{"id":"https://openalex.org/W7225660723","doi":"https://doi.org/10.3390/ijms272110018","title":"Luteolin and Naringenin from Herbal Medicines Suppress Pulmonary Arterial Smooth Muscle Cell Hyperproliferation in Pulmonary Arterial Hypertension by Modulating IGF1R/PI3K/AKT Signaling","display_name":"Luteolin and Naringenin from Herbal Medicines Suppress Pulmonary Arterial Smooth Muscle Cell Hyperproliferation in Pulmonary Arterial Hypertension by Modulating IGF1R/PI3K/AKT Signaling","publication_year":2026,"publication_date":"2026-11-08","ids":{"openalex":"https://openalex.org/W7225660723","doi":"https://doi.org/10.3390/ijms272110018"},"language":"en","primary_location":{"id":"doi:10.3390/ijms272110018","doi":"https://doi.org/10.3390/ijms272110018","is_oa":true,"landing_page_url":"https://doi.org/10.3390/ijms272110018","pdf_url":null,"source":{"id":"https://openalex.org/S10623703","display_name":"International Journal of Molecular Sciences","issn_l":"1422-0067","issn":["1422-0067","1661-6596"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International Journal of Molecular Sciences","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3390/ijms272110018","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5122893234","display_name":"Hanghang Gou","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I53411278","display_name":"Chengdu University of Traditional Chinese Medicine","ror":"https://ror.org/00pcrz470","country_code":"CN","type":"education","lineage":["https://openalex.org/I53411278"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Hanghang Gou","raw_affiliation_strings":["Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China","institution_ids":["https://openalex.org/I53411278"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5135388296","display_name":"Liping Chen","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I53411278","display_name":"Chengdu University of Traditional Chinese Medicine","ror":"https://ror.org/00pcrz470","country_code":"CN","type":"education","lineage":["https://openalex.org/I53411278"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Liping Chen","raw_affiliation_strings":["Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China","institution_ids":["https://openalex.org/I53411278"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5053709863","display_name":"Chengxun He","orcid":"https://orcid.org/0009-0007-0989-7511","observed_orcids":["https://orcid.org/0009-0007-0989-7511","https://orcid.org/0000-0002-3986-0978"]},"institutions":[{"id":"https://openalex.org/I53411278","display_name":"Chengdu University of Traditional Chinese Medicine","ror":"https://ror.org/00pcrz470","country_code":"CN","type":"education","lineage":["https://openalex.org/I53411278"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Chengxun He","raw_affiliation_strings":["Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China","institution_ids":["https://openalex.org/I53411278"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110526835","display_name":"Qi Liang","orcid":"https://orcid.org/0000-0002-3678-4893","observed_orcids":["https://orcid.org/0000-0002-3678-4893"]},"institutions":[{"id":"https://openalex.org/I53411278","display_name":"Chengdu University of Traditional Chinese Medicine","ror":"https://ror.org/00pcrz470","country_code":"CN","type":"education","lineage":["https://openalex.org/I53411278"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Qi Liang","raw_affiliation_strings":["Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China","institution_ids":["https://openalex.org/I53411278"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161336459","display_name":"Ke Liu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I53411278","display_name":"Chengdu University of Traditional Chinese Medicine","ror":"https://ror.org/00pcrz470","country_code":"CN","type":"education","lineage":["https://openalex.org/I53411278"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Ke Liu","raw_affiliation_strings":["Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China","institution_ids":["https://openalex.org/I53411278"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161312254","display_name":"Yi Zhu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I53411278","display_name":"Chengdu University of Traditional Chinese Medicine","ror":"https://ror.org/00pcrz470","country_code":"CN","type":"education","lineage":["https://openalex.org/I53411278"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yi Zhu","raw_affiliation_strings":["Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China","institution_ids":["https://openalex.org/I53411278"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161317917","display_name":"Xiuli Yang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I53411278","display_name":"Chengdu University of Traditional Chinese Medicine","ror":"https://ror.org/00pcrz470","country_code":"CN","type":"education","lineage":["https://openalex.org/I53411278"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xiuli