Berberine is an alkaloid that is widely used in pharmacology and medicinal chemistry. [1] Its principal natural source is the genus Berberis (barberry), which is made up of between 45 and 500 different plant species. Berberine has an extensive history of use as medicine.
Many parts of the plant contain berberine and have been employed throughout the centuries as medicine. Barberry fruit was used as a “blood purifying agent” as early as 650 BC. The stems, bark, and roots have been documented as being used in Asia for over 3,000 years for a host of ailments, including infections, wounds, hemorrhoids, snakebites, and even obesity.
In addition to the genus Berberis, berberine has been identified in several other plant families. These include Annonaceae (custard apple), Menispermaceae (moonseed), Ranunculaceae (buttercup), and Rutaceae (rue).
Berberine is a quaternary protoberberine alkaloid (QPA) and can be isolated in various ways. Some popular methods include maceration, percolation, and Soxhlet extraction, and various solvents can be used, including methanol and ethanol.
When extracting berberine, it’s important to know that the alkaloid is sensitive to light and heat, both of which can cause it to degrade rapidly. This degradation can happen before and after the berberine is extracted. Thus, care must be taken during the handling and drying of plant sources before and during the extraction and storage stages as well.
For instance, source material dried in the shade instead of direct sun or in an oven will contain more berberine when processing begins. [2] Also, hot extraction using methanol or ethanol yields less berberine than cold extraction using those solvents [2].
Acidified solvents – ~0.5% acid content – can also be used in extraction (using both inorganic and organic acids). Hydrochloric, phosphoric, nitric, sulfuric, and acetic acids were all tested in rhizomes of Coptis chinesis Franch (Chinese goldthread) by Teng and Choi. [3] Phosphoric acid was superior; they found that cool acid-assisted extraction (25º C) gave 1.1 times more berberine content than reflux (70º C) and Soxhlet extraction (70º C).
Conventional extraction methods have their problems including large solvent volumes and extended extraction times. However, some newer techniques are highly relevant to berberine. They include ultrasound-assisted solvent extraction (USE), microwave-assisted solvent extraction (MAE), ultrahigh pressure extraction (UPE), supercritical fluid extraction (SFE), and pressurized liquid extraction (PLE).
As an example, one study illustrated the supercritical carbon dioxide can be combined with a surfactant, 1,2-propanediol at 200-500 bar to maximize berberine yield (rather than using an ethanol cosolvent which reduced berberine content). [4]
These newer methods have better results compared to conventional methods. Most notably, they all reduce extraction time and raise yields. They also produce higher quality extracts. [1]
Image Source: Laila from Pixabay
References:
- Neag MA, et al. Berberine: Botanical occurrence, traditional uses, extraction methods, and relevance in cardiovascular, metabolic, hepatic, and renal disorders. Frontiers in Pharmacology. 2018;9(557). https://doi.org/10.3389/fphar.2018.00557. [Impact Factor: 4.400; Times Cited: 62 (Semantic Scholar)]
- Babu NHR, Thriveni HN, Vasudeva R. Influence of drying methods and extraction procedures on the recovery of berberine content in Coscinium fenestratum. J Nat ProdPlant Resour. 2012;2:540–544. [Impact Factor: 3.779; Times Cited: 5 (Semantic Scholar)]
- Teng H, Choi O. Optimum extraction of bioactive alkaloid compounds from Rhizome coptidis(Coptis chinensis) using response surface methodology. Solvent Extr Res Dev. 2013;20:91–104. [Impact Factor: 1.321; Times Cited: 7 (Semantic Scholar)]
- Liu B, et al. Extraction of berberine from rhizome of Coptis chinensisFranch using supercritical fluid J Pharm Biomed Anal. 2006;41:1056–1060. doi:10.1016/j.jpba.2006.01.034. [Impact Factor: 3.209; Times Cited: 63 (Semantic Scholar)]