Bioactive components and mechanisms of Pu-erh tea in improving levodopa metabolism in rats through COMT inhibition

Catechol- O -methyltransferase (COMT) plays a central role in the metabolic inactivation of endogenous neurotransmitters and xenobiotic drugs and hormones having catecholic structures. Its inhibitors are used in clinical practice to treat Parkinson's disease. In this study, a fluorescence-based...

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Veröffentlicht in:Food & function 2024-05, Vol.15 (1), p.5287-5299
Hauptverfasser: Zhou, Ziqiong, Li, Yan, Wang, Fangyuan, Zhu, Guanghao, Qi, Shenglan, Wang, Haonan, Ma, Yuhe, Zhu, Rong, Zheng, Yuejuan, Ge, Guangbo, Wang, Ping
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container_issue 1
container_start_page 5287
container_title Food & function
container_volume 15
creator Zhou, Ziqiong
Li, Yan
Wang, Fangyuan
Zhu, Guanghao
Qi, Shenglan
Wang, Haonan
Ma, Yuhe
Zhu, Rong
Zheng, Yuejuan
Ge, Guangbo
Wang, Ping
description Catechol- O -methyltransferase (COMT) plays a central role in the metabolic inactivation of endogenous neurotransmitters and xenobiotic drugs and hormones having catecholic structures. Its inhibitors are used in clinical practice to treat Parkinson's disease. In this study, a fluorescence-based visualization inhibitor screening method was developed to assess the inhibition activity on COMT both in vitro and in living cells. Following the screening of 94 natural products, Pu-erh tea extract exhibited the most potent inhibitory effect on COMT with an IC 50 value of 0.34 μg mL −1 . In vivo experiments revealed that Pu-erh tea extract substantially hindered COMT-mediated levodopa metabolism in rats, resulting in a significant increase in levodopa levels and a notable decrease in 3- O -methyldopa in plasma. Subsequently, the chemical components of Pu-erh tea were analyzed using UHPLC-Q-Exactive Orbitrap HRMS, identifying 24 major components. Among them, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, and catechin gallate exhibited potent inhibition of COMT activity with IC 50 values from 93.7 nM to 125.8 nM and were the main bioactive constituents in Pu-erh tea responsible for its COMT inhibition effect. Inhibition kinetics analyses and docking simulations revealed that these compounds competitively inhibit COMT-mediated O -methylation at the catechol site. Overall, this study not only explained how Pu-erh tea catechins inhibit COMT, suggesting Pu-erh tea as a potential dietary intervention for Parkinson's disease, but also introduced a new strategy for discovering COMT inhibitors more effectively. Pu-erh tea can enhance the efficacy of levodopa in treating Parkinson's disease by inhibiting COMT activity and improving levodopa's pharmacokinetic behavior in rats.
doi_str_mv 10.1039/d4fo00538d
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Its inhibitors are used in clinical practice to treat Parkinson's disease. In this study, a fluorescence-based visualization inhibitor screening method was developed to assess the inhibition activity on COMT both in vitro and in living cells. Following the screening of 94 natural products, Pu-erh tea extract exhibited the most potent inhibitory effect on COMT with an IC 50 value of 0.34 μg mL −1 . In vivo experiments revealed that Pu-erh tea extract substantially hindered COMT-mediated levodopa metabolism in rats, resulting in a significant increase in levodopa levels and a notable decrease in 3- O -methyldopa in plasma. Subsequently, the chemical components of Pu-erh tea were analyzed using UHPLC-Q-Exactive Orbitrap HRMS, identifying 24 major components. Among them, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, and catechin gallate exhibited potent inhibition of COMT activity with IC 50 values from 93.7 nM to 125.8 nM and were the main bioactive constituents in Pu-erh tea responsible for its COMT inhibition effect. Inhibition kinetics analyses and docking simulations revealed that these compounds competitively inhibit COMT-mediated O -methylation at the catechol site. Overall, this study not only explained how Pu-erh tea catechins inhibit COMT, suggesting Pu-erh tea as a potential dietary intervention for Parkinson's disease, but also introduced a new strategy for discovering COMT inhibitors more effectively. 