Pine ( Pinus densiflora ) needle extract could promote the expression of PCNA and Ki-67 after partial hepatectomy in rat

Lee, Gyeong Seok; Yang, Hyeon Gung; Kim, Ji Hun; Ahn, Young Mo; Han, Man Deuk; Kim, Wan Jong

doi:10.1590/s0102-865020190060000006

Cited by 7 publications

(5 citation statements)

References 25 publications

(23 reference statements)

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“…As expected, the expression of Ki‐67 increased after treatment with CCl 4 , whereas the administration of GM significantly mitigated the expression of these indicators in HSCs (Figure 2a). PCNA, a cofactor of DNA polymerase, is extensively expressed in the nuclei of proliferating hepatocytes (Lee et al, 2019). We found that PCNA expression was significantly increased in the hepatocytes of rats after treatment with CCl 4 .…”

Section: Resultsmentioning

confidence: 99%

Germacrone improves liver fibrosis by regulating the PI3K/AKT/mTOR signalling pathway

Zhao

Qin

et al. 2021

Cell Biology International

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Liver fibrosis is a primary threat to public health, owing to limited therapeutic options. Germacrone (GM) has been shown to exert various curative effects against human diseases, including liver injury. The aim of this study was to investigate the pharmacological effects of GM in the pathophysiology of hepatic fibrosis and determine its potential mechanisms of action. A liver fibrosis rat model was established via carbon tetrachloride (CCl4) treatment, and LX‐2 cells were stimulated with TGF‐β1. The effects of GM on liver fibrosis and its relationship with the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway were investigated. In the CCl4 fibrosis‐induced rat model, GM improved histological damage, inhibited the activity of hepatic α‐smooth muscle actin and improved serum alanine aminotransferase and aspartate aminotransferase levels in a dose‐dependent manner. GM potently inhibited hepatic stellate cells (HSCs) growth and epithelial–mesenchymal transition (EMT) progression, as reflected by the altered expression of proliferative (Ki‐67, PCNA and cleaved caspase‐3) and EMT‐related (E‐cadherin and vimentin) proteins. In TGF‐β1‐stimulated LX‐2 cells, GM significantly inhibited the survival and activation of HSCs and induced cell apoptosis. GM also suppressed the migration ability and reversed the EMT process in HSCs. Following GM treatment, the phosphorylation of the PI3K, AKT and mTOR proteins was reduced in the liver of CCl4‐treated rats and TGF‐β1‐stimulated LX‐2 cells, indicating that GM may attenuate hepatic fibrosis via the PI3K/AKT/mTOR signalling pathway. These outcomes highlight the anti‐fibrotic effects of GM and suggest that it is a potential therapeutic agent for the treatment of liver fibrosis.

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Section: Resultsmentioning

confidence: 99%

Germacrone improves liver fibrosis by regulating the PI3K/AKT/mTOR signalling pathway

Zhao

Qin

et al. 2021

Cell Biology International

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“…We also observed the changes in the number of PCNA-positive cells in the liver and kidney tissues. The changes in PCNA were usually closely related to tissue regeneration (Lee et al 2019). After LPS injection, the PCNA of rat liver and kidney tissues decreased signi cantly.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Ulinastatin Combined With Thrombomodulin Against Lipopolysaccharide Induced Liver and Kidney Injury in Septic Rats

