scholarly journals Explore the Molecular Mechanism of Apoptosis Induced by Tanshinone IIA on Activated Rat Hepatic Stellate Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Tai-Long Pan ◽  
Pei-Wen Wang
Keyword(s):  
Stellate Cell ◽  
Salvia Miltiorrhiza ◽  
Ethanol Extract ◽  
Stellate Cells ◽  
Tanshinone Iia ◽  
Cycle Arrest ◽  
Erk Phosphorylation ◽  
Liver Fibrogenesis ◽  
Potential Strategy ◽  
Induced Apoptosis

Since the activated hepatic stellate cell (HSC) is the predominant event in the progression of liver fibrosis, selective clearance of HSC should be a potential strategy in therapy.Salvia miltiorrhizaroots ethanol extract (SMEE) remarkably ameliorates liver fibrogenesis in DMN-administrated rat model. Next, tanshinone IIA (Tan IIA), the major compound of SMEE, significantly inhibited rat HSC viability and led to cell apoptosis. Proteome tools elucidated that increased prohibitin is involved in cell cycle arrest under Tan IIA is the treatment while knockdown of prohibitin could attenuate Tan IIA-induced apoptosis. In addition, Tan IIA mediated translocation of C-Raf which interacted with prohibitin activating MAPK and inhibiting AKT signaling in HSC. MAPK antagonist suppressed ERK phosphorylation which was necessary for Tan IIA-induced expression of Bax and cytochrome c. PD98059 also abolished Tan IIA-modulated cleavage of PARP. Our findings suggested that Tan IIA could contribute to apoptosis of HSC by promoting ERK-Bax-caspase pathways through C-Raf/prohibitin complex.

scholarly journals Pregnenolone-16α-carbonitrile inhibits rodent liver fibrogenesis via PXR (pregnane X receptor)-dependent and PXR-independent mechanisms

2005 ◽  
Vol 387 (3) ◽  
pp. 601-608 ◽  
Author(s):  
Carylyn J. MAREK ◽  
Steven J. TUCKER ◽  
Dimitrios K. KONSTANTINOU ◽  
Lucy J. ELRICK ◽  
Dee HAEFNER ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Hepatic Stellate Cells ◽  
Stellate Cell ◽  
Direct Interaction ◽  
Pregnane X Receptor ◽  
Stellate Cells ◽  
Liver Growth ◽  
Liver Fibrogenesis

The effect of liver growth stimulation [using the rodent PXR (pregnane X receptor) activator PCN (pregnenolone-16α-carbonitrile)] in rats chronically treated with carbon tetrachloride to cause repeated hepatocyte necrosis and liver fibrogenesis was examined. PCN did not inhibit the hepatotoxicity of carbon tetrachloride. However, transdifferentiation of hepatic stellate cells and the extent of fibrosis caused by carbon tetrachloride treatment was significantly inhibited by PCN in vivo. In vitro, PCN directly inhibited hepatic stellate cell transdifferentiation to a profibrogenic phenotype, although the cells did not express the PXR (in contrast with hepatocytes), suggesting that PCN acts independently of the PXR. Mice with a functionally disrupted PXR gene (PXR−/−) did not respond to the antifibrogenic effects of PCN, in contrast with wild-type (PXR+/+) mice, demonstrating an antifibrogenic role for the PXR in vivo. However, PCN inhibited the transdifferentiation of PXR−/−-derived mouse hepatic stellate cells in vitro, confirming that there is also a PXR-independent antifibrogenic effect of PCN through a direct interaction with hepatic stellate cells. These data suggest that the PXR is antifibrogenic in rodents in vivo and that a PXR-independent target for PXR activators exists in hepatic stellate cells that also functions to inhibit fibrosis.

Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocyte injury via lncRNA AK003290/miR-124-5p signaling

2020 ◽  
Author(s):  
Liye Chen ◽  
Lili Wei ◽  
Qiongyang Yu ◽  
Haozhe Shi ◽  
George Liu
Keyword(s):  
Mitochondrial Membrane ◽  
Salvia Miltiorrhiza ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Tanshinone Iia ◽  
Salvia Miltiorrhiza Bunge ◽  
Pharmacological Activities ◽  
Heavy Burden ◽  
Induced Apoptosis

Abstract Background: Acute myocardial infarction (AMI) is the leading cause of death globally and has thus placed a heavy burden on healthcare. Tanshinone IIA (TSA) is a major active compound, extracted from Salvia miltiorrhiza Bunge, that possesses various pharmacological activities. The aim of the present study was to investigate the role of TSA in AMI and its underlying mechanism of action.Results: We have shown that TSA decreased the apoptosis rate, the amount of LDH, MDA as well as ROS of cardiomyocytes. Meantime, it elevated mitochondrial membrane potential (MMP) which was decreased by H/R treatment. It was also determined that miR-124-5p targets AK003290 directly. TSA up-regulated the expression of AK003290 and its function can be reversed by knock down of AK003290 as well as miR-124-5p overexpression.Conclusion: TSA exerts the protective role against H/R induced apoptosis, oxidative and MMP loss of cardiomyocytes via regulating AK003290 and miR-124-5p signaling.

