Beta-Asarone
beta-asarone.png

Note that most of the facts available currently for beta-asarone are primarily obtained from in vitro tests using animal and human tissue, or in vivo tests performed only on animals. It's important to note that data collected from in vivo tests perform on animals and data from in vitro studies, even those using human tissues, can differ dramatically from real world results obtained from in vivo tests done with actual living human beings. Unfortunately, very few clinical test performed on actual human beings exist for beta-asarone.

Beta-asarone is an isomer of alpha-asarone in which the tail is bent inward towards the benzene ring. The aldehyde form of beta-asarone is Cis-2,4,5-Trimethoxycinnamaldehyde.


Natural Sources

Beta-asarone is a propenylbenzene found in Acorus calamus and related herbs. Calamus oil from Nepal is very high in beta-asarone, containing 78.1%-86.9% beta-asarone.[18]


Psychoactivity

A metabolite of beta-asarone is the reason Acurus calamus is known in some cultures as a psychedelic. However, not all Acorus calamus contains sufficient quantities of beta-asarone to be effective. Acorus calamus from Nepal typically contains a large amount of beta-asarone. Acorus calamus from India usually contains very little beta-asarone, and will cause extreme nausea before doses high enough to get some minor effects from beta-asarone are ingested.

It's important to note that beta-asarone itself is not active. One of it's metabolites can produce psychedelic effects in man. Not everyone's body metabolizes beta-asarone the same way, leading to different results for different individuals. Some people are not able to experience psychedelic effects from ingesting beta-asarone. This is because their bodies do not produce enough of the active metabolite to experience effects.

The active metabolite of beta-asarone is currently unidentified. There has been speculation of it being an amphetamine, but that has been disproven.

Many human tests show that beta-asarone in some people can be activated via several Oilahuasca formulas, and can even be activated naturally without combining it with other compounds. It's fairly easy to activate with doses as small as 1 drop having effects in some people, and it works in a high percentage of people, producing LSD-like effects. This activity is more typical of allylbenzenes rather than Propenylbenzens.

Beta-asarone's aldehyde metabolite, beta-3′-oxoasarone, is likely the metabolite that eventually leads to activity. Aldehydes, such as the very closely related cinnamaldehyde, are known to easily form adducts with many compounds. Cinnamaldehyde can, for example, form adducts with simple amino acids, and their potassium forms (such as potassium glycinate), at room temperature without any catalysts.[8] [10] It's unknown which adducts are possible with beta-3′-oxoasarone, but the chemical bears such a striking similarity to cinnamaldehyde, that it's likely a lot of adducts that are possible with cinnamaldehyde are also possible with beta-3′-oxoasarone.


Effects on Enzymes

Acetylcholinesterase

In one test acetylcholinesterase (AChE), in vitro, was potently inhibited by both beta-asarone and alpha-asarone, with beta-asarone being 13 times more effective.[12] In another test where beta-asarone was found to improve learning and memory in mice, beta-asarone was also found to inhibit acetylcholinesterase.[6]

Catechol-O-methyltransferase (COMT)

Co-administration of levodopa and beta-asarone increased conversion of levodopa to dopamine by inhibiting catechol-O-methyltransferase (COMT).[19]

Tyrosine hydroxylase

Beta-asarone was found to increase levels of tyrosine hydroxylase.[21][19]

Superoxide Dismutase

Beta-asarone was found to prevent superoxide dismutase increase normally seen in mice treated with scopolamine, indicating potential inhibition of superoxide dismutase.[20]


Effects on P-glycoprotein (P-gp)

In vitro tests showed that both beta-asarone, and to a lesser degree alpha-asarone, inhibited P-glycoprotein.[11]

In vitro studies showed that beta-asarone helped temozolomide absorption by inhibiting P-glycoprotein (P-gp).[13]


Use in Oilahuasca

Anecdotal reports indicate that beta-asarone is an extremely powerful admixture to use in Oilahuasca formulas, helping activate most allylbenzenes, especially elemicin which is very tough to activate. The exact reason for this is currently unknown, but probably related to one or more of it's effects on human enzymes. It's addition to nearly all Oilahuasca formulas will greatly increase the chances of successful activation. As little as 1 drop (about 10-20 mg) is extremely effective. An unknown metabolite of beta-asarone is itself psychedelic, but it's effects are very minor from 1 drop of beta-asarone, and won't color up the experience much.


