Limits...
Liquiritigenin Protects Rats from Carbon Tetrachloride Induced Hepatic Injury through PGC-1α Pathway.

Zhang Y, He Y, Yu H, Ma F, Wu J, Zhang X - Evid Based Complement Alternat Med (2015)

Bottom Line: The lack of effective treatment for liver cirrhosis and hepatocellular carcinomas imposes serious challenges to the healthcare system.The results demonstrated that liquiritigenin is effective in protecting liver from injury or treating chronic liver diseases.The modulation of PGC-1α and its downstream genes might play a critical role in relieving CCl4-induced hepatic pathogenesis by liquiritigenin.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China ; School of Basic Medical Science, Jiujiang University, Jiujiang, Jianxi 332000, China.

ABSTRACT
The lack of effective treatment for liver cirrhosis and hepatocellular carcinomas imposes serious challenges to the healthcare system. Here, we investigated the efficacy and mechanism of liquiritigenin involved in preventing or retarding the progression of liver diseases in a rat model with chronic carbon tetrachloride (CCl4) exposure. Sprague Dawley rats were given CCl4 and lliquiritigenin alone or simultaneously for 8 weeks before liver was harvested to check histological changes by Hematoxylin and Eosin (H&E) staining, apoptosis by TUNEL assay, ROS by dihydroethidium staining, antioxidant enzyme activities and malondialdehyde using specific kits, and gene expression by quantitative real-time PCR and western blot. Chronic CCl4 exposure caused profound changes in liver histology with extensive hepatocyte death (necrosis and apoptosis), fat accumulation, and infiltration of inflammatory cells, accompanied by depressed activities of antioxidant enzymes, increased oxidative stress, elevated expression of inflammation and fibrotic genes, and downregulation of PGC-1α, ND1, and Bcl-x in rat liver. All these changes were abolished or alleviated by lliquiritigenin. The results demonstrated that liquiritigenin is effective in protecting liver from injury or treating chronic liver diseases. The modulation of PGC-1α and its downstream genes might play a critical role in relieving CCl4-induced hepatic pathogenesis by liquiritigenin.

No MeSH data available.


Related in: MedlinePlus

A proposed model on how liquiritigenin alleviates CCl4-induced liver injuries. CCl4 inhibits the expression of PGC-1α, indirectly inhibits the expression of genes involved in mitochondrial function, antioxidant, and phase II detoxification, and directly inhibits the activities of antioxidant enzymes and phase II enzymes, which leads to oxidative stress, cell death inflammation, and fibrosis. Liquiritigenin prevents or reverse CCl4-induced liver injuries by derepressing PGC-1α expression and relieving the inhibition of antioxidant enzyme and phase II enzyme activities, leading to normalized expression of genes involved in mitochondrial function, antioxidant, and phase II detoxification, reduced oxidative stress, cell death inflammation, and fibrosis.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4496487&req=5

fig6: A proposed model on how liquiritigenin alleviates CCl4-induced liver injuries. CCl4 inhibits the expression of PGC-1α, indirectly inhibits the expression of genes involved in mitochondrial function, antioxidant, and phase II detoxification, and directly inhibits the activities of antioxidant enzymes and phase II enzymes, which leads to oxidative stress, cell death inflammation, and fibrosis. Liquiritigenin prevents or reverse CCl4-induced liver injuries by derepressing PGC-1α expression and relieving the inhibition of antioxidant enzyme and phase II enzyme activities, leading to normalized expression of genes involved in mitochondrial function, antioxidant, and phase II detoxification, reduced oxidative stress, cell death inflammation, and fibrosis.

Mentions: Although the involvement of antioxidant and phage II enzymes is the common theme, many pathways have been implicated in the protective effects of various compounds against CCl4-induced liver injuries [8–10, 20–22]. Ursolic acid alleviated the inhibition of nuclear factor E2-related factor 2 (Nrf2) by CCl4 and restored the expression of Nrf2 downstream antioxidative genes to protect against liver fibrosis [20]. Nrf2 was shown to inhibit transforming growth factor- (TGF-) β/Smad signaling and plasminogen activator inhibitor- (PAI-) 1 expression, which led to inhibition of fibrosis [23]. Paraoxonases (PON) 1 and 3, which inhibit lipoprotein oxidation and atherosclerosis, and other antioxidant enzymes were involved in CCl4-induced liver injury in rats [21]. Ribosomal S-6 kinase acting downstream of mitogen-activated protein kinase (MAPK) pathway/extracellular signal-regulated kinase (ERK1/2) signal pathway to phosphorylate C/EBP-beta in hepatic stellate cells was shown to play a critical role in the progression of CCl4-induced liver fibrosis [24]. A variety of pathways have been shown to be involved in liver injuries leading to cirrhosis and hepatocellular carcinoma. As the master regulator of bioenergetic homeostasis and responses to oxidative stress, PGC-1α was shown to mediate the effects of liquiritigenin to relieve CCl4 induced chronic liver injury in rat (Figure 6).


