Long-term oral administration of Epimedii Folium induced cholestasis in mice by interfering with bile acid transport
Copyright © 2022 Elsevier B.V. All rights reserved..
ETHNOPHARMACOLOGICAL RELEVANCE: Epimedii Folium (EF) is a common traditional Chinese medicine that functions as a tonifying kidney yang to strengthen bones and muscles and dispel wind dampness (limb pain, lethargy, nausea, anorexia, and loose stools). Several studies have reported the potential risk of cholestatic liver damage from EF use; however, there have been few investigations of EF-induced cholestasis, particularly the underlying mechanisms.
AIMS OF THE STUDY: The purpose of this study was to evaluate the risk of EF-induced cholestasis in vivo and to explore the mechanisms of action.
MATERIALS AND METHODS: ICR mice were orally administered a water extract of EF (WEF) in doses of 6.5 and 19.5 g/kg/day for 14 weeks. Liver-to-body weight ratios, body weight, histopathological examination, and biochemical analyses were performed to assess WEF-induced cholestasis in the mice. Genes associated with bile acid (BA) metabolism and transport, including sodium taurocholate cotransporting polypeptide (NTCP), cytochrome P450 8B1 (CYP8B1), bile-salt export pump (BSEP), multidrug resistance P-glycoproteins 1 (MDR1), and farnesoid X receptor (FXR), were measured at the transcript and protein levels to investigate the potential mechanisms through which cholestasis is aroused by EF.
RESULTS: After administration of WEF for 14 weeks, mice in the high-dose WEF group showed poor health with an increased liver-to-body weight ratio as well as higher serum aminotransferase, alkaline phosphatase, direct bilirubin, and total BA levels. Compared with the control group, mRNA expression of NTCP and cholesterol 7a-hydroxylase (CYP7A1) increased, and levels of BSEP, MDR1, multidrug resistance-associated protein 2, and multidrug resistance-associated protein 3 decreased in the WEF-treated group. NTCP, BSEP, MDR1, and CYP8B1 showed similar mRNA and protein expression trends.
CONCLUSION: We demonstrated that the long-term oral administration of WEF causes cholestatic liver injury in mice, which is consistent with reported clinical cases. Furthermore, we found that the destruction of BA metabolism and transport is involved in WEF-induced cholestasis. The fine-scale molecular mechanisms of WEF-induced cholestasis and the active compounds of EF need further study.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:293 |
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| Enthalten in: |
Journal of ethnopharmacology - 293(2022) vom: 15. Juli, Seite 115254 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Jin-Quan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.05.2022 Date Revised 17.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jep.2022.115254 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339111143 |
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| 100 | 1 | |a Zhao, Jin-Quan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Long-term oral administration of Epimedii Folium induced cholestasis in mice by interfering with bile acid transport |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 17.05.2022 | ||
| 500 | |a Date Revised 17.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
| 520 | |a ETHNOPHARMACOLOGICAL RELEVANCE: Epimedii Folium (EF) is a common traditional Chinese medicine that functions as a tonifying kidney yang to strengthen bones and muscles and dispel wind dampness (limb pain, lethargy, nausea, anorexia, and loose stools). Several studies have reported the potential risk of cholestatic liver damage from EF use; however, there have been few investigations of EF-induced cholestasis, particularly the underlying mechanisms | ||
| 520 | |a AIMS OF THE STUDY: The purpose of this study was to evaluate the risk of EF-induced cholestasis in vivo and to explore the mechanisms of action | ||
| 520 | |a MATERIALS AND METHODS: ICR mice were orally administered a water extract of EF (WEF) in doses of 6.5 and 19.5 g/kg/day for 14 weeks. Liver-to-body weight ratios, body weight, histopathological examination, and biochemical analyses were performed to assess WEF-induced cholestasis in the mice. Genes associated with bile acid (BA) metabolism and transport, including sodium taurocholate cotransporting polypeptide (NTCP), cytochrome P450 8B1 (CYP8B1), bile-salt export pump (BSEP), multidrug resistance P-glycoproteins 1 (MDR1), and farnesoid X receptor (FXR), were measured at the transcript and protein levels to investigate the potential mechanisms through which cholestasis is aroused by EF | ||
| 520 | |a RESULTS: After administration of WEF for 14 weeks, mice in the high-dose WEF group showed poor health with an increased liver-to-body weight ratio as well as higher serum aminotransferase, alkaline phosphatase, direct bilirubin, and total BA levels. Compared with the control group, mRNA expression of NTCP and cholesterol 7a-hydroxylase (CYP7A1) increased, and levels of BSEP, MDR1, multidrug resistance-associated protein 2, and multidrug resistance-associated protein 3 decreased in the WEF-treated group. NTCP, BSEP, MDR1, and CYP8B1 showed similar mRNA and protein expression trends | ||
| 520 | |a CONCLUSION: We demonstrated that the long-term oral administration of WEF causes cholestatic liver injury in mice, which is consistent with reported clinical cases. Furthermore, we found that the destruction of BA metabolism and transport is involved in WEF-induced cholestasis. The fine-scale molecular mechanisms of WEF-induced cholestasis and the active compounds of EF need further study | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bile acid homeostasis | |
| 650 | 4 | |a Bile acid transport | |
| 650 | 4 | |a Drug-induced cholestasis | |
| 650 | 4 | |a Epimedii folium | |
| 650 | 7 | |a Bile Acids and Salts |2 NLM | |
| 650 | 7 | |a Drugs, Chinese Herbal |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Receptors, Cytoplasmic and Nuclear |2 NLM | |
| 650 | 7 | |a epimedii flavone |2 NLM | |
| 650 | 7 | |a Steroid 12-alpha-Hydroxylase |2 NLM | |
| 650 | 7 | |a EC 1.14.18.8 |2 NLM | |
| 700 | 1 | |a Zhao, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Cai |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Jia-Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Feng-Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hui-Jun |e verfasserin |4 aut | |
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