Yang","raw_affiliation_strings":["Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China","institution_ids":["https://openalex.org/I53411278"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5076806220","display_name":"Wei Peng","orcid":"https://orcid.org/0000-0003-0511-9564","observed_orcids":["https://orcid.org/0000-0003-0511-9564"]},"institutions":[{"id":"https://openalex.org/I53411278","display_name":"Chengdu University of Traditional Chinese Medicine","ror":"https://ror.org/00pcrz470","country_code":"CN","type":"education","lineage":["https://openalex.org/I53411278"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Wei Peng","raw_affiliation_strings":["Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"],"raw_orcid":"https://orcid.org/0000-0003-0511-9564","affiliations":[{"raw_affiliation_string":"Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China","institution_ids":["https://openalex.org/I53411278"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5076806220"],"corresponding_institution_ids":["https://openalex.org/I53411278"],"apc_list":{"value":2900,"currency":"CHF","value_usd":3499},"apc_paid":{"value":2900,"currency":"CHF","value_usd":3499},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"27","issue":"21","first_page":"10018","last_page":"10018"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10728","display_name":"Pulmonary Hypertension Research and Treatments","score":0.9868000149726868,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10728","display_name":"Pulmonary Hypertension Research and Treatments","score":0.9868000149726868,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12582","display_name":"Flavonoids in Medical Research","score":0.002899999963119626,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.0027000000700354576,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/pulmonary-arterial-hypertension","display_name":"pulmonary arterial hypertension","score":0.9629999995231628},{"id":"https://openalex.org/keywords/luteolin","display_name":"luteolin","score":0.9330000281333923},{"id":"https://openalex.org/keywords/naringenin","display_name":"naringenin","score":1.0},{"id":"https://openalex.org/keywords/herbal-medicine-constituents","display_name":"herbal medicine constituents","score":0.7900000214576721},{"id":"https://openalex.org/keywords/pulmonary-arterial-smooth-muscle-cell-proliferation","display_name":"pulmonary arterial smooth muscle cell proliferation","score":0.8700000047683716},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.8659999966621399},{"id":"https://openalex.org/keywords/pdgf-bb","display_name":"PDGF-BB","score":0.8529999852180481},{"id":"https://openalex.org/keywords/cyclin-d1","display_name":"cyclin D1","score":0.7799999713897705},{"id":"https://openalex.org/keywords/bcl-2","display_name":"Bcl-2","score":0.8709999918937683},{"id":"https://openalex.org/keywords/vascular-microenvironment","display_name":"vascular microenvironment","score":0.7089999914169312},{"id":"https://openalex.org/keywords/drug-target-engagement","display_name":"drug-target engagement","score":0.4129999876022339}],"concepts":[{"id":"https://openalex.org/C2776080593","wikidata":"https://www.wikidata.org/wiki/Q415011","display_name":"Luteolin","level":4,"score":0.765999972820282},{"id":"https://openalex.org/C2776848411","wikidata":"https://www.wikidata.org/wiki/Q418374","display_name":"Naringenin","level":4,"score":0.7494999766349792},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.6240000128746033},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.48429998755455017},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.4498000144958496},{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.40139999985694885},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.38350000977516174},{"id":"https://openalex.org/C2779395532","wikidata":"https://www.wikidata.org/wiki/Q7916469","display_name":"Vascular smooth muscle","level":3,"score":0.32010000944137573},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.30730000138282776},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.3061000108718872},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.30149999260902405},{"id":"https://openalex.org/C62112901","wikidata":"https://www.wikidata.org/wiki/Q189159","display_name":"Cell growth","level":2,"score":0.2948000133037567},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.2791000008583069},{"id":"https://openalex.org/C2777714996","wikidata":"https://www.wikidata.org/wiki/Q7886","display_name":"Lung","level":2,"score":0.27250000834465027},{"id":"https://openalex.org/C144174609","wikidata":"https://www.wikidata.org/wiki/Q14901457","display_name":"Insulin-like growth factor 1 receptor","level":4,"score":0.26660001277923584},{"id":"https://openalex.org/C2780930700","wikidata":"https://www.wikidata.org/wiki/Q1128595","display_name":"Pulmonary