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Its inhibitors are used in clinical practice to treat Parkinson's disease. In this study, a fluorescence-based visualization inhibitor screening method was developed to assess the inhibition activity on COMT both in vitro and in living cells. Following the screening of 94 natural products, Pu-erh tea extract exhibited the most potent inhibitory effect on COMT with an IC 50 value of 0.34 μg mL −1 . In vivo experiments revealed that Pu-erh tea extract substantially hindered COMT-mediated levodopa metabolism in rats, resulting in a significant increase in levodopa levels and a notable decrease in 3- O -methyldopa in plasma. Subsequently, the chemical components of Pu-erh tea were analyzed using UHPLC-Q-Exactive Orbitrap HRMS, identifying 24 major components. Among them, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, and catechin gallate exhibited potent inhibition of COMT activity with IC 50 values from 93.7 nM to 125.8 nM and were the main bioactive constituents in Pu-erh tea responsible for its COMT inhibition effect. Inhibition kinetics analyses and docking simulations revealed that these compounds competitively inhibit COMT-mediated O -methylation at the catechol site. Overall, this study not only explained how Pu-erh tea catechins inhibit COMT, suggesting Pu-erh tea as a potential dietary intervention for Parkinson's disease, but also introduced a new strategy for discovering COMT inhibitors more effectively. 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function</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Ziqiong</au><au>Li, Yan</au><au>Wang, Fangyuan</au><au>Zhu, Guanghao</au><au>Qi, Shenglan</au><au>Wang, Haonan</au><au>Ma, Yuhe</au><au>Zhu, Rong</au><au>Zheng, Yuejuan</au><au>Ge, Guangbo</au><au>Wang, Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bioactive components and mechanisms of Pu-erh tea in improving levodopa metabolism in rats through COMT inhibition</atitle><jtitle>Food &amp; function</jtitle><addtitle>Food Funct</addtitle><date>2024-05-20</date><risdate>2024</risdate><volume>15</volume><issue>1</issue><spage>5287</spage><epage>5299</epage><pages>5287-5299</pages><issn>2042-6496</issn><issn>2042-650X</issn><eissn>2042-650X</eissn><abstract>Catechol- O -methyltransferase (COMT) plays a central role in the metabolic inactivation of endogenous neurotransmitters and xenobiotic drugs and hormones having catecholic structures. Its inhibitors are used in clinical practice to treat Parkinson's disease. In this study, a fluorescence-based visualization inhibitor screening method was developed to assess the inhibition activity on COMT both in vitro and in living cells. Following the screening of 94 natural products, Pu-erh tea extract exhibited the most potent inhibitory effect on COMT with an IC 50 value of 0.34 μg mL −1 . In vivo experiments revealed that Pu-erh tea extract substantially hindered COMT-mediated levodopa metabolism in rats, resulting in a significant increase in levodopa levels and a notable decrease in 3- O -methyldopa in plasma. Subsequently, the chemical components of Pu-erh tea were analyzed using UHPLC-Q-Exactive Orbitrap HRMS, identifying 24 major components. Among them, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, and catechin gallate exhibited potent inhibition of COMT activity with IC 50 values from 93.7 nM to 125.8 nM and were the main bioactive constituents in Pu-erh tea responsible for its COMT inhibition effect. Inhibition kinetics analyses and docking simulations revealed that these compounds competitively inhibit COMT-mediated O -methylation at the catechol site. Overall, this study not only explained how Pu-erh tea catechins inhibit COMT, suggesting Pu-erh tea as a potential dietary intervention for Parkinson's disease, but also introduced a new strategy for discovering COMT inhibitors more effectively. Pu-erh tea can enhance the efficacy of levodopa in treating Parkinson's disease by inhibiting COMT activity and improving levodopa's pharmacokinetic behavior in rats.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>38639730</pmid><doi>10.1039/d4fo00538d</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-9670-4349</orcidid><orcidid>https://orcid.org/0000-0003-1078-899X</orcidid></addata></record>
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source MEDLINE; Royal Society Of Chemistry Journals 2008-
subjects Animals
Biological activity
Camellia sinensis - chemistry
Catechin
Catechin - analogs & derivatives
Catechin - chemistry
Catechin - pharmacology
Catechol
Catechol O-methyltransferase
Catechol O-Methyltransferase - metabolism
Catechol O-Methyltransferase Inhibitors - pharmacology
Components
Epicatechin
Epigallocatechin gallate
Fluorescence
Hormones
Humans
Inactivation
Inhibitors
Kinetics
Levodopa
Levodopa - metabolism
Male
Metabolism
Methylation
Methyldopa
Methyltransferase
Molecular Docking Simulation
Movement disorders
Natural products
Neurodegenerative diseases
Neurotransmitters
Parkinson Disease - drug therapy
Parkinson Disease - metabolism
Parkinson's disease
Plant Extracts - chemistry
Plant Extracts - pharmacology
Rats
Rats, Sprague-Dawley
Tea
Tea - chemistry
title Bioactive components and mechanisms of Pu-erh tea in improving levodopa metabolism in rats through COMT inhibition
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