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Activity and mechanism of palbinone against hepatic fibrosis and inflammation
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Yi-ming LI, Yun-yang BAO, Hong-wei HE, Na ZHANG*
Acta Pharmaceutica Sinica | 2023, 58(2) : 371 - 376
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Acta Pharmaceutica Sinica | 2023, 58(2): 371-376
Original Articles
Activity and mechanism of palbinone against hepatic fibrosis and inflammation
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Yi-ming LI, Yun-yang BAO, Hong-wei HE, Na ZHANG*
Affiliations
  • Institute of Medical Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
Published: 2023-02-12 doi: 10.16438/j.0513-4870.2022-1050
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The study aims to investigate the anti-hepatic fibrosis and anti-inflammatory activities of palbinone, and to explore the internal regulatory mechanism, so as to lay an active foundation for its development as an anti-non-alcoholic steatohepatitis (NASH) candidate. First, sulforhodamine B (SRB) method was used to detect the effect of palbinone on the proliferation of human hepatic stellate cells LX-2 and rat hepatic stellate cells HSC-T6. Following, in the in vitro hepatic fibrosis cell model that activated by transforming growth factor beta 1 (TGF-β1), quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the inhibitory effect of different concentrations of palbinone on the transcription level and protein expression level of hepatic fibrosis markers. And the regulating mechanism of palbinone on fibrosis-related genes was analyzed at the same time. In addition, in the inflammatory cell model that induced by lipopolysaccharide (LPS) and nigericin, ELISA was used to detect the effect of palbinone on the released interleukin-1β (IL-1β) level. At the same time, Western blot was used to detect the effect of palbinone on the related proteins of inflammatory pathway. The results showed that palbinone could significantly inhibit the proliferation activity of LX-2 and HSC-T6, and their half maximal inhibitory concentration (IC50) values were (375.11 ± 55.45) and (260.27 ± 36.81) nmol·L-1, respectively. In addition, palbinone showed a dose-dependent inhibitory effect on the expression levels of TGF-β1-induced fibrosis-related genes, including collagen type Ⅰ α 1 (COL1A1), TGF-β1, α-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinase 1 (TIMP1). Mechanism study showed that palbinone may decrease the expression level of Yes-associated protein (YAP), thereby weakening its activation effect on the downstream fibrosis pathway. In addition, palbinone also exerted an anti-inflammatory effect by inhibiting the activity of nuclear factor kappa-B (NF-κB) signaling pathway and reducing inflammatory factors cysteinyl aspartate specific proteinase-1 (caspase-1) and IL-1β release. In conclusion, palbinone can not only inhibit the proliferation and activation of hepatic stellate cells by inhibiting the expression of YAP, but also inhibit the expression and release of inflammatory factors at the same time. All these studies provide theoretical support for the development of palbinone as an anti-nonalcoholic steatohepatitis drug.

hepatic fibrosis  /  inflammation  /  palbinone  /  Yes-associated protein  /  nuclear factor kappa-B
Yi-ming LI, Yun-yang BAO, Hong-wei HE, Na ZHANG. Activity and mechanism of palbinone against hepatic fibrosis and inflammation[J]. Acta Pharmaceutica Sinica, 2023 , 58 (2) : 371 -376 . DOI: 10.16438/j.0513-4870.2022-1050
Year 2023 volume 58 Issue 2
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doi: 10.16438/j.0513-4870.2022-1050
  • Receive Date:2022-09-09
  • Online Date:2025-11-21
  • Published:2023-02-12
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  • Received:2022-09-09
  • Revised:2022-09-30
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    Institute of Medical Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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