Huyang yangkun formula protects against 4-Vinylcyclohexene diepoxide-induced premature ovarian insufficiency in rats via the Hippo-JAK2/STAT3 signaling pathway.
Identifieur interne : 000400 ( Main/Exploration ); précédent : 000399; suivant : 000401Huyang yangkun formula protects against 4-Vinylcyclohexene diepoxide-induced premature ovarian insufficiency in rats via the Hippo-JAK2/STAT3 signaling pathway.
Auteurs : Li Xie [République populaire de Chine] ; Sining Wu [République populaire de Chine] ; Dongdong Cao [République populaire de Chine] ; Meifang Li [République populaire de Chine] ; Jian Liu [République populaire de Chine] ; Guangning Nie [République populaire de Chine] ; Yang Li [République populaire de Chine] ; Hongyan Yang [République populaire de Chine]Source :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [ 1950-6007 ] ; 2019.
Descripteurs français
- KwdFr :
- Agents protecteurs (pharmacologie), Agents protecteurs (usage thérapeutique), Analyse de regroupements (MeSH), Animaux (MeSH), Composés vinyliques (MeSH), Cyclohexènes (MeSH), Facteur de transcription STAT-3 (métabolisme), Femelle (MeSH), Foie (anatomopathologie), Foie (effets des médicaments et des substances chimiques), Follicule ovarique (anatomopathologie), Follicule ovarique (effets des médicaments et des substances chimiques), Gene Ontology (MeSH), Hormone antimullérienne (sang), Insuffisance ovarienne primitive (génétique), Insuffisance ovarienne primitive (induit chimiquement), Insuffisance ovarienne primitive (sang), Insuffisance ovarienne primitive (traitement médicamenteux), Kinase Janus-2 (métabolisme), Modèles animaux de maladie humaine (MeSH), Modèles biologiques (MeSH), Médicaments issus de plantes chinoises (pharmacologie), Médicaments issus de plantes chinoises (usage thérapeutique), Normes de référence (MeSH), Protein-Serine-Threonine Kinases (métabolisme), Rat Sprague-Dawley (MeSH), Rein (anatomopathologie), Rein (effets des médicaments et des substances chimiques), Transduction du signal (MeSH).
- MESH :
- anatomopathologie : Foie, Follicule ovarique, Rein.
- effets des médicaments et des substances chimiques : Foie, Follicule ovarique, Rein.
- génétique : Insuffisance ovarienne primitive.
- induit chimiquement : Insuffisance ovarienne primitive.
- métabolisme : Facteur de transcription STAT-3, Kinase Janus-2, Protein-Serine-Threonine Kinases.
- pharmacologie : Agents protecteurs, Médicaments issus de plantes chinoises.
- sang : Hormone antimullérienne, Insuffisance ovarienne primitive.
- traitement médicamenteux : Insuffisance ovarienne primitive.
- usage thérapeutique : Agents protecteurs, Médicaments issus de plantes chinoises.
- Analyse de regroupements, Animaux, Composés vinyliques, Cyclohexènes, Femelle, Gene Ontology, Modèles animaux de maladie humaine, Modèles biologiques, Normes de référence, Rat Sprague-Dawley, Transduction du signal.
English descriptors
- KwdEn :
- Animals (MeSH), Anti-Mullerian Hormone (blood), Cluster Analysis (MeSH), Cyclohexenes (MeSH), Disease Models, Animal (MeSH), Drugs, Chinese Herbal (pharmacology), Drugs, Chinese Herbal (therapeutic use), Female (MeSH), Gene Ontology (MeSH), Janus Kinase 2 (metabolism), Kidney (drug effects), Kidney (pathology), Liver (drug effects), Liver (pathology), Models, Biological (MeSH), Ovarian Follicle (drug effects), Ovarian Follicle (pathology), Primary Ovarian Insufficiency (blood), Primary Ovarian Insufficiency (chemically induced), Primary Ovarian Insufficiency (drug therapy), Primary Ovarian Insufficiency (genetics), Protective Agents (pharmacology), Protective Agents (therapeutic use), Protein-Serine-Threonine Kinases (metabolism), Rats, Sprague-Dawley (MeSH), Reference Standards (MeSH), STAT3 Transcription Factor (metabolism), Signal Transduction (MeSH), Vinyl Compounds (MeSH).