Total Tanshinones-Induced Apoptosis and Autophagy Via Reactive Oxygen Species in Lung Cancer 95D Cells

2015 ◽  
Vol 43 (06) ◽  
pp. 1265-1279 ◽  
Author(s):  
Hongwei Gao ◽  
Wen Sun ◽  
Wenwen Zhao ◽  
Wenhui Hao ◽  
Chung-Hang Leung ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Salvia Miltiorrhiza ◽  
Chinese Herb ◽  
Reactive Oxygen ◽  
Beclin 1 ◽  
Tanshinone Iia ◽  
Oxygen Species ◽  
Bioactive Constituents ◽  
Induced Apoptosis

Tanshinones are a group of bioactive constituents isolated from Salvia miltiorrhiza Bunge, a widely prescribed traditional Chinese herb. In the current study, the anticancer properties of total tanshinones (TDT) were evaluated using 95D lung cancer cells. Tanshinone IIA was identified as the main component of TDT. Compared with tanshinone IIA, TDT showed more cytotoxic effects on the 95D cells. Annexin V/7-AAD double staining, the depolarization of mitochondrial membrane potential (MMP) (Δψ), the up-regulation of pro-apoptotic proteins, such as cleaved-PARP, cleaved-caspase-3, Bax, and Bad, and the down-regulation of anti-apoptotic protein Bcl-2 were evidence of TDT-induced apoptosis. Furthermore, TDT-induced autophagy as demonstrated by monodansylcadaverine (MDC) staining and the up-regulation of autophagy-associated proteins, such as LC3-II, Beclin-1, Atg3, Atg5, Atg7, and Atg12. Autophagy inhibitors, 3-methyladenine (3-MA) and bafilomycin A1, enhanced TDT-induced cell death. 3-MA pretreatment enhanced the TDT-induced up-regulation of Bax and cleaved-PARP. In addition, TDT induced the generation of reactive oxygen species (ROS), which was reversed by N-acetylcysteine (NAC). NAC also reversed TDT-induced depolarization of Δψ, MDC staining, up-regulation of Bax, cleaved-PARP, Beclin-1, LC3-II, and cell viability. In conclusion, our findings showed that TDT-induced apoptosis and protective autophagy in 95D cells mediated by increasing intracellular ROS production.

scholarly journals Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocyte injury via lncRNA AK003290/miR-124-5p signaling

2020 ◽  
Author(s):  
Liye Chen ◽  
Lili Wei ◽  
Qiongyang Yu ◽  
Haozhe Shi ◽  
George Liu
Keyword(s):  
Mitochondrial Membrane ◽  
Salvia Miltiorrhiza ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Tanshinone Iia ◽  
Salvia Miltiorrhiza Bunge ◽  
Pharmacological Activities ◽  
Heavy Burden ◽  
Induced Apoptosis

Abstract Background: Acute myocardial infarction (AMI) is the leading cause of death globally and has thus placed a heavy burden on healthcare. Tanshinone IIA (TSA) is a major active compound, extracted from Salvia miltiorrhiza Bunge, that possesses various pharmacological activities. The aim of the present study was to investigate the role of TSA in AMI and its underlying mechanism of action.Results: We have shown that TSA decreased the apoptosis rate, the amount of LDH, MDA as well as ROS of cardiomyocytes. Meantime, it elevated mitochondrial membrane potential (MMP) which was decreased by H/R treatment. It was also determined that miR-124-5p targets AK003290 directly. TSA up-regulated the expression of AK003290 and its function can be reversed by knock down of AK003290 as well as miR-124-5p overexpression.Conclusion: TSA exerts the protective role against H/R induced apoptosis, oxidative and MMP loss of cardiomyocytes via regulating AK003290 and miR-124-5p signaling.

scholarly journals Schisandrin B Attenuates Hepatic Stellate Cell Activation and Promotes Apoptosis to Protect against Liver Fibrosis

