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[Objectives] By clustering analysis of tissue distribution data of brucine and strychnine in gastric ulcer model rat, the impact of Zuota on tissue distribution of basic components was studied. [Methods] Based on system clustering method of SPSS19.0 statistical analysis software, using inter-group join method and squared Euclidean distance, brucine and strychnine contents of different tissues and organs in non- Zuota group and Zuota group were taken as characteristic variables for clustering analysis, and phylogenetic tree was established. [Results] When clustering distance was 1, (i) taking brucine content as the index, there were three kinds of convergences in non-Zuota group. A1 class: skin, liver, epididymitis and jejunum; A2 class: brain and uterus; A class: testis and muscle. Brucine contents of the three classes showed a A1 < A2 < A. There were two classes of convergences in Zuota group. B1 class : jejunum, epididymis, kidney, brain, skin and uterus; B2 class: muscle and (bottom) submandibular gland. Brucine contents of the two classes showed as B1 < B2. (ii) Taing strychnine content as the index, there were three classes of convergences in non-Zuota group. C1 class: muscle, testicle and oarrum; C2 class: heart and lung; C3 class: uterus and liver. Strychnine contents of the three classes showed a C3 <C1 < C2. There were two kinds of convergences in Zuota group. D1 class : kidney and heart; D2 class : brain tissue and uterus. Strychnine contents of the two classes showed as D1 > D2. [Conclusions] When clustering distance was 1, low-content tissues and orgas firstly clustered, and its toxicological eefect(or pharmacodynamic action)was insignificant, and this kind of tissues and organs were relatively safe. A1 class and A2 class in Zuota group were merged into B1 class, in which liver was replaced by kidney. It iilustrated that Zuota could decline the toxicity of kidney, and enlarged the safe action range of brucine. Kidney and heart in C2 class were clustered into D1 class, and average strychnine content in C2 class was higher than that of D1 class. It could be deduced that Zuota had the effect of protecting heat.

Compound Phyllanthus urinaria L (CP) is a traditional formula widely used in clinical practice for hepatocellular carcinoma (HCC), especially HBV-related HCC. HBx, HBV X gene encoded X protein, has positive correlation with the abnormal SHH pathway in HBV-related HCC. So, we predicted that CP has the capability of anti-HBV-related HCC maybe via inactivating the HBx-Hedgehog pathway axis. HepG2-HBx cells, HBx overexpression, were treated with CP (70μg/ml and 35 μg/ml, respectively) for 48 hours and the mice which received the HepG2-HBx cells were treated with CP (625mg/kg and 300 mg/kg, respectively) for 17 days to evaluate the effect of CP on HBV-related HCC. HBx could accelerate HepG2 cells proliferation, clone formation, and migration in vitro and also could strengthen tumor growth in mice. However, CP could significantly decrease HepG2-HBx cells proliferation, clone formation, and migration in vitro and also could inhibit tumors growth in mice in a dose-dependent manner. Mechanism studies suggested that HBx upregulated the mRNA and proteins expression of Sonic hedgehog (SHH), transmembrane receptor patched (PTCH-1), smoothened (SMO), oncogene homolog transcription factors-1 (GLI-1), and oncogene homolog transcription factors-2 (GLI-2), which are compositions of the SHH pathway. CP could inhibit the mRNA and proteins expression of SHH, PTCH-1, GLI-1, and HBx. It may be one of the underlying mechanisms of CP to delay the HBV-related HCC development through the HBx-SHH pathway axis inactivation. [ABSTRACT FROM AUTHOR]