ABSTRACT
OBJECTIVE: To predict the anti-diabetes effects of Corydalis yanhusuo alkaloids with pharmacological network technology and verify the results in animal models. METHODS: Targets of Corydalis yanhusuo alkaloids were collected from Pubmed, CNKI, Wangfang and VIP databases, and targets for treatment of diabetes and diabetic complications were searched from OMIM database. The "components-targets-diabetes" network was constructed and analyzed with cytoscape 2.8.2. Diabetes model was established by STZ injection. RESULTS: The targets of Corydalis yanhusuo alkaloids covered many kinds of protein, including ion channel, G coupled protein, and signal proteins such as potassium channel, MAPK/ERK, VEGF and NOS3. In the network, Corydalis yanhusuo alkaloids associated with diabetes and diabetic complications, especially, non-insulin dependent diabetes, obesity, and diabetic complications via modulation of NOS3, VEGF, INSR, KCNJ11 and IRS1, indicating potential effects of Corydalis yanhusuo for diabetes and diabetic complications. Corydalis yanhusuo alkaloids decreased blood glucose in normal and diabetic ICR mice and improved sugar tolerance in insulin-resistant mice, which was in conformity with the prediction. CONCLUSION: Corydalis yanhusuo alkaloids show potential effects on diabetes and diabetic complications.
ABSTRACT
<p><b>OBJECTIVE</b>To study the curative effects of pirfenidone (PF) on pulmonary fibrosis induced by paraquat (PQ) in mice and to provide the theoretical basis for clinical treatment.</p><p><b>METHODS</b>Ninety adult healthy male ICR mice were randomly divided into six groups: control group, PQ group, 2 mg/kg Dexamethasone group, 25 mg/kg PF group, 50 mg/kg PF group and 100 mg/kg PF group, there were 15 mice in each group. The corresponding volume of normal saline was given to the each mouse in control group according to the weight, after 2 h 0.1% CMC was given to the each mouse of control group one time by intragastric administration, then the CMC was administrated at regular time until sacrifice. All mice for other 5 groups were exposed to 100 mg/kg PQ by intragastric administration. At 2 h after exposure to PQ, 0.02 ml/10 g dexamethasone and 25, 50, 100 mg/kg PF were given to mice for dexamethasone group and for 3 PF groups by intragastric administration each day for 49 days, respectively. The lung coefficient was calculated and pathological changes of lung tissue were observed by HE staining for each mouse. The hydroxyproline (HYP) level in lung tissue was measured for each mouse. The mRNA level of and the protein level of TGF-β(1) in lung tissue for each mouse were determined, and the protein level of TGF-β(1) in the bronchus-alveolus lavage fluid (BALF) of each mouse was detected.</p><p><b>RESULTS</b>The survival rates on the 3rd day in PQ group, 3 PF groups and dexamethasone group were 53.33%, 46.67%, 73.33%, 86.67% and 80%, respectively. The survival rates on the 3rd day in dexamethasone group, 50 mg/kg and 100 mg/kg PF groups were significantly higher than those of PQ group and 25 mg/kg PF group (P < 0.05). The lung coefficients of 3 PF groups were significantly lower than that of the PQ group (P < 0.05). The lung tissue HYP levels of dexamethasone group and 3 PF groups were 50.95 ± 11.65, 44.52 ± 9.48, 43.27 ± 6.01 and 40.82 ± 5.90 mg/g respectively, which were significantly lower than that (74.27 ± 3.68) of PQ group (P < 0.01). The TGF-β(1) protein levels of BALF in dexamethasone group, 50 and 100 mg/kg PF groups were 22.03 ± 7.27, 27.75 ± 5.84 and 21.31 ± 6.82 ng/ml respectively, which were significantly lower than that (52.52 ± 15.51) ng/ml of PQ group (P < 0.01) The expression level of TGF-β(1) mRNA in 100 mg/kg PF group decreased significantly, as compared with PQ group (P < 0.01).</p><p><b>CONCLUSION</b>PF could reduce the collagen deposition and pulmonary fibrosis induced by PQ in mice lungs.</p>