Chemistry:Berberine

From HandWiki

Berberine is an organic compound classified as benzylisoquinoline alkaloid.[1][2] Chemically, it is a quaternary ammonia compound.[1][2]

Its name is derived from the genus of plants, Berberis. Berberine occurs in the roots, bark, stems, and leaves of Berberis vulgaris (barberry), Berberis aristata (tree turmeric), Mahonia aquifolium (Oregon grape) and Hydrastis canadensis (goldenseal).[1]

Due to their yellow pigmentation, raw Berberis materials were once commonly used to dye wool, leather, and wood.[1][3][4] Under ultraviolet light, berberine shows a strong yellow fluorescence.[1][4] As a natural dye, berberine has a color index of 75160.

Plants containing berberine have been used in traditional medicine, and berberine extracts are sold as dietary supplements. Other than in China as an over-the-counter drug, berberine is not approved as a prescription drug, regulated or proven safe in any country.[5]

Biological sources

Berberine is the yellow color of celandine poppies.

The following plants are biological sources of berberine:

Berberine is usually found in the roots, rhizomes, stems, and bark.[1]

Structure and biosynthesis

early stages in berberine biosynthesis
middle stages in berberine biosynthesis

Berberine has a tetracyclic skeleton as is common for alkaloids classified as a benzylisoquinoline alkaloid. The overall skeleton is derived from two equivalents of L-tyrosine. L-Tyrosine is the precursor to L-DOPA and 4-hydroxyphenylacetaldehyde.[7][8]

The incorporation of an extra carbon atom as a bridge is distinctive. Formation of the berberine bridge is rationalized as an oxidative process in which the N-methyl group, supplied by S-adenosyl methionine (SAM), is oxidized to an iminium ion, and a cyclization to the aromatic ring occurs by virtue of the phenolic group.[9]

Pyrolysis of berberine gives "berberrubine", which protonates to "protoberberine"

Reticuline is a precursor to some protoberberine alkaloids in plants.[10]

Heating at 190 °C, berberine demethylates giving berberrubine. Alkylation of the resulting zwitterion gives access to many berberine-like derivatives.[11]

Research

Although plants containing berberine are used in traditional medicine, berberine has low bioavailability, indicating limited biological activity in vivo, with no patents issued for its use as a drug.[1][5] Clinical research investigating the use of berberine in humans is limited.[5][12] Although numerous clinical trials have been conducted or are underway, as of 2025, berberine has frequently been withdrawn as a drug candidate, and is not approved as a prescription drug in any country.[5][13]

A 2023 review concluded that berberine may improve lipid concentrations.[13] High-quality, large clinical studies would be required to properly evaluate the effectiveness and safety of berberine in various health conditions.[12]

Supplements, regulation, and safety

Berberine powder

Although widely available, dietary supplements have not been approved in the United States for any specific medical use.[5] The quality of berberine supplements can vary across brands: a 2017 study found that out of 15 different products sold, only six contained at least 90% of the specified berberine quantity.[14]

From 2020 to 2022, the US Food and Drug Administration issued warning letters to eight manufacturers of berberine dietary supplements for false advertising and misbranded drug products.[15] In the United States, berberine is not generally recognized as safe (GRAS).[15]

Adverse effects

Longer-term human clinical trials have reported flatulence and diarrhea as common issues.[16]

Drug interactions

Berberine is known to inhibit the activity of CYP3A4, an enzyme important to drug metabolism and clearance of endogenous substances, including steroid hormones such as cortisol, progesterone, and testosterone.[1][5] Several studies have demonstrated that berberine can increase the concentrations of cyclosporine in renal transplant patients and midazolam in healthy adult volunteers, confirming its inhibitory effect on CYP3A4.[17][18][19]

Use in China

It is approved in China as an over-the-counter drug for diarrhea treatment, with the package insert claiming efficacy against E. coli and Shigella spp.[20]

