1,3-Benzodioxol-5-yl)ethenyl]-5,6-dihydro-4-methoxy-2H-pyran-2-one/6-(3',4'-Methylenedioxystyryl)-4-methoxy-5,6-dihydro-2H-pyran-2-one/Kavahin/(6S)-6-[(E)-2-(1,3-Benzodioxol-5-yl)vinyl]-4-methoxy-5,6-dihydro-2H-pyran-2-one/Methysticin/4-Methoxy-6-[b-(3',4'-methylenedioxyphenyl)vinyl]-5,6-dihydro-a-pyrone/(6R)-6-[(E)-2-(1,3-benzodioxol-5-yl)ethenyl]-4-methoxy-5,6-dihydro-2H-pyran-2-one/5-Hydroxy-3-methoxy-7-[3,4-(methylenedioxy)phenyl]-2,6-heptadienoic Acid d-Lactone/6-(2-benzo[1,3]dioxol-5-yl-vinyl)-4-methoxy-5,6-dihydro-pyran-2-one/(E)-6-[2-(benzo[d][1,3]dioxol-5-yl)vinyl]-4-methoxy-5,6-dihydro-2H-pyran-2-one/(R)-5,6-Dihydro-4-methoxy-6-(3,4-(methylenedioxy)styryl)-2H-pyran-2-one/(6R)-6-[(E)-2-(1,3-Benzodioxol-5-yl)vinyl]-4-methoxy-5,6-dihydro-2H-pyran-2-one/Kavatin
Ethyl Acetate; Chloroform
496.5±45.0 °C at 760 mmHg
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For Reference Standard and R&D, Not for Human Use Directly.
provides coniferyl ferulate(CAS#:495-85-2) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate
There is increasing evidence for the involvement of chronic inflammation and oxidative stress in the pathogenesis of Alzheimer’s disease (AD). Nuclear factor erythroid 2-related factor 2 (Nrf2) is an anti-inflammatory transcription factor that regulates the oxidative stress defense. Our previous experiments demonstrated that kavalactones protect neuronal cells against Amyloid β (Aβ)-induced oxidative stress in vitro by Nrf2 pathway activation. Here, we tested an in vivo kavalactone treatment in a mouse model of AD.
The kavalactone methysticin was administered once a week for a period of 6 months to 6 month old transgenic APP/Psen1 mice by oral gavage. Nrf2 pathway activation was measured by methysticin treatment of ARE-luciferase mice, by qPCR of Nrf2-target genes and immunohistochemical detection of Nrf2. Aβ burden was analyzed by CongoRed staining, immunofluorescent detection and ELISA. Neuroinflammation was assessed by immunohistochemical stainings for microglia and astrocytes. Pro-inflammatory cytokines in the hippocampus was determined by Luminex multi-plex assays. The hippocampal oxidative damage was detected by oxyblot technique and immunohistochemical staining against DT3 and 4-HNE. The cognitive ability of mice was evaluated using Morris water maze.
Methysticin treatment activated the Nrf2 pathway in the hippocampus and cortex of mice. The Aβ deposition in brains of methysticin-treated APP/Psen1 mice was not altered compared to untreated mice. However, methysticin treatment significantly reduced microgliosis, astrogliosis and secretion of the pro-inflammatory cytokines TNF-α and IL-17A. In addition, the oxidative damage of hippocampi from APP/Psen1 mice was reduced by methysticin treatment. Most importantly, methysticin treatment significantly attenuated the long-term memory decline of APP/Psen1 mice.
In summary, these findings show that methysticin administration activates the Nrf2 pathway and reduces neuroinflammation, hippocampal oxidative damage and memory loss in a mouse model of AD. Therefore, kavalactones might be suitable candidates to serve as lead compounds for the development of a new class of neuroprotective drugs.
Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Alzheimer's disease; Astrogliosis; Kava kava; Kavalactone; Methysticin; Neuroinflammation; Nrf2; Oxidative stress
Oral administration of methysticin improves cognitive deficits in a mouse model of Alzheimer's disease.
Fragoulis A1, Siegl S2, Fendt M3, Jansen S4, Soppa U5, Brandenburg LO6, Pufe T7, Weis J8, Wruck CJ9.
Kava is a plant traditionally used for making beverages in Pacific Basin countries and has been used for the treatment of nervous disorders in the United States. The pharmacological activity of kava is achieved through kavalactones in kava extract, which include kawain, 7,8-dihydrokawain, yangonin, 5,6-dehydrokawain, methysticin, and 7,8-dihydromethysticin. Recent studies have shown that kava extract induces hepatic CYP1A1 enzyme; however, the mechanisms of CYP1A1 induction have not been elucidated, and the kavalactones responsible for CYP1A1 induction have not yet been identified. Using a combination of biochemical assays and molecular docking tools, we determined the functions of kava extract and kavalactones and delineated the underlying mechanisms involved in CYP1A1 induction. The results showed that kava extract displayed a concentration-dependent effect on CYP1A1 induction. Among the six major kavalactones, methysticin triggered the most profound inducing effect on CYP1A1 followed by 7,8-dihydromethysticin. The other four kavalactones (yangonin, 5,6-dehydrokawain, kawain, and 7,8-dihydrokawain) did not show significant effects 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 revealed favorable binding to AhR for methysticin and 7,8-dihydromethysticin compared with the remaining kavalactones. Additionally, results from a luciferase gene reporter assay suggested that kava extract, methysticin, and 7,8-dihydromethysticin were able to activate the AhR signaling pathway. Moreover, kava extract-, methysticin-, and 7,8-dihydromethysticin-mediated CYP1A1 induction was blocked by an AhR antagonist and abolished in AhR-deficient cells. These findings suggest that kava extract induces the expression of CYP1A1 via an AhR-dependent mechanism and that methysticin and 7,8-dihydromethysticin contribute to CYP1A1 induction. The induction of CYP1A1 indicates a potential interaction between kava or kavalactones and CYP1A1-mediated chemical carcinogenesis.
Methysticin and 7,8-dihydromethysticin are two major kavalactones in kava extract to induce CYP1A1.
Li Y1, Mei H, Wu Q, Zhang S, Fang JL, Shi L, Guo L.
While cases of severe kava hepatotoxicity have been reported, studies examining the toxicity of individual kavalactones are limited. The present study examined the in vitro hepatotoxicity of kavain, methysticin and yangonin on human hepatocytes (HepG2) and the possible mechanism(s) involved. Cytotoxicity was assessed using lactate dehydrogenase (LDH) and ethidium bromide (EB) assays. The mode of cell death was analysed with acridine orange/ethidium bromide dual staining with fluorescence microscopy. Glutathione oxidation was measured using the ortho-phthalaldehyde (OPT) fluorescence assay. Kavain had minimal cytotoxicity, methysticin showed moderate concentration-dependent toxicity and yangonin displayed marked toxicity with ~ 40% reduction in viability in the EB assay. Acridine orange/ethidium bromide staining showed the predominant mode of cell death was apoptosis rather than necrosis. No significant changes were observed in glutathione levels, excluding this as the primary mechanism of cell death in this model. Further studies may elucidate the precise apoptotic pathways responsible and whether toxic kavalactone metabolites are involved.
Copyright © 2010 John Wiley & Sons, Ltd.
Kavalactones Yangonin and Methysticin induce apoptosis in human hepatocytes (HepG2) in vitro.
Tang J1, Dunlop RA, Rowe A, Rodgers KJ, Ramzan I.