- MESH :
- chemical , blood : Anti-Mullerian Hormone.
- chemical , metabolism : Janus Kinase 2, Protein-Serine-Threonine Kinases, STAT3 Transcription Factor.
- chemical , pharmacology : Drugs, Chinese Herbal, Protective Agents.
- chemical , therapeutic use : Drugs, Chinese Herbal, Protective Agents.
- blood : Primary Ovarian Insufficiency.
- chemically induced : Primary Ovarian Insufficiency.
- drug effects : Kidney, Liver, Ovarian Follicle.
- drug therapy : Primary Ovarian Insufficiency.
- genetics : Primary Ovarian Insufficiency.
- pathology : Kidney, Liver, Ovarian Follicle.
- Animals, Cluster Analysis, Cyclohexenes, Disease Models, Animal, Female, Gene Ontology, Models, Biological, Rats, Sprague-Dawley, Reference Standards, Signal Transduction, Vinyl Compounds.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE
Huyang Yangkun Formula (HYF) has been prescribed for premature ovarian insufficiency (POI) for decades in the clinical setting. Little is known regarding its underlying molecular mechanism. This study was conducted to elucidate the possible mechanism of the protective potential of HYF against POI induced by the industrial chemical 4-vinylcyclohexene diepoxide (VCD) in rats.
AIM OF THE STUDY
Quality control of HYF was conducted via HPLC and UPLC-MS. Female rats were injected with VCD (160 mg/kg) daily for 15 days. Then, 1.35 g/kg (low dose) or 0.235 g/kg (high dose) HYF was administered once/day for 25 days. Serum AMH, FSH, E2, ALT, AST, BUN and Cr levels were detected through ELISA and HE-stained follicles were counted in ovarian sections. Additionally, RNA-seq profiling analysis and functional assays were used to screen for differentially expressed genes and key regulators with potentially important roles associated with HYF.
RESULTS
The ovaries of POI rats contained fewer antral and maturing follicles (p < 0.05) than those of control rats, whereas atretic follicles were increased significantly (p < 0.05), and AMH levels were significantly lower in the VCD group than in the control group (p < 0.05). These conditions showed some improvement after low- and high-dose HYF treatment. Low- and high-dose HYF increased AMH levels by 42.4% and 25.9% and decreased FSH levels by 17.5% and 24.1%, respectively, in comparison to the VCD group. The two HYF dosage groups showed significantly increased numbers of antral and maturing follicles but a reduced number of atretic follicles (p < 0.05). HYF down-regulation of JAK, Lats2 and YAP mRNA expression gene expression (p < 0.05) compared with the VCD group. HYF resulted in a strongly attenuated VCD-induced phosphorylation of JAK2 and STAT3 (p < 0.01) and YAP (p < 0.001), but induced an increase in protein levels of LATS2 (p < 0.05).
CONCLUSION
Our findings demonstrated the treatment efficacy of HYF in POI rats and showed that HYF repairs the dysfunction and enhances the ovarian function of POI rats through the Hippo-JAK2/STAT3 signaling pathway.
