Methysticin | CAS#495-85-2 | inhibits NF-χB activation | activates Nrf2

MedKoo Cat#: 540297 | Name: Methysticin

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Methysticin is found in Piper methysticum (kava plant). It inhibits activation of NF-χB in lung adenocarcinoma tissue, activates Nrf2 in neurons and astroglia, decreases peak amplitude of voltage-gated Na+ channels in hippocampal neurons, and suppresses growth of Fusarium, Trichoderma, and Colletotrichum.

Chemical Structure

Methysticin

CAS#495-85-2

Theoretical Analysis

MedKoo Cat#: 540297

Name: Methysticin

CAS#: 495-85-2

Chemical Formula: C15H14O5

Exact Mass: 274.0841

Molecular Weight: 274.27

Elemental Analysis: C, 65.69; H, 5.15; O, 29.17

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 385.00	2 weeks

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Related CAS #

No Data

Synonym

Kavatin; Methysticin; NSC 112158; NSC112158; NSC-112158

IUPAC/Chemical Name

(R,E)-6-(2-(benzo[d][1,3]dioxol-5-yl)vinyl)-4-methoxy-5,6-dihydro-2H-pyran-2-one

InChi Key

GTEXBOVBADJOQH-FWEMWIAWSA-N

InChi Code

InChI=1S/C15H14O5/c1-17-12-7-11(20-15(16)8-12)4-2-10-3-5-13-14(6-10)19-9-18-13/h2-6,8,11H,7,9H2,1H3/b4-2+/t11-/m0/s1

SMILES Code

O=C1C=C(OC)C[C@H](/C=C/C2=CC=C(OCO3)C3=C2)O1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

Methysticin inhibits activation of NF-χB in lung adenocarcinoma tissue, activates Nrf2 in neurons and astroglia, decreases peak amplitude of voltage-gated Na+ channels in hippocampal neurons, and suppresses growth of Fusarium, Trichoderma, and Colletotrichum.

In vitro activity:

Methysticin exhibited time-, concentration-, and NADPH-dependent inhibition on CYP2C9 using diclofenac as a probe substrate. Approximately 85% of CYP2C9 activity was inhibited by methysticin at 50 μM after a 30 min preincubation with human liver microsomes in the presence of NADPH. Reference: Chem Res Toxicol. 2022 Jun 20;35(6):1117-1124. https://pubmed.ncbi.nlm.nih.gov/35583123/

In vivo activity:

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. Most importantly, methysticin treatment significantly attenuated the long-term memory decline of APP/Psen1 mice. Reference: Redox Biol. 2017 Aug;12:843-853. https://pubmed.ncbi.nlm.nih.gov/28448946/

	Solvent	mg/mL	mM
Solubility
	DMSO	15.0	54.69
	DMSO:PBS (pH 7.2) (1:6)	0.1	0.51
	Ethanol	1.0	3.65

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 274.27 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zhang Q, Liu H, Wu D, Yu H, Wang K, Jiao W, Zhao X. Methysticin Acts as a Mechanism-Based Inactivator of Cytochrome P450 2C9. Chem Res Toxicol. 2022 Jun 20;35(6):1117-1124. doi: 10.1021/acs.chemrestox.2c00098. Epub 2022 May 18. PMID: 35583123. 2. Li Y, Mei H, Wu Q, Zhang S, Fang JL, Shi L, Guo L. Methysticin and 7,8-dihydromethysticin are two major kavalactones in kava extract to induce CYP1A1. Toxicol Sci. 2011 Dec;124(2):388-99. doi: 10.1093/toxsci/kfr235. Epub 2011 Sep 9. PMID: 21908763; PMCID: PMC5736320. 4. Fragoulis A, Siegl S, Fendt M, Jansen S, Soppa U, Brandenburg LO, Pufe T, Weis J, Wruck CJ. Oral administration of methysticin improves cognitive deficits in a mouse model of Alzheimer's disease. Redox Biol. 2017 Aug;12:843-853. doi: 10.1016/j.redox.2017.04.024. Epub 2017 Apr 19. PMID: 28448946; PMCID: PMC5406548.

In vitro protocol:

In vivo protocol:

1. Fragoulis A, Siegl S, Fendt M, Jansen S, Soppa U, Brandenburg LO, Pufe T, Weis J, Wruck CJ. Oral administration of methysticin improves cognitive deficits in a mouse model of Alzheimer's disease. Redox Biol. 2017 Aug;12:843-853. doi: 10.1016/j.redox.2017.04.024. Epub 2017 Apr 19. PMID: 28448946; PMCID: PMC5406548.

