Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota

Wang, Yan; Tong, Qian; Ma, Shu-Rong; Zhao, Zhen-Xiong; Pan, Li-Bin; Cong, Lin; Han, Pei; Peng, Ran; Yu, Hang; Lin, Yuan; Gao, Tian-Le; Shou, Jia-Wen; Li, Xiao-Yang; Zhang, Xian-Feng; Zhang, Zheng-Wei; Fu, Jie; Wen, Bao-Ying; Yu, Jin-Bo; Cao, Xuetao; Jiang, Jian-Dong

doi:10.1038/s41392-020-00456-5

Cited by 319Parkinson's Disease Mechanisms and TreatmentsBerberine and alkaloids researchGut microbiota and health

Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota

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Wang, Yan, Tong, Qian, Ma, Shu-Rong, Zhao, Zhen-Xiong, Pan, Li-Bin, Cong, Lin, Han, Pei, Peng, Ran +12 more·2021·Signal Transduction and Targeted Therapy

DOI 10.1038/s41392-020-00456-5PMC PMC7902645

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Abstract

The phenylalanine–tyrosine–dopa–dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa ( l -dopa) with tetrahydrobiopterin (BH 4 ) as a coenzyme. Here, we show that oral berberine (BBR) might supply H • through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH 4 from dihydrobiopterin; the increased BH 4 enhances TH activity, which accelerates the production of l -dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The l -dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut–brain dialog activated by BBR’s effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson’s disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus , and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of l -dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal l -dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of l -dopa in the gut microbiota through a vitamin-like effect.

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Gut microbiota is capable of producing or stimulating the production of neurotransmitters, including serotonin, dopamine, and γ-aminobutyric acid (GABA).
“Studies have shown that gut microbiota is capable of producing or stimulating the production of neurotransmitters, including serotonin,33–35 dopamine,36 and γ-aminobutyric acid (GABA).37”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [36]
Upon oral berberine intake, the enterococcal tyrosine hydroxylase enzyme synthetizes L-dopa, which is then converted to dopamine in the brain, thus improving cognitive symptoms.
“upon oral berberine intake, the enterococcal TH enzyme synthetizes L-dopa, which is then converted to dopamine in the brain, thus improving cognitive symptoms [204]”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [204]

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Authors: Wang, Y., Tong, Q., Ma, S.-R., Zhao, Z.-X., Pan, L.-B., Cong, L., Han, P., Peng, R., Yu, H., Lin, Y., Gao, T.-L., Shou, J.-W., Li, X.-Y., Zhang, X.-F., Zhang, Z.-W., Fu, J., Wen, B.-Y., Yu, J.-B., Cao, X., & Jiang, J.-D.
Affiliations: Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
First Hospital of Jilin University (CN)
Corresponding author: Wang, Yan
Cao, Xuetao
Jiang, Jian-Dong
ORCID: Tong, Qian
Cong, Lin
Han, Pei
Peng, Ran
Yu, Hang
Lin, Yuan
Shou, Jia-Wen
Fu, Jie
Cao, Xuetao
Jiang, Jian-Dong
Venue: Signal Transduction and Targeted Therapy
Publisher: Springer Science and Business Media LLC
Published: 2021-02-24
Volume: 6
Issue: 1
Pages: 77-77
ISSN: 2059-3635 (ISSN-L)
DOI: 10.1038/s41392-020-00456-5
PMC: PMC7902645
OpenAlex: W3132116259
Cited by: 319
References: 81
Citations by year: 2026: 31 · 2025: 98 · 2024: 61 · 2023: 64 · 2022: 48 · 2021: 17
FWCI: 22.73
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Natural Science Foundation of China (81973290, 81573493, Z141102004414062)
Topics: Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords: berberine, Parkinson's disease, gut microbiota, dopamine, tyrosine hydroxylase, tetrahydrobiopterin, levodopa, dihydroberberine, Enterococcus faecalis, Enterococcus faecium, gut-brain axis, hyperlipidemia
MeSH terms: Gastrointestinal Microbiome, Animals, Berberine, Corpus Striatum, Dihydroxyphenylalanine, Dopamine, Humans, Levodopa, Parkinson Disease, Enterococcus faecalis, Tyrosine 3-Monooxygenase, Enterococcus faecium, Mice

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Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota

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