Protective effect of Juzen-taiho-to on hepatocarcinogenesis is mediated through the inhibition of Kupffer cell-induced oxidative stress.
Protective effect of Juzen-taiho-to on hepatocarcinogenesis is mediated through the inhibition of Kupffer cell-induced oxidative stress.
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Juzen-taiho-to 对肝癌发生的保护作用是通过抑制枯否细胞诱导的氧化应激来介导的。
DOI：
10.1002/ijc.23828
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发表时间：
2008
影响因子：
6.4
通讯作者：
Rusyn,Ivan
中科院分区：
文献类型：
--
作者：
Tsuchiya,Masato;Kono,Hiroshi;Matsuda,Masanori;Fujii,Hideki;Rusyn,Ivan
传统草药配方，如十善太凤汤 (TJ-48)，在亚洲的医疗实践中被广泛使用，尽管其作用机制仍然难以捉摸。这项研究测试了一个假设，即 TJ-48 通过阻止库普弗细胞诱导的氧化应激来预防肝癌发生。 48 名患者在肝细胞癌 (HCC) 手术治疗后被随机分配接受 TJ-48 (n = 10) 或不补充 (n = 38) 长达 6 年。此外，为了研究 TJ-48 的保护作用机制，给喂食常规食物或含 TJ-48 饮食的雄性小鼠注射含二乙基亚硝胺的水 22 周。评估了肝肿瘤发生率、细胞增殖、8-羟基-2'-脱氧鸟苷或F4/80阳性细胞的数量以及细胞因子表达。尽管大多数患者经历了 HCC 复发，但在 TJ-48 组中观察到肝内无复发生存期显着延长。在小鼠中，TJ-48 抑制肝脏肿瘤的发展，减少氧化 DNA 损伤、炎症细胞浸润和细胞因子表达。 TJ-48 的给药可改善肝细胞癌手术治疗后的肝内无复发生存率。根据动物实验，我们推断 TJ-48 的保护机制涉及抑制 Kupffer 细胞。这会导致肝脏中促炎细胞因子和氧化剂的水平降低，从而可能减缓肝癌发生的过程并提高肝癌患者的肝脏无复发生存率。 © 2008 Wiley-Liss, Inc.
Traditional herbal formulations, such as Juzen‐taiho‐to (TJ‐48), are used extensively in medical practice in Asia even though their mechanism of action remains elusive. This study tested a hypothesis that TJ‐48 is protective against hepatocarcinogenesis by impeding Kupffer cell‐induced oxidative stress. Forty‐eight patients were randomly assigned to receive TJ‐48 (n= 10), or no supplementation (n= 38) for up to 6 years after surgical treatment for hepatocellular carcinoma (HCC). In addition, to investigate the mechanism of protective action of TJ‐48, diethylnitrosamine‐containing water was administered for 22 weeks to male mice that were fed regular chow or TJ‐48‐containing diet. Liver tumor incidence, cell proliferation, number of 8‐hydroxy‐2′‐deoxyguanosine‐ or F4/80‐positive cells, and cytokine expression were evaluated. Although most of the patients experienced recurrence of HCC, a significantly longer intrahepatic recurrence‐free survival was observed in the TJ‐48 group. In mice, TJ‐48 inhibited the development of liver tumors, reduced oxidative DNA damage, inflammatory cell infiltration and cytokine expression. Administration of TJ‐48 improves intrahepatic recurrence‐free survival after surgical treatment of hepatocellular carcinoma. On the basis of animal experiments, we reason that the protective mechanism of TJ‐48 involves inhibition of Kupffer cells. This leads to lower levels of pro‐inflammatory cytokines and oxidants in liver which may slow down the process of hepatocarcinogenesis and improves hepatic recurrence‐free survival in patients with HCC. © 2008 Wiley‐Liss, Inc.