Berberine
Berberine.png

Berberine is an alkaloid found in goldenseal (hydrastis canadensis) at concentrations typically between 2.5-6% dry weight.


Effects On Cytochrome P450 Enzymes

Berberine has been shown to be a very potent CYP2D6 inhibitor. It also strongly inhibits CYP2C9 and weakly inhibits CYP3A4. Goldenseal is known to have no effect on CYP2E1 in humans. Berberine is also likely to have no effect on CYP2E1, but tests in humans using pure berberine appear to be currently lacking.

Effects On Cytochrome P450 Enzymes
Enzyme Effect Dosage Verified In Humans
CYP1A2 no effect [1] 300 mg for 2 weeks[1] Yes[1]
CYP2A6 ? ? ?
CYP2C19 no effect [1] 300 mg for 2 weeks[1] Yes[1]
CYP2C9 inhibition (200% increase in substrates)[1] 300 mg for 2 weeks[1] Yes[1]
CYP2D6 inhibition (900% increase in substrates)[1] 300 mg for 2 weeks[1] Yes[1]
CYP2E1 ? ? ?
CYP3A4 inhibition (40% increase in substrates)[1] 300 mg for 2 weeks[1] Yes[1]

Promising Use In Oilahuasca

THE ANECDOTAL REPORTS IN THIS SECTION REQUIRE FURTHER VALIDATION BEFORE BEING CONSIDERED FACTUAL

Berberine has been tested by several individuals as an oilahuasca admixture. Doses tested were 300 mg and above taken as berberine hydrochloride. In one report as little as 20 mg of elemicin taken together with 300 mg berberine hydrochloride and 100 mg steviosides, produced effects described as nearly equal to a 50 mg dose of mescaline hydrochloride. Larger doses of elemicin were also tested, with similar results, giving activated elemicin a potency roughly 250% the potency of mescaline.

Berberine is believed to help activate elemicin because it inhibits CYP2D6, CYP3A4 and CYP2C9, while leaving CYP2E1 fully active. CYP2D6, CYP3A4 and CYP2C9 can all theoretically O-demethylate elemicin into methoxyeugenol. By inhibiting these enzymes, elemicin is more likely to be attacked by CYP2E1. CYP2E1 is not known to O-demethylate allylbenzenes, but is known to 1'-hydroxylate them. By shifting attack of elemicin to CYP2E1, it is likely to prevent the formation of methoxyeugenol and favor the formation of 1'-hydroxyelemicin. The metabolite 1'-hydroxyelemicin can then theoretically form 1'-oxoelemicin (by the action of the enzyme Estradiol 17beta-dehydrogenase Type 2), which can then form alkaloids in vivo (see oilahuasca for more details).

Note that in the tests reported UGT2B7 was also inhibited by using 100 mg or more of pure steviosides (isolated sweeteners extracted from the stevia plant). This is done to prevent attack of 1'-hydroxyelemicin by UGT2B7. If 1'-hydroxyelemicin is attacked by UGT2B7 it forms 1'-hydroxyelemicin glucuronide which is not capable of forming alkaloids in vivo. By inhibiting UGT2B7, the metabolite 1'-oxoelemicin is favored over 1'-hydroxyelemicin glucuronide.


Bibliography
1. Repeated administration of berberine inhibits cytochromes P450 in humans
Ying Guo, Yao Chen, Zhi-rong Tan, Curtis D. Klaassen, Hong-hao Zhou; Published online 2011 Aug 26.; Eur J Clin Pharmacol. 2012 Feb; 68(2): 213–217.; doi: 10.1007/s00228-011-1108-2; NIHMSID: NIHMS583946; PMCID: PMC4898966

Chemical Properties

Synonyms: Berberin; Umbellatine; Berberal; Thalsine
CAS #: 2086-83-1
Molecular Formula: C20H18NO4+
Canonical SMILES: COC1=C(C2=C[N+]3=C(C=C2C=C1)C4=CC5=C(C=C4CC3)OCO5)OC
InChI Key: YBHILYKTIRIUTE-UHFFFAOYSA-N
InChI: InChI=1S/C20H18NO4/c1-22-17-4-3-12-7-16-14-9-19-18(24-11-25-19)8-13(14)5-6-21(16)10-15(12)20(17)23-2/h3-4,7-10H,5-6,11H2,1-2H3/q+1
Molecular Weight: 336.36122 g/mol
XLogP3: 3.6
Melting Point: 145 °C
PubChem CID: 2353

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