Berberine is a

quaternary ammonium In organic chemistry, quaternary ammonium cations, also known as quats, are positively-charged polyatomic ions of the structure , where R is an alkyl group, an aryl group or organyl group. Unlike the ammonium ion () and the primary, secondary, o ...

salt from the protoberberine group of

benzylisoquinoline alkaloids The benzylisoquinoline alkaloids are natural products that can be classified as isoquinoline alkaloids and are derived from benzylisoquinoline. They also include the benzyl(tetrahydro)isoquinoline alkaloids. Occurrence Benzylisoquinoline alkal ...

, occurring naturally as a

secondary metabolite Secondary metabolites, also called ''specialised metabolites'', ''secondary products'', or ''natural products'', are organic compounds produced by any lifeform, e.g. bacteria, archaea, fungi, animals, or plants, which are not directly involved ...

in some plants including species of ''

Berberis ''Berberis'' (), commonly known as barberry, is a large genus of deciduous and evergreen shrubs from tall, found throughout temperate and subtropical regions of the world (apart from Australia). Species diversity is greatest in South America a ...

'', from which its name is derived. Due to their yellow

pigment A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), chemically unreactive in water or another medium; in contrast, dyes are colored sub ...

ation, raw ''Berberis'' materials were once commonly used to dye wool, leather, and wood. Under

ultraviolet light Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of th ...

, berberine shows a strong yellow

fluorescence Fluorescence is one of two kinds of photoluminescence, the emission of light by a substance that has absorbed light or other electromagnetic radiation. When exposed to ultraviolet radiation, many substances will glow (fluoresce) with colore ...

, making it useful in

histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...

for

staining Staining is a technique used to enhance contrast in samples, generally at the Microscope, microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissue (biology), tissues), in cytology (microscopic ...

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, ...

mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a p ...

s. As a natural dye, berberine has a

color index In astronomy, the color index is a simple numerical expression that determines the color of an object, which in the case of a star gives its temperature. The lower the color index, the more blue (or hotter) the object is. Conversely, the larg ...

of 75160.

Biological sources

The following plants are biological sources of berberine: * ''

Berberis vulgaris ''Berberis vulgaris'', also known as common barberry, European barberry or simply barberry, is a shrub in the genus ''Berberis'' native to the Old World. It produces edible but sharply acidic berries, which people in many countries eat as a tar ...

'' (barberry) * ''

Berberis aristata ''Berberis aristata'', also known as Indian barberry, Mara manjal (மரமஞ்சள்), chutro, sumba, or tree turmeric, is a shrub belonging to the family Berberidaceae and the genus ''Berberis''. ''B. aristata'' is native to the Himalayas ...

'' (tree turmeric) * ''

Berberis thunbergii ''Berberis thunbergii'', the Japanese barberry, Thunberg's barberry, or red barberry, is a species of flowering plant in the barberry family Berberidaceae, native plant, native to Japan and eastern Asia, though widely naturalized in China and No ...

'' * ''

Fibraurea tinctoria ''Fibraurea tinctoria'' is a species of flowering plant native to South Asia, where it grows in wet tropical areas between India and the Philippines. It is considered locally common. It fruits in April and May, producing yellow-orange drupes. Com ...

'' * ''

Mahonia aquifolium ''Berberis aquifolium'', the Oregon grape or holly-leaved barberry, is a North American species of flowering plant in the family Berberidaceae. It is an evergreen shrub growing up to tall and wide, with pinnate leaves consisting of spiny leafle ...

'' (Oregon grape) * ''

Hydrastis canadensis Goldenseal (''Hydrastis canadensis''), also called orangeroot or yellow puccoon, is a perennial plant, perennial herb in the buttercup family Ranunculaceae, native to North America. It may be distinguished by its thick, yellow knotted rootstock ...

'' (goldenseal) * ''

Xanthorhiza simplicissima ''Xanthorhiza simplicissima'' (yellowroot) is the only member of the genus ''Xanthorhiza'', and one of very few genera in the family Ranunculaceae with a woody stem (the other notable example being ''Clematis''). It is native to the eastern Uni ...

'' (yellowroot) * ''

Phellodendron amurense ''Phellodendron amurense'' is a species of tree in the family Rutaceae, commonly called the Amur cork tree. It is a major source of ''huáng bò'' ( or wiktionary:黄, 黄wiktionary:檗, 檗), one of the 50 fundamental herbs used in traditional Ch ...

'' (Amur cork tree) * ''

Coptis chinensis ''Coptis chinensis'', the Chinese goldthread, is a species of goldthread flowering plant native to China. Etymology *''Coptis chinensis'' Franch. var. ''chinensis''

'' (Chinese goldthread) * ''

Tinospora cordifolia ''Tinospora cordifolia'', the heart-leaved moonseed, is a herbaceous vine of the family Menispermaceae native to South and Southeast Asia. It has been used in Ayurveda in an attempt to treat various disorders. There is no good evidence ''Tinospo ...

'' * ''

Argemone mexicana ''Argemone mexicana'', also known by the common names Mexican poppy, Mexican prickly poppy, flowering thistle, cardo, and cardosanto, is a species of poppy found in Mexico and now widely naturalized in many parts of the world. An extremely hardy ...

