Medical Intensive Care Unit, The First Affiliated Hospital of Anhui University of Chinese Medicine.
Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine.
Biol Pharm Bull. 2022;45(5):596-604. doi: 10.1248/bpb.b21-00965.
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.
药物性肝损伤（DILI）在全球范围内较为常见。对乙酰氨基酚（APAP）是导致 DILI 的常见药物。目前的治疗方法难以取得满意的效果。因此，迫切需要为患者提供安全有效的治疗方法。五味子素 B（Sch B）是五味子的主要成分，对肝脏具有保护作用。然而，Sch B 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 Sch B 对保护受损肝细胞的作用，并探讨了其降低 APAP 肝损伤能力的潜在机制。我们发现 Sch B 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 Sch B 的剂量呈正相关。Sch B 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。Sch B 可以抑制丝裂原活化蛋白激酶（MAPK）-c-Jun N 端激酶（JNK）-细胞外信号调节激酶（ERK）信号通路，并调节凋亡相关蛋白的表达，从而降低细胞凋亡的发生率。此外，Sch B 降低了肝细胞中活性氧和炎症细胞因子的表达水平。因此，我们首次描述了 Sch B 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 Sch B 在治疗 APAP 诱导的肝损伤方面具有潜在的应用价值。