DOI: 10.1016/j.biopha.2019.109008
PubMed: 31152926
Affiliations:
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Electronic address: yangzi_lee@126.com.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Hongyan" sort="Yang, Hongyan" uniqKey="Yang H" first="Hongyan" last="Yang">Hongyan Yang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, China. Electronic address: hongyanyang@gzucm.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31152926</idno><idno type="pmid">31152926</idno><idno type="doi">10.1016/j.biopha.2019.109008</idno><idno type="wicri:Area/Main/Corpus">000349</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000349</idno><idno type="wicri:Area/Main/Curation">000349</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000349</idno><idno type="wicri:Area/Main/Exploration">000349</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Huyang yangkun formula protects against 4-Vinylcyclohexene diepoxide-induced premature ovarian insufficiency in rats via the Hippo-JAK2/STAT3 signaling pathway.</title><author><name sortKey="Xie, Li" sort="Xie, Li" uniqKey="Xie L" first="Li" last="Xie">Li Xie</name><affiliation wicri:level="1"><nlm:affiliation>Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006</wicri:regionArea><wicri:noRegion>510006</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Sining" sort="Wu, Sining" uniqKey="Wu S" first="Sining" last="Wu">Sining Wu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120</wicri:regionArea><wicri:noRegion>510120</wicri:noRegion></affiliation></author><author><name sortKey="Cao, Dongdong" sort="Cao, Dongdong" uniqKey="Cao D" first="Dongdong" last="Cao">Dongdong Cao</name><affiliation wicri:level="1"><nlm:affiliation>Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006</wicri:regionArea><wicri:noRegion>510006</wicri:noRegion></affiliation></author><author><name sortKey="Li, Meifang" sort="Li, Meifang" uniqKey="Li M" first="Meifang" last="Li">Meifang Li</name><affiliation wicri:level="1"><nlm:affiliation>Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006</wicri:regionArea><wicri:noRegion>510006</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Jian" sort="Liu, Jian" uniqKey="Liu J" first="Jian" last="Liu">Jian Liu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Nie, Guangning" sort="Nie, Guangning" uniqKey="Nie G" first="Guangning" last="Nie">Guangning Nie</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yang" sort="Li, Yang" uniqKey="Li Y" first="Yang" last="Li">Yang Li</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, China. Electronic address: yangzi_lee@126.com.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Hongyan" sort="Yang, Hongyan" uniqKey="Yang H" first="Hongyan" last="Yang">Hongyan Yang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, China. Electronic address: hongyanyang@gzucm.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author></analytic><series><title level="j">Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie</title><idno type="eISSN">1950-6007</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Anti-Mullerian Hormone (blood)</term><term>Cluster Analysis (MeSH)</term><term>Cyclohexenes (MeSH)</term><term>Disease Models, Animal (MeSH)</term><term>Drugs, Chinese Herbal (pharmacology)</term><term>Drugs, Chinese Herbal (therapeutic use)</term><term>Female (MeSH)</term><term>Gene Ontology (MeSH)</term><term>Janus Kinase 2 (metabolism)</term><term>Kidney (drug effects)</term><term>Kidney (pathology)</term><term>Liver (drug effects)</term><term>Liver (pathology)</term><term>Models, Biological (MeSH)</term><term>Ovarian Follicle (drug effects)</term><term>Ovarian Follicle (pathology)</term><term>Primary Ovarian Insufficiency (blood)</term><term>Primary Ovarian Insufficiency (chemically induced)</term><term>Primary Ovarian Insufficiency (drug therapy)</term><term>Primary Ovarian Insufficiency (genetics)</term><term>Protective Agents (pharmacology)</term><term>Protective Agents (therapeutic use)</term><term>Protein-Serine-Threonine Kinases (metabolism)</term><term>Rats, Sprague-Dawley (MeSH)</term><term>Reference Standards (MeSH)</term><term>STAT3 Transcription Factor (metabolism)</term><term>Signal Transduction (MeSH)</term><term>Vinyl Compounds (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Agents protecteurs (pharmacologie)</term><term>Agents protecteurs (usage thérapeutique)</term><term>Analyse de regroupements (MeSH)</term><term>Animaux (MeSH)</term><term>Composés vinyliques (MeSH)</term><term>Cyclohexènes (MeSH)</term><term>Facteur de transcription STAT-3 (métabolisme)</term><term>Femelle (MeSH)</term><term>Foie (anatomopathologie)</term><term>Foie (effets des médicaments et des substances chimiques)</term><term>Follicule ovarique (anatomopathologie)</term><term>Follicule ovarique (effets des médicaments et des substances chimiques)</term><term>Gene