Cancer Fighting Action

Despite some tests showing some potential of beta-asarone to be a carcinogen, beta-asarone has been found to be effective in fighting certain forms of cancer. Beta-asarone effectively inhibits the proliferation of human gastric cancer cells.[1] It also suppress the growth of colon cancer.[4][14]


Nootropic Effects

Beta-asarone improves learning and memory.[6] It also alleviates depression.[2]

Tests performed on rats showed that beta-asarone caused antidepressant-like behavioral effects associated with increased hippocampal neurogenesis.[9]


Neuroprotective Effects

Beta-asarone shows neuroprotective effects against dopamine-induced neurotoxicity.[3] Beta-asarone may also help fight cognitive impairment associated with conditions such as Alzheimer's disease.[5] Beta-asarone was found to inhibit neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway.[16] It shows potential promise as a treatment for Alzheimer's disease.[16]


Antifungal Activity

Beta-asarone was found to be fungicidal at 8 mg/ml against Candida albicans, killing 99.9% within 120 minutes of exposure. The tests also showed that the concentration of beta-asarone used was non-toxic and may be safe for use as a topical antifungal agent.[15]

In another study Beta-asarone was found to be fungicidal against Cladosporium cucumerinum, Colletotrichum orbiculare, Magnaporthe grisea, and Pythium ultimum.[17]


Possible Metabolites of Beta-Asarone

No clinical tests on human subjects examining the full metabolites of beta-asarone exist. In vitro tests using liver microsomes of humans have given some light as to what might occur in humans. In human liver microsomes, 71-75% of beta-asarone was metabolized into beta-asarone-1',2'-erythro-diol, beta-asarone-1',2'-threo-diol, and the ketone 2,4,5-trimethoxyphenylacetone via a theoretical transient epoxidation step.[7]

Epoxidation Route
beta-asarone Beta-asarone-1′,2′-epoxide1 Beta-asarone-1',2'-erythro-diol beta-asarone-1',2'-threo-diol 2,4,5-trimethoxyphenylacetone
beta-asarone.png beta-asarone-1′,2′-epoxide.png beta-asarone-1',2'-erythro-diol.png beta-asarone-1',2'-threo-diol.png 2,4,5-trimethoxyphenylacetone.png
Synonyms: 2-(2,4,5-Trimethoxyphenyl)-3-methyloxirane; 2-methyl-3-(2,4,5-trimethoxyphenyl)oxirane
PubChem CID: 101689827
Synonyms: (1R,2R)-1-(2,4,5-Trimethoxyphenyl)-1,2-propanediol; 1,2-Propanediol, 1-(2,4,5-trimethoxyphenyl)-, (1R,2R)-
ChemSpider ID: 9497404
Synonyms: (1R,2S)-1-(2,4,5-Trimethoxyphenyl)-1,2-propanediol; 1,2-Propanediol, 1-(2,4,5-trimethoxyphenyl)-, (1R,2S)-
ChemSpider ID: 9599894
Synonyms: Acoramone; 1-(2,4,5-trimethoxyphenyl)propan-2-one;
PubChem CID: 3083746

21-15% of the beta-asarone was metabolized via hydroxylation, forming 1′-hydroxyasarone, beta-3'-hydroxyasarone and small amounts of beta-3'-oxoasarone.[7]

Hydroxylation Routes
beta-asarone 1′-Hydroxyasarone Beta-3'-hydroxyasarone Beta-3′-oxoasarone
beta-asarone.png 1′-hydroxyasarone.png beta-3′-hydroxyasarone.png beta-3′-oxoasarone.png
Synonyms: 1-(2,4,5-Trimethoxyphenyl)-2-propen-1-ol
ChemSpider ID: 37615873
Synonyms: (2Z)-3-(2,4,5-Trimethoxyphenyl)-2-propen-1-ol
ChemSpider ID: 28525828
Synonyms: (2Z)-3-(2,4,5-Trimethoxyphenyl)acrylaldehyde
ChemSpider ID: 25028478

