scholarly journals Active Compounds Derived from Fuzheng Huayu Formula Protect Hepatic Parenchymal Cells from Apoptosis Based on Network Pharmacology and Transcriptomic Analysis

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 338 ◽  
Author(s):  
Rong Wu ◽  
Shu Dong ◽  
Fei-Fei Cai ◽  
Xiao-Le Chen ◽  
Meng-Die Yang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Stellate Cell ◽  
Parenchymal Cell ◽  
Transcriptomic Analysis ◽  
Tanshinone Iia ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Parenchymal Cells

Fuzheng huayu formula (FZHY), an antifibrotic traditional Chinese medicine, is frequently used for the treatment of liver fibrosis. In this study, network analysis, transcriptomic analysis, assays of cell apoptosis, viability and protein expression were used for investigating the effects and mechanisms of compounds derived from FZHY on hepatic parenchymal cell (HPC) protection and hepatic stellate cell activation. Network pharmacology analysis found that 6 major compounds and 39 potential targets were important network nodes. Our analysis predicted that the active compounds of FZHY, including hederagenin, luteolin and tanshinone IIA inhibited cell apoptosis (p < 0.05), increased PI3K expression and reduced cleaved caspase 3 expression and the Bax/Bcl-w ratio (p < 0.05) in L02 cells that had apoptosis induced by TNF-α. Few significant changes caused by FZHY, hederagenin, luteolin and tanshinone IIA were observed in hepatic stellate Lx2 cells upon TGF-β1 induction. These data suggest that FZHY is active against liver fibrosis, protects hepatic parenchymal cells from apoptosis, and recovers liver function, possibly through the effects of its active compounds hederagenin, luteolin and tanshinone IIA and is involved in the inhibition of apoptosis in HPCs, possibly through regulating the PI3K, ERK, cleaved caspase 3 and Bax/Bcl-w levels.

scholarly journals Autophagy: A Multifaceted Partner in Liver Fibrosis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ariane Mallat ◽  
Jasper Lodder ◽  
Fatima Teixeira-Clerc ◽  
Richard Moreau ◽  
Patrice Codogno ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Parenchymal Cell ◽  
High Morbidity ◽  
Antifibrotic Therapy ◽  
End Stage ◽  
Matrix Accumulation ◽  
Parenchymal Cells ◽  
Apoptosis And Necrosis

Liver fibrosis is a common wound healing response to chronic liver injury of all causes, and its end-stage cirrhosis is responsible for high morbidity and mortality worldwide. Fibrosis results from prolonged parenchymal cell apoptosis and necrosis associated with an inflammatory reaction that leads to recruitment of immune cells, activation and accumulation of fibrogenic cells, and extracellular matrix accumulation. The fibrogenic process is driven by hepatic myofibroblasts, that mainly derive from hepatic stellate cells undergoing a transdifferentiation from a quiescent, lipid-rich into a fibrogenic myofibroblastic phenotype, in response to paracrine/autocrine signals produced by neighbouring inflammatory and parenchymal cells. Autophagy is an important regulator of liver homeostasis under physiological and pathological conditions. This review focuses on recent findings showing that autophagy is a novel, but complex, regulatory pathway in liver fibrosis, with profibrogenic effects relying on its direct contribution to the process of hepatic stellate cell activation, but with antifibrogenic properties via indirect hepatoprotective and anti-inflammatory properties. Therefore, cell-specific delivery of drugs that exploit autophagic pathways is a prerequisite to further consider autophagy as a potential target for antifibrotic therapy.

A network pharmacology approach to investigating the mechanism of Tanshinone IIA for the treatment of liver fibrosis

2020 ◽  
Vol 253 ◽  
pp. 112689 ◽  
Author(s):  
Miao-Juan Shi ◽  
Xiu-Li Yan ◽  
Ben-Sheng Dong ◽  
Wen-Na Yang ◽  
Shi-Bing Su ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Tanshinone Iia ◽  
Network Pharmacology

Effects of Siniruangan Recipe on Proliferation, Apoptosis and Activation of Human Hepatic Stellate Cell Line LX-2

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 342-351 ◽  
Author(s):  
Jinming Liu ◽  
Guorong Zhao ◽  
Bichen Ai ◽  
Yirong He ◽  
Ming Mei ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Fibrosis ◽  
Cell Apoptosis ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Cell Activity ◽  
Relative Content ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Cell Counting ◽  
Tgf Β1

