Integrating Pharmacology and Gut Microbiota Analysis to Explore the Mechanism of Citri Reticulatae Pericarpium Against Reserpine-Induced Spleen Deficiency in Rats.
Identifieur interne : 000129 ( Main/Exploration ); précédent : 000128; suivant : 000130Integrating Pharmacology and Gut Microbiota Analysis to Explore the Mechanism of Citri Reticulatae Pericarpium Against Reserpine-Induced Spleen Deficiency in Rats.
Auteurs : Yuying Zheng [République populaire de Chine] ; Xuan Zeng [République populaire de Chine] ; Pan Chen [République populaire de Chine] ; Tingting Chen [République populaire de Chine] ; Wei Peng [République populaire de Chine] ; Weiwei Su [République populaire de Chine]Source :
- Frontiers in pharmacology [ 1663-9812 ] ; 2020.
Abstract
Citri Reticulatae Pericarpium (CRP), dried peels of Citrus reticulata Blanco and its cultivars, is an important traditional Chinese medicine for the treatment of spleen deficiency-related diseases. To date, the mechanism of CRP alleviating spleen deficiency has not been well investigated. This study aimed to explore corresponding mechanisms with integrating pharmacology and gut microbiota analysis. Firstly, the therapeutic effects of CRP against spleen deficiency were evaluated in reserpine-treated rats. CRP was found to effectively relieve the typical symptoms of spleen deficiency, including poor digestion and absorption capacity, and disorder in gastrointestinal hormones, immune cytokines and oxidative stress. Secondly, high throughput 16S rRNA gene sequencing revealed that CRP could not only up-regulate some short-chain fatty acids producing and anti-inflammatory bacteria but also down-regulate certain spleen deficiency aggravated related bacteria, eventually led to the rebalance of gut microbiota in spleen deficiency rats. In addition, a total of 49 compounds derived from CRP were identified in rat urine using ultra-high performance liquid chromatography-quadrupole- time of flight tandem mass spectrometry. Network pharmacology analysis showed that apigenin, luteolin, naringenin, hesperidin, hesperetin, homoeriodictyol, dihydroxy-tetramethoxyflavone, and monohydroxy-tetramethoxyflavone were the core bioactive components for CRP against spleen deficiency. Further Gene Ontology analysis and pathway enrichment suggested that therapeutic effects of CRP against spleen deficiency involved multiple pathways such as tumor necrosis factor signaling, hypoxia-inducible factor-1 signaling and Toll-like receptor signaling pathway. These results would help to understand the mechanism of CRP alleviating spleen deficiency and provide a reference for further studies.
DOI: 10.3389/fphar.2020.586350
PubMed: 33192528
PubMed Central: PMC7606944
Affiliations:
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and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Zeng, Xuan" sort="Zeng, Xuan" uniqKey="Zeng X" first="Xuan" last="Zeng">Xuan Zeng</name><affiliation wicri:level="3"><nlm:affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Chen, Pan" sort="Chen, Pan" uniqKey="Chen P" first="Pan" last="Chen">Pan Chen</name><affiliation wicri:level="3"><nlm:affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Chen, Tingting" sort="Chen, Tingting" uniqKey="Chen T" first="Tingting" last="Chen">Tingting Chen</name><affiliation wicri:level="3"><nlm:affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Peng, Wei" sort="Peng, Wei" uniqKey="Peng W" first="Wei" last="Peng">Wei Peng</name><affiliation wicri:level="3"><nlm:affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Su, Weiwei" sort="Su, Weiwei" uniqKey="Su W" first="Weiwei" last="Su">Weiwei Su</name><affiliation wicri:level="3"><nlm:affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></affiliation></author></analytic><series><title level="j">Frontiers in pharmacology</title><idno type="ISSN">1663-9812</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Citri Reticulatae Pericarpium (CRP), dried peels of <i>Citrus reticulata</i> Blanco and its cultivars, is an important traditional Chinese medicine for the treatment of spleen deficiency-related diseases. To date, the mechanism of CRP alleviating spleen deficiency has not been well investigated. This study aimed to explore corresponding mechanisms with integrating pharmacology and gut microbiota analysis. Firstly, the therapeutic effects of CRP against spleen deficiency were evaluated in reserpine-treated rats. CRP was found to effectively relieve the typical symptoms of spleen deficiency, including poor digestion and absorption capacity, and disorder in gastrointestinal hormones, immune cytokines and oxidative stress. Secondly, high throughput 16S rRNA gene sequencing revealed that CRP could not only up-regulate some short-chain fatty acids producing and anti-inflammatory bacteria but also down-regulate certain spleen deficiency aggravated related bacteria, eventually led to the rebalance of gut microbiota in spleen deficiency rats. In addition, a total of 49 compounds derived from CRP were identified in rat urine using ultra-high performance liquid chromatography-quadrupole- time of flight tandem mass spectrometry. Network pharmacology analysis showed that apigenin, luteolin, naringenin, hesperidin, hesperetin, homoeriodictyol, dihydroxy-tetramethoxyflavone, and monohydroxy-tetramethoxyflavone were the core bioactive components for CRP against spleen deficiency. Further Gene Ontology analysis and pathway enrichment suggested that therapeutic effects of CRP against spleen deficiency involved multiple pathways such as tumor necrosis factor signaling, hypoxia-inducible factor-1 signaling and Toll-like receptor signaling pathway. These results would help to understand the mechanism of CRP alleviating spleen deficiency and provide a reference for further studies.