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The Ethanol Supernatant Extracts of Liushenwan Could Alleviate Nanodiethylnitrosamine-Induced Liver C 时间:2018-09-26 21:55 来源:未知作者:admin 点击: 次 Abstract:Liver cancer is one of the leading causes of cancerous deaths worldwide. At present, the treatment of hepatocellular carcinoma (HCC) remains to be a problem globally. Liushenwan (LSW), an ancient Chinese medicine previously used to treat localized infections, was recently reported to possess anticancer activity. Here in this study, we aim to examine the effect of LSW-ET (LSW-ET is the supernatant fraction of LSW from ultrasound assisted ethanol extraction) in prevention and treatment on nanodiethylnitrosamine- (nanoDEN-) induced HCC in mice. In nanoDEN-induced HCC mice treated with LSW-ET by oral (po) or intragastric gavage (ig), we observed an alleviation of serum ALT and AST levels, amelioration in histopathological stainings, and an inhibition in liver tumor growth. In addition, compared with the nanoDEN group, downregulation of multiple pivotal factors (COX-2, β-catenin, PCNA, and HMGB-1) was observed in LSW-ET-po and LSW-ET-ig groups. Taken together, the delivery of LSW-ET by oral could be a potential prevention and treatment of liver cancer.
1. Introduction
Liver cancer, also called hepatocellular carcinoma (HCC), has been and would remain to be one of the leading causes of cancerous deaths worldwide nowadays and in the near future [1]. In China particular, liver diseases affect approximately 300 million people, which contributes much to the global burden of liver diseases [2]. A large fraction of these patients would probably progress into liver cancer at advanced stages due to late diagnoses [3]. In addition, large variability of treatment choices and disease-relate survival also confirmed such heterogeneity. However, a so-called “best” choice for patients with HCC could be quite hard [4]. Thus, alternative agents with better efficacy and less detriment for the management (prevention and treatment included) of HCC are urgently needed [5].
Traditional Chinese Medicine has been widely used for anticancer treatment in China with a long history and many substances possess application prospect, such as bufadienolide [6, 7]. Liushenwan (LSW), a well-known heat clearing and detoxifying herbal preparation, is composed of Niu-huang (Calculus bovis), She-xiang (Moschus), Chan-shu (Bufonis venenum), Xiong-huang (Realgar), Zhen-zhu (Margarita), and Bing-pian (Camphora). This ancient prescription is quite effective in treating localized infections and inflammation associated pain [8]. During the past 200 years, many other applications of LSW have been uncovered, including the treatment of diphtheria, scarlet fever, pharyngotonsillitis, acute tonsillitis, purulent parotitis, encephalitis B, and leukemia [9, 10]. Recently, it was also reported that LSW had a potential anticancer activity [9]. In the meantime, LSW has also been suggested to be associated with some toxicity due to the constituents of Realgar and Bufonis venenum, both of which were found to be hazardous once administered alone [11]. In our previous study, we demonstrated that the ethanol fraction of LSW (LSW-ET), which maintained its analgesic and anticancer activities, possessed a minimum side effect to a normal human hepatic cell line L02, while inhibiting cell proliferation and inducing apoptosis of the human cancerous cell line HepG2 in a dose-dependent manner via the downregulation of NK-1 receptor [12]. However, experiments on cancerous animal models were required to investigate the efficacy of LSW-ET in vivo.