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    Home > Active Ingredient News > Study of Nervous System > STTT Jiang Jiandong/Cao Xuetao/Wang Yan proved for the first time that oral berberine can improve Parkinson's disease

    STTT Jiang Jiandong/Cao Xuetao/Wang Yan proved for the first time that oral berberine can improve Parkinson's disease

    • Last Update: 2021-11-14
    • Source: Internet
    • Author: User
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    Editor’s note iNature is China’s largest academic official account.
    It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
    The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
    .

    The iNature phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain
    .

    In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme, which can hydroxylate tyrosine and use tetrahydrobiopterin (BH4) as a coenzyme to produce levodopa (L-dopa)
    .

    Recently, the Chinese Academy of Medical Sciences/Peking Union Medical College Jiang Jiandong, Cao Xuetao and Wang Yan jointly published an online communication titled "Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson's disease by regulating gut microbiota" in Signal Transduction and Targeted Therapy (IF=18.
    19).
    "The research paper shows that oral berberine (BBR) may provide H• and promote BH4 produced by dihydrobiopterin through dihydroberberine (reducing BBR produced by bacterial nitrification reductase)
    .

    The increased BH4 enhances TH activity, thereby accelerating the production of L-dopa by intestinal bacteria
    .

    Oral BBR behaves like vitamins
    .

    Levodopa produced by intestinal bacteria enters the brain through the circulation and is converted into dopamine
    .

    In order to verify that the effect of BBR activates the gut-brain axis, Enterococcus faecalis was transplanted into Parkinson's disease (PD) mice
    .

    This bacterium significantly increased brain dopamine in mice and improved PD performance
    .

    In addition, the combination of BBR and bacteria showed a better therapeutic effect than bacteria alone
    .

    In addition, 2,4,6-trimethylpyrantetrafluoroborate (TMP-TFB)-derived MALDI-MS imaging of dopamine confirmed that the level of dopamine in the striatum of mice receiving oral enterococcus was elevated, while BBR was enhanced.
    The imaging intensity of brain dopamine
    .

    These results indicate that BBR is an agonist of TH in enterococci and may lead to the production of L-dopa in the intestine
    .

    In addition, a study of 28 patients with hyperlipidemia confirmed that oral BBR can increase the blood/fecal levodopa of intestinal bacteria
    .

    Therefore, BBR may up-regulate the biosynthesis of L-dopa in the intestinal flora through vitamin-like effects, thereby improving brain function
    .

    Intestinal flora is a recognized factor affecting brain function, but its mechanism is still unclear
    .

    Dopamine is a major neurotransmitter, and its level in the brain is closely related to brain function
    .

    Dopamine is mainly synthesized in brain neurons
    .

    In the human body, the main synthesis pathway of dopamine is "L-phenylalanine (Phe)→L-tyrosine (Tyr)→(s)-3,4-dihydroxyphenylalanine (levodopa, L -Dopa→dopamine (Phe-Tyr-dopa-dopamine)" metabolic pathway
    .

    In this process, the first stage (Phe-Tyr step) is catalyzed by phenylalanine hydroxylase (PAH), and the conversion mainly occurs in Liver and kidneys
    .

    The liver (or kidney) and/or blood-derived tyrosine (in the diet) can cross the blood-brain barrier and enter the brain
    .

    Tyr-dopa-dopamine conversion is the second stage, which is completed in the brain by tyrosine hydroxylase (TH) and dopa decarboxylase (DDC)
    .

    Disruption of this pathway can cause neurological diseases, such as phenylketonuria and Parkinson’s disease (PD)
    .

    Tyrosine hydroxylase (TH) is the rate-limiting enzyme for catecholamine biosynthesis, which can hydroxylate L-Tyr to L-dopa
    .

    Tyrosine hydroxylase (TH) is an iron-containing monooxygenase that requires tetrahydrobiopterin (BH4) as a cofactor
    .

    When L-dopa is produced, BH4 is converted to 7,8-dihydrobiopterin (BH2), during which BH4 is continuously consumed
    .

    BH4 can be synthesized in the cytoplasm in two ways
    .

    Under normal conditions, BH4 can be synthesized by the GTP (guanosine triphosphate)-NH2P3 (D-erythro-7,8-dihydropterin triphosphate)-PPH4 (6-pyruvyltetrahydropterin)-BH4 pathway , Called "source synthesis"; on the other hand, BH4 can be supplemented by the repair pathway of Sepaapterin→BH2→BH4, and dihydrofolate reductase (DHFR) is the key enzyme responsible for converting BH2 into BH4
    .

    Therefore, it was found that DHFR agonists may be an effective method to increase BH4 levels and enhance TH activity
    .

    The article pattern (picture from Signal Transduction and Targeted Therapy) has confirmed the BH4 producing bacteria in the intestinal flora, and the Phe-Tyr-dopa-dopamine metabolic pathway is also present in the microorganisms
    .

    This suggests that the bacteria may contain homologues of the gene for the enzyme that mammals use to produce dopamine
    .

    In fact, some bacteria can be regarded as biotech factories that produce dopa/dopamine
    .

    Recent studies have shown that the intestinal flora can regulate brain function through microbial-derived metabolites (such as serotonin)
    .

    Therefore, the key question becomes how to regulate brain function in a practical way
    .

    Berberine (BBR) is a natural compound (molecular weight 371.
    8) extracted from herbs, such as berberine and berberine
    .

    BBR has been used as an over-the-counter (OTC) drug in China to treat patients with diarrhea
    .

    Since 2004, BBR has been identified as a safe and effective hyperlipidemia and type 2 diabetes drug with a novel mechanism
    .

    In the past ten years, the clinical efficacy of BBR in reducing blood lipids and blood sugar has been widely confirmed
    .

    In addition, independent research teams have repeatedly reported that BBR has a beneficial effect on brain function
    .

    The study found that oral BBR can trigger the biosynthesis of BH4 in the intestinal flora, increase blood and brain dopa/dopamine concentration to enhance TH activity to produce L-dopa, and ultimately improve the animal's body function
    .

    Detection of pathway intermediates in clinical subjects confirmed the effects of BBR on humans
    .

    These results may provide new ideas for controlling the crosstalk between the intestine and the brain
    .

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