berberine

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){{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 }}
• Coptis chinensis (Chinese goldthread)
• Tinospora cordifolia
• Argemone mexicana (prickly poppy)
• Eschscholzia californica (California poppy)

Berberine is usually found in the roots, rhizomes, stems, and bark.{{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}}

{{Technical|section|date=February 2025}}

File:Biosynthesis of berberine.svg

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.{{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}}

Reticuline is the immediate precursor of protoberberine alkaloids in plants.{{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 = }} 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|date=February 2025}}; the remaining carbon atoms come from tyrosine via 4-hydroxyphenylacetaldehyde.{{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}}

Studies on the pharmacological effects of berberine, including medical uses, are preliminary: some studies consider cell cultures or animal models, whereas clinical trials investigating the use of berberine in humans are limited.{{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=}}

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

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.{{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=}}{{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 }}

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.{{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 }}

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.{{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=}}{{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=}}{{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=}}

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.{{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}}

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.

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{{Other antibacterials}}

{{Muscarinic acetylcholine receptor modulators}}

{{PPAR modulators}}

{{Sigma receptor modulators}}

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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