8-10% was metabolized via demethylation.[7]

Demethylation Routes
beta-asarone 6-demethyl-beta-asarone 4-demethyl-beta-asarone 3-demethyl-beta-asarone
beta-asarone.png 6-demethyl-beta-asarone.png 4-demethyl-beta-asarone.png 3-demethyl-beta-asarone.png

Chemical Properties

Synonyms: β-asarone; (Z)-asaronel cis-asarone
Melting Point: 57-61 ° C; 62-63 ° C @ 760 mmHg. This information needs further verification. This information is suspected of being incorrect because calamus oil high in beta-asarone does not crystallize on standing at room temperature. Many sources confuse alpha-asarone for beta-asarone. Alpha-asarone is a solid at room temperature. One source states that beta-asrone is a colorless to pale yellow clear liquid, indicating that the melting point is far below room temperature (21 C).
Boiling Point: 296 °C at 760 mmHg. A few sources state 264-267 ° C @ 760 mmHg; This information needs further verification.
PubChem Compound ID: 5281758
Molecular Weight: 208.25364 [g/mol]
Molecular Formula: C12H16O3
XLogP3: 3
H-Bond Donor: 0
H-Bond Acceptor: 3
IUPAC Name: 1,2,4-trimethoxy-5-[(Z)-prop-1-enyl]benzene
InChI: InChI=1S/C12H16O3/c1-5-6-9-7-11(14-3)12(15-4)8-10(9)13-2/h5-8H,
1-4H3/b6-5-
InChIKey: RKFAZBXYICVSKP-WAYWQWQTSA-N
Canonical SMILES: CC=CC1=CC(=C(C=C1OC)OC)OC
Isomeric SMILES: C/C=C\C1=CC(=C(C=C1OC)OC)OC
CAS #: 5273-86-9


