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芪术汤提取物通过抑制 NF-κB 信号通路抑制体外和 C57BL/6 小鼠的肝炎和肝癌。

Extracts of Qizhu decoction inhibit hepatitis and hepatocellular carcinoma in vitro and in C57BL/6 mice by suppressing NF-κB signaling.

机构信息

Department of Infectious Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 HanZhong Road, Nanjing, 210029, Jiangsu, China.

Department of Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 HanZhong Road, Nanjing, 210029, Jiangsu, China.

出版信息

Sci Rep. 2019 Feb 5;9(1):1415. doi: 10.1038/s41598-018-38391-9.

Abstract

Hepatitis and hepatocellular carcinoma are serious human diseases. Here, we examined the in vivo and in vitro inhibitory effect of extracts of Qizhu decoction (a traditional Chinese medicine) on hepatitis caused by diethylnitrosamine or hepatitis B virus and on diethylnitrosamine-induced hepatocellular carcinoma. The results showed that both the aqueous and ethanol extracts (QC and QS, respectively) of Qizhu decoction significantly inhibited hepatic inflammation and liver cancer induced by diethylnitrosamine or hepatitis B virus by suppressing NF-κB signaling and decreasing the levels of TNF-α and IL-1β. Both QC and QS inhibited the proliferation and migration of primary cancer hepatocytes by reducing cyclin B1, cyclin D1 and N-cadherin expression and increasing E-cadherin expression. QC and QS also promoted the apoptosis of primary cancer hepatocytes by upregulating caspase-3 and downregulating BCL-2 expression. The knockdown of p65 in NF-κB signaling inhibited the ability of QC and QS to significantly reduce the colony formation ability of liver cancer cells. Additionally, QC and QS might significantly inhibit the DNA replication of hepatitis B virus in vivo and in vitro, and we found that corilagin and polydatin were the active compounds of QC and QS. Taken together, our in vitro findings and our results in C57BL/6 mice showed that extracts of Qizhu decoction might inhibit hepatitis and hepatocellular carcinoma by suppressing NF-κB signaling.

摘要

肝炎和肝细胞癌是严重的人类疾病。在这里,我们研究了七珠汤(一种中药)提取物对二乙基亚硝胺或乙型肝炎病毒引起的肝炎以及二乙基亚硝胺诱导的肝细胞癌的体内和体外抑制作用。结果表明,七珠汤的水提物和醇提物(QC 和 QS)均通过抑制 NF-κB 信号通路和降低 TNF-α 和 IL-1β 的水平,显著抑制二乙基亚硝胺或乙型肝炎病毒引起的肝炎症和肝癌。QC 和 QS 通过降低 cyclin B1、cyclin D1 和 N-cadherin 的表达水平,增加 E-cadherin 的表达水平,抑制原代肝癌细胞的增殖和迁移。QC 和 QS 通过上调 caspase-3 和下调 BCL-2 的表达水平,促进原代肝癌细胞的凋亡。NF-κB 信号通路中 p65 的敲低抑制了 QC 和 QS 显著降低肝癌细胞集落形成能力的能力。此外,QC 和 QS 可能在体内和体外显著抑制乙型肝炎病毒的 DNA 复制,我们发现柯里拉京和白藜芦醇是 QC 和 QS 的活性化合物。综上所述,我们的体外研究结果和 C57BL/6 小鼠的结果表明,七珠汤提取物可能通过抑制 NF-κB 信号通路来抑制肝炎和肝细胞癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/639d/6363746/0bc7ab8c8705/41598_2018_38391_Fig1_HTML.jpg

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