College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China.
College of Forestry, Beijing Forestry University, Beijing 100083, China.
Phytomedicine. 2023 Oct;119:154960. doi: 10.1016/j.phymed.2023.154960. Epub 2023 Jul 8.
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.
刺梨（Rosa roxburghii Tratt）是中国西南地区著名的药食同源水果，具有一定的保肝作用。然而，其活性成分，如刺梨果实中的三萜酸（TAR），是否具有抗肝癌（HCC）作用及潜在的分子机制尚不清楚。
本研究旨在探讨刺梨果实三萜成分的抗 HCC 作用及潜在作用机制。
采用 UPLC-Q-Exactive Orbitrap/MS 分析 TAR 中的三萜酸，基于药效团和富集分析对主要成分进行虚拟筛选。采用 HepG2 细胞进行体外实验，包括 MTT 检测、划痕愈合实验和流式细胞术检测细胞周期、活性氧（ROS）水平、caspase-3 活性和线粒体膜电位（MMP）变化。此外，采用 Western blot 检测线粒体凋亡和 ROS/c-Jun N 末端激酶（JNK）信号通路相关蛋白。
TAR 的主要成分是五环三萜酸（主要为羽扇豆酸和罗克柏酸）。TAR 可通过 G2/M 细胞周期阻滞抑制 HepG2 细胞活力和迁移能力，抑制细胞增殖。另一方面，TAR 可诱导 HepG2 细胞凋亡，其通过引起 ROS 积累和 JNK 信号通路激活来实现，我们的研究表明，这种凋亡是通过线粒体途径介导的。此外，自由基清除剂 N-乙酰半胱氨酸（NAC）可减弱 TAR 诱导的 ROS 积累和 JNK 信号通路激活，从而最终逆转线粒体凋亡。
TAR 可通过激活 ROS/JNK 信号通路，通过 G2/M 细胞周期阻滞抑制 HCC 细胞增殖，通过线粒体途径促进凋亡。这支持了刺梨果实的抗肿瘤潜力。
