Berberine

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of berberine
Counterion (mostly chloride) not shown
General
Surname Berberine
other names
  • 5,6-dihydro-9,10-dimethoxybenzo [ g ] -1,3-benzodioxolo [5,6- a ] quinolizinium chloride
  • 16,17-dimethoxy-5,7-dioxa-13-azoniapentacyclo [11.8.0.0 2.10 .0 4.8 .0 15.20 ] henicosa-1 (13), 2.4 (8), 9.14 , 16,18,20-octaene
  • Natural Yellow 18
  • Umbellatin
Molecular formula C 20 H 18 ClNO 4 (as chloride)
Brief description

dark yellow solid (hemisulfate)

External identifiers / databases
CAS number
  • 2086-83-1 (berberine)
  • 633-65-8 (chloride)
  • 633-66-9 (hemisulfate)
  • 316-41-6 (sulfate)
EC number 218-229-1
ECHA InfoCard 100.016.572
PubChem 2353
DrugBank DB04115
Wikidata Q176525
properties
Molar mass 371.81 g mol −1
Physical state

firmly

Melting point

147-148 ° C

safety instructions
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 302-312-332
P: 280
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Berberine is an alkaloid from the group of isoquinoline alkaloids . It occurs among other things in the plants barberry ( Berberis vulgaris ), which gave the alkaloid its name, the orange root ( Hydrastis canadensis ) and Coptis chinensis , mainly in the roots , in the rhizome , in the trunk and in the bark.

Berberine has a strong yellow color, which is why barberry was used to dye wool and leather in the past . Even today, wool is dyed yellow with berberine in North India . Berberine fluoresces brightly yellow under UV light . It is therefore also for staining of heparin in mast cells used. As a natural dye , berberine has the Color Index CI 75160.

Occurrence

Husemann writes about the berberine:

Milky juice from celandine contains berberine
Also Jeffersonia diphylla contains berberine

“Berberine is one of the few alkaloids that are not only distributed across different genera of the same plant family, but also occur in plants of the most diverse families. It is found in the Jamaican worm bark, the bark of Geoffroya jamaicensis Mur. or Andria inermis Kuth. (Fam. Casealpineae) according to Gastell, in the bark of Xanthoxylum clava Herculis L. (Fam. Xanthoxyleae) according to Perrins, in Podophyllum peltatum . Leontice thalictroides and Jeffersonia diphylla (Fam. Papaveraceae ) according to F. F. Mayer (Amer. Journ. Pharm. XXXV. 97), in the West African Abeocouta bark of Coelocline polycarpa De C. (Fam. Anonaceae) according to Stenhouse, in the roots of Hydrastis canadensis L. , Xanthorhiza Apiifolia Herit. and Coptis Teeta (Fam. Ranunculaceae ) according Mahla and Perrins in Colombo root, the root of Cocculus palmatus De C. and in the Ceylon Colombo wood, the wood from Coscinium fenestratum Colebr. (Fam. Menispermeae) according to Bödeker and Perrins, in roots, bark, flowers, unripe berries and leaves of Berberis vulgaris L., as well as in the Indian and Mexican Berberis species (Fam. Berberidaceae ) according to Buchner, Polex, Ferrein, Solley , Wittstein and others, after Perrins finally also in the St. John's root from the Rio grande, in the bark of the Pachnelo tree from Bogota and in a yellow wood from Upper Assam called Woodunpar by the locals . "

discovery

Berberine was isolated from the root bark of the common barberry ( Berberis vulgaris L.) by Johann Andreas Buchner and Johann Eduard Herberger in 1830 . As early as 1824 had Karl Gustav Friedrichshütte Schmid from the Jamaican worm bark ( Geoffroya jamaicensis isolated) Jamaicin. Gastell realized in 1866 that jamaicine and berberine are identical.

properties

Berberine has antiseptic , fungicidal , antibiotic and antiprotozoic properties against some bacteria . By reacting with nucleophilic or anionic groups of proteins and nucleic acids, it is able to inhibit enzymes such as sodium-potassium-ATPase , which is attributed to the quaternary structure (in the iminium form ). In the form of berberine chloride, the substance was previously used in eye drops for conjunctivitis . In the Orient, berberine was formerly used to treat oriental bumps , and it was also used as an antimalarial agent.

Health related use

There are reports of various medical uses of berberine, which are based on supposed effects, for example on the sugar and lipid metabolism , blood pressure and in the case of skin ulcers or sore skin. However, according to an extensive 2019 statement from the United States National Library of Medicine , none of these uses are backed by good scientific evidence.

