Corosolic acid ameliorates vascular remodeling in pulmonary arterial hypertension via the downregulation of STAT3 signaling
Copyright © 2022 The Authors. Production and hosting by Elsevier B.V. All rights reserved..
Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that is characterized by vascular remodeling of the pulmonary artery. PAH remodeling is primarily caused by the excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs). Therefore, an inhibitory mechanism is expected as a target for the treatment of PAH. Corosolic acid (CRA) is a pentacyclic triterpenoid extracted from the leaves of Banaba (Lagerstroemia speciosa) that exerts anti-diabetic, anti-inflammatory, and anti-tumor effects. In the present study, the effects of CRA on PAH remodeling were examined using PASMCs from idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline (MCT)-induced pulmonary hypertensive (PH) rats. CRA inhibited the excessive proliferation of IPAH-PASMCs in a concentration-dependent manner (IC50 = 14.1 μM). It also reduced the migration of IPAH-PASMCs. The CRA treatment downregulated the expression of signal transducer and activator of transcription 3 (STAT3) in IPAH-PASMCs. In MCT-PH rats, the administration of CRA (1 mg/kg/day) attenuated increases in right ventricular systolic pressure, pulmonary vascular remodeling, and right ventricular hypertrophy. CRA also decreased the expression of STAT3 in pulmonary arterial smooth muscles from MCT-PH rats. In conclusion, the anti-proliferative and anti-migratory effects of CRA in PASMCs ameliorated PAH remodeling by downregulating STAT3 signaling pathways.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:151 |
|---|---|
| Enthalten in: |
Journal of pharmacological sciences - 151(2023), 2 vom: 27. Feb., Seite 119-127 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kawade, Akiko [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
AMX2I57A98 |
|---|
| Anmerkungen: |
Date Completed 31.01.2023 Date Revised 02.02.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jphs.2022.12.007 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM352176377 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM352176377 | ||
| 003 | DE-627 | ||
| 005 | 20231226053122.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jphs.2022.12.007 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1173.xml |
| 035 | |a (DE-627)NLM352176377 | ||
| 035 | |a (NLM)36707177 | ||
| 035 | |a (PII)S1347-8613(22)00095-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kawade, Akiko |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Corosolic acid ameliorates vascular remodeling in pulmonary arterial hypertension via the downregulation of STAT3 signaling |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 31.01.2023 | ||
| 500 | |a Date Revised 02.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Production and hosting by Elsevier B.V. All rights reserved. | ||
| 520 | |a Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that is characterized by vascular remodeling of the pulmonary artery. PAH remodeling is primarily caused by the excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs). Therefore, an inhibitory mechanism is expected as a target for the treatment of PAH. Corosolic acid (CRA) is a pentacyclic triterpenoid extracted from the leaves of Banaba (Lagerstroemia speciosa) that exerts anti-diabetic, anti-inflammatory, and anti-tumor effects. In the present study, the effects of CRA on PAH remodeling were examined using PASMCs from idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline (MCT)-induced pulmonary hypertensive (PH) rats. CRA inhibited the excessive proliferation of IPAH-PASMCs in a concentration-dependent manner (IC50 = 14.1 μM). It also reduced the migration of IPAH-PASMCs. The CRA treatment downregulated the expression of signal transducer and activator of transcription 3 (STAT3) in IPAH-PASMCs. In MCT-PH rats, the administration of CRA (1 mg/kg/day) attenuated increases in right ventricular systolic pressure, pulmonary vascular remodeling, and right ventricular hypertrophy. CRA also decreased the expression of STAT3 in pulmonary arterial smooth muscles from MCT-PH rats. In conclusion, the anti-proliferative and anti-migratory effects of CRA in PASMCs ameliorated PAH remodeling by downregulating STAT3 signaling pathways | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Corosolic acid | |
| 650 | 4 | |a Pulmonary artery | |
| 650 | 4 | |a Pulmonary hypertension | |
| 650 | 4 | |a Signal transducer and activator of transcription 3 | |
| 650 | 4 | |a Smooth muscle | |
| 650 | 7 | |a corosolic acid |2 NLM | |
| 650 | 7 | |a AMX2I57A98 |2 NLM | |
| 650 | 7 | |a STAT3 Transcription Factor |2 NLM | |
| 700 | 1 | |a Yamamura, Aya |e verfasserin |4 aut | |
| 700 | 1 | |a Kondo, Rubii |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Yoshiaki |e verfasserin |4 aut | |
| 700 | 1 | |a Yamamura, Hisao |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of pharmacological sciences |d 2003 |g 151(2023), 2 vom: 27. Feb., Seite 119-127 |w (DE-627)NLM124584721 |x 1347-8648 |7 nnns |
| 773 | 1 | 8 | |g volume:151 |g year:2023 |g number:2 |g day:27 |g month:02 |g pages:119-127 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jphs.2022.12.007 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 151 |j 2023 |e 2 |b 27 |c 02 |h 119-127 | ||