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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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 |
format | Article |
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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.</description><identifier>ISSN: 2042-6496</identifier><identifier>ISSN: 2042-650X</identifier><identifier>EISSN: 2042-650X</identifier><identifier>DOI: 10.1039/d4fo00538d</identifier><identifier>PMID: 38639730</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>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</subject><ispartof>Food & function, 2024-05, Vol.15 (1), p.5287-5299</ispartof><rights>Copyright Royal Society of Chemistry 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c296t-2224576e3008a639949fdd4ade375ef2f454d19b7287d51eda9823b7943e04293</cites><orcidid>0000-0002-9670-4349 ; 0000-0003-1078-899X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38639730$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Ziqiong</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Wang, Fangyuan</creatorcontrib><creatorcontrib>Zhu, Guanghao</creatorcontrib><creatorcontrib>Qi, Shenglan</creatorcontrib><creatorcontrib>Wang, Haonan</creatorcontrib><creatorcontrib>Ma, Yuhe</creatorcontrib><creatorcontrib>Zhu, Rong</creatorcontrib><creatorcontrib>Zheng, Yuejuan</creatorcontrib><creatorcontrib>Ge, Guangbo</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><title>Bioactive components and mechanisms of Pu-erh tea in improving levodopa metabolism in rats through COMT inhibition</title><title>Food & function</title><addtitle>Food Funct</addtitle><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.</description><subject>Animals</subject><subject>Biological activity</subject><subject>Camellia sinensis - chemistry</subject><subject>Catechin</subject><subject>Catechin - analogs & derivatives</subject><subject>Catechin - chemistry</subject><subject>Catechin - pharmacology</subject><subject>Catechol</subject><subject>Catechol O-methyltransferase</subject><subject>Catechol O-Methyltransferase - metabolism</subject><subject>Catechol O-Methyltransferase Inhibitors - pharmacology</subject><subject>Components</subject><subject>Epicatechin</subject><subject>Epigallocatechin gallate</subject><subject>Fluorescence</subject><subject>Hormones</subject><subject>Humans</subject><subject>Inactivation</subject><subject>Inhibitors</subject><subject>Kinetics</subject><subject>Levodopa</subject><subject>Levodopa - metabolism</subject><subject>Male</subject><subject>Metabolism</subject><subject>Methylation</subject><subject>Methyldopa</subject><subject>Methyltransferase</subject><subject>Molecular Docking Simulation</subject><subject>Movement disorders</subject><subject>Natural products</subject><subject>Neurodegenerative diseases</subject><subject>Neurotransmitters</subject><subject>Parkinson Disease - drug therapy</subject><subject>Parkinson Disease - metabolism</subject><subject>Parkinson's disease</subject><subject>Plant Extracts - chemistry</subject><subject>Plant Extracts - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Tea</subject><subject>Tea - chemistry</subject><issn>2042-6496</issn><issn>2042-650X</issn><issn>2042-650X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0U1LxDAQBuAgiop68a4EvIhQTZO0TY666xesrAcFbyVtpjbSJmvSLvjvzbp-gLkkJA_DOxmEDlNynhImLzRvHCEZE3oD7VLCaZJn5GXz58xlvoMOQngjcTEphRTbaIeJnMmCkV3kr4xT9WCWgGvXL5wFOwSsrMY91K2yJvQBuwY_jgn4Fg-gsLHY9Avvlsa-4g6WTruFinxQleuiXwGvYpWh9W58bfFk_vAUL1tTmcE4u4-2GtUFOPje99DzzfXT5C6ZzW_vJ5ezpKYyHxJKKc-KHBghQsW4kstGa640sCKDhjY84zqVVUFFobMUtJKCsqqQnEFsXbI9dLquG7O-jxCGsjehhq5TFtwYSkY4IwUTIo305B99c6O3MV1UWZ4JSbmI6mytau9C8NCUC2965T_KlJSrYZRTfjP_GsY04uPvkmPVg_6lP18fwdEa-FD_vv5Nk30CfqCNvQ</recordid><startdate>20240520</startdate><enddate>20240520</enddate><creator>Zhou, Ziqiong</creator><creator>Li, Yan</creator><creator>Wang, Fangyuan</creator><creator>Zhu, Guanghao</creator><creator>Qi, Shenglan</creator><creator>Wang, Haonan</creator><creator>Ma, Yuhe</creator><creator>Zhu, Rong</creator><creator>Zheng, Yuejuan</creator><creator>Ge, Guangbo</creator><creator>Wang, Ping</creator><general>Royal Society of Chemistry</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9670-4349</orcidid><orcidid>https://orcid.org/0000-0003-1078-899X</orcidid></search><sort><creationdate>20240520</creationdate><title>Bioactive components and mechanisms of Pu-erh tea in improving levodopa metabolism in rats through COMT inhibition</title><author>Zhou, Ziqiong ; Li, Yan ; Wang, Fangyuan ; Zhu, Guanghao ; Qi, Shenglan ; Wang, Haonan ; Ma, Yuhe ; Zhu, Rong ; Zheng, Yuejuan ; Ge, Guangbo ; Wang, Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c296t-2224576e3008a639949fdd4ade375ef2f454d19b7287d51eda9823b7943e04293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Biological activity</topic><topic>Camellia sinensis - chemistry</topic><topic>Catechin</topic><topic>Catechin - analogs & derivatives</topic><topic>Catechin - chemistry</topic><topic>Catechin - pharmacology</topic><topic>Catechol</topic><topic>Catechol O-methyltransferase</topic><topic>Catechol O-Methyltransferase - metabolism</topic><topic>Catechol O-Methyltransferase Inhibitors - pharmacology</topic><topic>Components</topic><topic>Epicatechin</topic><topic>Epigallocatechin gallate</topic><topic>Fluorescence</topic><topic>Hormones</topic><topic>Humans</topic><topic>Inactivation</topic><topic>Inhibitors</topic><topic>Kinetics</topic><topic>Levodopa</topic><topic>Levodopa - metabolism</topic><topic>Male</topic><topic>Metabolism</topic><topic>Methylation</topic><topic>Methyldopa</topic><topic>Methyltransferase</topic><topic>Molecular Docking Simulation</topic><topic>Movement disorders</topic><topic>Natural products</topic><topic>Neurodegenerative diseases</topic><topic>Neurotransmitters</topic><topic>Parkinson Disease - drug therapy</topic><topic>Parkinson Disease - metabolism</topic><topic>Parkinson's disease</topic><topic>Plant Extracts - chemistry</topic><topic>Plant Extracts - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Tea</topic><topic>Tea - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Ziqiong</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Wang, Fangyuan</creatorcontrib><creatorcontrib>Zhu, Guanghao</creatorcontrib><creatorcontrib>Qi, Shenglan</creatorcontrib><creatorcontrib>Wang, Haonan</creatorcontrib><creatorcontrib>Ma, Yuhe</creatorcontrib><creatorcontrib>Zhu, Rong</creatorcontrib><creatorcontrib>Zheng, Yuejuan</creatorcontrib><creatorcontrib>Ge, Guangbo</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Food & 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 & 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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