Ontology (MeSH)</term><term>Hormone antimullérienne (sang)</term><term>Insuffisance ovarienne primitive (génétique)</term><term>Insuffisance ovarienne primitive (induit chimiquement)</term><term>Insuffisance ovarienne primitive (sang)</term><term>Insuffisance ovarienne primitive (traitement médicamenteux)</term><term>Kinase Janus-2 (métabolisme)</term><term>Modèles animaux de maladie humaine (MeSH)</term><term>Modèles biologiques (MeSH)</term><term>Médicaments issus de plantes chinoises (pharmacologie)</term><term>Médicaments issus de plantes chinoises (usage thérapeutique)</term><term>Normes de référence (MeSH)</term><term>Protein-Serine-Threonine Kinases (métabolisme)</term><term>Rat Sprague-Dawley (MeSH)</term><term>Rein (anatomopathologie)</term><term>Rein (effets des médicaments et des substances chimiques)</term><term>Transduction du signal (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Anti-Mullerian Hormone</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Janus Kinase 2</term><term>Protein-Serine-Threonine Kinases</term><term>STAT3 Transcription Factor</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Drugs, Chinese Herbal</term><term>Protective Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Drugs, Chinese Herbal</term><term>Protective Agents</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Foie</term><term>Follicule ovarique</term><term>Rein</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Primary Ovarian Insufficiency</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Primary Ovarian Insufficiency</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Kidney</term><term>Liver</term><term>Ovarian Follicle</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Primary Ovarian Insufficiency</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Foie</term><term>Follicule ovarique</term><term>Rein</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Primary Ovarian Insufficiency</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Insuffisance ovarienne primitive</term></keywords><keywords scheme="MESH" qualifier="induit chimiquement" xml:lang="fr"><term>Insuffisance ovarienne primitive</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de transcription STAT-3</term><term>Kinase Janus-2</term><term>Protein-Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Kidney</term><term>Liver</term><term>Ovarian Follicle</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Agents protecteurs</term><term>Médicaments issus de plantes chinoises</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Hormone antimullérienne</term><term>Insuffisance ovarienne primitive</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Insuffisance ovarienne primitive</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Agents protecteurs</term><term>Médicaments issus de plantes chinoises</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cluster Analysis</term><term>Cyclohexenes</term><term>Disease Models, Animal</term><term>Female</term><term>Gene Ontology</term><term>Models, Biological</term><term>Rats, Sprague-Dawley</term><term>Reference Standards</term><term>Signal Transduction</term><term>Vinyl Compounds</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de regroupements</term><term>Animaux</term><term>Composés vinyliques</term><term>Cyclohexènes</term><term>Femelle</term><term>Gene Ontology</term><term>Modèles animaux de maladie humaine</term><term>Modèles biologiques</term><term>Normes de référence</term><term>Rat Sprague-Dawley</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>ETHNOPHARMACOLOGICAL RELEVANCE</b></p><p>Huyang Yangkun Formula (HYF) has been prescribed for premature ovarian insufficiency (POI) for decades in the clinical setting. Little is known regarding its underlying molecular mechanism. This study was conducted to elucidate the possible mechanism of the protective potential of HYF against POI induced by the industrial chemical 4-vinylcyclohexene diepoxide (VCD) in rats.</p></div><div type="abstract" xml:lang="en"><p><b>AIM OF THE STUDY</b></p><p>Quality control of HYF was conducted via HPLC and UPLC-MS. Female rats were injected with VCD (160 mg/kg) daily for 15 days. Then, 1.35 g/kg (low dose) or 0.235 g/kg (high dose) HYF was administered once/day for 25 days. Serum AMH, FSH, E2, ALT, AST, BUN and Cr levels were detected through ELISA and HE-stained follicles were counted in ovarian sections. Additionally, RNA-seq profiling analysis and functional assays were used to screen for differentially expressed genes and key regulators with potentially important roles associated with HYF.