Berberine

Names
Other names Umbellatine; 5,6-Dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium
Identifiers
CAS Number	2086-83-1 N
3D model (JSmol)	Interactive image
ChEBI	CHEBI:16118 Y
ChEMBL	ChEMBL12089 N
ChemSpider	2263 Y
DrugBank	DB04115 Y
ECHA InfoCard	100.016.572
PubChem CID	2353
UNII	0I8Y3P32UF Y
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 Y Key: YBHILYKTIRIUTE-UHFFFAOYSA-N Y 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
SMILES O1c2c(OC1)cc5c(c2)c4cc3ccc(OC)c(OC)c3c[n+]4CC5
Properties
Chemical formula	C20H18NO4+
Molar mass	7002336366000000000♠336.366 g·mol−1
Appearance	Yellow solid
Melting point	145 °C (293 °F; 418 K)[1]
Solubility in water	Slowly soluble[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as Berberis (e.g. Berberis vulgaris – barberry, Berberis aristata – tree turmeric, Mahonia aquifolium – Oregon-grape, Hydrastis canadensis – goldenseal, Xanthorhiza simplicissima – yellowroot, Phellodendron amurense^[2] – Amur cork tree, Coptis chinensis – Chinese goldthread, Tinospora cordifolia, Argemone mexicana – prickly poppy, and Eschscholzia californica – Californian poppy). Berberine is usually found in the roots, rhizomes, stems, and bark.^{[citation needed]}

Due to berberine's strong yellow color, Berberis species were used to dye wool, leather, and wood. Wool is still dyed with berberine today in northern India.^[3] Under ultraviolet light, berberine shows a strong yellow fluorescence,^[4] so it is useful in histology for staining heparin in mast cells.^[5] As a natural dye, berberine has a color index of 75160.

Folk medicine[edit]

Berberine was supposedly used in China as a folk medicine by Shennong around 3000 BC. This first recorded use of berberine is described in the ancient Chinese medical book The Divine Farmer's Herb-Root Classic.^[6]

Research[edit]

Although the clinical research has been low in quality, studies have been conducted to determine if berberine may affect diabetes^[7] or blood lipids.^[8][9] As of 2018, there is insufficient evidence to conclude that berberine is safe or effective for any condition.^[10]

Biosynthesis[edit]

Biosynthesis of berberine

The alkaloid berberine has a tetracyclic skeleton derived from a benzyltetrahydroisoquinoline system with the incorporation of an extra carbon atom provided by S-adenosyl methionine via an N-methyl group. Formation of the berberine bridge is readily rationalized as an oxidative process in which the N-methyl group is oxidized to an iminium ion, and a cyclization to the aromatic ring occurs by virtue of the phenolic group.^[11]

Reticuline is known as the immediate precursor of protoberberine alkaloids in plants.^[12] 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 phenylethylamine fragment of the tetrahydroisoquinoline ring system is formed via DOPA, the remaining carbon atoms come from tyrosine via 4-hydroxyphenylacetaldehyde. L-DOPA loses carbon dioxide to form dopamine 1. Likewise, 4-hydroxypyruvic acid also loses carbon dioxide to form 4-hydroxyphenylacetaldehyde 2. Dopamine 1 then reacts with 4-hydroxy-phenylacetaldehyde 2 to form (S)-norcolaurine 3 in a reaction similar to the Mannich reaction. After oxidation and methylation by SAM, (S)-reticuline 4 is formed. (S)-reticuline serves as a pivotal intermediate to other alkaloids. Oxidation of the tertiary amine then occurs and an iminium ion is formed 5. In a Mannich-like reaction the ortho position to the phenol is nucleophilic, and electrons are pushed to form 6. Product 6 then undergoes keto-enol tautomerism to form (S)-scoulerine, which is then methylated by SAM to form (S)-tetrahydrocolumbamine 7. Product 7 is then oxidized to form the methylenedioxy ring from the ortho-methoxyphenol, via an O₂-, NADPH- and cytochrome P-450-dependent enzyme, giving (S)-canadine 8. (S)-canadine is then oxidized to give the quaternary isoquinolinium system of berberine. This happens in two separate oxidation steps, both requiring molecular oxygen, with H₂O₂ and H₂O produced in the successive processes.^[13]

See also[edit]

• 
  Coptisine for a related pharmacological discussion


• 
  Goldenseal for a related pharmacological discussion


• 
  Jatrorrhizine, another protoberberine alkaloid


• 
  Sanguinarine, a plant-based compound with very similar chemical classification as berberine

References[edit]