College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea.
Molecules. 2023 Nov 8;28(22):7484. doi: 10.3390/molecules28227484.
Zaluzanin C (ZC), a sesquiterpene lactone isolated from L., has been reported to have anti-inflammatory and antioxidant effects. However, the mechanistic role of ZC in its protective effects in Kupffer cells and hepatocytes has not been elucidated. The purpose of this study was to elucidate the efficacy and mechanism of action of ZC in Kupffer cells and hepatocytes. ZC inhibited LPS-induced mitochondrial ROS (mtROS) production and subsequent mtROS-mediated NF-κB activity in Kupffer cells (KCs). ZC reduced mRNA levels of pro-inflammatory cytokines (Il1b and Tnfa) and chemokines (Ccl2, Ccl3, Ccl4, Cxcl2 and Cxcl9). Tumor necrosis factor (TNF)-α-induced hepatocyte mtROS production was inhibited by ZC. ZC was effective in alleviating mtROS-mediated mitochondrial dysfunction. ZC enhanced mitophagy and increased mRNA levels of fatty acid oxidation genes (Pparα, Cpt1, Acadm and Hadha) and mitochondrial biosynthetic factors (Pgc1α, Tfam, Nrf1 and Nrf2) in hepatocytes. ZC has proven its anti-lipid effect by improving lipid accumulation in hepatocytes by enhancing mitochondrial function to facilitate lipid metabolism. Therefore, our study suggests that ZC may be an effective compound for hepatoprotection by suppressing inflammation and lipid accumulation through regulating mtROS.
扎鲁扎宁 C（ZC）是从 中分离出来的一种倍半萜内酯，已被报道具有抗炎和抗氧化作用。然而，ZC 在其对枯否细胞和肝细胞的保护作用中的机制作用尚未阐明。本研究旨在阐明 ZC 在枯否细胞和肝细胞中的疗效和作用机制。ZC 抑制 LPS 诱导的枯否细胞（KCs）线粒体 ROS（mtROS）产生和随后的 mtROS 介导的 NF-κB 活性。ZC 降低了促炎细胞因子（Il1b 和 Tnfa）和趋化因子（Ccl2、Ccl3、Ccl4、Cxcl2 和 Cxcl9）的 mRNA 水平。ZC 抑制 TNF-α诱导的肝细胞 mtROS 产生。ZC 在缓解 mtROS 介导的线粒体功能障碍方面有效。ZC 增强了自噬，并增加了脂肪酸氧化基因（Pparα、Cpt1、Acadm 和 Hadha）和线粒体生物合成因子（Pgc1α、Tfam、Nrf1 和 Nrf2）的 mRNA 水平在肝细胞中。ZC 通过增强线粒体功能促进脂质代谢来改善肝细胞中的脂质积累，从而证明了其抗脂质作用。因此，我们的研究表明，ZC 可能通过抑制炎症和脂质积累来有效保护肝脏，这是通过调节 mtROS 实现的。
