Application of Traditional Chinese Medicine injection in treatment of primary liver cancer:a review

OBJECTIVE:To investigate the application of Traditional Chinese Medicine Injections(TCMIs) for treatment of primary liver cancer(PLC).METHODS:A literature review was conducted using PubMed/Medline,Cochrane Library Controlled Clinical Trials Database,China National Knowledge Infrastructure(CNKI),China Scientific Journal Database(CSJD) and China Biology Medicine(CBM).Online websites including journal websites and databases of ongoing trials,as well as some Traditional Chinese Medicine journals that are not indexed in the electronic databases were also searched.RESULTS:The literature review showed that TCMIs as adjunctive medication for the treatment of PLC could regulate patient immunity,reduce bone marrow suppression,relieve clinical symptoms,and improve quality of life,as well as control disease progression and prolong survival time.CONCLUSION:Within the limitations of this review,we conclude that application of TCMIs as adjunctive medication may provide benefits for patients with PLC.Further large,high-quality trials are warranted.

Xiayuxue Decoction(下瘀血汤)Attenuates Hepatic Stellate Cell Activation and Sinusoidal Endothelium Defenestration in CCI_4-Induced Fibrotic Liver of Mice

Objective： To investigate the effects of ancient Chinese medical formula Xiayuxue Decoction （下瘀血汤, XYXD） on activation of hepatic stellate cells （HSCs） and defenestration of sinusoidal endothelial cells （SECs） in CCI4-induced fibrotic liver of mice. Methods： High performance liquid chromatography was used to identify the main components of XYXD and control the quality of extraction. C57BL/6 mice were induced liver fibrosis by CCI4 exposure and administered with XYXD for 6 weeks simultaneously. Liver tissue was investigated by hematoxylin-eosin and Sirius-red staining. Sinusoidal fenestrations were observed by scanning electronic microscopy and fluorescent immunohistochemistry of PECAM-1 （CD31）. Whole liver lysates were detected of α-smooth muscle actin （α-SMA） and type-I collagen by Western blot. Primary rat HSCs-T6 cells were analyzed by detecting α-SMA, F-actin, DNA fragmentation through confocal microscopy, Western blot, terminal-deoxynucleoitidyl transferase mediated nick end labeling （TUNEL） assay and cellomics arrayscan, respectively. Results： Amygdalin and emodin in XYXD were identified. XYXD （993 mg/kg） inhibited Sirius red positive area up to 70.1% （P〈0.01）, as well as protein levels of α-SMA and type- I collagen by 42.0% and 18.5% （P〈0.05） respectively. In vitro, XYXD （12.5 μg/mL, 50 μg/mL） suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent, demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% （P〈0.05）. Besides, XYXD induced the apoptosis of HSC-T6 cells by 20.0% （P〈0.05） and 49.5% （P〈0.01）, evidenced by enhanced TUNEL positivity. Moreover, ultrastructural observation suggested XYXD inhibited defenestration of SECs, which was confirmed by 31.1% reduction of protein level of CD31 （P〈0.05）. Conclusions： XYXD inhibited both HSCs activation and SECs defenestration which accompany chronic liver injuries. These data may help to understand the underlying mechanisms of XYXD for prevetion of chronic liver diseases.

Bioinformatics Research on Chronic Superficial Gastritis of Pi-deficiency Syndrome by Gene Arrays

Objective： To determine the bioinformatical characteristics of differential gene expression in patients with chronic superficial gastritis （CSG） with the Pi-deficiency syndrome （PDS） and those of the non- Pi-deficiency syndrome （non-PDS）, i.e. patients of CSG with Pi （脾）-Wei （胃） dampnese-heat syndrome and healthy persons. Methods： With the BRB-Array Tools software package, original data collection and bioinformatic analysis of gene arrays were conducted in 6 CSG patients of PDS （CSG-PDS）, 6 CSG patients of non-PDS （CSG-nPDS）, and 6 healthy volunteers （Normal）. Results： Compared with non-PDS, the gene expressions in PDS with regards to protein synthesis, energy metabolism, immune reaction and ionic transport tended to be down-regulated, while those concerning secretion, cytoskeleton and ubiquitinization were up-regulated dominantly. Conclusions： The two kinds of samples, CSG-PDS/Normal and CSG-PDS/CSG-nPDS, have their respective gene expression profiles with different characteristics. Gene expression profile has certain referential significance in syndrome classification.

Aidi Injection (艾迪注射液) Alters the Expression Profiles of MicroRNAs in Human Breast Cancer Cells

Objective: To investigate the effects of Aidi Injection (艾迪注射液 ADI) on the MicroRNAs (miRNA) expression profiles in human breast cancer cells and explore the potential targets of the cancer treatment. Methods: MCF-7 breast cancer cells were grown in RPMI 1640 medium supplemented with different concentrations of ADI. The inhibition of cell proliferation was measured by MTT assay. MCF-7 cells were treated by ADI with above 50% inhibiting concentration (IC50) for 48 h. The expression profiles of miRNA in ADI-treated and ADI-untreated MCF-7 cells were detected with miRNA microarray chips and the array data were verified by quantitative RT-PCR. MCF-7 cells were transiently transfected with miRNA mimics by liposome method. Potential mRNA targets were predicted by informatics analysis with TargetScan and PicTar software. Results: ADI significantly inhibited the proliferation of MCF-7 cells in a dose-dependent manner. The IC50 of ADI was 55.71 mg/mL after treatment for 48 h. The 60 mg/mL ADI was used as the therapeutic drug concentration. Microarray analysis identified 45 miRNAs that were up-regulated and 55 miRNAs that were down-regulated in response to ADI treatment. Many ADI-induced miRNAs were related to breast cancers. The microarray data were validated by qRT-PCR. Ectopic expression of 100 nmol/L mir-126 mimics significantly inhibited the proliferation of MCF-7 cells. The 12 potential target genes of mir-126 were predicted by both TargetScan and PicTar software. Conclusions: The miRNA may serve as therapeutic targets, and the modulation of miRNA expression is an important mechanism of ADI inhibiting breast cancer cell growth.

