Oh Taehoon, Kwon Mincheol, Yu Jae Sik, Jang Mina, Kim Gun-Hee, Kim Ki Hyun, Ko Sung-Kyun, Ahn Jong Seog
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea.
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Korea.
Pharmaceutics. 2020 Dec 18;12(12):1229. doi: 10.3390/pharmaceutics12121229.
Studies on ethanol-induced stress and acetaldehyde toxicity are actively being conducted, owing to an increase in alcohol consumption in modern society. In this study, -peniciherqueinone (EPQ) isolated from a Hawaiian volcanic soil-associated fungus FT729 was found to reduce the acetaldehyde-induced cytotoxicity and oxidative stress in PC12 cells. EPQ increased cell viability in the presence of acetaldehyde-induced cytotoxicity in PC12 cells. In addition, EPQ reduced cellular reactive oxygen species (ROS) levels and restored acetaldehyde-mediated disruption of mitochondrial membrane potential. Western blot analyses revealed that EPQ treatment increased protein levels of ROS-scavenging heme oxygenase-1 and superoxide dismutase, as well as the levels of aldehyde dehydrogenase (ALDH) 1, ALDH2, and ALDH3, under acetaldehyde-induced cellular stress. Finally, EPQ reduced acetaldehyde-induced phosphorylation of p38 and c-Jun N-terminal kinase, which are associated with ROS-induced oxidative stress. Therefore, our results demonstrated that EPQ prevents cellular oxidative stress caused by acetaldehyde and functions as a potent agent to suppress hangover symptoms and alcohol-related stress.
由于现代社会酒精消费量的增加，关于乙醇诱导的应激和乙醛毒性的研究正在积极开展。在本研究中，从夏威夷火山土壤相关真菌FT729中分离出的-青霉赫克酮（EPQ）被发现可降低乙醛诱导的PC12细胞的细胞毒性和氧化应激。在PC12细胞存在乙醛诱导的细胞毒性时，EPQ可提高细胞活力。此外，EPQ降低了细胞活性氧（ROS）水平，并恢复了乙醛介导的线粒体膜电位破坏。蛋白质印迹分析显示，在乙醛诱导的细胞应激下，EPQ处理可提高ROS清除酶血红素加氧酶-1和超氧化物歧化酶的蛋白质水平，以及醛脱氢酶（ALDH）1、ALDH2和ALDH3的水平。最后，EPQ降低了乙醛诱导的p38和c-Jun氨基末端激酶的磷酸化，这与ROS诱导的氧化应激有关。因此，我们的结果表明，EPQ可预防乙醛引起的细胞氧化应激，并作为一种有效的药物来抑制宿醉症状和与酒精相关的应激。
