Plumbagin ameliorates bile duct ligation-induced cholestatic liver injury in rats
Plumbagin, a natural bicyclic naphthoquinone, has diverse pharmacological properties and biological benefits against a number of disorders, including liver disease. Though plumbagin’s hepatoprotective potential attracts attention, currently no experimental evidence exists on its effectiveness agains...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222005224 |
| _version_ | 1811336570079281152 |
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| author | Pin-Ho Pan Ya-Yu Wang Shih-Yi Lin Su-Lan Liao Yu-Fang Chen Wei-Chi Huang Chun-Jung Chen Wen-Ying Chen |
| author_facet | Pin-Ho Pan Ya-Yu Wang Shih-Yi Lin Su-Lan Liao Yu-Fang Chen Wei-Chi Huang Chun-Jung Chen Wen-Ying Chen |
| author_sort | Pin-Ho Pan |
| collection | DOAJ |
| description | Plumbagin, a natural bicyclic naphthoquinone, has diverse pharmacological properties and biological benefits against a number of disorders, including liver disease. Though plumbagin’s hepatoprotective potential attracts attention, currently no experimental evidence exists on its effectiveness against cholestatic liver injury. The present study investigated its hepatoprotection in the rat model of extrahepatic cholestasis using Bile Duct Ligation (BDL). We found that daily plumbagin supplementation protected the liver from cholestatic damage. Hepatoprotective actions of plumbagin were accompanied by reduction of Transforming Growth Factor β1 (TGF-β1)/Smad, High Mobility Group Box-1 (HMGB1)/Toll-Like Receptor-4 (TLR4), Hypoxia-Inducible Factor-1α (HIF-1α), Aryl Hydrocarbon Receptor (AhR), Heat Shock Protein 90 (HSP90), caveolin-1, NF-κB/AP-1, Dynamin Related Protein-1 (Drp1), malondialdehyde level, Interleukin-1β (IL-1β), p62/SQSTM1, and caspase 3 as well as increase of Farnesoid X Receptor (FXR), bile acid efflux transporters, glutathione, LC3-II, Beclin1, and nuclear NF-E2-Related Factor-2 (Nrf2) and Transcription Factor EB (TFEB). The activation of nuclear Nrf2 caused by plumbagin correlated well with the improvement in bile acid retention, liver histology, serum biochemical, ductular reaction, mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, impaired autophagy, and fibrosis, involving interplay of multiple intracellular signaling pathways. Plumbagin is likely a candidate drug to protect the liver from cholestatic damages. Despite the promising findings from this study, translational implication of plumbagin on cholestatic liver injury warrants further investigation. |
| first_indexed | 2024-04-13T17:42:21Z |
| format | Article |
| id | doaj.art-556ec9d375364a6eaf46dff934502886 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-13T17:42:21Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-556ec9d375364a6eaf46dff9345028862022-12-22T02:37:09ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-07-01151113133Plumbagin ameliorates bile duct ligation-induced cholestatic liver injury in ratsPin-Ho Pan0Ya-Yu Wang1Shih-Yi Lin2Su-Lan Liao3Yu-Fang Chen4Wei-Chi Huang5Chun-Jung Chen6Wen-Ying Chen7Department of Veterinary Medicine, National Chung Hsing University, Taichung City 402, Taiwan; Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung City 435, TaiwanDepartment of Family Medicine, Taichung Veterans General Hospital, Taichung City 407, TaiwanCenter for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung City 407, Taiwan; Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei City 112, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung City 407, TaiwanDepartment of Medical Laboratory Science, I-Shou University, Kaohsiung City 840, TaiwanDepartment of Veterinary Medicine, National Chung Hsing University, Taichung City 402, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung City 407, Taiwan; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung City 404, Taiwan; Correspondence to: Department of Medical Research, Taichung Veterans General Hospital, No. 1650, Section 4, Taiwan Boulevard, Taichung City 407, Taiwan.Department of Veterinary Medicine, National Chung Hsing University, Taichung City 402, Taiwan; Correspondence to: Department of Veterinary Medicine, National Chung Hsing University, 145 Xingda Rd., South Dist., Taichung City 402, Taiwan.Plumbagin, a natural bicyclic naphthoquinone, has diverse pharmacological properties and biological benefits against a number of disorders, including liver disease. Though plumbagin’s hepatoprotective potential attracts attention, currently no experimental evidence exists on its effectiveness against cholestatic liver injury. The present study investigated its hepatoprotection in the rat model of extrahepatic cholestasis using Bile Duct Ligation (BDL). We found that daily plumbagin supplementation protected the liver from cholestatic damage. Hepatoprotective actions of plumbagin were accompanied by reduction of Transforming Growth Factor β1 (TGF-β1)/Smad, High Mobility Group Box-1 (HMGB1)/Toll-Like Receptor-4 (TLR4), Hypoxia-Inducible Factor-1α (HIF-1α), Aryl Hydrocarbon Receptor (AhR), Heat Shock Protein 90 (HSP90), caveolin-1, NF-κB/AP-1, Dynamin Related Protein-1 (Drp1), malondialdehyde level, Interleukin-1β (IL-1β), p62/SQSTM1, and caspase 3 as well as increase of Farnesoid X Receptor (FXR), bile acid efflux transporters, glutathione, LC3-II, Beclin1, and nuclear NF-E2-Related Factor-2 (Nrf2) and Transcription Factor EB (TFEB). The activation of nuclear Nrf2 caused by plumbagin correlated well with the improvement in bile acid retention, liver histology, serum biochemical, ductular reaction, mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, impaired autophagy, and fibrosis, involving interplay of multiple intracellular signaling pathways. Plumbagin is likely a candidate drug to protect the liver from cholestatic damages. Despite the promising findings from this study, translational implication of plumbagin on cholestatic liver injury warrants further investigation.http://www.sciencedirect.com/science/article/pii/S0753332222005224CholestasisHepatoprotectionMitochondrial dysfunctionNrf2 |
| spellingShingle | Pin-Ho Pan Ya-Yu Wang Shih-Yi Lin Su-Lan Liao Yu-Fang Chen Wei-Chi Huang Chun-Jung Chen Wen-Ying Chen Plumbagin ameliorates bile duct ligation-induced cholestatic liver injury in rats Biomedicine & Pharmacotherapy Cholestasis Hepatoprotection Mitochondrial dysfunction Nrf2 |
| title | Plumbagin ameliorates bile duct ligation-induced cholestatic liver injury in rats |
| title_full | Plumbagin ameliorates bile duct ligation-induced cholestatic liver injury in rats |
| title_fullStr | Plumbagin ameliorates bile duct ligation-induced cholestatic liver injury in rats |
| title_full_unstemmed | Plumbagin ameliorates bile duct ligation-induced cholestatic liver injury in rats |
| title_short | Plumbagin ameliorates bile duct ligation-induced cholestatic liver injury in rats |
| title_sort | plumbagin ameliorates bile duct ligation induced cholestatic liver injury in rats |
| topic | Cholestasis Hepatoprotection Mitochondrial dysfunction Nrf2 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222005224 |
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