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>The ovaries of POI rats contained fewer antral and maturing follicles (p < 0.05) than those of control rats, whereas atretic follicles were increased significantly (p < 0.05), and AMH levels were significantly lower in the VCD group than in the control group (p < 0.05). These conditions showed some improvement after low- and high-dose HYF treatment. Low- and high-dose HYF increased AMH levels by 42.4% and 25.9% and decreased FSH levels by 17.5% and 24.1%, respectively, in comparison to the VCD group. The two HYF dosage groups showed significantly increased numbers of antral and maturing follicles but a reduced number of atretic follicles (p < 0.05). HYF down-regulation of JAK, Lats2 and YAP mRNA expression gene expression (p < 0.05) compared with the VCD group. HYF resulted in a strongly attenuated VCD-induced phosphorylation of JAK2 and STAT3 (p < 0.01) and YAP (p < 0.001), but induced an increase in protein levels of LATS2 (p < 0.05).</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Our findings demonstrated the treatment efficacy of HYF in POI rats and showed that HYF repairs the dysfunction and enhances the ovarian function of POI rats through the Hippo-JAK2/STAT3 signaling pathway.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31152926</PMID><DateCompleted><Year>2020</Year><Month>01</Month><Day>13</Day></DateCompleted><DateRevised><Year>2020</Year><Month>01</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1950-6007</ISSN><JournalIssue CitedMedium="Internet"><Volume>116</Volume><PubDate><Year>2019</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie</Title><ISOAbbreviation>Biomed Pharmacother</ISOAbbreviation></Journal><ArticleTitle>Huyang yangkun formula protects against 4-Vinylcyclohexene diepoxide-induced premature ovarian insufficiency in rats via the Hippo-JAK2/STAT3 signaling pathway.</ArticleTitle><Pagination><MedlinePgn>109008</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0753-3322(19)31059-5</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.biopha.2019.109008</ELocationID><Abstract><AbstractText Label="ETHNOPHARMACOLOGICAL RELEVANCE" NlmCategory="BACKGROUND">Huyang Yangkun Formula (HYF) has been prescribed for premature ovarian insufficiency (POI) for decades in the clinical setting. Little is known regarding its underlying molecular mechanism. This study was conducted to elucidate the possible mechanism of the protective potential of HYF against POI induced by the industrial chemical 4-vinylcyclohexene diepoxide (VCD) in rats.</AbstractText><AbstractText Label="AIM OF THE STUDY" NlmCategory="OBJECTIVE">Quality control of HYF was conducted via HPLC and UPLC-MS. Female rats were injected with VCD (160 mg/kg) daily for 15 days. Then, 1.35 g/kg (low dose) or 0.235 g/kg (high dose) HYF was administered once/day for 25 days. Serum AMH, FSH, E2, ALT, AST, BUN and Cr levels were detected through ELISA and HE-stained follicles were counted in ovarian sections. Additionally, RNA-seq profiling analysis and functional assays were used to screen for differentially expressed genes and key regulators with potentially important roles associated with HYF.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">The ovaries of POI rats contained fewer antral and maturing follicles (p < 0.05) than those of control rats, whereas atretic follicles were increased significantly (p < 0.05), and AMH levels were significantly lower in the VCD group than in the control group (p < 0.05). These conditions showed some improvement after low- and high-dose HYF treatment. Low- and high-dose HYF increased AMH levels by 42.4% and 25.9% and decreased FSH levels by 17.5% and 24.1%, respectively, in comparison to the VCD group. The two HYF dosage groups showed significantly increased numbers of antral and maturing follicles but a reduced number of atretic follicles (p < 0.05). HYF down-regulation of JAK, Lats2 and YAP mRNA expression gene expression (p < 0.05) compared with the VCD group. HYF resulted in a strongly attenuated VCD-induced phosphorylation of JAK2 and STAT3 (p < 0.01) and YAP (p < 0.001), but induced an increase in protein levels of LATS2 (p < 0.05).</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Our findings demonstrated the treatment efficacy of HYF in POI rats and showed that HYF repairs the dysfunction and enhances the ovarian function of POI rats through the Hippo-JAK2/STAT3 signaling pathway.</AbstractText><CopyrightInformation>Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Li</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Sining</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cao</LastName><ForeName>Dongdong</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Meifang</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Jian</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nie</LastName><ForeName>Guangning</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Yang</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, China. Electronic address: yangzi_lee@126.