Berberine

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Berberine
Berberin.svg
Berberine 3D.png
Names
IUPAC name
9,10-Dimethoxy-7,8,13,13a-tetradehydro-2′H-[1,3]dioxolo[4′,5′:2,3]berbin-7-ium
Systematic IUPAC name
9,10-Dimethoxy-5,6-dihydro-2H-7λ5-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ylium [1]
Other names
Umbellatine; [2]
5,6-Dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium; [2]
7,8,13,13a-Tetradehydro-9,10-dimethoxy-2,3-(methylenedioxy)berbinium [2]
Identifiers
3D model (JSmol)
3570374
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.016.572 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 218-229-1
KEGG
PubChem CID
UNII
  • 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 Yes check.svgY
    Key: YBHILYKTIRIUTE-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/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
    Key: YBHILYKTIRIUTE-UHFFFAOYAJ
  • O1c2c(OC1)cc5c(c2)c4cc3ccc(OC)c(OC)c3c[n+]4CC5
Properties
C20H18NO4+
Molar mass 336.366 g·mol−1
AppearanceYellow solid
Melting point 145 °C (293 °F; 418 K) [3]
Slowly soluble [3]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids, occurring naturally as a secondary metabolite in some plants including species of Berberis , from which its name is derived.

Due to their yellow pigmentation, raw Berberis materials were once commonly used to dye wool, leather, and wood. [4] Under ultraviolet light, berberine shows a strong yellow fluorescence, [5] making it useful in histology for staining heparin in mast cells. [6] As a natural dye, berberine has a color index of 75160.

Biological sources

The following plants are biological sources of berberine:

Berberine is usually found in the roots, rhizomes, stems, and bark. [8]

Biosynthesis

Biosynthesis of berberine Biosynthesis of berberine.svg
Biosynthesis of berberine

The alkaloid berberine has a tetracyclic skeleton derived from a benzyltetrahydroisoquinoline system with the incorporation of an extra carbon atom as a bridge. 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]

Reticuline is the immediate precursor of protoberberine alkaloids in plants. [10] Berberine is an alkaloid derived from tyrosine. L-DOPA and 4-hydroxypyruvic acid both come from L-tyrosine. Although two tyrosine molecules are used in the biosynthetic pathway, only the phenethylamine fragment of the tetrahydroisoquinoline ring system is formed via DOPA[ definition needed ]; the remaining carbon atoms come from tyrosine via 4-hydroxyphenylacetaldehyde. [11]

Research

Studies on the pharmacological effects of berberine, including its potential use as a medicine, are preliminary basic research: some studies are conducted on cell cultures or animal models, whereas clinical trials investigating the use of berberine in humans are limited. [12] A 2023 review study stated that berberine may improve lipid concentrations. [13] High-quality, large clinical studies are needed to properly evaluate the effectiveness and safety of berberine in various health conditions, because existing studies are insufficient to draw reliable conclusions. [12]

Berberine supplements are widely available in the U.S. but have not been approved by the U.S. Food and Drug Administration (FDA) for any specific medical use. Researchers publicly warn that studies linking berberine to supposed health benefits are limited. Furthermore, the quality of berberine supplements can vary between different brands. A study conducted in 2017 found that out of 15 different products sold in the U.S., only six contained at least 90% of specified berberine amount. [14] [15]

Adverse effects

Longer-term human clinical trials have reported flatulence and diarrhea as common issues. The problem can be replicated in rats, with disruption of the gut microbiome to blame. [16]

