Molecular Mechanism of Ligustri Lucidi Fructus-Astragali Radix for Anti-cancer Based on Network Pharmacology / 中国实验方剂学杂志

Objective: To screen out active ingredients, and predict the anti-cancer targets of Ligustri Lucidi Fructus-Astragali Radix based on the "herbs-active ingredient-action targets" network. Method: The traditional Chinese medicine (TCM) system pharmacology platform (TCMSP) was employed to screen out the active ingredients and putative targets of anti-cancer of glossy privet fruit and astragalus. DisGeNET database and Online Mendelian Inheritance in Man (OMIM database) were employed to predict the targets for treating cancer, and then "herbs-active ingredients-key targets" network was constructed by using Cytoscape software. The omicshare platform was employed to match the putative targets of ingredients and the targets for treating cancer. Finally, the protein interaction network of key targets was constructed by using String database, and the analysis of biological functions and pathways of them was carried out by using DAVID database. Result: Totally 33 drug active ingredients were screened out, involving a total of 203 targets, and 14 of them were related to cancer. These 14 key targets played an therapeutic role in treating cancer by regulating target proteins, such as ERBB2, AR, SRC, EGFR, ESR1, as well as proteoglycans in cancer, cancer pathways, microRNAs in cancer and other pathways. Conclusion: The therapeutic mechanism of Ligustri Lucidi Fructus-Astragali Radix reflects the multi-component, multi-target, and multi-pathway characteristics of TCMs, providing the scientific basis for further study and the material basis of Ligustri Lucidi Fructus-Astragali Radix against cancer.

Effect of Compound Zhajin Granule on Toll-like Receptor 4 Signaling Pathway in Nonalcoholic Steatohepatitis Mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Compound Zhajin Granule (CZG) on Toll-like re-ceptor 4 (TLR4) signaling pathway in high-fructose corn syrup induced NASH mice.</p><p><b>METHODS</b>Thirty 6-week-old male C3H mice were divided into the high fat and high fructose (HFHFr) group (n = 20) and the control group (n = 10) according to body weight. Mice in the HFHFr group ate high fat diet and drank 20% fructose water, while those in the control group ate common diet and drank common water. After 8 weeks mice in the HFHFr group were divided into two group according to body weight, the HFHFr group and the CZG group, 10 in each group. Mice in the CZG group were fed with high fat forage and 20% fructose water, and administered with 50 mL/kg 12. 8% CZG (prepared by hawthorn, Radix Curcumae, Alisma Orientale, Fritillaria Thunbergii, Silybum Marianum, peach seed in the ratio of 3:1.5:1.5:2:1.5:2:1) by gastrogavage. Mice in the HFHFr group were fed in the same way and daily administered with equal volume of distilled water by gastrogavage. Sixteen weeks later all mice were sacrificed. Body weight, liver wet weight, liver function, and lipid metabolism were detected. Pathological changes of liver tissues were assessed by HE staining, oil red O staining, and Masson staining. Expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α) were detected using immunohistochemical staining and real-time fluorescent quantitative PCR.</p><p><b>RESULTS</b>Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST) were obviously lower in the CZG group than in the HFHFr group (P < 0.05); oil red O stained area and density were decreased more in the CZG group than in the control group. HE staining showed ballooning inflammation was reduced more in the CZG group than in the HFHFr group. Masson staining was negative. Positive rates of TLR4 and MyD88 and mRNA expressions were significantly lower in the CZG group than in the HFHFr group (all P < 0.05).</p><p><b>CONCLUSION</b>CZG could significantly inhibit TLR4 signaling pathway of liver in NASH mice.</p>

Effect of constituents combination on pharmacokinetics of Shuxiong tablet / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of combination components on pharmacokinetics of Shuxiong tablet to provide evidence for the new recipe.</p><p><b>METHOD</b>Six groups of rats (6 for each group) were orally administered with co-extractum of chuanxiong and honghua (CHE), mixed solution of hydroxysafflor yellow A (HSYA) and ferulic acid (FA) (HFM). Panax notoginseng saponins solution (PNS), mixed solution of PNS and CHE (PCHE), mixed solution of PNS and HFM (PHFM) and mixed emulsion of Chuanxiong volatile oil (CVO) and PHFM (CVO-PHFM), respectively. The concentrations of HSYA, FA, ginsnenoside Rg1 and Rb1 in rat plasma were determined by HPLC. Pharmacokinetic parameters (Ka, Kel, Cmax, Tmax and AUC) were calculated by model simulation. The differences of HSYA, FA, Rg1 and Rb1 in pharmacokinetics parameters after administration of six preparations were demonstrated by statistical analysis.</p><p><b>RESULT</b>After oral administration of six preparations to rats, the concentration-time curve of HSYA and Rg1 fitted to one-compartment model, and that of FA fitted to double-compartment model. After oral administration of CHE, Kel of FA reduced; Cmax decreased; but K12 increased, significantly, compared with oral administration of HFM. Other parameters were not significant differences. After co-administration of PNS and CHE (PCHE) or PNS and HFM (PHFM), Ka of HSYA increased; Tmax reduced, significantly. After oral administration of PNS and HFM (PHFM), Ka of Rg1 improved, Tmax decreased, significantly. However, the parameters of FA and Rb1 were not significantly changed. After co-administration of CVO and PHFM (CVO-PHFM), Cmax of Rb1 decreased, K12 improved, significantly. Meanwhile, the oral bioavailability of HSYA, FA and Rg1 was improved by 6.056, 2.854 and 2.055 folds, respectively.</p><p><b>CONCLUSION</b>After oral administration of different combinations of Shuxiong tablet constituents, some pharmacokinetics parameters of active ingredients are significantly changed, but the bioavailability is improved only when CVO is co-administered.</p>

Heavy load exercise induced dysfunction of immunity and neuroendocrine responses in rats.

To determine whether immunity and neuroendocrine system is altered by different loads of exercise training in rats, eight-week-old male Sprague-Dawley rats were randomly assigned to one of the three groups: 1) cage control group (CCG); 2) moderate load training (MLT) (swimming at the intensity of 1.4 m/sec water flowing for 60 min per day); 3) heavy load training (HLT) (swimming at the intensity of 1.8 m/sec water flowing for 120 min per day). MLT and HLT rats were assigned to swim for 6 days per week for total of 6 weeks. All rats were sacrificed 36 h after their last training session. Splenocytes were pooled for assay of cell proliferation and neuropeptide contents in the hypothalamus, hypophysis and plasma were determined by radioimmunoassay while glucocorticoid specific binding in intact thymus was measured by radioligand binding assay. All rats were weighed weekly. The results showed that after 6-week training, rat splenocyte proliferation in response to Con A and LPS decreased in HLT rats compared with MLT and CCG rats. In addition, the contents of beta-endorphin, dynorphin A, arginine vasopressin and oxytocin in the hypothalamus, hypophysis and plasma were altered by HLT, as shown by increased plasma concentration of glucocorticoids and decreased glucocorticoids specific binding in intact thymus compared with MLT and CCG. Furthermore, a decreased body mass in HLT rats has been observed. The body mass of HLT rats was significantly lower than that in CCG and MLT rats at the end of the swimming training period. These data suggest that 6-week heavy load training induces the dysfunction of immunity and neuroendocrine responses, which might be one of the underlying mechanisms of immune dysfunction in overtraining.