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槲果提取物的保肝活性可减轻对乙酰氨基酚诱导的肝毒性。

Hepatoprotective Activity of Gaertn. Seedpod Extract Attenuated Acetaminophen-Induced Hepatotoxicity.

机构信息

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.

出版信息

Molecules. 2022 Jun 23;27(13):4030. doi: 10.3390/molecules27134030.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b99/9268144/7122f2d66166/molecules-27-04030-g001.jpg

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