Bibliography
1. β-Asarone inhibits gastric cancer cell proliferation.
Wu J, Zhang XX, Sun QM, Chen M, Liu SL, Zhang X, Zhou JY, Zou X. PubMed PMID: 26502896; DOI: 10.3892/or.2015.4316
2. β-asarone from Acorus gramineus alleviates depression by modulating MKP-1.
Sun YR, Wang XY, Li SS, Dong HY, Zhang XJ. PubMed PMID: 25966222; DOI: 10.4238/2015.May.4.7
3. Neuroprotective Effects of β-Asarone Against 6-Hydroxy Dopamine-Induced Parkinsonism via JNK/Bcl-2/Beclin-1 Pathway.
Zhang S, Gui XH, Huang LP, Deng MZ, Fang RM, Ke XH, He YP, Li L, Fang YQ. PubMed PMID: 25404088; DOI: 10.1007/s12035-014-8950-z
4. Beta-asarone induces LoVo colon cancer cell apoptosis by up-regulation of caspases through a mitochondrial pathway in vitro and in vivo.
Zou X, Liu SL, Zhou JY, Wu J, Ling BF, Wang RP. PubMed PMID: 23244151;
5. Beta-asarone improves cognitive function by suppressing neuronal apoptosis in the beta-amyloid hippocampus injection rats.
Geng Y, Li C, Liu J, Xing G, Zhou L, Dong M, Li X, Niu Y. PubMed PMID: 20460763;
6. β-asarone improves learning and memory and reduces Acetyl Cholinesterase and Beta-amyloid 42 levels in APP/PS1 transgenic mice by regulating Beclin-1-dependent autophagy.
Deng M, Huang L, Ning B, Wang N, Zhang Q, Zhu C, Fang Y. PubMed PMID: 27737765; DOI: 10.1016/j.brainres.2016.10.008
7. Hepatic metabolism of carcinogenic β-asarone.
Cartus AT, Stegmüller S, Simson N, Wahl A, Neef S, Kelm H, Schrenk D. PubMed PMID: 26273788; DOI: 10.1021/acs.chemrestox.5b00223
8. The antimicrobial activities of the cinnamaldehyde adducts with amino acids.
Wei QY, Xiong JJ, Jiang H, Zhang C, Wen Ye. PubMed PMID: 21856030 DOI: 10.1016/j.ijfoodmicro.2011.07.034 (Download Attached PDF Document)
9. β-asarone reverses chronic unpredictable mild stress-induced depression-like behavior and promotes hippocampal neurogenesis in rats.
Dong H, Gao Z, Rong H, Jin M, Zhang X. PMID: 24786848; DOI: 10.3390/molecules19055634
10. Arthur D. Little
SUPPORT FOR CHEMICAL NOMINATION AND SELECTION PROCESS OF THE NATIONAL TOXICOLOGY PROGRAM, EXECUTIVE SUMMARY OF DATA, CINNAMALDEHYDE; DECEMBER 14, 1989 (Download Attached PDF Document)
11. Reversing P-glycoprotein-mediated multidrug resistance in vitro by α-asarone and β-asarone, bioactive cis-trans isomers from Acorus tatarinowii.
Meng X, Liao S, Wang X, Wang S, Zhao X, Jia P, Pei W, Zheng X, Zheng X. PMID: 24322772; DOI: 10.1007/s10529-013-1419-8
12. In vitro acetylcholinesterase inhibitory activity of the essential oil from Acorus calamus and its main constituents.
Mukherjee PK, Kumar V, Mal M, Houghton PJ. PMID: 17286241 DOI: 10.1055/s-2007-967114
13. β-Asarone promotes Temozolomide's entry into glioma cells and decreases the expression of P-glycoprotein and MDR1.
Wang N, Zhang Q, Ning B, Luo L, Fang Y. PMID: 28380412; DOI: 10.1016/j.biopha.2017.03.083
14. β-Asarone induces senescence in colorectal cancer cells by inducing lamin B1 expression.
Liu L, Wang J, Shi L, Zhang W, Du X, Wang Z, Zhang Y. PMID: 23357361; DOI: 10.1016/j.phymed.2012.12.008
15. β-Asarone, an active principle of Acorus calamus rhizome, inhibits morphogenesis, biofilm formation and ergosterol biosynthesis in Candida albicans.
Rajput SB, Karuppayil SM. PMID: 23123225; DOI: 10.1016/j.phymed.2012.09.029
16. β-Asarone inhibits neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in an in vitro model and AβPP/PS1 mice.
Wei G, Chen YB, Chen DF, Lai XP, Liu DH, Deng RD, Zhou JH, Zhang SX, Li YW, Lii H, Liu LF, Wang Q, Nie H. PMID: 23064259; DOI: 10.3233/JAD-2012-120865
17. Antifungal activity of beta-asarone from rhizomes of Acorus gramineus.
Lee JY, Lee JY, Yun BS, Hwang BK. PMID: 14969530; DOI: 10.1021/jf035204o
18. Chemical compositions, phytotoxicity, and biological activities of Acorus calamus essential oils from Nepal.
Satyal P, Paudel P, Poudel A, Dosoky NS, Moriarity DM, Vogler B, Setzer WN. PMID: 24079199
19. Coadministration of β-asarone and levodopa increases dopamine in rat brain by accelerating transformation of levodopa: a different mechanism from Madopar.
Huang L, Deng M, Zhang S, Fang Y, Li L. PMID: 24910244; DOI: 10.1111/1440-1681.12270
20. Cognitive enhancing effects of alpha asarone in amnesic mice by influencing cholinergic and antioxidant defense mechanisms.
Kumar H, Kim BW, Song SY, Kim JS, Kim IS, Kwon YS, Koppula S, Choi DK. PMID: 22878197 DOI: 10.1271/bbb.120247
21. β-asarone increases MEF2D and TH levels and reduces α-synuclein level in 6-OHDA-induced rats via regulating the HSP70/MAPK/MEF2D/Beclin-1 pathway: Chaperone-mediated autophagy activation, macroautophagy inhibition and HSP70 up-expression.
Huang L, Deng M, He Y, Lu S, Liu S, Fang Y. PMID: 27444243; DOI: 10.1016/j.bbr.2016.07.028
Unless otherwise stated, the content of this page is licensed under Creative Commons Attribution-ShareAlike 3.0 License