View source for Berberine

{{short description|Quaternary ammonium cation}}
{{cs1 config|name-list-style=vanc}}{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 457785306
| ImageFile1_Ref = {{chemboximage|correct|??}}
| ImageFile1 =Berberin.svg
| ImageSize1 =
| ImageFile2_Ref = {{chemboximage|correct|??}}
| ImageFile2 =Berberine 3D.png
| ImageSize2 =
| IUPACName = 9,10-Dimethoxy-7,8,13,13a-tetradehydro-2′''H''-[1,3]dioxolo[4′,5′:2,3]berbin-7-ium
| SystematicName = 9,10-Dimethoxy-5,6-dihydro-2''H''-7λ<sup>5</sup>-[1,3]dioxolo[4,5-''g'']isoquinolino[3,2-''a'']isoquinolin-7-ylium<ref>{{BlueBook2013|rec=73.3.1}}</ref>
| OtherNames =Umbellatine;<ref name="merck14"/><br />5,6-Dihydro-9,10-dimethoxybenzo[''g'']-1,3-benzodioxolo[5,6-''a'']quinolizinium;<ref name="merck14"/><br />7,8,13,13a-Tetradehydro-9,10-dimethoxy-2,3-(methylenedioxy)berbinium<ref name="merck14">The Merck Index, 14th ed., 1154. Berberine</ref>
|Section1={{Chembox Identifiers
| 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
| InChIKey = YBHILYKTIRIUTE-UHFFFAOYAJ
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = YBHILYKTIRIUTE-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|changed|??}}
| CASNo =2086-83-1
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2263
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 12089
| PubChem =2353
| EC_number = 218-229-1
| KEGG = C00757
| 3DMet =
| Beilstein = 3570374
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 0I8Y3P32UF
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16118
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB04115
| SMILES = O1c2c(OC1)cc5c(c2)c4cc3ccc(OC)c(OC)c3c[n+]4CC5
}}
|Section2={{Chembox Properties
| C=20|H=18|N=1|O=4
| Formula_Charge =+
| Appearance =Yellow solid
| Density =
| MeltingPtC = 145
| MeltingPt_ref = <ref name = Merck>''[[The Merck Index]]'', 10th Ed. (1983), p.165, Rahway: Merck & Co.</ref>
| BoilingPt =
| Solubility =Slowly soluble<ref name = Merck/>
  }}
|Section3={{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
}}
}}

'''Berberine''' is a [[Quaternary ammonium cation|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 [[pigment]]ation, raw ''Berberis'' materials were once commonly used to dye wool, leather, and wood.<ref>{{cite journal|vauthors=Gulrajani ML|date=2001|title=Present status of natural dyes|url=http://nopr.niscair.res.in/handle/123456789/24928|journal=Indian Journal of Fibre & Textile Research|language=en-US|volume=26|pages=191–201|via=NISCAIR Online Periodicals Repository|access-date=2017-12-28|archive-date=2021-11-20|archive-url=https://web.archive.org/web/20211120183428/http://nopr.niscair.res.in/handle/123456789/24928|url-status=live}}</ref> Under [[ultraviolet light]], berberine shows a strong yellow [[fluorescence]],<ref name="unijena">{{cite web |title=Fluoreszenzfarbstoffe in der Natur |url=http://www.chemie.uni-jena.de/institute/oc/weiss/naturstoffe.htm |vauthors=Weiß D |year=2008 |access-date=17 July 2009 |language=de |archive-date=9 March 2007 |archive-url=https://web.archive.org/web/20070309172021/http://www.chemie.uni-jena.de/institute/oc/weiss/naturstoffe.htm |url-status=live }}</ref> making it useful in [[histology]] for [[staining]] [[heparin]] in [[mast cell]]s.<ref name="sigma2">{{cite web |title=B3251 Berberine chloride form |url=http://www.sigmaaldrich.com/catalog/product/sigma/b3251?lang=en&region=US |publisher=[[Sigma-Aldrich]] |year=2013 |access-date=2 Aug 2013 |archive-date=7 September 2012 |archive-url=https://web.archive.org/web/20120907195333/http://www.sigmaaldrich.com/catalog/product/sigma/b3251?lang=en&region=US |url-status=live }}</ref> As a natural dye, berberine has a [[Colour Index International|color index]] of 75160.

