Berberine


Berberine is an organic compound classified as benzylisoquinoline alkaloid. Chemically, it is a quaternary ammonia compound.
Its name is derived from the genus of plants, Berberis. Berberine occurs in the roots, bark, stems, and leaves of Berberis vulgaris, Berberis aristata, Mahonia aquifolium and Hydrastis canadensis.
Due to their yellow pigmentation, raw Berberis materials were once commonly used to dye wool, leather, and wood. Under ultraviolet light, berberine shows a strong yellow fluorescence. As a natural dye, berberine has a color index of 75160.
Plants containing berberine have been used in traditional medicine, and berberine extracts 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:
  • Berberis vulgaris
  • Berberis aristata
  • Berberis thunbergii
  • Fibraurea tinctoria
  • Mahonia aquifolium
  • Hydrastis canadensis
  • Xanthorhiza simplicissima
  • Phellodendron amurense
  • Coptis chinensis
  • Tinospora cordifolia
  • Argemone mexicana
  • Eschscholzia californica
Berberine is usually found in the roots, rhizomes, stems, and bark.

Structure and biosynthesis

Berberine has a tetracyclic skeleton as is common for alkaloids 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 oxidative process in which the N-methyl group, supplied by S-adenosyl methionine, is oxidized to an iminium ion, and a cyclization to the aromatic ring occurs by virtue of the phenolic group.
File:BerberrubineSyn.svg|thumb|320px|class=skin-invert-image|Pyrolysis of berberine gives "berberrubine", which protonates to "protoberberine"
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 patents issued for its use as a drug. Clinical research investigating the use of berberine in humans is limited. Although numerous clinical trials have been conducted or are underway, as of 2025, berberine has frequently been withdrawn as a drug candidate, and is not approved as a prescription drug in any country.
A 2023 review concluded that berberine may improve lipid concentrations. High-quality, large clinical studies would be required to properly evaluate the effectiveness and safety of berberine in various health conditions.

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. In the United States, berberine is not generally recognized as safe.

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 E. coli and Shigella spp.
The Chinese package insert contraindicates berberine for people with hemolytic anemia and with glucose-6-phosphate dehydrogenase deficiency. The insert also specifically precautions its use in children with G6PD deficiency because it can produce hemolytic anemia and jaundice.