Pyrolysis of berberine gives "berberrubine", whichprotonates to "protoberberine"
Reticuline is a precursor to some protoberberine alkaloids in plants.[13]
Heating at 190 °C, berberine demethylates givingberberrubine. Alkylation of the resultingzwitterion gives access to many berberine-like derivatives.[14]
Although plants containing berberine are used in traditional medicine, berberine has lowbioavailability, indicating limited biological activityin vivo, with nopatents issued for its use as a drug.[4][8]Clinical research investigating the use of berberine in humans is limited.[8][15] Although numerousclinical trials have been conducted or are underway, as of 2025, berberine has frequently been withdrawn as adrug candidate, and is not approved as a prescription drug in any country.[8][16]
A 2023 review concluded that berberine may improve lipid concentrations.[16] High-quality, large clinical studies would be required to properly evaluate the effectiveness and safety of berberine in various health conditions.[15]
Although widely available, dietary supplements have not been approved in the United States for any specific medical use.[8] 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.[17]
Berberine is known to inhibit the activity ofCYP3A4, an enzyme important to drug metabolism and clearance of endogenous substances, including steroid hormones such as cortisol, progesterone, and testosterone.[4][8] Several studies have demonstrated that berberine can increase the concentrations ofcyclosporine in renal transplant patients andmidazolam in healthy adult volunteers, confirming its inhibitory effect on CYP3A4.[20][21][22]
^abcdefgh"Berberine". The Human Metabolome Database. 7 March 2022. Retrieved21 August 2025.
^ab"Berberine". PubChem, US National Library of Medicine. 16 August 2025. Retrieved21 August 2025.
^Gulrajani ML (2001)."Present status of natural dyes".Indian Journal of Fibre & Textile Research.26:191–201.Archived from the original on 20 November 2021. Retrieved28 December 2017 – via NISCAIR Online Periodicals Repository.
^abcdef"Berberine". DrugBank. 19 August 2025. Retrieved21 August 2025.
^Cicero AF, Baggioni A (2016). "Berberine and Its Role in Chronic Disease".Anti-inflammatory Nutraceuticals and Chronic Diseases. Advances in Experimental Medicine and Biology. Vol. 928. Cham: Springer International Publishing. pp. 27–45.doi:10.1007/978-3-319-41334-1_2.ISBN978-3-319-41332-7.ISSN0065-2598.PMID27671811.
^Park SU, Facchini PJ (June 2000). "Agrobacterium rhizogenes-mediated transformation of opium poppy,Papaver somniferum l., and California poppy,Eschscholzia californica cham., root cultures".Journal of Experimental Botany.51 (347):1005–16.doi:10.1093/jexbot/51.347.1005.PMID10948228.
^abHernandez AV, Hwang J, Nasreen I, et al. (2023). "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 of Dietary Supplements.21 (2):242–259.doi:10.1080/19390211.2023.2212762.PMID37183391.S2CID258687419.
^Niwa T, Murayama N, Imagawa Y, et al. (May 2015). "Regioselective hydroxylation of steroid hormones by human cytochromes P450".Drug Metab Rev.47 (2):89–110.doi:10.3109/03602532.2015.1011658.PMID25678418.
^ab精华制药集团股份有限公司."盐酸小檗碱片说明书" [Package Insert: Berberine Hydrochloride Tablets].ypk.39.net (in Chinese).
