红果蔷薇（Rosa roxburghii Tratt，简称RRT）是中国西南地区著名的健康和药用食品，已被证明具有一定的肝保护特性。然而，来自红果蔷薇的萜类酸类等活性成分（TAR）是否具有抗肝细胞癌（HCC）的效果以及潜在的分子机制仍不清楚。本研究旨在研究红果蔷薇果实中萜类成分的抗HCC效应和潜在作用机制。通过使用UPLC-Q-Exactive Orbitrap/MS分析TAR中的萜类酸类，并基于药效团进行靶点的虚拟筛选，然后进行富集分析。使用HepG2细胞进行体外实验，包括MTT法，划痕愈合实验和流式细胞术，以检测细胞周期、活性氧（ROS）水平、半胱氨酸天冬酰基酶（caspase-3）活性和线粒体膜电位（MMP）的改变。此外，西方印迹法用于检测线粒体凋亡以及与ROS/JNK信号通路相关的蛋白质。TAR中的主要成分是五环萜类酸（主要是异草酸和罗伯酸）。TAR可以通过G2/M细胞周期阻滞抑制HepG2细胞的细胞活力、细胞迁移能力和增殖。另一方面，TAR可引起HepG2细胞的凋亡，通过引起ROS积累和JNK信号通路的激活来实现，我们的研究显示这种凋亡通过线粒体途径介导。此外，自由基清除剂N-乙酰半胱氨酸（NAC）可减轻TAR引起的ROS积累和JNK信号通路的激活，从而最终逆转线粒体凋亡。TAR可以激活ROS/JNK信号通路，通过G2/M细胞周期阻滞抑制增殖，并通过线粒体途径促进凋亡，这支持了红果蔷薇果实的抗肿瘤潜力。版权所有 © 2023 Elsevier GmbH 发表。

Rosa roxburghii Tratt (RRT) is a famous healthy and medicinal edible fruit in southwest China and has been shown to have some hepatoprotective properties. However, whether the active components, such as the triterpene acids from Rosa roxburghii Tratt fruits (TAR), have anti-hepatocellular carcinoma (HCC) effects and the potential molecular mechanisms are still unclear.This study aimed to investigate the anti-HCC effects and potential action mechanisms of triterpene components in RRT fruits.The triterpene acids in TAR were analyzed by using UPLC-Q-Exactive Orbitrap/MS, and the main components were virtual screening for targets based on pharmacophore and then performed enrichment analysis. HepG2 cells were used for in vitro experiments, including MTT assay, wound healing assay, and flow cytometry to detect cell cycle, reactive oxygen species (ROS) level, caspase-3 activity, and mitochondrial membrane potential (MMP) changes. Moreover, the western blot was used to detect mitochondrial apoptosis and ROS/ c-Jun N-terminal kinase (JNK) signaling pathway-related proteins.The main components in TAR are pentacyclic triterpene acids (mainly euscaphic acid and roxburic acid). TAR could inhibit cell viability, cell migration ability and suppress the proliferation of HepG2 cells through G2/M cell cycle arrest. On the other hand, TAR could induce HepG2 cells apoptosis, which was achieved by causing the accumulation of ROS and activation of the JNK signaling pathway, and our research showed that this apoptosis was mediated through the mitochondrial pathway. In addition, the free radical scavenger N-acetyl cysteine (NAC) could attenuate TAR-induced ROS accumulation and JNK signaling pathway activation, which ultimately reversed mitochondrial apoptosis.TAR could activate the ROS/JNK signaling pathway, which could inhibit the proliferation through G2/M cell cycle arrest and promote apoptosis through the mitochondrial pathway in HCC cells. This supports the anti-tumor potential in RRT fruits.Copyright © 2023. Published by Elsevier GmbH.