Analysis of Molecular Mechanism of Huangliantang in Treatment of Gastritis Based on Integrated Pharmacology Platform of Traditional Chinese Medicine / 中国实验方剂学杂志

Objective: To investigate the effective substance basis and possible mechanism of Huangliantang in treatment of gastritis. Method: Integrated pharmacology platform of traditional Chinese medicine was employed to predict the main active ingredients and functional targets of Huangliantang in treatment of gastritis, network of composition target-disease target of Huangliantang was constructed, key nodes were screened for enrichment analysis of pathways, and the possible mechanism of Huangliantang in treatment of gastritis with multiple ingredients-multiple targets-multiple pathways was explored. Result: A total of 175 predicted active ingredients of Huangliantang interacted with 538 key targets about gastritis, the regulation and treatment of gastritis during its different pathological stages, such as Helicobacter pylori infection, gastric mucosal damage and gastric mucosal atrophy, were involved through chemokine, T cell receptor, estrogen and other signaling pathways. Conclusion: This research may reveal the potential active ingredients of Huangliantang in treatment of gastritis and its possible mechanism, and it also provides a theoretical basis for further experimental research of pharmacodynamic substance basis and mechanism of action.

Molecular mechanism of Danggui Beimu Kushen Pills in treating prostatic diseases based on TCM-IP / 中草药

Objective To analyze the material basis and molecular mechanisms of Danggui Beimu Kushen (DBK) Pills in treating prostatic diseases based on the method of integrated pharmacology. Method The platform of Integrative Pharmacology of Traditional Chinese Medicine (TCM-IP, www.tcmip.cn) was utilized to predict the main active ingredients and functional targets of DBK Pills in treating prostatic disease, key targets were screened for enrichment analysis of pathways, and the network of “herb-core component-key target-main pathway” was constructed, and the possible mechanisms of DBK Pills in treating prostatic diseases were explored. Results A total of 532 candidate key targets for the treatment of prostatic diseases by DBK Pills were predicted, and 1 840 terms of gene function and 194 signal pathways were analyzed by gene ontology (GO) and KEGG, respectively. The network analysis of “herb-core component-key target-main pathway” showed that 65 core components were predicted, including 29 ingredients from Angelica sinensis, 11 from Fritillaria thunbergii and 26 from Sophora flavescens. Those predicted components acted on the key targets of prostatic diseases, such as transcription factor binding, negative regulation of apoptosis, et al, through the estrogen, apoptosis, chemokines and other signal pathways, and thus played a role in the regulation of cell cycle, apoptosis and proliferation imbalance, which might be the molecular mechanisms of DBK Pills for the treatment of prostatic disease. Conclusion DBK Pills regulate the development of BPH, prostate cancer and other diseases through multiple pathways with multi-component interacting with multiple targets.

Wenxia Changfu Formula () induces apoptosis of lung adenocarcinoma in a transplanted tumor model of drug-resistance nude mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the apoptosis mechanism of Wenxia Changfu Formula (, WCF) in reversing drug resistance of lung cancer in vivo.</p><p><b>METHODS</b>Thirty model mice were randomly assigned to three groups: control group, cisplatin (CDDP) group, and WCF group. A transplanted tumor model of lung adenocarcinoma was established in all groups. Mice in the WCF group received intragastric administration of WCF (0.2 mL/10 g body weight) everyday in addition to CDDP intraperitoneally (5 mg/kg body weight) twice a week. The mice in the CDDP group received CDDP intraperitoneally (5 mg/kg body weight) twice a week, while the control group received normal saline intraperitoneally (0.2 mL/10 g body weight) everyday. The weight of the nude mice and respective tumors, tumor volume and tumor-inhibiting rate were measured. Electron microscopy was used to observe the existence of apoptosis body. Apoptosis index (AI) was detected by TdT-mediated dUTP nick end labeling staining. The expression of Fas and FasL mRNA was investigated by reverse transcription polymerase chain reaction, while immunohistochemistry was applied to detect the protein expression of Fas and FasL, caspase-3 and caspase-activated DNase (CAD), respectively.</p><p><b>RESULTS</b>Compared with CDDP group and control group, WCF could significantly reduce the tumor volume from the 19th day and alleviate the tumor weight (P <0.05), and the apoptosis body was found in tumor cells in the WCF group. WCF could also enhance the level of AI, up-regulate the expression of caspase apoptosis pathway related protein caspase-3 and CAD, as well as the expression of Fas, FasL mRNA and protein (P <0.05).</p><p><b>CONCLUSION</b>WCF could improve the sensitivity of tumor cells to CDDP and reverse the drug resistance by inducing the apoptosis.</p>

Study on the networks of "Nature-Family-Component" of Chinese medicinal herbs based on association rules mining / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore appropriate methods for the research of the theory of Chinese medicine nature property and find the relationship between Nature-Family-Component of Chinese herbs.</p><p><b>METHODS</b>From perspective of systems biology, we used Associate Network to identify useful relationships among "Nature-Family-Component" of Herbs. In this work, Associate Network combines association rules mining method and network construction method to evaluate the complicate relationship among "Nature-Family-Component" of herbs screened.</p><p><b>RESULTS</b>The results of association rules mining showed that the families had a close relationship with nature properties of herbs. For example, the families of Magnoliaceae, Araceae had a close relationship with hot nature with confidence of 100%, the families of Cucurbitaceae has a close relationship to cold nature with confidence of 90.91%. Moreover, the results of constructed Associate Network implied that herbs belonging to the same families generally had the same natures. In addition, some herbs belonging to different families may also have same natures when they contain the same main components.</p><p><b>CONCLUSION</b>These results implied that the main components of herbs might affect their natures; the relationships between families and natures were based on the main compounds of herbs.</p>