==Biological sources==
The following plants are biological sources of berberine:
* ''[[Berberis vulgaris]]'' (barberry)
* ''[[Berberis aristata]]'' (tree turmeric)
* ''[[Berberis thunbergii]]''
* ''[[Fibraurea tinctoria]]''
* ''[[Mahonia aquifolium]]'' (Oregon grape)
* ''[[Hydrastis canadensis]]'' (goldenseal)
* ''[[Xanthorhiza simplicissima]]'' (yellowroot)
* ''[[Phellodendron amurense]]'' (Amur cork tree)<ref name="Cicero Baggioni 2016 pp. 27–45">{{cite book | last1=Cicero | first1=Arrigo F. G. | last2=Baggioni | first2=Alessandra | title=Anti-inflammatory Nutraceuticals and Chronic Diseases | series=Advances in Experimental Medicine and Biology | chapter=Berberine and Its Role in Chronic Disease | publisher=Springer International Publishing | publication-place=Cham | year=2016 | volume=928 | isbn=978-3-319-41332-7 | issn=0065-2598 | doi=10.1007/978-3-319-41334-1_2 | pages=27–45| pmid=27671811 }}</ref>
* ''[[Coptis chinensis]]'' (Chinese goldthread)
* ''[[Tinospora cordifolia]]''
* ''[[Argemone mexicana]]'' (prickly poppy)
* ''[[Eschscholzia californica]]'' (California poppy)

Berberine is usually found in the roots, [[rhizome]]s, stems, and bark.<ref name="pubchem">{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/2353|title=Berberine|publisher=PubChem, National Library of Medicine, US National Institutes of Health|date=March 9, 2020|access-date=March 10, 2020|archive-date=March 5, 2016|archive-url=https://web.archive.org/web/20160305223654/https://pubchem.ncbi.nlm.nih.gov/compound/2353|url-status=live}}</ref>

== Biosynthesis ==
{{Technical|section|date=February 2025}}
[[File:Biosynthesis of berberine.svg|thumb|right|300px|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|''S''-adenosyl methionine]] (SAM), is oxidized to an [[iminium ion]], and a [[cyclization]] to the [[aromatic ring]] occurs by virtue of the [[phenolic group]].<ref>{{cite book | vauthors = Dewick P |title=Medicinal Natural Products: A Biosynthetic Approach |url=https://archive.org/details/medicinalnatural00dewi_015 |url-access=limited |edition=3rd |publisher=Wiley |location=West Sussex, England |year=2009 |page=[https://archive.org/details/medicinalnatural00dewi_015/page/n354 357] |isbn=978-0-471-49641-0}}</ref>

[[Reticuline]] is the immediate precursor of [[protoberberine]] alkaloids in plants.<ref>{{cite journal | vauthors = Park SU, Facchini PJ | title = Agrobacterium rhizogenes-mediated transformation of opium poppy, ''Papaver somniferum l.'', and California poppy, ''Eschscholzia californica cham.'', root cultures | journal = Journal of Experimental Botany | volume = 51 | issue = 347 | pages = 1005–16 | date = June 2000 | pmid = 10948228 | doi = 10.1093/jexbot/51.347.1005 | doi-access =  }}</ref> Berberine is an alkaloid derived from [[tyrosine]]. [[L-DOPA|<small>L</small>-DOPA]] and [[4-hydroxypyruvic acid]] both come from [[L-tyrosine|<small>L</small>-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|date=February 2025}}; the remaining carbon atoms come from tyrosine via [[4-Hydroxyphenylacetaldehyde|4-hydroxyphenylacetaldehyde]].<ref>{{cite book | vauthors = Dewick P |title=Medicinal Natural Products: A Biosynthetic Approach |url=https://archive.org/details/medicinalnatural00dewi_347 |url-access=limited |edition=3rd |publisher=Wiley |location=West Sussex, England |year=2009 |page=[https://archive.org/details/medicinalnatural00dewi_347/page/n355 358] |isbn=978-0-471-49641-0}}</ref>

==Research==
Studies on the pharmacological effects of berberine, including medical uses, are preliminary: some studies consider cell cultures or animal models, whereas [[clinical trial]]s investigating the use of berberine in humans are limited.<ref name="pmid32335802">{{cite journal |vauthors=Song D, Hao J, Fan D |title=Biological properties and clinical applications of berberine |journal=Front Med |volume=14 |issue=5 |pages=564–582 |date=October 2020 |pmid=32335802 |doi=10.1007/s11684-019-0724-6 |s2cid=216111561 |url=}}</ref> 

A 2023 review concluded that berberine may improve lipid concentrations.<ref name="pmid37183391">{{cite journal |vauthors=Hernandez AV, Hwang J, Nasreen I, Sicignano D, Pasupuleti V, Snow-Caroti K |display-authors=3 |title=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=J Diet Suppl |year=2023 |volume=21 |issue=2 |pages=242–259 |pmid=37183391 |doi=10.1080/19390211.2023.2212762 |pmc= |s2cid=258687419 |url=https://pubmed.ncbi.nlm.nih.gov/37183391 |access-date=2023-08-28 |archive-date=2023-06-01 |archive-url=https://web.archive.org/web/20230601233652/https://pubmed.ncbi.nlm.nih.gov/37183391/ |url-status=live}}</ref> High-quality, large clinical studies would be required to properly evaluate the effectiveness and safety of berberine in various health conditions.<ref name="pmid32335802" />