hypertension","level":2,"score":0.26249998807907104},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.251800000667572}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.3390/ijms272110018","doi":"https://doi.org/10.3390/ijms272110018","is_oa":true,"landing_page_url":"https://doi.org/10.3390/ijms272110018","pdf_url":null,"source":{"id":"https://openalex.org/S10623703","display_name":"International Journal of Molecular Sciences","issn_l":"1422-0067","issn":["1422-0067","1661-6596"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International Journal of Molecular Sciences","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.3390/ijms272110018","doi":"https://doi.org/10.3390/ijms272110018","is_oa":true,"landing_page_url":"https://doi.org/10.3390/ijms272110018","pdf_url":null,"source":{"id":"https://openalex.org/S10623703","display_name":"International Journal of Molecular Sciences","issn_l":"1422-0067","issn":["1422-0067","1661-6596"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International Journal of Molecular Sciences","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9940000176429749,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320321001","display_name":"National Natural Science Foundation of China","ror":"https://ror.org/01h0zpd94"},{"id":"https://openalex.org/F4320322922","display_name":"Department of Science and Technology of Sichuan Province","ror":"https://ror.org/04323m874"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4414686885","https://openalex.org/W3153216759","https://openalex.org/W3129224971","https://openalex.org/W4416224152","https://openalex.org/W7224427281","https://openalex.org/W2130323865","https://openalex.org/W7203614636","https://openalex.org/W4400613954","https://openalex.org/W4366751251","https://openalex.org/W4410012146"],"abstract_inverted_index":{"Pulmonary":[0],"arterial":[1,165],"hypertension":[2],"(PAH)":[3],"remains":[4],"a":[5,184],"progressive":[6],"disease":[7,115],"with":[8,56,114,173,180,258],"limited":[9],"therapies.":[10],"As":[11],"part":[12],"of":[13,32,111,146,226,242,260],"our":[14],"continuing":[15],"study":[16],"to":[17,60,96],"identify":[18],"effective":[19],"agents":[20],"for":[21,208],"PAH":[22],"from":[23,51],"natural":[24],"herbal":[25,36],"medicines,":[26],"we":[27],"analyzed":[28],"the":[29,98,109,118,144,147,224],"chemical":[30],"constituents":[31,50,64,148,241],"an":[33,170,255],"empirically":[34],"validated":[35],"formula":[37,41],"named":[38],"Guilou":[39],"Tongluo":[40],"(GLTL)":[42],"by":[43,84,125,134],"UHPLC-Q-Exactive":[44],"MS,":[45],"retrieved":[46],"its":[47],"putative":[48],"blood-absorbed":[49],"databases,":[52],"and":[53,90,103,128,132,138,159,190,196,201,203,215,223,231,236,247],"integrated":[54],"them":[55],"lung":[57],"RNA-sequencing":[58],"data":[59],"discover":[61],"potential":[62,239],"active":[63,240],"against":[65],"PAH.":[66],"A":[67],"compound\u2013disease":[68],"network":[69],"was":[70,123,149],"constructed;":[71],"drug\u2013disease":[72],"intersection":[73],"genes":[74],"underwent":[75],"functional":[76],"enrichment":[77],"analysis,":[78],"whereas":[79],"hub":[80],"targets":[81,113],"were":[82,94],"prioritized":[83],"protein\u2013protein":[85],"interaction":[86],"analysis.":[87],"Immune":[88],"infiltration":[89],"single-cell":[91],"RNA":[92],"sequencing":[93],"used":[95],"analyze":[97],"vascular":[99],"microenvironment,":[100],"while":[101],"nomogram":[102],"decision":[104],"curve":[105],"analyses":[106],"exploratorily":[107],"assessed":[108],"association":[110],"candidate":[112,186],"status":[116],"at":[117],"tissue":[119],"level.":[120],"Target":[121],"engagement":[122],"predicted":[124,193],"molecular":[126,129],"docking":[127,189],"dynamics":[130,191],"simulation":[131,192],"supported":[133],"cellular":[135],"thermal":[136],"shift":[137],"drug":[139],"affinity":[140],"target":[141],"stability":[142],"assays;":[143],"mechanism":[145],"then":[150],"examined.":[151],"The":[152],"results":[153],"showed":[154],"that":[155,194,244],"GLTL":[156,243],"attenuated":[157],"proliferation":[158,246],"promoted":[160],"apoptosis":[161,249],"in":[162,176,250,253],"PDGF-BB-stimulated":[163,251],"pulmonary":[164],"smooth":[166,177],"muscle":[167,178],"cells":[168],"(PASMCs),":[169],"effect":[171,256],"associated":[172,257],"IGF1R/PI3K/AKT":[174,261],"signaling":[175],"cells,":[179],"IGF1R":[181,209,214],"identified":[182],"as":[183],"key":[185],"target.":[187],"Molecular":[188],"naringenin":[195,237],"luteolin":[197,235],"could":[198],"bind":[199],"IGF1R,":[200],"CETSA":[202],"DARTS":[204],"provided":[205],"experimental":[206],"support":[207],"engagement.":[210],"Both":[211],"compounds":[212],"engaged":[213],"suppressed":[216],"IGF-1/IGF1R":[217],"signaling,":[218],"thereby":[219],"reducing":[220],"PI3K/AKT":[221],"phosphorylation":[222],"expression":[225],"Cyclin":[227],"D1,":[228],"BCL2,":[229],"PCNA,":[230],"Ki67.":[232],"In":[233],"summary,":[234],"are":[238],"suppress":[245],"promote":[248],"PASMCs":[252],"vitro,":[254],"suppression":[259],"signaling.":[262]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-10T00:00:00"}