Research Institute, Ato Q&A Co., LTD, Jeonju-si 55069, Korea.
Institute of Health Science, Jeonju University, Jeonju-si 55069, Korea.
Molecules. 2021 Mar 15;26(6):1635. doi: 10.3390/molecules26061635.
, also known as Kushen, has traditionally been used as a herbal medicine. In the present study we evaluated the ameliorative effects of kushenol C (KC) from against tBHP (tert-Butyl hydroperoxide)-induced oxidative stress in hepatocellular carcinoma (HEPG2) cells and acetaminophen (APAP)-induced hepatotoxicity in mice. KC pretreatment protected the HEPG2 cells against oxidative stress by reducing cell death, apoptosis and reactive oxygen species (ROS) generation. KC pretreatment also upregulated pro-caspase 3 and GSH (glutathione) as well as expression of 8-Oxoguanine DNA Glycosylase (OGG1) in the HEPG2 cells. The mechanism of action was partly related by KC's activation of Akt (Protein kinase B (PKB)) and Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) in the HepG2 cells. In in vivo investigations, coadministration of mice with KC and APAP significantly attenuated APAP-induced hepatotoxicity and liver damage, as the serum enzymatic activity of aspartate aminotransferase and alanine aminotransferase, as well as liver lipid peroxidation and cleaved caspase 3 expression, were reduced in APAP-treated mice. Coadministration with KC also up-regulated antioxidant enzyme expression and prevented the production of proinflammatory mediators in APAP-treated mice. Taken together, these results showed that KC treatment has potential as a therapeutic agent against liver injury through the suppression of oxidative stress.
苦参碱，又称苦参，传统上被用作草药。在本研究中，我们评估了苦参碱 C（KC）对 tBHP（叔丁基过氧化氢）诱导的肝癌（HEPG2）细胞氧化应激和对乙酰氨基酚（APAP）诱导的小鼠肝毒性的改善作用。KC 预处理通过减少细胞死亡、细胞凋亡和活性氧（ROS）的产生来保护 HEPG2 细胞免受氧化应激。KC 预处理还上调了原半胱天冬酶 3 和 GSH（谷胱甘肽）以及 8-氧鸟嘌呤 DNA 糖基化酶（OGG1）在 HEPG2 细胞中的表达。作用机制部分与 KC 在 HepG2 细胞中激活 Akt（蛋白激酶 B（PKB））和 Nrf2（核因子（红细胞衍生 2）样 2）有关。在体内研究中，KC 与 APAP 联合给药可显著减轻 APAP 诱导的肝毒性和肝损伤，因为 APAP 处理小鼠的血清天冬氨酸转氨酶和丙氨酸转氨酶的酶活性、肝脂质过氧化和裂解的半胱天冬酶 3 表达降低。KC 联合给药还上调了抗氧化酶的表达，并防止了 APAP 处理小鼠中促炎介质的产生。总之，这些结果表明，KC 治疗可能是一种通过抑制氧化应激来治疗肝损伤的治疗剂。
