Yang Min Hye, Kim Na-Hyun, Heo Jeong-Doo, Sung Sang Hyun, Jeong Eun Ju
College of Pharmacy, Pusan National University, Busan, Korea.
Gyeongnam Department of Environment & Toxicology, Korea Institute of Toxicology, Jegok-gil, Munsan-eup, Gyeongnam, Korea.
Pharmacogn Mag. 2014 Aug;10(Suppl 3):S563-8. doi: 10.4103/0973-1296.139783.
During the process of hepatic fibrosis, the activation of hepatic stellate cells (HSCs) is responsible for the increased formation and reduced degradation of extracellular matrix in the liver. By employing the hepatic stellate cell line, HSC-T6, it was found that the methanol extract of Limonium tetragonum, a halophyte living in salt marsh near south and western seashores of Korea significantly inhibited the proliferation of HSC-T6 cells.
In the present study, we attempted to investigate the antifibrotic effects of the mathanolic extract of L. tetragonum (MELT) in the activated HSC-T6 cells.
The proliferation of HSC-T6 was stimulated by culturing environment or platelet-derived growth factor (PDGF-BB) insult, and then the inhibitory activities of MELT were measured.
It was found that MELT suppressed the proliferation of the activated HSC-T6 in concentration- and time-dependent manners. The increased collagen deposition in the activated HSC-T6 cells was also decreased by the treatment of MELT. The maximal dose of MELT, however, had little effect on primary cultured rat hepatocytes. Wlammatory cytokine, tumor necrosis factor alpha (TNF-α) produced by lipopolysaccharide-stimulated RAW264.7 macrophages was inhibited by MELT.
Collectively, the above results demonstrated that MELT suppressed HSCs proliferation but not in hepatocytes, implying that L. tetragonum may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis.
在肝纤维化过程中,肝星状细胞(HSCs)的激活导致肝脏中细胞外基质形成增加和降解减少。通过使用肝星状细胞系HSC-T6,发现生长在韩国西南部沿海盐沼中的盐生植物四棱补血草的甲醇提取物能显著抑制HSC-T6细胞的增殖。
在本研究中,我们试图研究四棱补血草甲醇提取物(MELT)对激活的HSC-T6细胞的抗纤维化作用。
通过培养环境或血小板衍生生长因子(PDGF-BB)刺激HSC-T6的增殖,然后测定MELT的抑制活性。
发现MELT以浓度和时间依赖性方式抑制激活的HSC-T6的增殖。MELT处理也降低了激活的HSC-T6细胞中胶原蛋白沉积的增加。然而,MELT的最大剂量对原代培养的大鼠肝细胞几乎没有影响。MELT抑制了脂多糖刺激的RAW264.7巨噬细胞产生的炎性细胞因子肿瘤坏死因子α(TNF-α)。
综上所述,上述结果表明MELT抑制HSCs增殖,但不抑制肝细胞增殖,这意味着四棱补血草可能是开发预防和治疗肝纤维化治疗药物的有用候选物。