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6882
Author(s):  
Zhiman Li ◽  
Lijuan Zhao ◽  
Yunshi Xia ◽  
Jianbo Chen ◽  
Mei Hua ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Schisandrin B ◽  
Proliferation And Apoptosis ◽  
Induced Apoptosis ◽  
Tgf Β1 ◽  
Different Doses

The activation of hepatic stellate cells (HSC) plays a key role in the progression of hepatic fibrosis, it is essential to remove activated HSC through apoptosis to reverse hepatic fibrosis. Schisandrin B (Sch B) is the main chemical component of schisandrin lignan, and it has been reported to have good hepatoprotective effects. However, Schisandrin B on HSC apoptosis remains unclear. In our study, we stimulated the HSC-T6 and LX-2 cell lines with TGF-β1 to induce cell activation, and the proliferation and apoptosis of the activated HSC-T6 and LX-2 cells were detected after treatment with different doses of Schisandrin B. Flow cytometry results showed that Sch B significantly reduced the activity of activated HSC-T6 and LX-2 cells and significantly induced apoptosis. In addition, the cleaved-Caspase-3 levels were increased, the Bax activity was increased, and the Bcl-2 expression was decreased in HSC-T6 and LX-2 cells treated with Sch B. Our study showed that Sch B inhibited the TGF-β1-induced activity of hepatic stellate cells by promoting apoptosis.

scholarly journals Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocytes injury via lncRNA AK003290/miR-124-5p signaling

2019 ◽  
Author(s):  
Liye Chen ◽  
Lili Wei ◽  
Qiongyang Yu ◽  
Haozhe Shi ◽  
George Liu
Keyword(s):  
Salvia Miltiorrhiza ◽  
Annexin V ◽  
Protective Role ◽  
Tanshinone Iia ◽  
Activity Assay ◽  
Western Blot Assay ◽  
Expression Of Genes ◽  
Commercial Kits ◽  
Induced Apoptosis

Abstract Objective Acute myocardial infarction (AMI) is the leading cause of death and one of the heaviest healthy burden globally nowadays. Tanshinone IIA (TSA) is the major active compound extracted form Salvia miltiorrhiza Bunge possessing various of pharmacology activities. The present study aimed at investigating the role of TSA in AMI and underlying mechsniam.Methods Quantitative real-time PCR (qRT-PCR) and western blot assay were performed to detect the expression of genes and proteins. Cell apoptosis was detected by Annexin/V PI staining and flow cytometry. The amount of LDH, MDA and ROS were detected using commercial kits. FISH experiment was used to detect the expression of AK003290 in cardiomyocytes. Luciferace activity assay was performed to verify the interaction between AK003290 and miR-124-5p.Results We have shown that TSA decreased the apoptosis rate, the amount of LDH, MDA as well as ROS of cardiomyocytes. Meantime, it elevated mitochondrial membrane potential (MMP) which was decreased by H/R treatment. It was also determined that miR-124-5p targets AK003290 directly. TSA up-regulated the expression of AK003290 and its function can be reversed by knock down of AK003290 as well as miR-124-5p overexpression.Conclusion TSA exerts the protective role against H/R induced apoptosis, oxidative and MMP loss of cardiomyocytes via regulating AK003290 and miR-124-5p signaling.

scholarly journals Hepatic Stellate Cell: A Double-Edged Sword in the Liver

2021 ◽  
pp. 821-829
Author(s):  
N. Luo ◽  
J. Li ◽  
Y. Wei ◽  
J. Lu ◽  
R. Dong
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cell ◽  
Normal Liver ◽  
Stellate Cells ◽  
Comprehensive Understanding ◽  
Fibrosis Progression ◽  
Liver Fibrogenesis ◽  
Fibrosis Regression ◽  
Space Of Disse

Hepatic stellate cells (HSCs) are located in the space of Disse, between liver sinusoidal endothelia cells (LSECs) and hepatocytes. They have surprised and excited hepatologists for their biological characteristics. Under physiological quiescent conditions, HSCs are the major vitamin A-storing cells of the liver, playing crucial roles in the liver development, regeneration, and tissue homeostasis. Upon injury-induced activation, HSCs convert to a pro-fibrotic state, producing the excessive extracellular matrix (ECM) and promoting angiogenesis in the liver fibrogenesis. Activated HSCs significantly contribute to liver fibrosis progression and inactivated HSCs are key to liver fibrosis regression. In this review, we summarize the comprehensive understanding of HSCs features, including their roles in normal liver and liver fibrosis in hopes of advancing the development of emerging diagnosis and treatment for hepatic fibrosis.

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