Zhang

Zhao

et al. 2021

Preprint

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Background: Sepsis, a systemic inflammatory disease that leads to life-threatening organ functions disorders, such as liver and kidney injury. Ulinastatin (UTI) and Thrombomodulin (TM) are active macromolecules isolated from human urine. UTI and TM have been found to have therapeutic effects on inflammatory diseases. In this study, we verified protective effect of UTI combined with TM on liver and kidney injury caused by sepsis, and further explored the mechanisms.Methods: The sepsis model was established by intravenous injection of LPS into the tail vein of rats. Blood, liver and kidney tissues were collected after injection of UTI or TM. ELISA was used to measure serum levels of pro-inflammatory cytokines. The characteristic functional indexes of liver and kidney in serum and multiple coagulation function indexes of rats were detected via corresponding kits. Histological changes of liver and kidney tissues were investigated by HE staining. Apoptosis in liver and kidney tissues were examined by TUNEL staining, and the expression levels of apoptosis-related proteins were also analyzed. HMGB1/TLR4/NF-κB pathway in liver and kidney tissues were examined by Western Blot. PCNA-positive cells were detected by immunohistochemistry. The survival rate of rats in each group was statistically analyzed.Results: UTI combined with TM reduced LPS-induced secretion of IL-6 and TNF-α in the serum. The drug combination reduced the liver and kidney functional indicators ALT, AST, BUN and Cr, and ameliorated liver and kidney pathology injury of rats. It inhibited apoptosis of liver and kidney cells via down-regulating the expression of apoptotic protein Bax, Cleaved caspase-3, up-regulating the expression of anti-apoptotic protein bcl-2, and promoted the proliferation of liver and kidney cells. The drug combination reversed the up-regulation of HMGB1, TLR4, and phosphorylated NF-κB protein mediated by LPS. Anticoagulation test indicated UTI does not affect the anticoagulant effect of TM when they are used in combination. Moreover, the drug combination significantly improved the survival rate of septic rats. Conclusions: These results indicate that UTI combined with TM plays a key role in protecting liver and kidney injury in septic rats, which will suggest a promising treatment for sepsis-induced organ injury.

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“…β-actin was used as loading control. The relative expression level of target protein was expressed as ratio of β-actin [ 64 ].…”

Section: Methodsmentioning

confidence: 99%

Astragaloside IV Suppresses Hepatic Proliferation in Regenerating Rat Liver after 70% Partial Hepatectomy via Down-Regulation of Cell Cycle Pathway and DNA Replication

et al. 2021

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Astragaloside IV (AS-IV) is one of the major bio-active ingredients of huang qi which is the dried root of Astragalus membranaceus (a traditional Chinese medicinal plant). The pharmacological effects of AS-IV, including anti-oxidative, anti-cancer, and anti-diabetic effects have been actively studied, however, the effects of AS-IV on liver regeneration have not yet been fully described. Thus, the aim of this study was to explore the effects of AS-IV on regenerating liver after 70% partial hepatectomy (PHx) in rats. Differentially expressed mRNAs, proliferative marker and growth factors were analyzed. AS-IV (10 mg/kg) was administrated orally 2 h before surgery. We found 20 core genes showed effects of AS-IV, many of which were involved with functions related to DNA replication during cell division. AS-IV down-regulates MAPK signaling, PI3/Akt signaling, and cell cycle pathway. Hepatocyte growth factor (HGF) and cyclin D1 expression were also decreased by AS-IV administration. Transforming growth factor β1 (TGFβ1, growth regulation signal) was slightly increased. In short, AS-IV down-regulated proliferative signals and genes related to DNA replication. In conclusion, AS-IV showed anti-proliferative activity in regenerating liver tissue after 70% PHx.

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Pine ( Pinus densiflora ) needle extract could promote the expression of PCNA and Ki-67 after partial hepatectomy in rat

Cited by 7 publications

References 25 publications

Germacrone improves liver fibrosis by regulating the PI3K/AKT/mTOR signalling pathway

Germacrone improves liver fibrosis by regulating the PI3K/AKT/mTOR signalling pathway

Protective Effects of Ulinastatin Combined With Thrombomodulin Against Lipopolysaccharide Induced Liver and Kidney Injury in Septic Rats

Astragaloside IV Suppresses Hepatic Proliferation in Regenerating Rat Liver after 70% Partial Hepatectomy via Down-Regulation of Cell Cycle Pathway and DNA Replication

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