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Hongyan</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Gynaecology, The Second Affiliated Hosipital of Guangzhou University of Chinese Medicine, Dade Road, Yuexiu District, Guangzhou, Guangdong, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, China. Electronic address: hongyanyang@gzucm.edu.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>05</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Biomed Pharmacother</MedlineTA><NlmUniqueID>8213295</NlmUniqueID><ISSNLinking>0753-3322</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053138">Cyclohexenes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004365">Drugs, Chinese Herbal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D020011">Protective Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050796">STAT3 Transcription Factor</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014753">Vinyl Compounds</NameOfSubstance></Chemical><Chemical><RegistryNumber>596C064IG4</RegistryNumber><NameOfSubstance UI="C012606">4-vinyl-1-cyclohexene dioxide</NameOfSubstance></Chemical><Chemical><RegistryNumber>80497-65-0</RegistryNumber><NameOfSubstance UI="D054304">Anti-Mullerian Hormone</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.2</RegistryNumber><NameOfSubstance UI="C507927">Jak2 protein, rat</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.2</RegistryNumber><NameOfSubstance UI="D053614">Janus Kinase 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D017346">Protein-Serine-Threonine Kinases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054304" MajorTopicYN="N">Anti-Mullerian Hormone</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016000" MajorTopicYN="N">Cluster Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053138" MajorTopicYN="N">Cyclohexenes</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004365" MajorTopicYN="N">Drugs, Chinese Herbal</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D063990" MajorTopicYN="N">Gene Ontology</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053614" MajorTopicYN="N">Janus Kinase 2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007668" MajorTopicYN="N">Kidney</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008099" MajorTopicYN="N">Liver</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008954" MajorTopicYN="N">Models, Biological</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006080" MajorTopicYN="N">Ovarian Follicle</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016649" MajorTopicYN="N">Primary Ovarian Insufficiency</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020011" MajorTopicYN="N">Protective Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017346" MajorTopicYN="N">Protein-Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012015" MajorTopicYN="N">Reference Standards</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D050796" MajorTopicYN="N">STAT3 Transcription Factor</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="Y">Signal Transduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014753" MajorTopicYN="N">Vinyl Compounds</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Hippo pathway</Keyword><Keyword MajorTopicYN="N">Huyang yangkun formula (HYF)</Keyword><Keyword MajorTopicYN="N">JAK2/STAT3 pathway</Keyword><Keyword MajorTopicYN="N">Premature ovarian insufficiency (POI)</Keyword><Keyword MajorTopicYN="N">RNA-seq analysis</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>03</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>05</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>05</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>6</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>1</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>6</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31152926</ArticleId><ArticleId IdType="pii">S0753-3322(19)31059-5</ArticleId><ArticleId IdType="doi">10.1016/j.biopha.2019.109008</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Xie, Li" sort="Xie, Li" uniqKey="Xie L" first="Li" last="Xie">Li Xie</name></noRegion><name sortKey="Cao, Dongdong" sort="Cao, Dongdong" uniqKey="Cao D" first="Dongdong" last="Cao">Dongdong Cao</name><name sortKey="Li, Meifang" sort="Li, Meifang" uniqKey="Li M" first="Meifang" last="Li">Meifang Li</name><name sortKey="Li, Yang" sort="Li, Yang" uniqKey="Li Y" first="Yang" last="Li">Yang Li</name><name sortKey="Liu, Jian" sort="Liu, Jian" uniqKey="Liu J" first="Jian" last="Liu">Jian Liu</name><name sortKey="Nie, Guangning" sort="Nie, Guangning" uniqKey="Nie G" first="Guangning" last="Nie">Guangning Nie</name><name sortKey="Wu, Sining" sort="Wu, Sining" uniqKey="Wu S" first="Sining" last="Wu">Sining Wu</name><name sortKey="Yang, Hongyan" sort="Yang, Hongyan" uniqKey="Yang H" first="Hongyan" last="Yang">Hongyan Yang</name></country></tree></affiliations></record>Pour manipuler ce 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