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. Studies linking berberine to health benefits are limited. The quality of berberine supplements can vary across brands. A 2017 study found that out of 15 different products sold in the U.S., only six contained at least 90% of the specified berberine quantity.<ref name="pmid28792254">{{cite journal |vauthors=Funk RS, Singh RK, Winefield RD, Kandel SE, Ruisinger JF, Moriarty PM, Backes JM |title=Variability in Potency Among Commercial Preparations of Berberine |journal=J Diet Suppl |volume=15 |issue=3 |pages=343–351 |date=May 2018 |pmid=28792254 |pmc=5807210 |doi=10.1080/19390211.2017.1347227 |url=}}</ref><ref>{{cite news |url=https://www.wsj.com/articles/berberine-natures-ozempic-weight-loss-902e097 |title=The Cheaper Weight-Loss Alternative Riding the Ozempic Wave |newspaper=Wall Street Journal |date=14 June 2023 |last1=Subbaraman |first1=Nidhi |access-date=29 December 2023 |archive-date=29 December 2023 |archive-url=https://web.archive.org/web/20231229164947/https://www.wsj.com/articles/berberine-natures-ozempic-weight-loss-902e097 |url-status=live }}</ref>

== 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 microbiota|gut microbiome]] to blame.<ref>{{cite journal |last1=Yue |first1=Shi-Jun |last2=Liu |first2=Juan |last3=Wang |first3=Wen-Xiao |last4=Wang |first4=Ai-Ting |last5=Yang |first5=Xin-Yu |last6=Guan |first6=Hua-Shi |last7=Wang |first7=Chang-Yun |last8=Yan |first8=Dan |title=Berberine treatment-emergent mild diarrhea associated with gut microbiota dysbiosis |journal=Biomedicine & Pharmacotherapy |date=August 2019 |volume=116 |pages=109002 |doi=10.1016/j.biopha.2019.109002|pmid=31154270 |doi-access=free }}</ref>

== 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.<ref name="pmid34620272">{{cite journal |vauthors=Abushammala I |title=Tacrolimus and herbs interactions: a review |journal=Pharmazie |volume=76 |issue=10 |pages=468–472 |date=October 2021 |pmid=34620272 |doi=10.1691/ph.2021.1684 |url=}}</ref><ref name="pmid22855269">{{cite journal |vauthors=Hermann R, von Richter O |title=Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions |journal=Planta Med |volume=78 |issue=13 |pages=1458–77 |date=September 2012 |pmid=22855269 |doi=10.1055/s-0032-1315117 |url=}}</ref><ref name="pmid25678418">{{cite journal |vauthors=Niwa T, Murayama N, Imagawa Y, Yamazaki H |title=Regioselective hydroxylation of steroid hormones by human cytochromes P450 |journal=Drug Metab Rev |volume=47 |issue=2 |pages=89–110 |date=May 2015 |pmid=25678418 |doi=10.3109/03602532.2015.1011658 |url=}}</ref>

==Use in China==
It is approved in China as an [[Over-the-counter drug|over-the-counter]] (OTC) drug for [[diarrhea]] treatment. The [[package insert]] claims efficacy against ''[[Escherichia coli|E. coli]]'' and ''[[Shigella]]'' spp.<ref name=pki>{{cite web |last1=精华制药集团股份有限公司 |title=盐酸小檗碱片说明书 |url=https://ypk.39.net/843793/manual |website=ypk.39.net |language=zh|trans-title=Package Insert: Berberine Hydrochloride Tablets}}</ref>

The Chinese package insert contraindicates berberine for people with [[hemolytic anemia]] and with [[glucose-6-phosphate dehydrogenase]] deficiency ([[G6PD deficiency]]).<!-- The quote is: 【禁忌】溶血性贫血患者及葡萄糖-6-磷酸脱氢酶缺乏患者禁用。--> The insert also specifically precautions its use in children with [[G6PD deficiency]] because it can produce [[hemolytic anemia]] and [[jaundice]].<ref name=pki/><!-- The quote is: 遗传6-磷酸葡萄糖脱氢酶缺乏的儿童应禁用, 因本品可引起溶血性贫血以致黄疸.-->

== References ==
{{Reflist}}

{{Other antibacterials}}
{{Muscarinic acetylcholine receptor modulators}}
{{PPAR modulators}}
{{Sigma receptor modulators}}
{{Authority control}}

[[Category:Aromatase inhibitors]]
[[Category:Benzylisoquinoline alkaloids]]
[[Category:CYP2D6 inhibitors]]
[[Category:CYP3A4 inhibitors]]
[[Category:DNA-binding substances]]
[[Category:Hypolipidemic agents]]
[[Category:M2 receptor agonists]]
[[Category:Methylenedioxyphenethylamines]]
[[Category:Nitrogen heterocycles]]
[[Category:Quaternary ammonium compounds]]
[[Category:Traditional Chinese medicine]]