Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis
OBJECTIVE: Saikosaponin c (SSc), a compound purified from the traditional Chinese herb of Radix Bupleuri was previously identified to exhibit anti-HBV replication activity. However, the mechanism through which SSc acts against HBV remains unknown. In this study, we investigated the mechanism of SSc mediated anti-HBV activity.
METHODS: HepG2.2.15 cells were cultured at 37 ℃ in the presence of 1-40 μg/mL of SSc or DMSO as a control. The expression profile of HBV markers, cytokines, HNF1α and HNF4α were investigated by real-time quantitative PCR, Elisa, Western blot and Dot blotting. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells was mediated by two small siRNAs specifically targeting HNF1α or HNF4α.
RESULTS: We found that SSc stimulates IL-6 expression, leading to attenuated HNF1α and HNF4α expression, which further mediates suppression of HBV pgRNA synthesis. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells by RNA interference abrogates SSc's anti-HBV role. Moreover, SSc is effective to both wild-type and drug-resistant HBV mutants.
CONCLUSION: SSc inhibits pgRNA synthesis by targeting HNF1α and HNF4α. These results indicate that SSc acts as a promising compound for modulating pgRNA transcription in the therapeutic strategies against HBV infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:68 |
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| Enthalten in: |
Inflammation research : official journal of the European Histamine Research Society ... [et al. - 68(2019), 12 vom: 06. Dez., Seite 1025-1034 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pan, Yanchao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.04.2020 Date Revised 09.12.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00011-019-01284-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM301399441 |
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| 100 | 1 | |a Pan, Yanchao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 03.04.2020 | ||
| 500 | |a Date Revised 09.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: Saikosaponin c (SSc), a compound purified from the traditional Chinese herb of Radix Bupleuri was previously identified to exhibit anti-HBV replication activity. However, the mechanism through which SSc acts against HBV remains unknown. In this study, we investigated the mechanism of SSc mediated anti-HBV activity | ||
| 520 | |a METHODS: HepG2.2.15 cells were cultured at 37 ℃ in the presence of 1-40 μg/mL of SSc or DMSO as a control. The expression profile of HBV markers, cytokines, HNF1α and HNF4α were investigated by real-time quantitative PCR, Elisa, Western blot and Dot blotting. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells was mediated by two small siRNAs specifically targeting HNF1α or HNF4α | ||
| 520 | |a RESULTS: We found that SSc stimulates IL-6 expression, leading to attenuated HNF1α and HNF4α expression, which further mediates suppression of HBV pgRNA synthesis. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells by RNA interference abrogates SSc's anti-HBV role. Moreover, SSc is effective to both wild-type and drug-resistant HBV mutants | ||
| 520 | |a CONCLUSION: SSc inhibits pgRNA synthesis by targeting HNF1α and HNF4α. These results indicate that SSc acts as a promising compound for modulating pgRNA transcription in the therapeutic strategies against HBV infection | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HBV pgRNA | |
| 650 | 4 | |a HNF1α | |
| 650 | 4 | |a HNF4α | |
| 650 | 4 | |a Saikosaponin c | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
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| 650 | 7 | |a HNF4A protein, human |2 NLM | |
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| 650 | 7 | |a saikosaponin D |2 NLM | |
| 650 | 7 | |a UR635J3F00 |2 NLM | |
| 700 | 1 | |a Ke, Zhiyi |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Lina |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Xiaoyan |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Runze |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Jing |e verfasserin |4 aut | |
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