Gong Xiaobao, Yang You, Huang Ligua, Zhang Qingyan, Wan Rong-Zhen, Zhang Peng, Zhang Baoshun
College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China.
College of Animal Science and Technology, Southwest University, Chongqing 400716, PR China.
Int Immunopharmacol. 2017 May;46:124-132. doi: 10.1016/j.intimp.2017.03.003. Epub 2017 Mar 7.
To evaluate the hepatoprotective effects and potential mechanisms of paeonol (Pae) against acute liver failure (ALF) induced by lipopolysaccharide (LPS)/d-galactosamine (d-GalN) in mice, we examined anti-oxidative, anti-inflammatory and anti-apoptotic activities of Pae. We found that Pae pretreatment markedly reduced the activities of alanine transaminase and aspartate transaminase as well as the histopathological changes induced by LPS/d-GalN. Catalase, glutathione and superoxide dismutase activities increased and reactive oxygen species activity decreased after Pae treatment compared with LPS/d-GalN treatment. Pretreatment with Pae also significantly inhibited the expression levels of iNOS, nitric oxide (NO), COX-2 and prostaglandin E (PGE). In addition, Pae administration prevented the phosphorylated expression of IκB kinase, inhibitor kappa B in the nuclear factor-kappa B (NF-κB) signaling pathway, and suppressed the phosphorylated expression of extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase and p38 in the MAPK signaling pathway. Pretreatment with Pae also inhibited hepatocyte apoptosis by reducing the expression of caspases 3, 8, 9, and Bax, and increasing Bcl-2. In total, protective effects of Pae against LPS/d-GalN-induced ALF in mice are attributed to its antioxidative effect, inflammatory suppression in NF-κB and MARK signaling pathways, and inhibition of hepatocyte apoptosis inhibition. Therefore, Pae can be a potential therapeutic agent in attenuating LPS/d-GalN-induced ALF in the future.
为了评估丹皮酚（Pae）对脂多糖（LPS）/D-氨基半乳糖（D-GalN）诱导的小鼠急性肝衰竭（ALF）的肝保护作用及其潜在机制，我们检测了Pae的抗氧化、抗炎和抗凋亡活性。我们发现，Pae预处理显著降低了丙氨酸转氨酶和天冬氨酸转氨酶的活性以及LPS/D-GalN诱导的组织病理学变化。与LPS/D-GalN处理相比，Pae处理后过氧化氢酶、谷胱甘肽和超氧化物歧化酶活性增加，活性氧物种活性降低。Pae预处理还显著抑制了诱导型一氧化氮合酶、一氧化氮（NO）、环氧化酶-2和前列腺素E（PGE）的表达水平。此外，给予Pae可阻止核因子-κB（NF-κB）信号通路中IκB激酶、抑制蛋白κB的磷酸化表达，并抑制丝裂原活化蛋白激酶（MAPK）信号通路中细胞外信号调节激酶（ERK）、c-jun氨基末端激酶和p38的磷酸化表达。Pae预处理还通过降低半胱天冬酶3、8、9和Bax的表达以及增加Bcl-2来抑制肝细胞凋亡。总的来说，Pae对LPS/D-GalN诱导的小鼠ALF的保护作用归因于其抗氧化作用、对NF-κB和MARK信号通路的炎症抑制作用以及对肝细胞凋亡的抑制作用。因此，Pae未来可能成为减轻LPS/D-GalN诱导的ALF的潜在治疗药物。
