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10.1016/j.jss.2014.03.036

http://scihub22266oqcxt.onion/10.1016/j.jss.2014.03.036
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suck abstract from ncbi


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pmid24742622
      J+Surg+Res 2014 ; 190 (1 ): 55-63
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  • Oridonin inhibits hepatic stellate cell proliferation and fibrogenesis #MMPMID24742622
  • Bohanon FJ ; Wang X ; Ding C ; Ding Y ; Radhakrishnan GL ; Rastellini C ; Zhou J ; Radhakrishnan RS
  • J Surg Res 2014[Jul]; 190 (1 ): 55-63 PMID24742622 show ga
  • BACKGROUND: Liver fibrosis is a common response to liver injury and, in severe cases, leads to cirrhosis. The hepatic stellate cells (HSCs) become activated after liver injury and play a significant role in fibrogenesis. The activated HSC is characterized by increased proliferation, overexpression of ? smooth muscle actin, and excessive production of extracellular matrix (ECM) proteins. Oridonin, a naturally occurring diterpenoid, has been shown to induce apoptosis in liver and gastric cancer cells. However, its effects on the HSC are unknown. METHODS: We tested the effects of oridonin on the activated human and rat HSC lines LX-2 and HSC-T6, and the human hepatocyte cell line C3A. Transforming growth factor ?1 (TGF-?1) was used to stimulate LX-2 cells. RESULTS: Oridonin significantly inhibited LX-2 and HSC-T6 proliferation. In contrast, oridonin had no antiproliferative effect on C3A cells at our tested range. Oridonin induced apoptosis and S-phase arrest in LX-2 cells. These findings were associated with an increase in p53, p21, p16, and cleaved Poly (ADP-ribose) Polymerase (PARP), and with a decrease in Cyclin-dependent kinase 4 (Cdk4). Oridonin markedly decreased expression of ? smooth muscle actin and ECM protein type I collagen and fibronectin, blocked TGF-?1-induced Smad2/3 phosphorylation and type I collagen expression. CONCLUSIONS: Oridonin induces apoptosis and cell cycle arrest involving the p53-p21 pathway in HSC and appears to be nontoxic to hepatocytes. In addition, oridonin suppressed endogenous and TGF-?1-induced ECM proteins. Thus, oridonin may act as a novel agent to prevent hepatic fibrosis.
  • |Actins/antagonists & inhibitors [MESH]
  • |Animals [MESH]
  • |Apoptosis/drug effects [MESH]
  • |Cell Cycle Checkpoints/drug effects [MESH]
  • |Cell Proliferation/*drug effects [MESH]
  • |Cells, Cultured [MESH]
  • |Diterpenes, Kaurane/*pharmacology [MESH]
  • |Extracellular Matrix Proteins/analysis [MESH]
  • |Hepatic Stellate Cells/*drug effects/physiology [MESH]
  • |Humans [MESH]
  • |Liver Cirrhosis/*prevention & control [MESH]
  • |Rats [MESH]


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