  • The third grade on a seven-point scale of possible effectiveness was assigned for five areas of application, namely Possibly Effective .
  • The last grade was awarded for 19 application areas, namely Insufficient Evidence to Rate (insufficient data for an assessment).

toxicity

Berberine has significant toxicity. There are only preliminary assessments on questions of tolerability for medical use. Special warnings are given against use during pregnancy and breastfeeding, and in general against combination with a wide range of certain other drugs.

metabolism

Berberine is largely metabolized in the body. Less than 5% of the original amount of berberine was found in the urine of rabbits after an intravenous dose of 2 mg / kg. Only 0.5% berberine was excreted via the bile and the intestinal tract in the same experiment , with only 5.5% of the orally ingested berberine leaving the body unchanged.

In the liver , berberine is demethylated by cytochrome P450 in phase I and glucuronidated in phase II, i.e. reacted with glucuronic acid. Correspondingly, the metabolites : berberrubine (simply demethylated berberine), thalifendine and jatrorrhizin , free or bound to glucuronic acid, can be detected in the plasma of rats .

synthesis

biosynthesis

Berberine biosynthesis

The steps in the synthesis of berberine in barberries go over ten stages and were elucidated in the early 1990s. The two starting compounds are 4-hydroxyphenylacetaldehyde and dopamine , which in the first step form norcoclaurine in a condensation reaction . This is monomethylated to form coclaurin . After two more steps, reticulin is formed , which in turn becomes scoulerin . Canadine is produced via a further intermediate stage , from which berberine is ultimately produced.

Technical synthesis

Several syntheses for the production of berberine are described. The best known is the Pictet-Gams-isoquinoline synthesis developed by Pictet and Gams in 1910 .

literature

Illustration of the common barberry
  • M. Imanshahidi and H. Hosseinzadeh: Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. In: Phytother Res 22, 2008, pp. 999-1012; PMID 18618524 .
  • K. Hayashi et al. a .: Antiviral activity of berberine and related compounds against human cytomegalovirus In: Bioorg Med Chem Lett 17, 2007, pp. 1562-1564; PMID 17239594 .
  • SK Mantena: Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. In: Mol Cancer Ther 5, 2006, pp. 296-308; PMID 16505103 .
  • R. Ovádeková u. a .: Nanostructured electrochemical DNA biosensors for detection of the effect of berberine on DNA from cancer cells. In: Anal Bioanal Chem 386, 2006, pp. 2055-2062; PMID 17053918 .
  • T. Efferth et al. a .: Molecular determinants of response of tumor cells to berberine. In: Cancer Genomics Proteomics 2, 2005, pp. 115-124.
  • HH Yu: Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. In: J Med Food 8, 2005, pp. 454-461; PMID 16379555 .
  • K. Weijia et al. a .: Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. In: Nature Medicine 10, 2004, pp. 1344-1351; PMID 15531889 .
  • CC Lin et al. a .: Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukemia cell growth. In: Clin Exp Pharmacol Physiol 31, 2004, pp. 65-69; PMID 14756686 .
  • CW Lau u. a .: Cardiovascular actions of berberine. In: Cardiovasc Drug Rev 19, 2001, pp. 234-244; PMID 11607041 .
  • CW Wright et al. a .: In vitro antiplasmodial, antiamoebic, and cytotoxic activities of some monomeric isoquinoline alkaloids. In: J Nat Prod . 63, 2000, pp. 1638-1640; PMID 11141105 .
  • HL Lin et al. a .: Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to paclitaxel. In: British Journal of Cancer 81, 1999, pp. 416-422; PMID 10507765 ; PMC 2362909 (free full text).
  • GH Rabbani et al. a .: Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic E. coli and Vibrio cholerae. In: The Journal of Infectious Diseases 155, 1987, pp. 979-984; PMID 3549923 .
  • H. Schmitz: On the influence of berberine on cell metabolism. In: Zeitschrift für Krebsforschung 57, 1950, pp 137-141. doi : 10.1007 / BF00524722

