Abstract
BackgroundLaminaria japonica has frequently been used as a food supplement and drug in traditional oriental medicine. Among the major active constituents responsible for the bioactivities of L. japonica, fucoxanthin (FX) has been considered as a potential antioxidant. This study was conducted to examine the effects of L. japonica extract (LJE) or FX against oxidative stress on hepatocytes and to elucidate the overall their cellular mechanisms of the effects.MethodsWe constructed an in vitro model with the treatment of arachidonic acid (AA) + iron in HepG2 cells to stimulate the oxidative damage. The cells were pre-treated with LJE or FX for 1 h, and incubated with AA + iron. The effect on oxidative damage and cellular mechanisms of LJE or FX were assessed by cytological examination and several biochemical assays under conditions with or without kinase inhibitiors.ResultsLJE or FX pretreatment effectively blocked the pathological changes caused by AA + iron treatment, such as cell death, altered expression of apoptosis-related proteins such as procaspase-3 and poly (ADP-ribose) polymerase, and mitochondria dysfunction. Moreover, FX induced AMPK activation and AMPK inhibitor, compound C, partially reduced the protective effect of FX on mitochondria dysfunction. Consistent with AMPK activation, FX increased the protein levels of autophagic markers (LC3II and beclin-1) and the number of acridine orange stained cells, and decreased the phosphorylation of mTOR and simultaneously increased the phosphorylation of ULK1. And the inhibition of autophagy by 3-methylanine or bafilomycin A1 partially inhibited the protective effect of FX on mitochondria dysfunction.ConclusionThese findings suggest that FX have the function of being a hepatic protectant against oxidative damages through the AMPK pathway for the control of autophagy.
Highlights
Laminaria japonica has frequently been used as a food supplement and drug in traditional oriental medicine
L. japonica Extract (LJE) decreases arachidonic acid (AA) + iron induced cytotoxicity in HepG2 cells An MTT assay for cell viability indicated that L. japonica extract (LJE) pretreatment (3, 10, 30, and 50 μg/ml) significantly protected cells from the potential injury induced by AA + iron
Treatment of AA + iron markedly induced decreases in the protein levels of procaspase-3 and BclXL, verifying AA + iron induction of apoptosis, which was completely blocked by LJE pretreatment (Fig. 1b)
Summary
Laminaria japonica has frequently been used as a food supplement and drug in traditional oriental medicine. Among the major active constituents responsible for the bioactivities of L. japonica, fucoxanthin (FX) has been considered as a potential antioxidant. Excess ROS can be involved in oxidative stress that destroys the structure of vital biomolecules, potentially leading to cellular dysfunction and remodeling [9]. Oxidative stress is known to activate the AMP-activated protein kinase (AMPK) signaling system in neuronal, heart, muscle, pancreatic and liver cells [10, 11]. AMPK is known to be involved in ROS-induced autophagy that promotes cell survival in response to cellular stress such as malnutrition, hypoxia or ischemia [12]. Oxygen and nutrient deprivation induce the activation of AMPK leading to autophagy by inhibition of mTORC1 and phosphorylation of ULK1 [13, 14]
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