Drug interactions

Berberine is known to inhibit the activity of CYP3A4, an important enzyme involved in drug metabolism and clearance of endogenous substances, including steroid hormones such as cortisol, progesterone and testosterone. 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 (OTC) drug for diarrhea treatment. The package insert claims 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. ↑ IUPAC Chemical Nomenclature and Structure Representation Division (2013). "P-73.3.1". In Favre HA, Powell WH (eds.). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. IUPAC–RSC. ISBN   978-0-85404-182-4.
  2. 1 2 3 The Merck Index, 14th ed., 1154. Berberine
  3. 1 2 The Merck Index , 10th Ed. (1983), p.165, Rahway: Merck & Co.
  4. ↑ Gulrajani ML (2001). "Present status of natural dyes". Indian Journal of Fibre & Textile Research. 26: 191–201. Archived from the original on 2021-11-20. Retrieved 2017-12-28– via NISCAIR Online Periodicals Repository.
  5. ↑ Weiß D (2008). "Fluoreszenzfarbstoffe in der Natur" (in German). Archived from the original on 9 March 2007. Retrieved 17 July 2009.
  6. ↑ "B3251 Berberine chloride form". Sigma-Aldrich. 2013. Archived from the original on 7 September 2012. Retrieved 2 Aug 2013.
  7. ↑ Cicero AF, Baggioni A (2016). "Berberine and Its Role in Chronic Disease". Anti-inflammatory Nutraceuticals and Chronic Diseases. Advances in Experimental Medicine and Biology. Vol. 928. Cham: Springer International Publishing. pp. 27–45. doi:10.1007/978-3-319-41334-1_2. ISBN   978-3-319-41332-7. ISSN   0065-2598. PMID   27671811.
  8. ↑ "Berberine". PubChem, National Library of Medicine, US National Institutes of Health. March 9, 2020. Archived from the original on March 5, 2016. Retrieved March 10, 2020.
  9. ↑ Dewick P (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). West Sussex, England: Wiley. p.  357. ISBN   978-0-471-49641-0.
  10. ↑ Park SU, Facchini PJ (June 2000). "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. doi:10.1093/jexbot/51.347.1005. PMID   10948228.
  11. ↑ Dewick P (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). West Sussex, England: Wiley. p.  358. ISBN   978-0-471-49641-0.
  12. 1 2 Song D, Hao J, Fan D (October 2020). "Biological properties and clinical applications of berberine". Front Med. 14 (5): 564–582. doi:10.1007/s11684-019-0724-6. PMID   32335802. S2CID   216111561.
  13. ↑ Hernandez AV, Hwang J, Nasreen I, et al. (2023). "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". J Diet Suppl. 21 (2): 242–259. doi:10.1080/19390211.2023.2212762. PMID   37183391. S2CID   258687419. Archived from the original on 2023-06-01. Retrieved 2023-08-28.
  14. ↑ Funk RS, Singh RK, Winefield RD, Kandel SE, Ruisinger JF, Moriarty PM, Backes JM (May 2018). "Variability in Potency Among Commercial Preparations of Berberine". J Diet Suppl. 15 (3): 343–351. doi:10.1080/19390211.2017.1347227. PMC   5807210 . PMID   28792254.
  15. ↑ Subbaraman N (14 June 2023). "The Cheaper Weight-Loss Alternative Riding the Ozempic Wave". Wall Street Journal. Archived from the original on 29 December 2023. Retrieved 29 December 2023.
  16. ↑ Yue SJ, Liu J, Wang WX, Wang AT, Yang XY, Guan HS, Wang CY, Yan D (August 2019). "Berberine treatment-emergent mild diarrhea associated with gut microbiota dysbiosis". Biomedicine & Pharmacotherapy. 116: 109002. doi:10.1016/j.biopha.2019.109002. PMID   31154270.
  17. ↑ Abushammala I (October 2021). "Tacrolimus and herbs interactions: a review". Pharmazie. 76 (10): 468–472. doi:10.1691/ph.2021.1684. PMID   34620272.
  18. ↑ Hermann R, von Richter O (September 2012). "Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions". Planta Med. 78 (13): 1458–77. doi:10.1055/s-0032-1315117. PMID   22855269.
  19. ↑ Niwa T, Murayama N, Imagawa Y, Yamazaki H (May 2015). "Regioselective hydroxylation of steroid hormones by human cytochromes P450". Drug Metab Rev. 47 (2): 89–110. doi:10.3109/03602532.2015.1011658. PMID   25678418.
  20. 1 2 精华制药集团股份有限公司. "盐酸小檗碱片说明书" [Package Insert: Berberine Hydrochloride Tablets]. ypk.39.net (in Chinese).
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