Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular docking
Abstract Psoraleae Fructus (PF) is a widely-used herb with diverse pharmacological activities, while its related hepatic injuries have aroused public concerns. In this work, a systematic approach based on RNA sequencing (RNA-seq), high-content screening (HCS) and molecular docking was developed to i...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-50454-0 |
| _version_ | 1797349917460529152 |
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| author | Huiying Shang Xian Liu Jinchao Pan Hongbo Cheng Zengchun Ma Chengrong Xiao Yue Gao |
| author_facet | Huiying Shang Xian Liu Jinchao Pan Hongbo Cheng Zengchun Ma Chengrong Xiao Yue Gao |
| author_sort | Huiying Shang |
| collection | DOAJ |
| description | Abstract Psoraleae Fructus (PF) is a widely-used herb with diverse pharmacological activities, while its related hepatic injuries have aroused public concerns. In this work, a systematic approach based on RNA sequencing (RNA-seq), high-content screening (HCS) and molecular docking was developed to investigate the potential mechanism and identify major phytochemicals contributed to PF-induced hepatotoxicity. Animal experiments proved oral administration of PF water extracts disturbed lipid metabolism and promoted hepatic injuries by suppressing fatty acid and cholesterol catabolism. RNA-seq combined with KEGG enrichment analysis identified mitochondrial oxidative phosphorylation (OXPHOS) as the potential key pathway. Further experiments validated PF caused mitochondrial structure damage, mtDNA depletion and inhibited expressions of genes engaged in OXPHOS. By detecting mitochondrial membrane potential and mitochondrial superoxide, HCS identified bavachin, isobavachalcone, bakuchiol and psoralidin as most potent mitotoxic compounds in PF. Moreover, molecular docking confirmed the potential binding patterns and strong binding affinity of the critical compounds with mitochondrial respiratory complex. This study unveiled the underlying mechanism and phytochemicals in PF-induced liver injuries from the view of mitochondrial dysfunction. |
| first_indexed | 2024-03-08T12:38:20Z |
| format | Article |
| id | doaj.art-50b732337b12400eb5fb66d772613496 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T12:38:20Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-50b732337b12400eb5fb66d7726134962024-01-21T12:20:22ZengNature PortfolioScientific Reports2045-23222024-01-0114111510.1038/s41598-023-50454-0Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular dockingHuiying Shang0Xian Liu1Jinchao Pan2Hongbo Cheng3Zengchun Ma4Chengrong Xiao5Yue Gao6Tianjin University of Traditional Chinese MedicineDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation MedicineDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation MedicineDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation MedicineDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation MedicineDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation MedicineDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation MedicineAbstract Psoraleae Fructus (PF) is a widely-used herb with diverse pharmacological activities, while its related hepatic injuries have aroused public concerns. In this work, a systematic approach based on RNA sequencing (RNA-seq), high-content screening (HCS) and molecular docking was developed to investigate the potential mechanism and identify major phytochemicals contributed to PF-induced hepatotoxicity. Animal experiments proved oral administration of PF water extracts disturbed lipid metabolism and promoted hepatic injuries by suppressing fatty acid and cholesterol catabolism. RNA-seq combined with KEGG enrichment analysis identified mitochondrial oxidative phosphorylation (OXPHOS) as the potential key pathway. Further experiments validated PF caused mitochondrial structure damage, mtDNA depletion and inhibited expressions of genes engaged in OXPHOS. By detecting mitochondrial membrane potential and mitochondrial superoxide, HCS identified bavachin, isobavachalcone, bakuchiol and psoralidin as most potent mitotoxic compounds in PF. Moreover, molecular docking confirmed the potential binding patterns and strong binding affinity of the critical compounds with mitochondrial respiratory complex. This study unveiled the underlying mechanism and phytochemicals in PF-induced liver injuries from the view of mitochondrial dysfunction.https://doi.org/10.1038/s41598-023-50454-0 |
| spellingShingle | Huiying Shang Xian Liu Jinchao Pan Hongbo Cheng Zengchun Ma Chengrong Xiao Yue Gao Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular docking Scientific Reports |
| title | Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular docking |
| title_full | Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular docking |
| title_fullStr | Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular docking |
| title_full_unstemmed | Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular docking |
| title_short | Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular docking |
| title_sort | exploring the mechanism and phytochemicals in psoraleae fructus induced hepatotoxicity based on rna seq in vitro screening and molecular docking |
| url | https://doi.org/10.1038/s41598-023-50454-0 |
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