Park Dae Won, Jeon Hyelin, Kwon Jeong Eun, Lee Young Geun, So Rina, Choe Tae Hwan, Jeong Yong Joon, Kang Se Chan
Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin, Gyeonggi-do 17104 Republic of Korea.
BioMedical Research Institute, Kyung Hee University, Yongin, Gyeonggi-do 17104 Republic of Korea.
Toxicol Res. 2020 Sep 7;37(2):261-275. doi: 10.1007/s43188-020-00063-0. eCollection 2021 Apr.
-acetyl--aminophenol (acetaminophen, APAP) is a well-known component of analgesic and antipyretic monotherapy products. However, exceeding the recommended dose can lead to serious injury to the liver. We conducted this study to determine the potential of as a natural substance to protect against APAP-induced liver injury. When acute hepatotoxicity was induced in mice by APAP overdose, their liver weight decreased significantly ( < 0.05). However, mice treated with 50% ethanol extract (CA-HE50, 200 mg/kg) for a week before induction of hepatotoxicity by APAP had similar liver weights to those of mice in which hepatotoxicity was not induced. In particular, levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, which are biomarkers of liver injury, were significantly increased by APAP and dose-dependently decreased by CA-HE50 ( < 0.05). Glutathione and malondialdehyde, indicators of oxidative stress, were significantly changed by APAP and CA-HE50 ( < 0.05). In addition, hepatic necrosis and expression of genes encoding pro-inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, and IL-4) induced by APAP were inhibited by CA-HE50, and these results were dose-dependent. Through our in vivo studies, we found that CA-HE50 can help prevent APAP-induced hepatic tissue injury in BALB/c mice. Furthermore, CA-HE50 was effective at protecting RAW 264.7 cells from lipopolysaccharide-induced cytotoxicity and inhibiting the release of nitric oxide from these cells; in particular, asiaticoside was found to be a key component of CA-HE50 responsible for these effects. Therefore, we suggest that CA-HE50 has potential applications in functional health foods and drugs.
对乙酰氨基酚（扑热息痛，APAP）是止痛和解热单药产品中一种广为人知的成分。然而，超过推荐剂量会导致肝脏严重损伤。我们开展这项研究以确定[具体物质未明确，原文此处表述有误]作为一种天然物质预防APAP诱导的肝损伤的潜力。当通过APAP过量在小鼠中诱导急性肝毒性时，它们的肝脏重量显著下降（P<0.05）。然而，在通过APAP诱导肝毒性前一周用50%乙醇提取物（CA - HE50，200mg/kg）处理的小鼠，其肝脏重量与未诱导肝毒性的小鼠相似。特别是，作为肝损伤生物标志物的天冬氨酸转氨酶、丙氨酸转氨酶和乳酸脱氢酶水平因APAP显著升高，并因CA - HE50呈剂量依赖性降低（P<0.05）。作为氧化应激指标的谷胱甘肽和丙二醛因APAP和CA - HE50发生显著变化（P<0.05）。此外，APAP诱导的肝坏死以及促炎细胞因子（肿瘤坏死因子-α、白细胞介素（IL）-1β和IL - 4）编码基因的表达被CA - HE50抑制，且这些结果呈剂量依赖性。通过我们的体内研究，我们发现CA - HE50有助于预防BALB/c小鼠中APAP诱导的肝组织损伤。此外，CA - HE50在保护RAW 264.7细胞免受脂多糖诱导的细胞毒性以及抑制这些细胞释放一氧化氮方面有效；特别是，积雪草苷被发现是CA - HE50中负责这些作用的关键成分。因此，我们认为CA - HE50在功能性健康食品和药物中有潜在应用。
