PF2401-SF, standardized fraction of Salvia miltiorrhiza, induces apoptosis of activated hepatic stellate cells in vitro and in vivo.

PF2401-SF, standardized fraction of Salvia miltiorrhiza, induces apoptosis of activated hepatic stellate cells in vitro and in vivo.
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DOI:
10.3390/molecules18022122
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发表时间:
2013-02-06
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Lee SH
Lee SH
中科院分区:
其他
文献类型:
--
作者:
Parajuli DR;Park EJ;Che XH;Jiang WY;Kim YC;Sohn DH;Lee SH

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在我们尝试开发潜在草药的过程中,我们之前制备了 PF2401-SF(丹参的标准化部分),并报告了其体外和体内的保肝活性。由于激活的肝星状细胞 (HSC) 凋亡是一种广为接受的抗纤维化策略,因此在本研究中,我们研究了 PF2401-SF 对体外 t-HSC/Cl-6 细胞和体内 CCl4 诱导的肝损伤的直接影响。我们评估了细胞凋亡标志物(即 caspase 3、8、9 和 PARP)的激活和裂解。还分析了促凋亡 Bax 蛋白的上调和抗凋亡 Bcl2 蛋白的下调。此外,在 PF2401-SF 治疗的大鼠中,通过体内 α-SMA 阳性细胞分布的减少和大量 TUNEL 阳性细胞的存在,证明了活化的 HSC 的凋亡诱导。我们的数据表明,PF2401-SF 可以介导 HSC 凋亡诱导,并且可能是治疗肝纤维化的潜在草药。
During the course of our attempts to develop a potential herbal medicine, we had previously prepared PF2401-SF, a standardized fraction of S. miltiorrhiza, and reported its hepatoprotective activity in vitro as well as in vivo. Since apoptosis of activated hepatic stellate cells (HSCs) is a well-accepted anti-fibrotic strategy, in this study, we investigated the direct effect of PF2401-SF on t-HSC/Cl-6 cells in vitro and on CCl4-induced liver injury in vivo. We evaluated the activation and cleavage of hallmarkers of apoptosis, namely, caspase 3, 8, 9 and PARP. Upregulation of the pro-apoptotic Bax protein and downregulation of the anti-apoptotic Bcl2 protein were also analyzed. Furthermore, in the PF2401-SF treated rats, apoptosis induction of activated HSCs was demonstrated by reduced distribution of α-SMA-positive cells and the presence of high number of TUNEL-positive cells in vivo. Our data suggest that PF2401-SF can mediate HSCs apoptosis induction, and may be a potential herbal medicine for the treatment of liver fibrosis.
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