February 24, 2021, Professor Jian-Dong Jiang and Professor Yan Wang from State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, and Academician Xuetao Cao from Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, jointly published a paper online in Signal Transduction and Targeted Therapy titled "Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota" as co-corresponding authors. It is the first to demonstrate that berberine (BBR) ameliorates Parkinson's disease by increasing dopamine/dopamine levels in the brain through the gut microbiota.
Dopamine is synthesized mainly in neurons in the brain. In this paper, they found that there is a phenylalanine-tyrosine-dopa-dopamine synthesis pathway in the intestinal bacterial, and oral BBR may provide H• through dihydroberberine (a reduced BBR produced by nitroreductase of bacteria) and promote the conversion of dihydrobiopterin (BH2) to tetrahydrobiopterin (BH4). Increased BH4 enhances tyrosine hydroxylase (TH) activity, which in turn accelerates the production of levodopa by the gut microbiota. Levodopa, produced by gut microbiota, travels through the circulation to the brain, where it is converted into dopamine.
To verify that BBR may activate the "gut-brain" pathway, Enterococcus faecalis and Enterococcus faecium were transplanted into mice with Parkinson's disease (PD). These two bacteria significantly increased dopamine in the brain of mice and improved PD symptoms; BBR in combination with bacteria showed a better therapeutic effect than bacteria alone. In addition, 2,4,6-trimethylpyrano-tetrafluoroborate (TMP-TFB)-derived dopamine MALDI-MS mass spectrometry was used to detect elevated dopamine levels in the striatum of mice given Enterococcus, and BBR enhanced the imaging intensity of dopamine in the brain. These results suggest that BBR acts as an agonist for TH in Enterococcus and may lead to the production of levodopa in the gut. A clinical study of 28 patients with hyperlipidemia further confirmed that oral BBR increased levodopa levels in blood and feces through the gut microbiota. Therefore, BBR may improve brain function by upregulating the biosynthesis of levodopa in the gut microbiota through vitamin-like effect. The mechanism is shown in the figure below.
The original link:https://www.nature.com/articles/s41392-020-00456-5
