Protective role of puerarin on LPS/D-Gal induced acute liver injury via restoring autophagy.

Acute liver injury is a destructive liver disorder resulting from overwhelming liver inflammation, oxidative stress and hepatocyte death. Puerarin is a natural flavonoid compound isolated from the traditional Chinese herb radix puerariae. This study investigated the protective effects of puerarin against lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced liver injury and the potential mechanisms in mice. Mice were given an intraperitoneal administration of puerarin 200 mg/kg 2 h prior to LPS (50 μg/kg)/D-Gal (400 mg/kg) injection and were sacrificed 6 h post LPS/D-Gal treatment. The results showed that administration of puerarin substantially alleviated LPS/D-Gal-induced acute liver injury in mice by increased survival rates, improved liver histopathology, reduced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, alleviated production of pro-inflammatory cytokines, and suppressed hepatocyte apoptosis. Moreover, puerarin pretreatment activated autophagy by increased the ratio of LC3B-II/I and the protein levels of Beclin-1, decreased the levels of p62 protein expression. Taken together, these findings demonstrated that puerarin could prevent the LPS/D-Gal-induced liver injury in mice, and its mechanisms might be associated with the increments of autophagy and suppression of apoptosis.

[1]  Suhuan Liu,et al.  Preventive effects of interleukin‐6 in lipopolysaccharide/d‐galactosamine induced acute liver injury via regulating inflammatory response in hepatic macrophages , 2017, International immunopharmacology.

[2]  Q. Cui,et al.  FAM3A mediates PPARγ's protection in liver ischemia-reperfusion injury by activating Akt survival pathway and repressing inflammation and oxidative stress , 2017, Oncotarget.

[3]  P. Sancho-Bru,et al.  Pentraxin‐3 modulates lipopolysaccharide‐induced inflammatory response and attenuates liver injury , 2017, Hepatology.

[4]  Yueqiu Gao,et al.  MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6–p47phox–oxidative stress pathway in neutrophils , 2016, Gut.

[5]  J. Dranoff,et al.  Sortilin Deficiency Reduces Ductular Reaction, Hepatocyte Apoptosis, and Liver Fibrosis in Cholestatic-Induced Liver Injury. , 2017, The American journal of pathology.

[6]  Xiaohui Xu,et al.  Puerarin, isolated from Pueraria lobata (Willd.), protects against diabetic nephropathy by attenuating oxidative stress. , 2016, Gene.

[7]  M. Jiang,et al.  Puerarin prevents inflammation and apoptosis in the neurocytes of a murine Parkinson's disease model. , 2016, Genetics and molecular research : GMR.

[8]  Xiuhui Li,et al.  Circulating histones are major mediators of systemic inflammation and cellular injury in patients with acute liver failure , 2016, Cell Death and Disease.

[9]  Hai-Ling Liu,et al.  BML-111 Protected LPS/D-GalN-Induced Acute Liver Injury in Rats , 2016, International journal of molecular sciences.

[10]  Z. Wang,et al.  PER1 prevents excessive innate immune response during endotoxin-induced liver injury through regulation of macrophage recruitment in mice , 2016, Cell death & disease.

[11]  A. Remaley,et al.  Human SR-BI and SR-BII Potentiate Lipopolysaccharide-Induced Inflammation and Acute Liver and Kidney Injury in Mice , 2016, The Journal of Immunology.

[12]  Haiyuan Yang,et al.  Puerarin Protects Pancreatic β-Cells in Obese Diabetic Mice via Activation of GLP-1R Signaling. , 2016, Molecular endocrinology.

[13]  Xiuping Chen,et al.  Puerarin Improves Diabetic Aorta Injury by Inhibiting NADPH Oxidase-Derived Oxidative Stress in STZ-Induced Diabetic Rats , 2016, Journal of diabetes research.

[14]  Pilar Martín,et al.  Eukaryotic Elongation Factor 2 Controls Tnf-alpha Translation in Lps-induced Hepatitis Recommended Citation Eukaryotic Elongation Factor 2 Controls Tnf-alpha Translation in Lps- Induced Hepatitis Eukaryotic Elongation Factor 2 Controls Tnf-α Translation in Lps-induced Hepatitis , 2022 .

[15]  Jie Ren,et al.  Oleoylethanolamide, an endogenous PPAR-α ligand, attenuates liver fibrosis targeting hepatic stellate cells , 2015, Oncotarget.

[16]  Taotao Ma,et al.  Hyperin attenuates inflammation by activating PPAR-γ in mice with acute liver injury (ALI) and LPS-induced RAW264.7 cells. , 2015, International immunopharmacology.

[17]  Suhuan Liu,et al.  Puerarin suppresses high glucose-induced MCP-1 expression via modulating histone methylation in cultured endothelial cells. , 2015, Life sciences.

[18]  Wei Zhao,et al.  Protective effect of oligomeric proanthocyanidins against alcohol-induced liver steatosis and injury in mice. , 2015, Biochemical and biophysical research communications.

[19]  Liuluan Zhu,et al.  Galactose protects hepatocytes against TNF-α-induced apoptosis by promoting activation of the NF-κB signaling pathway in acute liver failure , 2015, Laboratory Investigation.

[20]  Zhong-Qin Liang,et al.  The protective mechanism of schisandrin A in d-galactosamine-induced acute liver injury through activation of autophagy , 2014, Pharmaceutical biology.

[21]  H. Saya,et al.  Supplementary Figure Legends , 2012 .

[22]  Yijie Liu,et al.  Puerarin protects pancreatic β-cell survival via PI3K/Akt signaling pathway. , 2014, Journal of molecular endocrinology.

[23]  Myung-Shik Lee,et al.  Autophagy—a key player in cellular and body metabolism , 2014, Nature Reviews Endocrinology.

[24]  W. Ding Induction of autophagy, a promising approach for treating liver injury , 2014, Hepatology.

[25]  Ashutosh Kumar Singh,et al.  Anti-inflammatory potency of nano-formulated puerarin and curcumin in rats subjected to the lipopolysaccharide-induced inflammation. , 2013, Journal of medicinal food.

[26]  M. Czaja,et al.  Inhibition of hepatocyte autophagy increases tumor necrosis factor-dependent liver injury by promoting caspase-8 activation , 2013, Cell Death and Differentiation.

[27]  Xiaoqun Duan,et al.  Anti-fibrotic effects of puerarin on CCl4-induced hepatic fibrosis in rats possibly through the regulation of PPAR-γ expression and inhibition of PI3K/Akt pathway. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[28]  Mitchell R. McGill,et al.  Liver-specific loss of Atg5 causes persistent activation of Nrf2 and protects against acetaminophen-induced liver injury. , 2012, Toxicological sciences : an official journal of the Society of Toxicology.

[29]  Tingzhe Sun,et al.  Triptolide attenuate the oxidative stress induced by LPS/D‐GalN in mice , 2012, Journal of cellular biochemistry.

[30]  Ji-xiang Zhang,et al.  A Role of Cell Apoptosis in Lipopolysaccharide (LPS)-induced Nonlethal Liver Injury in d-galactosamine (d-GalN)-sensitized Rats , 2008, Digestive Diseases and Sciences.

[31]  Masaaki Komatsu,et al.  Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice , 2005, The Journal of cell biology.

[32]  L. Moldawer,et al.  LPS-induced liver injury ind-galactosamine-sensitized mice requires secreted TNF-α and the TNF-p55 receptor , 2000 .

[33]  J. Muntané,et al.  TNF-alpha dependent production of inducible nitric oxide is involved in PGE(1) protection against acute liver injury. , 2000, Gut.