Objective To synthesize the novel derivatives of 11-deoxyl glycyrrhetinic acid with high anti-inflammatory activities.Methods 11-Deoxylglycyrrhetinic acid was obtained by deoxidizing glycyrrhetinic acid with Zn(Hg)/HCl,and then a series of 11-deoxylglycyrrhetinic acid 30 acylamide derivatives were synthesized by coupling with R-Ar-isoxazole-methylamine.And the synthesized compounds were confirmed by the methods of IR,(()~1H-NMR),(()~(13)C-NMR),and MS.Two models were used to evaluate the preliminary anti-inflammatory activity of the compounds.Results The structures of all the new compound were identified by the spectra of IR,(()~1H-NMR),(()~(13)C-NMR),and MS.The compound 1,3,5 and 7 were proven to have a significant anti-inflammatory activity.Conclusion Some 30-acylamide derivatives of glycyrrhetinic acid have significant anti-inflammatory activities.

Objective Astrgaloside Ⅳ derivative (ASId) is one of Astragaloside Ⅳ (ASI) derivatives with higher water-solubility and may have more druggability than ASI. The present study aims at observing the effects of ASId on cardiovascular parameters in chronic heart failure in rats. Methods Using echocardiographic and haemodynamic measurements, the effects of ASId on congestive heart failure (CHF) induced by ligation of the left coronary artery in rats were investigated.ventricle (LV) pressure (dp/dt) in ASId treated groups were significantly increased. Both LV volumes in diastole and in systole were decreased significantly after ASId treatment, accompanied with a trend towards normalization of relative stress. ASId treatment also inhibited compensatory hypertrophy of depressed heart. Conclusion ASId could improve cardiac functions and inhibite compensatory hypertrophy and LV remodelling, which suggests the possibility of ASId as a new therapeutic drug for the treatment of CHF.

Objective The astragaloside Ⅳ(ASI)has been proved to play an important role in protecting against cell death on cardiovascular diseases.This study aims to investigate the effect of the astragaloside derivate.(ASId)on confronting oxidative stress and hypertrophy in myocardial cells.Methods Following exposure embryonic rat cardiac H9c2 cells to hydrogen peroxide(H2O2)and angiotensin Ⅱ for developing oxidative stress and hypertrophy,ASId at final concentrations(0.1,1,and 10 μmol/L)was added to study its role in protecting cardiomyocytes by biochemical detection and cell size measurement In addition,the mitochondrial permeability transition pore(mPTP)opener atractyloside(20 μmol/L)and inhibitor cyclosporin A(CSA)(1 μmol/L)were employed to investigate the possible mechanisms for anti-oxidation.Results ASId at 1 and 10 μmol/L in cultures suppressed oxidative stress at different degrees,which induced the decrease in LDH activity and MDA content,and also the increase in SOD activity in comparable with the model group; The mPTP opener atractyloside and inhibitor CSA weakened and strengthened the role of ASId,respectively.ASId at 10 μmol/L inhibited cell hypertrophy,and the cell diameter,surface area,and protein content were all decreased in comparable of those cells in model group.Conclusion ASId is involved in the cytoprotective effects on oxidative stress through a pathway mediated by mPTP,and also has a protective effect against hypertrophy.

Objective To observe the therapeutic effect of Di'ao Xinxuekang (DAXXK) on myocardial ischemia-reperfusion injury in rats, and to explore its mechanisms. Methods The myocardial ischemia-reperfusion injury model was established by the ligation of descending coronary artery in rats. Then animals after the modeling were randomized into model group, DAXXK-d (31.5 mg/kg) group, DAXXK-g (63.0 mg/kg) group and Diltiazem (24.8 mg/kg) group. A separate sham group was used as control. The treatment group was given DAXXK once a day for 7 days. Cardiac function and cardiac configuration were measured by color Doppler ultrasound diagnostic method. Hemodynamics was measured by Millar catheter method. The arterial oxygen saturation and blood oxygen pressure were measured by i-STAT 300 blood gas analyzer. Inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, adhesion molecules VCAM-1, ICAM-1, and apoptosis-related protein Bcl-2, Bax were detected by ELISA. Myocardial apoptosis was measured using TUNEL method. Results Compared with model group, the left ventricular fractional shortening (FS), the systolic and diastolic function were improved, and the left ventricular pressure maximum rise/ fall rates (± LVdp/dtmax) were increased, in DAXXK group. DAXXK improved lung function, increased arterial oxygen pressure and oxygen content. The inflammatory cytokines IL-1β, IL-6, TNF-α and adhesion molecules ICAM-1 and VCAM-1 were decreased in DAXXK group. The myocardial swelling and inflammatory infiltration were relieved, myocardial apoptosis was reduced, the expression of Bcl-2 protein was increased and the expression of Bax protein was decreased in DAXXK group. Conclusion DAXXK can protect myocardial ischemia-reperfusion injury, which involved in the inhibition of apoptosis and reduction of inflammatory cytokines.