The Chinese package insert contraindicates berberine for people with hemolytic anemia and with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency). The insert also specifically precautions its use in children with G6PD deficiency because it can produce hemolytic anemia and jaundice.[20]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "Berberine". The Human Metabolome Database. 7 March 2022. https://www.hmdb.ca/metabolites/HMDB0003409. 
  2. ↑ 2.0 2.1 "Berberine". PubChem, US National Library of Medicine. 16 August 2025. https://pubchem.ncbi.nlm.nih.gov/compound/2353. 
  3. ↑ "Present status of natural dyes" (in en-US). Indian Journal of Fibre & Textile Research 26: 191–201. 2001. http://nopr.niscair.res.in/handle/123456789/24928. Retrieved 2017-12-28. 
  4. ↑ 4.0 4.1 "Fluoreszenzfarbstoffe in der Natur" (in de). 2008. http://www.chemie.uni-jena.de/institute/oc/weiss/naturstoffe.htm. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 "Berberine". DrugBank. 19 August 2025. https://go.drugbank.com/drugs/DB04115. 
  6. ↑ Cicero, Arrigo F. G.; Baggioni, Alessandra (2016). "Berberine and Its Role in Chronic Disease". Anti-inflammatory Nutraceuticals and Chronic Diseases. Advances in Experimental Medicine and Biology. 928. Cham: Springer International Publishing. pp. 27–45. doi:10.1007/978-3-319-41334-1_2. ISBN 978-3-319-41332-7. 
  7. ↑ Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). West Sussex, England: Wiley. 2009. p. 358. ISBN 978-0-471-49641-0. https://archive.org/details/medicinalnatural00dewi_347. 
  8. ↑ Tjallinks, Gwen; Mattevi, Andrea; Fraaije, Marco W. (2024). "Biosynthetic Strategies of Berberine Bridge Enzyme-like Flavoprotein Oxidases toward Structural Diversification in Natural Product Biosynthesis". Biochemistry 63 (17): 2089–2110. doi:10.1021/acs.biochem.4c00320. PMID 39133819. 
  9. ↑ Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). West Sussex, England: Wiley. 2009. p. 357. ISBN 978-0-471-49641-0. https://archive.org/details/medicinalnatural00dewi_015. 
  10. ↑ "Agrobacterium rhizogenes-mediated transformation of opium poppy, Papaver somniferum l., and California poppy, Eschscholzia californica cham., root cultures". Journal of Experimental Botany 51 (347): 1005–16. June 2000. doi:10.1093/jexbot/51.347.1005. PMID 10948228. 
  11. ↑ "Berberine: New perspectives for old remedies". Biochemical Pharmacology 84 (10): 1260–1267. 2012. doi:10.1016/j.bcp.2012.07.018. PMID 22842630. http://dspace.utpl.edu.ec/handle/123456789/19237. 
  12. ↑ 12.0 12.1 "Biological properties and clinical applications of berberine". Frontiers of Medicine 14 (5): 564–582. October 2020. doi:10.1007/s11684-019-0724-6. PMID 32335802. 
  13. ↑ 13.0 13.1 "Impact of Berberine or Berberine Combination Products on Lipoprotein, Triglyceride and Biological Safety Marker Concentrations in Patients with Hyperlipidemia: A Systematic Review and Meta-Analysis.". Journal of Dietary Supplements 21 (2): 242–259. 2023. doi:10.1080/19390211.2023.2212762. PMID 37183391. 
  14. ↑ "Variability in Potency Among Commercial Preparations of Berberine". Journal of Dietary Supplements 15 (3): 343–351. May 2018. doi:10.1080/19390211.2017.1347227. PMID 28792254. 
  15. ↑ 15.0 15.1 "Warning letters regarding berberine supplements (search "berberine")". Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. 19 August 2025. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters. 
  16. ↑ Yue, Shi-Jun; Liu, Juan; Wang, Wen-Xiao; Wang, Ai-Ting; Yang, Xin-Yu; Guan, Hua-Shi; Wang, Chang-Yun; Yan, Dan (August 2019). "Berberine treatment-emergent mild diarrhea associated with gut microbiota dysbiosis". Biomedicine & Pharmacotherapy 116. doi:10.1016/j.biopha.2019.109002. PMID 31154270. 
  17. ↑ "Tacrolimus and herbs interactions: a review". Pharmazie 76 (10): 468–472. October 2021. doi:10.1691/ph.2021.1684. PMID 34620272. 
  18. ↑ "Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions". Planta Med 78 (13): 1458–77. September 2012. doi:10.1055/s-0032-1315117. PMID 22855269. Bibcode: 2012PlMed..78.1458H. 
  19. ↑ "Regioselective hydroxylation of steroid hormones by human cytochromes P450". Drug Metab Rev 47 (2): 89–110. May 2015. doi:10.3109/03602532.2015.1011658. PMID 25678418. 
  20. ↑ 20.0 20.1 精华制药集团股份有限公司. "盐酸小檗碱片说明书" (in zh). https://ypk.39.net/843793/manual. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Berberine&oldid=4310370"