Effects of Radix aconiti lateralis preparata and Rhizoma zingiberis on energy metabolism and expression of the genes related to metabolism in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the influence of Radix aconiti lateralis preparata and Rhizoma zingiberis, two species of Chinese medicinal herbs with hot property, on energy metabolism and gene expression spectrum, and to analyze the possible mechanism of their effects.</p><p><b>METHODS</b>Forty-eight specific pathogen free Wistar rats were randomly divided into a Radix aconiti lateralis preparata group, a Rhizoma zingiberis group, and a control group. They were intragastrically treated with concentrated decoction of Radix aconiti lateralis preparata, Rhizoma zingiberis and normal saline respectively for 20 days. Toe temperature (TT), energy intake (EI), digestible energy (DE), and metabolizable energy (ME) were measured. The content of adenosine triphosphate (ATP) and energy charge (EC) in hepatic tissue were measured with high performance liquid chromatography (HPLC). The activity of ATPase and succinate dehydrogenase (SDH) in the liver were detected with chemical colorimetry. The gene expression in the liver was detected with Illumina's rat Ref-12 gene array. The differential expression genes were selected, annotated and classified based on Gene Ontology (GO). Real-time quantitative reverse-transcriptase PCR (Q-RT-PCR) was used to test the accuracy of results.</p><p><b>RESULTS</b>Compared with the control group, the TT on the 10(th) day after the beginning of administration and ATP in the Radix aconiti lateralis preparata and Rhizoma zingiberis groups increased significantly (P<0.05). EI/body mass (BM), DE/BM, ME/BM, the hepatic EC and the activity of Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase and SDH of liver increased significantly only in the Radix aconiti lateralis preparata group (P<0.05). There were 592 differential expression genes in the Radix aconiti lateralis preparata group and 1 159 in the Rhizoma zingiberis group compared with the control group. Among the differential expression genes, genes related to metabolic processes were the most significant based on GO analysis. There were 337 strips of gene differential expression in common in both Radix aconiti lateralis preparata and Rhizoma zingiberis groups compared with the control group.</p><p><b>CONCLUSIONS</b>Herbs with hot property such as Radix aconiti lateralis preparata and Rhizoma zingiberis could improve the energy metabolism in rats, through influencing the metabolic process of sugar, lipid, and amino acid. It could also promote the production, storage, and utilization of energy by regulating the gene expression related to metabolism, which may be the main molecular mechanism of warming yang and dispelling cold for the treatment of the cold syndrome according to Chinese medicine theory.</p>

In vitro and in vivo inhibitory effect of the combination of Wenxia Changfu formula see text with cisplatin in non-small cell lung cancer / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of the combination of Wenxia Changfu Formula ([see text], WCF) with cisplatin (CDDP) on inhibiting non-small cell lung cancer (NSCLC) in vitro and In Vivo and explore its mechanism from its effect on cell cycle.</p><p><b>METHODS</b>In vitro, WCF-containing serum was prepared and the rhubarb b1, emodin, and aconitine were detected qualitatively by high-performance liquid chromatogram (HPLC). A549 cell lines were treated with blank control (dimethyl sulfoxide), normal serum, normal serum with CDDP (1.25, 2.5, and 5.0 μg/mL, respectively), WCF-containing serum plus different doses of CDDP (1.25, 2.5, and 5.0 μg/mL, respectively). The inhibitory effect was detected by 3-(4,5)-dimethylthiazo(-zy1)-3,5-diphenylterazolium bromide (MTT). The cell cycle was detected by flow cytometry. The protein and mRNA expressions of cyclin D1, proliferating cell nuclear antigen (PCNA), retinoblastoma (Rb), and p16 were observed with immunofluorescence and RT-PCR, respectively. In Vivo, nude mice xenograft model was established and grouped into the control, CDDP, WCF, and combination groups. The combination's inhibition of tumor growth and influence on the weight, spleen, and thymus gland were observed.</p><p><b>RESULTS</b>The inhibitory rate of the combination against A549 cell lines excelled the CDDP alone significantly (P <0.05); the combination showed a synergism inhibitory effect (Q=1.19). Compared with the monotherapy, the combination increased the cell percentage in G(0)/G(1) phase and decreased the cell percentage in S phase significantly (P <0.05); the protein and mRNA expressions of cyclin D1, PCNA, and Rb were significantly reduced; the protein and mRNA expressions of p16 were significantly enhanced. Compared with the monotherapy, the combination inhibited the tumor growth significantly In Vivo and reduced the weight of tumor (P <0.05); compared with the CDDP group, the spleen and thymus gland index of the combination group were enhanced significantly (P <0.05).</p><p><b>CONCLUSIONS</b>The combination of WCF with CDDP significantly inhibited the A549 cell lines proliferation in vitro and the growth of the tumor In Vivo; it inhibited effectively the atrophy of the immune organ caused by chemotherapy. The combination inhibited overproliferation of A549 cell lines by arresting the G(0) /G(1) phase of cell cycle and affecting the protein and mRNA expressions of cell cycle-related proteins, cyclin D1, etc.</p>