ABSTRACT

We investigated the mechanism of action of panaxynol (PAL) extract from the root of Saposhnikovia diviaricata (Turcz.) Schischk for treating acute liver injury caused by lipopolysaccharide (LPS) and D-galactosamine (D-Gal N) in mice. A mouse model of acute liver failure induced by LPS/D-Gal N was established. Mice were divided randomly into three equal groups: control group, LPS/D-Gal N group and PAL group. After seven days of continuous PAL administration, all animals except controls were injected with 50 μg/kg LPS and 800 mg/kg D-Gal N; blood and liver samples were collected after 8 h. Compared to the LPS/D-Gal N group, the levels of catalase, glutathione and superoxide dismutase were increased in the liver of the PAL group. The inflammatory response index indicated that PAL attenuated LPS/D Gal N-induced liver pathological injury and decreased levels of hepatic malondialdehyde, serum alanine aminotransferase, aspartate transaminase, tumor necrosis factor-α, and interleukins 1β and 6. PAL also inhibited LPS/D-Gal N induced nuclear factor-kappa B (Nf-κB), inhibitor kappa B-α (IκB-α) activation, and up-regulated Nrf2 and heme oxygenase-1 (HO-1) expression. PAL can prevent LPS/D-Gal N induced acute liver injury by activating Nrf2/HO-1 to stimulate antioxidant defense and inhibit the IkB-α/NF-κB signaling pathway.

摘要

我们调查了人参Saposhnikovia diviaricata根中人参炔醇（PAL）提取物的作用机理（Turcz。）Schischk用于治疗小鼠脂多糖（LPS）和D-半乳糖胺（D-Gal N）引起的急性肝损伤。建立了LPS / D-Gal N诱导的急性肝衰竭小鼠模型。将小鼠随机分为三个相等的组：对照组，LPS / D-Gal N组和PAL组。连续PAL给药7天后，除对照组外，所有动物均注射50μg/ kg LPS和800 mg / kg D-Gal N；8小时后收集血液和肝脏样本。与LPS / D-Gal N组相比，PAL组的肝脏中过氧化氢酶，谷胱甘肽和超氧化物歧化酶水平升高。炎症反应指数表明PAL可减轻LPS / D Gal N诱导的肝脏病理损伤，并降低肝丙二醛，血清丙氨酸氨基转移酶，天冬氨酸转氨酶，肿瘤坏死因子-α和白介素1β和6。PAL还抑制LPS / D-Gal N诱导的核因子-κB（Nf-κB），抑制剂κ-B（IκB-α）活化和上调的Nrf2和血红素加氧酶-1（HO-1）的表达。PAL可以通过激活Nrf2 / HO-1刺激抗氧化防御并抑制IkB-α/NF-κB信号通路来预防LPS / D-Gal N诱导的急性肝损伤。