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33192528</PMID><DateRevised><Year>2020</Year><Month>11</Month><Day>17</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1663-9812</ISSN><JournalIssue CitedMedium="Print"><Volume>11</Volume><PubDate><Year>2020</Year></PubDate></JournalIssue><Title>Frontiers in pharmacology</Title><ISOAbbreviation>Front Pharmacol</ISOAbbreviation></Journal><ArticleTitle>Integrating Pharmacology and Gut Microbiota Analysis to Explore the Mechanism of Citri Reticulatae Pericarpium Against Reserpine-Induced Spleen Deficiency in Rats.</ArticleTitle><Pagination><MedlinePgn>586350</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/fphar.2020.586350</ELocationID><Abstract><AbstractText>Citri Reticulatae Pericarpium (CRP), dried peels of <i>Citrus reticulata</i> Blanco and its cultivars, is an important traditional Chinese medicine for the treatment of spleen deficiency-related diseases. To date, the mechanism of CRP alleviating spleen deficiency has not been well investigated. This study aimed to explore corresponding mechanisms with integrating pharmacology and gut microbiota analysis. Firstly, the therapeutic effects of CRP against spleen deficiency were evaluated in reserpine-treated rats. CRP was found to effectively relieve the typical symptoms of spleen deficiency, including poor digestion and absorption capacity, and disorder in gastrointestinal hormones, immune cytokines and oxidative stress. Secondly, high throughput 16S rRNA gene sequencing revealed that CRP could not only up-regulate some short-chain fatty acids producing and anti-inflammatory bacteria but also down-regulate certain spleen deficiency aggravated related bacteria, eventually led to the rebalance of gut microbiota in spleen deficiency rats. In addition, a total of 49 compounds derived from CRP were identified in rat urine using ultra-high performance liquid chromatography-quadrupole- time of flight tandem mass spectrometry. Network pharmacology analysis showed that apigenin, luteolin, naringenin, hesperidin, hesperetin, homoeriodictyol, dihydroxy-tetramethoxyflavone, and monohydroxy-tetramethoxyflavone were the core bioactive components for CRP against spleen deficiency. Further Gene Ontology analysis and pathway enrichment suggested that therapeutic effects of CRP against spleen deficiency involved multiple pathways such as tumor necrosis factor signaling, hypoxia-inducible factor-1 signaling and Toll-like receptor signaling pathway. These results would help to understand the mechanism of CRP alleviating spleen deficiency and provide a reference for further studies.</AbstractText><CopyrightInformation>Copyright © 2020 Zheng, Zeng, Chen, Chen, Peng and Su.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Yuying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zeng</LastName><ForeName>Xuan</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Pan</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Tingting</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peng</LastName><ForeName>Wei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Su</LastName><ForeName>Weiwei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-Market Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>10</Month><Day>20</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Pharmacol</MedlineTA><NlmUniqueID>101548923</NlmUniqueID><ISSNLinking>1663-9812</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Citri Reticulatae Pericarpium</Keyword><Keyword MajorTopicYN="N">gut microbiota</Keyword><Keyword MajorTopicYN="N">metabolites</Keyword><Keyword MajorTopicYN="N">network pharmacology</Keyword><Keyword MajorTopicYN="N">spleen deficiency</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>07</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>09</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>11</Month><Day>16</Day><Hour>8</Hour><Minute>44</Minute></PubMedPubDate><PubMedPubDate 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sortKey="Peng, Wei" sort="Peng, Wei" uniqKey="Peng W" first="Wei" last="Peng">Wei Peng</name><name sortKey="Su, Weiwei" sort="Su, Weiwei" uniqKey="Su W" first="Weiwei" last="Su">Weiwei Su</name><name sortKey="Zeng, Xuan" sort="Zeng, Xuan" uniqKey="Zeng X" first="Xuan" last="Zeng">Xuan Zeng</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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