Background: Experimental and clinical evidence suggests that liver fibrosis is potentially reversible. Hepatic stellate cells (HSCs) play a key role in the development of hepatic fibrosis. Previous clinical applications and researches showed that Siniruangan recipe (SNRG) reversed liver fibrosis and even liver cirrhosis. This experimental study aimed to elucidate the effects of SNRG on the proliferation, apoptosis and activation of HSCs. Methods: The human HSCs line LX-2 was cultured with normal culture medium and multi-dose SNRG water decoction for 48 h. Cell Counting Kit-8 assay was used to detect the proliferation and cytotoxicity of LX-2 cells. Annexin V-FITC/PI double staining was performed to identify apoptotic cells. Immunofluorescence staining was used to determine the relative content of cleaved caspase-3, tissue inhibitor of metalloproteinase-1 (TIMP-1) and transforming growth factor-β1 (TGF-β1) in LX-2 cells. Western blot was used to detect the relative content of Bcl-2, Bax, α-smooth muscle actin, β-catenin and TIMP-1 protein expression in LX-2 cells. Results: The SNRG inhibited the proliferation of LX-2 and induced cell apoptosis through caspase-dependent and mitochondrial-dependent pathways. SNRG may inhibit the activation of LX-2 through the β-catenin pathway. The decrease in TIMP-1 and TGF-β1 protein induced by SNRG promoted the degradation of the extracellular matrix (ECM). Conclusions: SNRG induced LX-2 cell apoptosis, inhibited cell proliferation, decreased LX-2 cell activity and promoted the degradation of ECM in vitro, which may be important mechanisms for reversing liver fibrosis and liver cirrhosis.

Inhibition of inhibitor of κB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis

2005 ◽  
Vol 128 (1) ◽  
pp. 108-120 ◽  
Author(s):  
Fiona Oakley ◽  
Muriel Meso ◽  
John P. Iredale ◽  
Karen Green ◽  
Carylyn J. Marek ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Rat Liver ◽  
Hepatic Stellate Cell ◽  
Cell Apoptosis ◽  
Stellate Cell ◽  
Rat Liver Fibrosis

Silent information regulator 1 (SIRT1) ameliorates liver fibrosis via promoting activated stellate cell apoptosis and reversion

2015 ◽  
Vol 289 (2) ◽  
pp. 163-176 ◽  
Author(s):  
Yuting Wu ◽  
Xuejiao Liu ◽  
Qun Zhou ◽  
Cheng Huang ◽  
Xiaoming Meng ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Apoptosis ◽  
Stellate Cell ◽  
Silent Information Regulator 1

Tanshinone IIA Attenuates H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells

2012 ◽  
Vol 40 (06) ◽  
pp. 1307-1319 ◽  
Author(s):  
Paul Chan ◽  
Yen-Cheng Chen ◽  
Li-Jen Lin ◽  
Tzu-Hurng Cheng ◽  
Kazunori Anzai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Protective Effect ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Umbilical Vein ◽  
Tanshinone Iia ◽  
Cardiovascular Disorders ◽  
P53 Expression ◽  
Umbilical Vein Endothelial Cells

The injury of endothelial cell is the critical event of vascular disease. In endothelial cell, oxidative stress is regarded as critical to pathogenic factors in endothelial cell injury and apoptosis. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as "Danshen" in traditional Chinese medicine for treating cardiovascular disorders, but the mechanism by which it exerts the protective effect is not well established. The present study was designed to test the hypothesis that tanshinone IIA can inhibit hydrogen peroxide ( H2O2 )-induced injury and unravel its intracellular mechanism in human umbilical vein endothelial cells (HUVECs). In this study, HUVECs were treated with tanshinone IIA in the presence/absence of H2O2 . The protective effects of tanshinone IIA against H2O2 were evaluated. Our results show that HUVECs incubated with 200 μM H2O2 had significantly decreased the viability of endothelial cells, which was accompanied with apparent cell apoptosis, the activation of caspase-3 and the upregulation of p53 expression, which was known to play a key role in H2O2 -induced cell apoptosis. However, pretreatment with tanshinone IIA (3–10 μM) resulted in a significant resistance to H2O2 -induced apoptosis. In addition, pretreatment with tanshinone IIA decreased the activity of caspase-3 and p53 expression. Tanshinone IIA also induced activating transcription factor (ATF) 3 expression; while knockdown of ATF-3 with ATF-3 siRNAsignificantly reduced tanshinone IIA's protective effect. In conclusion, the present study shows that tanshinone IIA can protect endothelial cells against oxidative injury induced by H2O2 , suggesting that this compound may constitute a promising intervention against cardiovascular disorders and ATF-3 may play an important role in this process.

The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis

APOPTOSIS ◽  
2005 ◽  
Vol 10 (5) ◽  
pp. 927-939 ◽  
Author(s):  
A. M. Elsharkawy ◽  
F. Oakley ◽  
D. A. Mann
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Cell Apoptosis ◽  
Stellate Cell
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