Paeoniflorin protects cells from GalN/TNF-α-induced apoptosis via ER stress and mitochondria-dependent pathways in human L02 hepatocytes.
Paeoniflorin (PF) is one of the main effective components extracted from the root of Paeonia lactiflora, which has been used clinically to treat hepatitis in traditional Chinese medicine, but the details of the underlying mechanism remain unknown. The present study was designed to investigate the mechanism of protective effect of PF on d-galactosamine (GalN) and tumor necrosis factor-α (TNF-α)-induced cell apoptosis using human L02 hepatocytes. Our results confirmed that PF could attenuate GalN/TNF-α-induced apoptotic cell death in a dose-dependent manner. The disruption of mitochondrial membrane potential and the disturbance of intracellular Ca(2+) concentration were also recovered by PF. Western blot analysis revealed that GalN/TNF-α induced the activation of a number of signature endoplasmic reticulum (ER) stress and mitochondrial markers, while PF pre-treatment had a marked dose-dependent suppression on them. Additionally, the anti-apoptotic effect of PF was further evidenced by the inhibition of caspase-3/9 activities in L02 cells. These findings suggest that PF can effectively inhibit hepatocyte apoptosis and the underlying mechanism is related to the regulating mediators in ER stress and mitochondria-dependent pathways.
Department of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Zequn
Z
Jiang
Weiping
W
Chen
Xiaojing
X
Yan
Lei
L
Bi
Sheng
S
Guo
Zhen
Z
Zhan
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000502:physiology; D019004:Galanin / Q000502:physiology*; D005960:Glucosides / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D039821:Monoterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D006027:Glycosides
D053148:Caspase 3; D053453:Caspase 9; D019004:Galanin; D005960:Glucosides; D039821:Monoterpenes; D014409:Tumor Necrosis Factor-alpha; C056567:GAL protein, human; C015423:peoniflorin; D006027:Glycosides
GalN/TNF-α; L02 human hepatocytes; apoptosis; endoplasmic reticulum stress; mitochondria; paeoniflorin