Effect of Roucongrong(Herba Cistanches Deserticolae) on reproductive toxicity in mice induced by glycoside of Leigongteng(Radix et Rhizoma Tripterygii)

OBJECTIVE： The purpose of this research is to study the effect of Roucongrong （Herba Cistanches Deserticolae） on reproductive toxicity in mice in- duced by a glycoside extracted from Leigongteng （Radix et Rhizoma Tripterygii） （GRT）. METHODS： Forty-eight BALB/c mice were random-ly divided into two groups in the ratio of I ： 3, 12 in one group and 36 in the other. The 12-mouse group was the control group that was intragastrical- ly administered physiological saline for 3 weeks. The 36 mice in the other group were given 30 mg- kg ·^-1 d i GRT for 3 weeks, then randomly divided into 3 subgroups： the model group, GRI group and Roucongrong （Herba Cistanches Deserticolae） group, with 12 mice in each group. In the model group, 0.25 mL physiological saline was intragastri- cally administered; in the GRT group, GRT, 0.25 mL at 30 mg · kg ^-1· d ^-1 was intragastrically adminis- tered once a day; in the Roucongrong （Herba Cis- tanches Deserticolae） group, mice were adminis- tered Roucongrong （Herba Cistanches Deserticolae） decoction equivalent to 0.25 mL at a final dose of 10g.kg 1.d.1 crude drug （calculated as per 20 times of 0.5 g· kg^-1. d ^-1 for adults）, and GRT 0.25 mL at 30 mg- kg^-1· d^- 1 daily. After another 3 weeks of exposure, expression levels of the reproduction-re- lated genes DEAD （Asp-Glu-Ala-Asp） box polypep- tide 3, Y-linked, B-cell CLL/lymphoma 6 and Signal transducer and activator of transcription 3 were evaluated. RESULTS： After 6 weeks of GRT treatment, the sper- matogenic cell population in the convoluted tu- bule of testis was in disorder and the tubule cavity expanded. Sertoli cell and Leydig cells exhibited at- rophy or disappeared. The number of sperm de- creased. The spermatogenic cell level of testis for male mice was ranked in order and sperm was pro- duced in the cavity of the spermatogenic cell. The expression levels of DDX3Y, BCL6 and STAT3 were up-regulated.CONCLUSION： GRT affected reproduction-related genes. Roucongrong （Herba Cistanches Desertico- lae） reversed reproductive toxicity in mice induced by GRT.

Salvianolate Reduces Glucose Metabolism Disorders in Dimethylnitrosamine-Induced Cirrhotic Rats

Objective： To evaluate the preventive effect of salvianolate （Sal B） on glucose metabolism disorders of dimethylnitrosamine （DMN）-induced cirrhotic rats. Methods： Fiffy-five Wistar rats were randomly divided into a control group （n=10） and a cirrhotic group （n=45） according to a random number table. Liver cirrhosis was induced by intraperitoneal administration of DMN. The cirrhotic rats were divided into model, Sal B and metformin groups （n=15）, respectively. Rats in the model group were given saline, two treatment groups were given Sal B （50 mg/kg）, metformin （150 mg/kg） respectively for 28 consecutive days, while rats in the control group were injected 0.9% saline with same volume of vehicle. Body weight was measured everyday. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Organ index, glucose tolerance test （OGTT）, and fasting plasma glucose （FPG）, fasting insulin （FINS）, hepatic glycogen, hydroxyproline （HYP） and liver function were detected at the end of the treatment. Area under the curve （AUC） for OG3-1 was calculated. Liver and pancreas histology were determined by histopathological examination with hematoxylin and eosin staining （HE）, Sirius Red staining and Masson＇s trichrome staining, respectively. Hepatic expression of α-smooth muscle actin （oL-SMA） and collagen （Col I ） were evaluated by immunohistochemical staining. Results： Compared with the model group, Sal B significantly increased body and liver weight, liver-body ratio, glucose infusion rate （GIR）, FPG, FINS levels and hepatic glycogen at the end of administration （P〈0.05 or P〈0.01）. Meanwhile, Sal B significantly decreased AUC for OGI-I＇, spleen weight, spleen-body ratio, aminotransferase and HYP level （P〈0.05 or P〈0.01）. Sal B was also effective in alleviating necrosis of liver tissue, suppressing fibrosis progression and inhibiting the expression of oL-SMA and Col I in liver. Compared with the metformin group, Sal B had advantages in ameliorating FPG, hepatic glycogen, spleen weight, organ index, liver function and cirrhosis （P〈0.05）. Metformin increased insulin sensitivity more potently than Sal B （P〈0.05）. Conclusions： Sal B could improve glucose metabolism in cirrhotic rats by protecting hepatic glycogen reserve, increasing insulin sensitivity, and alleviating pancreatic morphology abnormalities. Sal B was clinically potential in preventing glucose metabolism anomalies accompanied with cirrhosis.