School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.
J Med Food. 2011 Oct;14(10):1135-43. doi: 10.1089/jmf.2010.1485. Epub 2011 Sep 6.
Chronic hepatitis/cirrhosis is the eighth leading cause of death in Taiwan. Excess accumulated extracellular matrix produced by activated hepatic stellate cells (HSCs) is the major cause of liver fibrosis. Ginsenoside Rb1, the most active compound purified from ginseng, has been considered to be hepatoprotective. This study investigated the effects of ginsenoside Rb1 (98.8% purity) on activation, proliferation, and profibrotic factors in rat HSC-T6 cells under H₂O₂ oxidative stress. Rat HSC-T6 cells were activated by 10 nM H₂O₂ and then incubated with different concentrations of ginsenoside Rb1 (5, 10, 20, 40, and 80 μg/mL) for 24 hours. Medium containing 0.08% dimethyl sulfoxide or 5 mM N-acetyl-l-cysteine was used as a negative or positive control, respectively. The results showed that ginsenoside Rb1 at 5-40 μg/mL significantly reduced α-smooth muscle actin levels and at 5-80 μg/mL inhibited cell proliferation in HSC-T6 cells after induction with H₂O₂ (P<.05). Collagen secreted by HSC-T6 cells was decreased by ginsenoside Rb1 at 5-80 μg/mL (P<.05). Protein expression of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase (MMP)-2, and tissue inhibitor of metalloproteinase (TIMP)-1 was suppressed by ginsenoside Rb1 at 10-80 μg/mL (P<.05). In addition, mRNA expression of type I and III collagen, TGF-β1, and TIMP-1 was inhibited by ginsenoside Rb1 (10 and 80 μg/mL) (P<.05). Therefore, ginsenoside Rb1 exerted an antifibrotic effect on HSCs by inhibiting activation, proliferation, and expression of collagen, TGF-β1, MMP-2, and TIMP-1.
慢性肝炎/肝硬化是台湾地区第八大死亡原因。活化的肝星状细胞（HSCs）产生的细胞外基质过度积累是肝纤维化的主要原因。人参皂苷 Rb1 是从人参中分离得到的最具活性的化合物，被认为具有保肝作用。本研究探讨了在 H₂O₂氧化应激下，人参皂苷 Rb1（纯度 98.8%）对大鼠 HSC-T6 细胞的活化、增殖和致纤维化因子的影响。用 10 nM H₂O₂激活大鼠 HSC-T6 细胞，然后用不同浓度的人参皂苷 Rb1（5、10、20、40 和 80 μg/mL）孵育 24 小时。0.08%二甲基亚砜或 5 mM N-乙酰-l-半胱氨酸的培养基分别作为阴性和阳性对照。结果表明，人参皂苷 Rb1 在 5-40 μg/mL 浓度下可显著降低 H₂O₂诱导的 HSC-T6 细胞中α-平滑肌肌动蛋白水平，在 5-80 μg/mL 浓度下抑制细胞增殖（P<.05）。人参皂苷 Rb1 可降低 HSC-T6 细胞分泌的胶原（P<.05）。人参皂苷 Rb1 在 10-80 μg/mL 浓度下抑制转化生长因子-β1（TGF-β1）、基质金属蛋白酶（MMP）-2 和金属蛋白酶组织抑制剂（TIMP）-1 的蛋白表达（P<.05）。此外，人参皂苷 Rb1（10 和 80 μg/mL）抑制Ⅰ型和Ⅲ型胶原、TGF-β1 和 TIMP-1 的 mRNA 表达（P<.05）。因此，人参皂苷 Rb1 通过抑制 HSCs 的活化、增殖和胶原、TGF-β1、MMP-2 和 TIMP-1 的表达发挥抗纤维化作用。
