Exploring the therapeutic potential of 18β-Glycyrrhetinic acid in pulmonary arterial hypertension by integrating network pharmacology and experimental validation
Background: Pulmonary arterial hypertension (PAH) is characterized by elevated pressure in the pulmonary arteries and can result in right heart failure and possible death.18β-Glycyrrhetinic acid (18β-GA), a beneficial substance found in licorice, shows great potential for medicinal use. Through netw...
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Elsevier
2025-01-01
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| Series: | Journal of Functional Foods |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S175646462400608X |
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| author | Wenli Yang Long Ma Meidong Si Fang Zhao Ru Zhou |
| author_facet | Wenli Yang Long Ma Meidong Si Fang Zhao Ru Zhou |
| author_sort | Wenli Yang |
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| description | Background: Pulmonary arterial hypertension (PAH) is characterized by elevated pressure in the pulmonary arteries and can result in right heart failure and possible death.18β-Glycyrrhetinic acid (18β-GA), a beneficial substance found in licorice, shows great potential for medicinal use. Through network pharmacology and experimental validation, this study examined the probable mechanism of 18β-GA in treating PAH. Methods: The analysis of the potential pharmacological activities of 18β-GA was conducted using the network pharmacology method. The network of interactions between proteins was created by identifying shared targets of 18β-GA and PAH across multiple databases. Pathway enrichment was then conducted to determine the key targets. Validation of the interactions between 18β-GA and key targets was performed by molecular docking. Ultimately, we confirmed the modes of operation by utilizing a monocrotaline (MCT)--induced PAH model in rats. Results: A total of 197 potential targets for 18β-GA and 1713 potential targets associated with PAH were successfully identified. Of these, 79 targets were identified as common to both 18β-GA and PAH. Through the analysis of the PPI network, identified key targets, including IL6, AKT1, ALB, BCL2, NFKB1, IL1B, SRC, MMP9, PPARG, MAPK3, PTGS2, ESR1, TNF, CTNNB1 and CASP3. Furthermore, the analysis of molecular docking indicated that SRC exhibited the highest affinity for 18β-GA. The efficacy of 18β-GA in mitigating the advancement of MCT-induced PAH in rats was proven by in vivo investigations. Conclusions: This study presents initial findings about the molecular mechanism by which 18β-GA exerts its therapeutic effects on PAH. The findings suggest that using 18β-GA for treating PAH may involve the deactivation of SRC and the reduction of oxidative stress. |
| format | Article |
| id | doaj-art-e808e77db2704fcc83dc7aedd48b863a |
| institution | Kabale University |
| issn | 1756-4646 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj-art-e808e77db2704fcc83dc7aedd48b863a2025-01-12T05:24:42ZengElsevierJournal of Functional Foods1756-46462025-01-01124106605Exploring the therapeutic potential of 18β-Glycyrrhetinic acid in pulmonary arterial hypertension by integrating network pharmacology and experimental validationWenli Yang0Long Ma1Meidong Si2Fang Zhao3Ru Zhou4School of Pharmacy, Ningxia Medical University, Yinchuan 750004, ChinaSchool of Pharmacy, Ningxia Medical University, Yinchuan 750004, ChinaSchool of Pharmacy, Ningxia Medical University, Yinchuan 750004, ChinaPediatric Intensive Care Unit, General Hospital of Ningxia Medical University, 750004 Yinchuan, China; Corresponding author.School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; Ningxia Characteristic Traditional Chinese Medicine Modernization Engineering Technology Research Center, Ningxia Medical University, Yinchuan 750004, China; Corresponding author at: School of Pharmacy, Ningxia Medical University, 1160, Shengli Street, Xingqing, Yinchuan 750004, Ningxia, China.Background: Pulmonary arterial hypertension (PAH) is characterized by elevated pressure in the pulmonary arteries and can result in right heart failure and possible death.18β-Glycyrrhetinic acid (18β-GA), a beneficial substance found in licorice, shows great potential for medicinal use. Through network pharmacology and experimental validation, this study examined the probable mechanism of 18β-GA in treating PAH. Methods: The analysis of the potential pharmacological activities of 18β-GA was conducted using the network pharmacology method. The network of interactions between proteins was created by identifying shared targets of 18β-GA and PAH across multiple databases. Pathway enrichment was then conducted to determine the key targets. Validation of the interactions between 18β-GA and key targets was performed by molecular docking. Ultimately, we confirmed the modes of operation by utilizing a monocrotaline (MCT)--induced PAH model in rats. Results: A total of 197 potential targets for 18β-GA and 1713 potential targets associated with PAH were successfully identified. Of these, 79 targets were identified as common to both 18β-GA and PAH. Through the analysis of the PPI network, identified key targets, including IL6, AKT1, ALB, BCL2, NFKB1, IL1B, SRC, MMP9, PPARG, MAPK3, PTGS2, ESR1, TNF, CTNNB1 and CASP3. Furthermore, the analysis of molecular docking indicated that SRC exhibited the highest affinity for 18β-GA. The efficacy of 18β-GA in mitigating the advancement of MCT-induced PAH in rats was proven by in vivo investigations. Conclusions: This study presents initial findings about the molecular mechanism by which 18β-GA exerts its therapeutic effects on PAH. The findings suggest that using 18β-GA for treating PAH may involve the deactivation of SRC and the reduction of oxidative stress.http://www.sciencedirect.com/science/article/pii/S175646462400608X18β-Glycyrrhetinic acidPulmonary arterial hypertensionNetwork pharmacologyMolecular docking |
| spellingShingle | Wenli Yang Long Ma Meidong Si Fang Zhao Ru Zhou Exploring the therapeutic potential of 18β-Glycyrrhetinic acid in pulmonary arterial hypertension by integrating network pharmacology and experimental validation Journal of Functional Foods 18β-Glycyrrhetinic acid Pulmonary arterial hypertension Network pharmacology Molecular docking |
| title | Exploring the therapeutic potential of 18β-Glycyrrhetinic acid in pulmonary arterial hypertension by integrating network pharmacology and experimental validation |
| title_full | Exploring the therapeutic potential of 18β-Glycyrrhetinic acid in pulmonary arterial hypertension by integrating network pharmacology and experimental validation |
| title_fullStr | Exploring the therapeutic potential of 18β-Glycyrrhetinic acid in pulmonary arterial hypertension by integrating network pharmacology and experimental validation |
| title_full_unstemmed | Exploring the therapeutic potential of 18β-Glycyrrhetinic acid in pulmonary arterial hypertension by integrating network pharmacology and experimental validation |
| title_short | Exploring the therapeutic potential of 18β-Glycyrrhetinic acid in pulmonary arterial hypertension by integrating network pharmacology and experimental validation |
| title_sort | exploring the therapeutic potential of 18β glycyrrhetinic acid in pulmonary arterial hypertension by integrating network pharmacology and experimental validation |
| topic | 18β-Glycyrrhetinic acid Pulmonary arterial hypertension Network pharmacology Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S175646462400608X |
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