Therapeutic potential of genipin in various acute liver injury, fulminant hepatitis, NAFLD and other non-cancer liver diseases : More friend than foe
Copyright © 2020 Elsevier Ltd. All rights reserved..
Genipin is an aglycone derived from the geniposide, the most abundant iridoid glucoside constituent of Gardenia jasminoides Ellis. For decades, genipin is the focus of studies as a versatile compound in the treatment of various pathogenic conditions. In particularly, Gardenia jasminoides Ellis has long been used in traditional Chinese medicine for the prevention and treatment of liver disease. Mounting experimental data has proved genipin possesses therapeutic potential for cholestatic, septic, ischemia/reperfusion-triggered acute liver injury, fulminant hepatitis and NAFLD. This critical review is a reflection on the valuable lessons from decades of research regarding pharmacological activities of genipin. Of note, genipin represents choleretic effect by potentiating bilirubin disposal and enhancement of genes in charge of the efflux of a number of organic anions. The anti-inflammatory capability of genipin is mediated by suppression of the production and function of pro-inflammatory cytokines and inflammasome. Moreover, genipin modulates various transcription factor and signal transduction pathway. Genipin appears to trigger the upregulation of several key genes encoding antioxidant and xenobiotic-metabolizing enzymes. Furthermore, the medicinal impact of genipin extends to modulation of regulated cell death, including autophagic cell death, apoptosis, necroptosis and pyroptosis, and modulation of quality of cellular organelle. Another crucial effect of genipin appears to be linked to dual role in targeting uncoupling protein 2 (UCP2). As a typical UCP2-inhibiting compound, genipin could inhibit AMP-activated protein kinase or NF-κB in circumstance. On the contrary, reactive oxygen species production and cellular lipid deposits mediated by genipin through the upregulation of UCP2 is observed in liver steatosis, suggesting the precise role of genipin is disease-specific. Collectively, we comprehensively summarize the mechanisms and pathways associated with the hepatoprotective activity of genipin and discuss potential toxic impact. Notably, our focus is the direct medicinal effect of genipin itself, whereas its utility as a crosslinking agent in tissue engineering is out of scope for the current review. Further studies are therefore required to disentangle these complicated pharmacological properties to confer this natural agent a far greater potency.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:159 |
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| Enthalten in: |
Pharmacological research - 159(2020) vom: 01. Sept., Seite 104945 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fan, Xiaofei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.07.2021 Date Revised 06.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.phrs.2020.104945 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Therapeutic potential of genipin in various acute liver injury, fulminant hepatitis, NAFLD and other non-cancer liver diseases |b More friend than foe |
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| 520 | |a Genipin is an aglycone derived from the geniposide, the most abundant iridoid glucoside constituent of Gardenia jasminoides Ellis. For decades, genipin is the focus of studies as a versatile compound in the treatment of various pathogenic conditions. In particularly, Gardenia jasminoides Ellis has long been used in traditional Chinese medicine for the prevention and treatment of liver disease. Mounting experimental data has proved genipin possesses therapeutic potential for cholestatic, septic, ischemia/reperfusion-triggered acute liver injury, fulminant hepatitis and NAFLD. This critical review is a reflection on the valuable lessons from decades of research regarding pharmacological activities of genipin. Of note, genipin represents choleretic effect by potentiating bilirubin disposal and enhancement of genes in charge of the efflux of a number of organic anions. The anti-inflammatory capability of genipin is mediated by suppression of the production and function of pro-inflammatory cytokines and inflammasome. Moreover, genipin modulates various transcription factor and signal transduction pathway. Genipin appears to trigger the upregulation of several key genes encoding antioxidant and xenobiotic-metabolizing enzymes. Furthermore, the medicinal impact of genipin extends to modulation of regulated cell death, including autophagic cell death, apoptosis, necroptosis and pyroptosis, and modulation of quality of cellular organelle. Another crucial effect of genipin appears to be linked to dual role in targeting uncoupling protein 2 (UCP2). As a typical UCP2-inhibiting compound, genipin could inhibit AMP-activated protein kinase or NF-κB in circumstance. On the contrary, reactive oxygen species production and cellular lipid deposits mediated by genipin through the upregulation of UCP2 is observed in liver steatosis, suggesting the precise role of genipin is disease-specific. Collectively, we comprehensively summarize the mechanisms and pathways associated with the hepatoprotective activity of genipin and discuss potential toxic impact. Notably, our focus is the direct medicinal effect of genipin itself, whereas its utility as a crosslinking agent in tissue engineering is out of scope for the current review. Further studies are therefore required to disentangle these complicated pharmacological properties to confer this natural agent a far greater potency | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Genipin | |
| 650 | 4 | |a Liver disease | |
| 650 | 4 | |a Regulated cell death | |
| 650 | 4 | |a Toxicity | |
| 650 | 4 | |a Traditional Chinese medicine | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Antioxidants |2 NLM | |
| 650 | 7 | |a Cholagogues and Choleretics |2 NLM | |
| 650 | 7 | |a Iridoids |2 NLM | |
| 650 | 7 | |a Uncoupling Protein 2 |2 NLM | |
| 650 | 7 | |a genipin |2 NLM | |
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| 700 | 1 | |a Cui, Binxin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Tianming |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Lihong |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Hongjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Qingxiang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Kui |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Xiaocang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Bangmao |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Chao |e verfasserin |4 aut | |
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