Antihepatotoxic effect of tadehaginoside, extracted from Tadehagi triquetrum (L.), against CCl4-lesioned rats through activating the Nrf2 signaling pathway and attenuating the inflammatory response.
Recently, an increasing number of studies suggest that oxidative stress and inflammation are associated with hepatocellular injuries. Thus, we aimed to evaluate the potential hepatoprotective role of tadehaginoside (TA) on liver lesions induced by carbon tetrachloride (CCl4). The results in vitro suggested that TA dose-dependently suppressed the cell proliferation of HepG2 cells, whereas the phosphorylated level of IκBα in cells was effectively inactivated. The study in vivo showed that TA significantly lowered the serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), immunoglobulin E (IgE), and leukotriene (LT) in CCl4-lesioned rats. Pathological examination indicated that CCl4-induced hepatocellular damage was effectively mitigated by TA treatment. Meanwhile, the contents of γ-glutamylcysteine synthetase (γ-GCS), glutathione (GSH), and catalase (CAT) in liver tissue were gradually elevated. In addition, cytochrome c oxidase (COX) mRNA expression in hepatocytes was markedly upregulated, and nuclear factor E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keapl) levels were progressively increased. Furthermore, the tumor necrosis factor alpha (TNF-α) and nuclear factor-kappa B (NF-κB)-expressed protein were downregulated. These findings demonstrate that tadehaginoside effectively protects against CCl4-induced oxidative injury and inflammatory reaction in hepatocytes, in which the underlying mechanisms are involved in activating the Nrf2 signaling pathway and inhibiting the NF-κB pathway, thereby attenuating oxidative stress and reducing the inflammation in liver cells.
The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 89 Dongge Road, Nanning City, Guangxi, 530023, People's Republic of China.
Aicun
A
Tang
Xiaoyu
X
Chen
Qiuyu
Q
Lu
Ni
N
Zheng
Yanfei
Y
Wei
Xiaoyan
X
Wu
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology*; D007887:Fabaceae / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008956:Models, Chemical; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D003373:Coumaric Acids; D005960:Glucosides; D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D010936:Plant Extracts; D012333:RNA, Messenger; C000595638:tadehaginoside; D007073:Immunoglobulin E; D002251:Carbon Tetrachloride