Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan.
Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan.
Molecules. 2022 Jun 23;27(13):4030. doi: 10.3390/molecules27134030.
The aim is to investigate the effect of lotus ( Gaertn.) seedpod extract (LSE) on acetaminophen (APAP)-induced hepatotoxicity. LSE is rich in polyphenols and has potent antioxidant capacity. APAP is a commonly used analgesic, while APAP overdose is the main reason for drug toxicity in the liver. Until now, there has been no in vitro test of LSE in drug-induced hepatotoxicity responses. LSEs were used to evaluate the effect on APAP-induced cytotoxicity, ROS level, apoptotic rate, and molecule mechanisms. The co-treatment of APAP and LSEs elevated the survival rate and decreased intracellular ROS levels on HepG2 cells. LSEs treatment could significantly reduce APAP-induced HepG2 apoptosis assessed by DAPI and Annexin V/PI. The further molecule mechanisms indicated that LSEs decreased Fas/FasL binding and reduced Bax and tBid to restore mitochondrial structure and subsequently suppress downstream apoptosis cascade activation. These declines in COX-2, NF-κB, and iNOS levels were observed in co-treatment APAP and LSEs, which indicated that LSEs could ameliorate APAP-induced inflammation. LSE protected APAP-induced apoptosis by preventing extrinsic, intrinsic, and JNK-mediated pathways. In addition, the restoration of mitochondria and inflammatory suppression in LSEs treatments indicated that LSEs could decrease oxidative stress induced by toxic APAP. Therefore, LSE could be a novel therapeutic option for an antidote against overdose of APAP.
目的在于研究莲子(Gaertn.)种皮提取物(LSE)对乙酰氨基酚(APAP)诱导的肝毒性的影响。LSE 富含多酚,具有强大的抗氧化能力。APAP 是一种常用的止痛药,而 APAP 过量是导致肝毒性的主要原因。到目前为止,还没有体外测试 LSE 在药物诱导的肝毒性反应中的作用。使用 LSE 来评估其对 APAP 诱导的细胞毒性、ROS 水平、细胞凋亡率和分子机制的影响。APAP 和 LSE 的共同处理可提高 HepG2 细胞的存活率并降低细胞内 ROS 水平。LSE 处理可显著降低 DAPI 和 Annexin V/PI 评估的 APAP 诱导的 HepG2 凋亡。进一步的分子机制表明,LSE 减少 Fas/FasL 结合,并降低 Bax 和 tBid 以恢复线粒体结构,从而抑制下游凋亡级联激活。在 APAP 和 LSE 的共同处理中观察到 COX-2、NF-κB 和 iNOS 水平下降,表明 LSE 可以改善 APAP 诱导的炎症。LSE 通过阻止外在、内在和 JNK 介导的途径来保护 APAP 诱导的细胞凋亡。此外,LSE 处理中线粒体的恢复和炎症的抑制表明,LSE 可以减少有毒的 APAP 引起的氧化应激。因此,LSE 可能成为治疗 APAP 过量的一种新的治疗选择。