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PubMed PMID: 1396990. 5: Fu S, Tattam BN, Duke CC, Ramzan I. High-performance liquid chromatography assays for desmethoxyyangonin, methysticin, kavain and their microsomal metabolites. Biomed Chromatogr. 2009 Jan;23(1):81-91. doi: 10.1002/bmc.1087. PubMed PMID: 18661482. 6: Magura EI, Kopanitsa MV, Gleitz J, Peters T, Krishtal OA. Kava extract ingredients, (+)-methysticin and (+/-)-kavain inhibit voltage-operated Na(+)-channels in rat CA1 hippocampal neurons. Neuroscience. 1997 Nov;81(2):345-51. Erratum in: Neuroscience 1998 May;84(1):323. PubMed PMID: 9300426. 7: Shaik AA, Hermanson DL, Xing C. Identification of methysticin as a potent and non-toxic NF-kappaB inhibitor from kava, potentially responsible for kava's chemopreventive activity. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5732-6. doi: 10.1016/j.bmcl.2009.08.003. Epub 2009 Aug 6. PubMed PMID: 19716299; PubMed Central PMCID: PMC2756981. 8: Abourashed EA, Khan IA. Microbial transformation of kawain and methysticin. Chem Pharm Bull (Tokyo). 2000 Dec;48(12):1996-8. PubMed PMID: 11145158. 9: Upadhyay A, Tuenter E, Ahmad R, Amin A, Exarchou V, Apers S, Hermans N, Pieters L. Kavalactones, a novel class of protein glycation and lipid peroxidation inhibitors. Planta Med. 2014 Aug;80(12):1001-8. doi: 10.1055/s-0034-1382949. Epub 2014 Aug 6. PubMed PMID: 25098935. 10: Fragoulis A, Siegl S, Fendt M, Jansen S, Soppa U, Brandenburg LO, Pufe T, Weis J, Wruck CJ. Oral administration of methysticin improves cognitive deficits in a mouse model of Alzheimer's disease. Redox Biol. 2017 Aug;12:843-853. doi: 10.1016/j.redox.2017.04.024. Epub 2017 Apr 19. PubMed PMID: 28448946; PubMed Central PMCID: PMC5406548. 11: Csupor L. [Quantitative determination of kawa lactones in Piper methysticum (Forster). 2. Determination of kawain, methysticin and yangonin]. Pharmazie. 1970 Mar;25(3):197-8. German. PubMed PMID: 5453803. 12: Fu S, Rowe A, Ramzan I. Kavalactone metabolism in the isolated perfused rat liver. Phytother Res. 2012 Dec;26(12):1813-6. doi: 10.1002/ptr.4656. Epub 2012 Mar 9. PubMed PMID: 22407838. 13: Csupor L. [Quantitative determination of kawa-lactones in Piper methysticum (Forster). 1. Determination methods with pure substances kawain, methysticin and yangonin]. Arch Pharm Ber Dtsch Pharm Ges. 1970 Mar;303(3):193-200. German. PubMed PMID: 5267714. 14: Fu S, Rowe A, Ramzan I. Kavalactone metabolism in rat liver microsomes. Phytother Res. 2012 Jul;26(7):1057-61. doi: 10.1002/ptr.3695. Epub 2011 Dec 22. PubMed PMID: 22807255. 15: Wang J, Qu W, Bittenbender HC, Li QX. Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solvents. J Food Sci Technol. 2015 Feb;52(2):1164-9. doi: 10.1007/s13197-013-1047-2. Epub 2013 Jun 25. PubMed PMID: 25694734; PubMed Central PMCID: PMC4325077. 16: Boonen G, Häberlein H. Influence of genuine kavapyrone enantiomers on the GABA-A binding site. Planta Med. 1998 Aug;64(6):504-6. PubMed PMID: 9776662. 17: Cheng X, van Breemen RB. Mass spectrometry-based screening for inhibitors of beta-amyloid protein aggregation. Anal Chem. 2005 Nov 1;77(21):7012-5. PubMed PMID: 16255603; PubMed Central PMCID: PMC1780175. 18: Xuan TD, Fukuta M, Wei AC, Elzaawely AA, Khanh TD, Tawata S. Efficacy of extracting solvents to chemical components of kava (Piper methysticum) roots. J Nat Med. 2008 Apr;62(2):188-94. doi: 10.1007/s11418-007-0203-2. Epub 2007 Nov 28. PubMed PMID: 18404321. 19: Robinson V, Bergfeld WF, Belsito DV, Klaassen CD, Marks JG Jr, Shank RC, Slaga TJ, Snyder PW; Cosmetic Ingredient Review Expert Panel, Andersen FA. Final report on the safety assessment of Piper methysticum leaf/root/stem extract and Piper methysticum root extract. Int J Toxicol. 2009 Nov-Dec;28(6 Suppl):175S-88S. doi: 10.1177/1091581809350934. PubMed PMID: 19966149. 20: Anke J, Fu S, Ramzan I. Kavalactones fail to inhibit alcohol dehydrogenase in vitro. Phytomedicine. 2006 Feb;13(3):192-5. Epub 2005 Jun 28. PubMed PMID: 16428028.