Berberine is an organic compound classified as benzylisoquinoline alkaloid.[
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Its name is derived from the genus of plants, Berberis. Berberine occurs in the roots, bark, stems, and leaves of Berberis vulgaris (barberry), Berberis aristata (tree turmeric), Mahonia aquifolium (Oregon grape) and Goldenseal (goldenseal).[
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Due to their yellow pigment, raw Berberis materials were once commonly used to dye wool, leather, and wood.[ Under ultraviolet light, berberine shows a strong yellow fluorescence.]
Plants containing berberine have been used in traditional medicine, and berberine are sold as dietary supplements. Other than in China as an over-the-counter drug, berberine is not approved as a prescription drug, regulated or proven safe in any country.
Biological sources
The following plants are biological sources of berberine:
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Berberis vulgaris (barberry)
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Berberis aristata (tree turmeric)
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Berberis thunbergii
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Fibraurea tinctoria
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Mahonia aquifolium (Oregon grape)
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Hydrastis canadensis (goldenseal)
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Xanthorhiza simplicissima (yellowroot)
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Phellodendron amurense (Amur cork tree)
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Coptis chinensis (Chinese goldthread)
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Tinospora cordifolia
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Argemone mexicana (prickly poppy)
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Eschscholzia californica (California poppy)
Berberine is usually found in the roots, , stems, and bark.[
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Structure and biosynthesis
Berberine has a tetracyclic skeleton as is common for classified as a benzylisoquinoline alkaloid. The overall skeleton is derived from two equivalents of L-tyrosine. L-Tyrosine is the precursor to L-DOPA and 4-hydroxyphenylacetaldehyde.
The incorporation of an extra carbon atom as a bridge is distinctive. Formation of the berberine bridge is rationalized as an redox 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.
Reticuline is a precursor to some protoberberine alkaloids in plants.
Heating at 190 °C, berberine demethylates giving berberrubine. Alkylation of the resulting zwitterion gives access to many berberine-like derivatives.
Research
Although plants containing berberine are used in traditional medicine, berberine has low bioavailability, indicating limited biological activity in vivo, with no issued for its use as a drug.[ Clinical research investigating the use of berberine in humans is limited.][
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A 2023 review concluded that berberine may improve lipid concentrations.[
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Supplements, regulation, and safety
Although widely available, dietary supplements have not been approved in the United States for any specific medical use.[ The quality of berberine supplements can vary across brands: a 2017 study found that out of 15 different products sold, only six contained at least 90% of the specified berberine quantity.]
From 2020 to 2022, the US Food and Drug Administration issued warning letters to eight manufacturers of berberine dietary supplements for false advertising and misbranded drug products.[
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Adverse effects
Longer-term human clinical trials have reported flatulence and diarrhea as common issues.
Drug interactions
Berberine is known to inhibit the activity of CYP3A4, an enzyme important to 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.]
Use in China
It is approved in China as an over-the-counter drug for diarrhea treatment, with the package insert claiming efficacy against Escherichia coli and Shigella spp.
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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