Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced activation of pancreatic stellate cells
Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced activation of pancreatic stellate cells
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DOI：
10.1111/j.1365-2362.2006.01599.x
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发表时间：
2006-02-01
影响因子：
5.5
通讯作者：
Otsuki, M
中科院分区：
文献类型：
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作者：
Asaumi, H;Watanabe, S;Otsuki, M
活化的胰腺星状细胞(PSCs)在胰腺纤维化和炎症的发病机制中起核心作用。乙醇是慢性胰腺炎的主要原因，直接诱导PSC激活和氧化应激。抑制PSC的激活或刺激PSC可能是预防胰腺纤维化的有效治疗策略，绿茶提取物的主要成分(-)-表没食子儿茶素没食子酸酯(EGCG)是一种有效的多酚类抗氧化剂。因此，我们研究了乙醇诱导PSCs氧化应激的机制，并评价了EGCG对乙醇刺激的PSCs激活和细胞功能的影响。分离的PSCs用乙醇(50 MM)与EGCG(5mM或25mM)共同培养，EGCG预处理可消除乙醇诱导的细胞膜脂质过氧化，总超氧化物歧化酶(SOD)活性丧失，并抑制乙醇诱导的锰和铜/锌-超氧化物歧化酶基因表达。EGCG还抑制乙醇诱导的PSCs中p38丝裂原活化蛋白(MAP)激酶的磷酸化，α-平滑肌肌动蛋白的产生，并激活转化生长因子-β1的分泌。此外，EGCG还能抑制乙醇诱导的I型前胶原生成和胶原分泌。此外，EGCG还可抑制新鲜分离的细胞向肌成纤维细胞样表型的转化。我们的结果表明，绿茶和多酚可能通过抗氧化作用抑制PSC的激活，从而预防胰腺纤维化。
Activated pancreatic stellate cells (PSCs) play a central role in the pathogenesis of pancreatic fibrogenesis and inflammation. Ethanol, a major cause of chronic pancreatitis, directly induces PSC activation and oxidative stress. Inhibition of PSC activation or stimulation to PSC might be an effective therapeutic strategy for the prevention of pancreatic fibrosis, and (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea extracts, is a potent antioxidant of polyphenols. Therefore, we examined the mechanisms through which ethanol induces oxidative stress on PSCs and evaluated the effect of EGCG on activation and cell functions of ethanol-stimulated PSCs.The PSCs were isolated from the pancreas of male Wister rats with Nycodenz gradient methods and cells between passages one and four were used. Isolated PSCs were cultured with ethanol (50 mM) in the absence or presence of EGCG (5 mu M or 25 mu M).The EGCG pre-treatment abolished ethanol-induced lipid peroxidation of the cell membrane, loss of total superoxide dismutase (SOD) activity and suppressed ethanol-induced gene expressions of Mn- and Cu/Zn-SOD. EGCG also suppressed ethanol-induced p38 mitogen-activated protein (MAP) kinase phosphorylation, alpha-smooth muscle actin production in PSCs and activated transforming growth factor-beta 1 secretion into the medium. Furthermore, EGCG inhibited ethanol-induced type-I procollagen production and collagen secretion. In addition, EGCG inhibited transformation of freshly isolated cells to activated myofibroblast-like phenotype.Our results suggest that green tea and polyphenols could prevent pancreatic fibrosis by inhibiting PSC activation through the antioxidative effect.