Fucoidan Alleviates Acetaminophen-Induced Hepatotoxicity via Oxidative Stress Inhibition and Nrf2 Translocation.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that leads to severe hepatotoxicity at excessive doses. Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. However, the impacts of fucoidan on APAP-induced liver injury have not been sufficiently addressed. In the present study, male Institute of Cancer Research (ICR) mice aged 6 weeks were subjected to a single APAP (500 mg/kg) intraperitoneal injection after 7 days of fucoidan (100 or 200 mg/kg/day) or bicyclol intragastric administration. The mice continued to be administered fucoidan or bicyclol once per day, and were sacrificed at an indicated time. The indexes evaluated included liver pathological changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum, levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) in the liver, and related proteins levels (CYP2E1, pJNK and Bax). Furthermore, human hepatocyte HL-7702 cell line was used to elucidate the potential molecular mechanism of fucoidan. The mitochondrial membrane potential (MMP) and nuclear factor-erythroid 2-related factor (Nrf2) translocation in HL-7702 cells were determined. The results showed that fucoidan pretreatment reduced the levels of ALT, AST, ROS, and MDA, while it enhanced the levels of GSH, SOD, and CAT activities. Additionally, oxidative stress-induced phosphorylated c-Jun N-terminal protein kinase (JNK) and decreased MMP were attenuated by fucoidan. Although the nuclear Nrf2 was induced after APAP incubation, fucoidan further enhanced Nrf2 in cell nuclei and total expression of Nrf2. These results indicated that fucoidan ameliorated APAP hepatotoxicity, and the mechanism might be related to Nrf2-mediated oxidative stress.

Antidepressant-like effects of ginsenoside Rg2 in a chronic mild stress model of depression.

Major depression is a common neuropsychiatric disease with high lifetime prevalence and high incidence of suicide. This study aimed to evaluate the antidepressant effects of ginsenoside Rg2 in mice, and the possible mechanism was also determined. A single injection of both Rg2 (10 and 20mg/kg) and fluoxetine (positive control, 20mg/kg) induced notable antidepressant-like effects in the forced swim test and tail suspension test without affecting the locomotor activity of mice, and the tests were done 30min after the injection. Also, repeated daily treatment of Rg2 and fluoxetine for the last 2 weeks fully reversed the chronic mild stress (6 weeks)-induced depressive-like symptoms in mice. Moreover, western blot analysis showed that Rg2 administration significantly increased the BDNF signaling pathway in hippocampus. Importantly, the usage of TrkB shRNA fully blocked the antidepressant effects of Rg2 in mice. Collectively, these results suggest that Rg2 produces an antidepressant-like effect in mice which is mediated, at least in part, through promoting the hippocampal BDNF signaling pathway.