'' (prickly poppy) * ''

Eschscholzia californica ''Eschscholzia californica'', the California poppy, golden poppy, Mexican poppy, California sunlight or cup of gold, is a species of flowering plant in the family Papaveraceae, native to the United States and Mexico. It is cultivated as an orn ...

'' (California poppy) Berberine is usually found in the roots,

rhizome In botany and dendrology, a rhizome ( ) is a modified subterranean plant stem that sends out roots and Shoot (botany), shoots from its Node (botany), nodes. Rhizomes are also called creeping rootstalks or just rootstalks. Rhizomes develop from ...

s, stems, and bark.

Biosynthesis

The

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

berberine has a

tetracyclic Tetracyclics are cyclic compound, cyclic chemical compounds that contain four fused ring (chemistry), rings of atoms, for example, Tröger's base. Some tricyclic compounds having three fused and one tethered ring (connected to main nucleus by ...

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 Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is t ...

in which the ''N''-

methyl group In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated a ...

, supplied by ''S''-adenosyl methionine (SAM), is oxidized to an

iminium ion In organic chemistry, an iminium cation is a polyatomic ion with the general structure . They are common in synthetic chemistry and biology. Structure Iminium cations adopt alkene-like geometries: the central C=N unit is nearly coplanar with al ...

, and a

cyclization A cyclic compound (or ring compound) is a term for a compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring. Rings may vary in size from three to many atoms, and include examples where ...

to the

aromatic ring In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibits a stabilization stronger than would be expected from conjugation alone. The e ...

occurs by virtue of the

phenolic group In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of one or more hydroxyl Functional group, groups (−Oxygen, O Hydrogen, H) Chemical bond, bonded directly to an aromatic hydrocarbon group. Th ...

Reticuline Reticuline is an alkaloid found in opium and a variety of plants including ''Lindera aggregata'', ''Annona squamosa'', and ''Ocotea#Selected species, Ocotea fasciculata'' (also known as ''Ocotea duckei''). Experiments in rodents suggest reticuli ...

is the immediate precursor of protoberberine alkaloids in plants. Berberine is an alkaloid derived from

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

. L-DOPA and 4-hydroxypyruvic acid both come from L-tyrosine. Although two

molecules are used in the biosynthetic pathway, only the

phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...

fragment of the

tetrahydroisoquinoline Tetrahydroisoquinoline (TIQ or THIQ), also known as AMPH-CR, is an organic compound with the chemical formula C9H11N. Classified as a secondary amine, it is derived from isoquinoline by hydrogenation. It is a colorless viscous liquid that is mis ...

ring system is formed via DOPA; the remaining carbon atoms come from tyrosine via 4-hydroxyphenylacetaldehyde.

Research

Studies on the pharmacological effects of berberine, including medical uses, are preliminary: some studies consider cell cultures or animal models, whereas

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s investigating the use of berberine in humans are limited. 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. Berberine supplements are widely available in the U.S. but have not been approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(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.

Adverse effects

Longer-term human clinical trials have reported

flatulence Flatulence is the expulsion of gas from the Gastrointestinal tract, intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swal ...

and

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

as common issues. The problem can be replicated in rats, with disruption of the

gut microbiome Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the g ...

to blame.

Drug interactions

Berberine is known to inhibit the activity of

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

, 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 Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, ecz ...

in renal transplant patients and

midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia, premedication before surgical anesthesia, and procedural sedation, and to treat psychomotor agitation, severe agitation. It induces ...

in healthy adult volunteers, confirming its inhibitory effect on CYP3A4.

Use in China

It is approved in China as an

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...

(OTC) drug for

treatment. The

package insert A package insert is a document included in the package of a medication that provides information about that drug and its use. For prescription medications, the insert is technical, providing information for medical professionals about how to pr ...

claims efficacy against ''

E. coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...

'' and ''

Shigella ''Shigella'' is a genus of bacteria that is Gram negative, facultatively anaerobic, non–spore-forming, nonmotile, rod shaped, and is genetically nested within ''Escherichia''. The genus is named after Kiyoshi Shiga, who discovered it in 1 ...

'' spp. The Chinese package insert contraindicates berberine for people with

hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonl ...

and with

glucose-6-phosphate dehydrogenase Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) () is a cytosolic enzyme that catalysis, catalyzes the chemical reaction : Glucose 6-phosphate, D-glucose 6-phosphate + NADP+ + 6-Phosphogluconolactone, 6-phospho-D-glucono-1,5-lactone + NADPH ...

deficiency (

G6PD deficiency Glucose-6-phosphate dehydrogenase deficiency (G6PDD), also known as favism, is the most common enzyme deficiency anemia worldwide. It is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are ...

). The insert also specifically precautions its use in children with

because it can produce

and

jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...

References

{{Authority control Aromatase inhibitors Benzylisoquinoline alkaloids CYP2D6 inhibitors CYP3A4 inhibitors DNA-binding substances Hypolipidemic agents M2 receptor agonists Methylenedioxyphenethylamines Nitrogen heterocycles Quaternary ammonium compounds Traditional Chinese medicine