Individual evidence

  1. ↑ a b c data sheet Berberine hemisulfate salt from Sigma-Aldrich , accessed on March 13, 2011 ( PDF ).
  2. ↑ Entry on berberine. In: Römpp Online . Georg Thieme Verlag, accessed on December 25, 2014.
  3. ↑ Yakugaku Zasshi. Journal of Pharmacy. Vol. 82, p. 726, 1962.
  4. ↑ a b Kiso to Rinsho. Clinical Report. Vol. 8, p. 654, 1974.
  5. ^ Dissertationes Pharmaceuticae. Vol. 17, p. 429, 1965.
  6. ↑ Fluorescent dyes in nature. Retrieved December 31, 2009.
  7. ↑ Data sheet Berberine chloride form from Sigma-Aldrich , accessed on December 31, 2009 ( PDF ).
  8. ↑ A. Husemann and T. Husemann, The plant substances in chemical, physiological, pharmacological and toxicological terms , Berlin, 1871, p. 245 Digitalisat Bayerische Staatsbibliothek
  9. ^ Johann Andreas Buchner and Johann Eduard Herberger. Chemical treatise on the barberry root . In: JA Buchner (Ed.) Repertorium für die Pharmacie , Schrag, Nürnberg 1830 (Volume 36), pp. 1–53 (digitized version )
  10. ↑ Jamaicin and surinamine, two new plant compounds discovered by Dr. Hüttenschmid from Zurich . In: Peter Jonas Bergius and John Adamson (eds.) Magazine for Pharmacy and the related sciences . 2nd year (volume 7), Chr. Fr. Müller, Karlsruhe 1824, pp. 251-256 (digitized version ) ; P. 283–289: Discussion of the dissertation (digitized version)
  11. ^ A b T. Dingermann, K. Hiller, G. Schneider, I. Zündorf: Schneider drug drugs. 5th edition. Elsevier 2004, ISBN 3-8274-1481-4 , pp. 469-470.
  12. ↑ a b Römpp Lexikon Chemie, 10th edition, 1996-1999: Volume 1. p. 407.
  13. ↑ Y. Kaneda et al. a .: In vitro effects of berberine sulphate on the growth and structure of Entamoeba histolytica, Giardia lamblia, and Trichomonas vaginalis. In: Annals of Tropical Medicine and Parasitology 85, 1991, pp. 417-425; PMID 1796883 .
  14. ↑ E. Teuscher: Biogenic Medicines. 5th edition, Wissenschaftliche Verlagsgesellschaft, 1997, p. 325 f. ISBN 3-8047-1482-X .
  15. ^ Harry Auterhoff : Textbook of Pharmaceutical Chemistry , 9th edition 1977, WVG Stuttgart. P. 335.
  16. ↑ a b Berberine: MedlinePlus Supplements . MedlinePlus, National Library of Medicine, US National Institutes of Health. January 19, 2019. Retrieved April 13, 2020.
  17. ↑ Berberine . PubChem, National Library of Medicine, US National Institutes of Health. March 9, 2020., accessed April 13, 2020.
  18. ↑ CM Chen and HC Chang: Determination of berberine in plasma, urine and bile by high-performance liquid chromatography. In: J. Chromatogr. B 665, 1995, pp. 117-123; PMID 7795781 .
  19. ↑ P. L. Tsai et al. a .: Hepatobiliary excretion of berberine. In: Drug Metab Dispos 32, 2003, pp. 405-412; PMID 15039293 .
  20. ↑ External identifiers or database links for berber ruby ​​chloride : CAS number: 15401-69-1, Wikidata : Q72443285 .
  21. ↑ External identifiers or database links for thalifendin : CAS number: 18207-71-1, PubChem : 3084288 , Wikidata : Q83041334 .
  22. ↑ External identifiers or database links to jatrorrhizin : CAS number: 3621-38-3, EC number: 222-817-3, ECHA InfoCard: 100.020.744 , PubChem : 72323 , ChemSpider : 65269 , Wikidata : Q10910369 .
  23. ↑ F. Zuo et al. a .: Pharmacokinetics of Berberine and Its Main Metabolites in Conventional and Pseudo Germ-Free Rats Determined by Liquid Chromatography / Ion Trap Mass Spectrometry. In: Drug Metabolism and Disposition 34, 2006, pp. 2064-2072; PMID 16956957 .
  24. ↑ JA Bjorklund: Cryptic Stereochemistry of Berberine Alkaloid Biosynthesis. In: J. Am. Chem. Soc. 1995 , 117 1533-1545 doi: 10.1021 / ja00110a009 .
  25. ↑ Biosynthesis of isoquinoline alkaloids. (PDF; 995 kB) of October 18, 2006.
  26. ↑ A. Pictet and A. Gams. In: Ber. German Chem. Ges. 43, 1910, pp. 2384-2391.
  27. ↑ CD Gilmore u. a .: Orthogonal Synthesis of Indolines and Isoquinolines via Aryne Annulation. In: Journal of the American Chemical Society 130, 2008, pp. 1558-1559; doi: 10.1021 / ja0780582 .