Liquiritigenin Protects Rats from Carbon Tetrachloride Induced Hepatic Injury through PGC-1α Pathway.

Zhang Y, He Y, Yu H, Ma F, Wu J, Zhang X - Evid Based Complement Alternat Med (2015)

A proposed model on how liquiritigenin alleviates CCl4-induced liver injuries. CCl4 inhibits the expression of PGC-1α, indirectly inhibits the expression of genes involved in mitochondrial function, antioxidant, and phase II detoxification, and directly inhibits the activities of antioxidant enzymes and phase II enzymes, which leads to oxidative stress, cell death inflammation, and fibrosis. Liquiritigenin prevents or reverse CCl4-induced liver injuries by derepressing PGC-1α expression and relieving the inhibition of antioxidant enzyme and phase II enzyme activities, leading to normalized expression of genes involved in mitochondrial function, antioxidant, and phase II detoxification, reduced oxidative stress, cell death inflammation, and fibrosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496487&req=5

fig6: A proposed model on how liquiritigenin alleviates CCl4-induced liver injuries. CCl4 inhibits the expression of PGC-1α, indirectly inhibits the expression of genes involved in mitochondrial function, antioxidant, and phase II detoxification, and directly inhibits the activities of antioxidant enzymes and phase II enzymes, which leads to oxidative stress, cell death inflammation, and fibrosis. Liquiritigenin prevents or reverse CCl4-induced liver injuries by derepressing PGC-1α expression and relieving the inhibition of antioxidant enzyme and phase II enzyme activities, leading to normalized expression of genes involved in mitochondrial function, antioxidant, and phase II detoxification, reduced oxidative stress, cell death inflammation, and fibrosis.
Mentions: Although the involvement of antioxidant and phage II enzymes is the common theme, many pathways have been implicated in the protective effects of various compounds against CCl4-induced liver injuries [8–10, 20–22]. Ursolic acid alleviated the inhibition of nuclear factor E2-related factor 2 (Nrf2) by CCl4 and restored the expression of Nrf2 downstream antioxidative genes to protect against liver fibrosis [20]. Nrf2 was shown to inhibit transforming growth factor- (TGF-) β/Smad signaling and plasminogen activator inhibitor- (PAI-) 1 expression, which led to inhibition of fibrosis [23]. Paraoxonases (PON) 1 and 3, which inhibit lipoprotein oxidation and atherosclerosis, and other antioxidant enzymes were involved in CCl4-induced liver injury in rats [21]. Ribosomal S-6 kinase acting downstream of mitogen-activated protein kinase (MAPK) pathway/extracellular signal-regulated kinase (ERK1/2) signal pathway to phosphorylate C/EBP-beta in hepatic stellate cells was shown to play a critical role in the progression of CCl4-induced liver fibrosis [24]. A variety of pathways have been shown to be involved in liver injuries leading to cirrhosis and hepatocellular carcinoma. As the master regulator of bioenergetic homeostasis and responses to oxidative stress, PGC-1α was shown to mediate the effects of liquiritigenin to relieve CCl4 induced chronic liver injury in rat (Figure 6).

Bottom Line: The lack of effective treatment for liver cirrhosis and hepatocellular carcinomas imposes serious challenges to the healthcare system.The results demonstrated that liquiritigenin is effective in protecting liver from injury or treating chronic liver diseases.The modulation of PGC-1α and its downstream genes might play a critical role in relieving CCl4-induced hepatic pathogenesis by liquiritigenin.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China ; School of Basic Medical Science, Jiujiang University, Jiujiang, Jianxi 332000, China.

ABSTRACT
The lack of effective treatment for liver cirrhosis and hepatocellular carcinomas imposes serious challenges to the healthcare system. Here, we investigated the efficacy and mechanism of liquiritigenin involved in preventing or retarding the progression of liver diseases in a rat model with chronic carbon tetrachloride (CCl4) exposure. Sprague Dawley rats were given CCl4 and lliquiritigenin alone or simultaneously for 8 weeks before liver was harvested to check histological changes by Hematoxylin and Eosin (H&E) staining, apoptosis by TUNEL assay, ROS by dihydroethidium staining, antioxidant enzyme activities and malondialdehyde using specific kits, and gene expression by quantitative real-time PCR and western blot. Chronic CCl4 exposure caused profound changes in liver histology with extensive hepatocyte death (necrosis and apoptosis), fat accumulation, and infiltration of inflammatory cells, accompanied by depressed activities of antioxidant enzymes, increased oxidative stress, elevated expression of inflammation and fibrotic genes, and downregulation of PGC-1α, ND1, and Bcl-x in rat liver. All these changes were abolished or alleviated by lliquiritigenin. The results demonstrated that liquiritigenin is effective in protecting liver from injury or treating chronic liver diseases. The modulation of PGC-1α and its downstream genes might play a critical role in relieving CCl4-induced hepatic pathogenesis by liquiritigenin.

No MeSH data available.


Related in: MedlinePlus