Abstract：
Drug-induced liver injury (DILI) occurs frequently worldwide. Acetaminophen (APAP) is a common drug causing DILI. Current treatment methods are difficult to achieve satisfactory results. Therefore, there is an urgent need to provide safe and effective treatment for patients. Schizandrin B (Sch B), the main component of Schisandra, has a protective effect on liver. However, the potential mechanism of Sch B in the treatment of APAP induced liver injury has not been elucidated to date. In our research, we studied the effect of Sch B on protecting damaged liver cells and explored the potential mechanism underlying its ability to reduce APAP liver injury. We found that Sch B could reduce hepatocyte apoptosis, oxidative stress injury and inflammatory response. These effects were positively correlated with the dose of Sch B. Sch B regulated glucose 6-phosphate dehydrogenase expression by upregulating the expression of p21-activated kinase 4 and polo-like kinase 1. Sch B could inhibit the mitogen-activated protein kinase (MAPK)-c-Jun N-terminal kinase (JNK)-extracellular signal-regulated kinase (ERK) signaling pathway and regulate the expression of apoptosis-related proteins to reduce the incidence of cell apoptosis. In addition, Sch B reduced the expression levels of reactive oxygen species and inflammatory cytokines in hepatocyte. Consequently, we described for the first time that Sch B could not only activate the pentose phosphate pathway but also inhibit the MAPK-JNK-ERK signaling pathway, thereby achieving antioxidative and anti-inflammatory effects and inhibiting hepatocyte apoptosis. These findings indicated the potential use of Sch B in curing liver damage induced by APAP.
摘要：
药物性肝损伤(DILI)在世界范围内频繁发生。对乙酰氨基酚（APAP）是引起DILI的常见药物。目前的治疗方法难以达到满意的效果。因此,迫切需要为患者提供安全有效的治疗。五味子B（SchB），五味子的主要成分，对肝脏有保护作用.然而,迄今为止，SchB治疗APAP诱导的肝损伤的潜在机制尚未阐明。在我们的研究中,我们研究了SchB对受损肝细胞的保护作用，并探讨了其减轻APAP肝损伤的潜在机制。我们发现SchB可以减少肝细胞凋亡，氧化应激损伤和炎症反应。这些作用与SchB的剂量呈正相关。SchB通过上调p21激活激酶4和polo样激酶1的表达来调节葡萄糖6-磷酸脱氢酶的表达。SchB能抑制丝裂原活化蛋白激酶(MAPK)-c-Jun氨基末端激酶(JNK)-细胞外信号调节激酶(ERK)信号通路,调节凋亡相关蛋白的表达,降低细胞凋亡的发生率。此外,SchB降低了肝细胞中活性氧和炎性细胞因子的表达水平。因此,我们首次描述了SchB不仅可以激活磷酸戊糖途径，还可以抑制MAPK-JNK-ERK信号通路，从而实现抗氧化和抗炎作用,抑制肝细胞凋亡。这些发现表明SchB在治疗APAP引起的肝损伤中的潜在用途。