Objective To explore the investigation method of complicated and profound traditional Chinese herbal medicine,the potential action mechanisms of flavonoids from Scutellaria baicalensis were studied by docking calculation.Methods In total, eight flavonoids (aglycones and their glicosides) from S. baicalensis were selected as ligands.The crystalline structures of targets related to common diseases were used as the receptors for calculation. The calculations were conducted with Schr(o)dinger software package. The grading standard of selectivity was developed according to G-score between ligands and receptors. Results Twenty-six pharmacologic actions have been reported.Among all effects in literature, nine of them can be deduced from the docking calculation of aglycone. From glycosides with grade ++, 25 reported effects can be estimated by calculation. Apparently, the target selectivity of aglycones and their glycosides are different form the virtual evaluation. The virtual evaluation results of glycosides were closer to the reported effects. Conclusion Our proposed virtual evaluation method seems an effective way to investigate the complicated system of traditional Chinese herbal medicine. It suggests that aglycones may be effective as the form of glucoside in vivo, and metabolism is a very important factor for virtual evaluation.

Objective To elucidate potential activities of phthalides and terpenoids from Angelica sinensis by theoreticaldocking calculation.Methods Eleven components of phthalides and terpenoids were selected as ligand.Thecrystalline structures of targets related to common diseases were used as the receptors for calculation.Thecalculations were conducted with Schr(o)dinger software package.The grading standard of selectivity was developedaccording to G-score between ligands and receptors.Results Selective targets of phthalides and terpenoids wererelated to nevous system diseases,cancer,pain,diabetes,cardiovascular disease,liver cirrhosis,nephrotic syndrome,inflammatory diseases,rheumatoid arthritis,dermatosis,leukemia,microbial inflections,immune diseases,andhypercholesterolemia.In addition to the medical treatments reported in the literature,our research also indicated thatthese two classes of compounds may be used for tumor,diabetes,rheumatoid arthritis,dermatosis,leukemia,livercirrhosis,and nephrotic syndrome.According to our research,the effects of phthalides and terpenoids may be not sostrong.Conclusion The effects of phthalides and terpenoids on diseases founded through virtual evaluation accord greatly with those reported in experiment and clinic.The combination of computer-aided drug evaluation technique and experiment is definitely an important and fast way to investigate the effects and mechanisms of traditional Chinese medicine.

Aim To investigate TY501′s role in bleo-mycin ( BLM )-induced pulmonary fibrosis in rats. Methods Forty rats were randomly divided into 5 groups, including the sham operation, BLM, PFD, TY501(high and low dose) groups. After administra-tion of BLM intratracheally, PFD and TY501 were giv-en in each group daily, according to the dosage de-signed during 21 days. Lung coefficient, PaO2 were tested before killing the rats. The contents of ALB, ALP, LDH, GSH, HYP were detected by regent kit respectively. PCⅢ and COL4 were determined by ELISA. Results ( 1 ) Some indicators of alveolitis in early stage of IPF: the contents of lung coefficient in three treatment groups were lower and PaO2 was higher than those in BLM group ( P<0. 05 ); compared with BLM group, the contents of ALB, ALP, LDH in the treatment groups reduced on 21 st day ( P<0. 05 );the expression of GSH in BLM group was increased for feedback regulation and higher than the treatment groups and the sham operation group (P<0. 05);(2) some indicators of pulmonary interstitial fibrosis in late stage of IPF:the expressions of HYP, PCⅢand COL4 were reduced after the treatment. There were signifi-cant differences compared with BLM group ( P <0. 05 ) . Conclusions TY501 is valuable for the ther-apy of IPF, the same as the positive drug pirfenidone. TY501 attenuates BLM-induced pulmonary fibrosis, which may be related to the affection of TGF-βpathway and inhibition of MMPs.

Objective To study the application of 99Tcm in rabbit cerebral thromboembolic stroke and thrombolysis effect of recombinant tissue plasminogen activator (rt-PA).Methods The 0.5 mL radioactive pertechnetate sodium (specification:5 mCi/2mL and radiation intensity 92.5 MBq/mL) was combined with 30 μL stannous chloride (5 mg/mL),and the 20 μL mixture was joined to whole blood,red blood cells,and plasma for labelling.Then 50 μL CaCl2 (0.5 mol/L) and bovine thrombin (50 IU/mL) were doped in mixture,and rapidly sucked into a polyethylene plastic pipe (PE80).Thrombus was formed for 2 h at 37 ℃ and cut into small pieces of 10 mm.Autologous blood clots combined with 99Tcm from external carotid artery were injected to internal carotid artery of rabbit,the radioactivity (counts per minute,CPM) was measured by gamma counting instrument,and the improvement of rt-PA 4.5 mg/kg (clinical equivalent dose) on this model was observed.Results After thromboembolism,CPM increased approximately by (5.1 ± 1.3) times,which suggested that the model was reliable.The rt-PA 4.5 mg/kg had significant progressive thrombolysis effect.Conclusion 99Tcm tracer technology could be applied to rabbit cerebral stroke model,which is stable and reliable

Objective:To investigate the effect of IL-17A on the differentiation and maturation of murine bone marrow-derived dendritic cells( BMDCs ) . Methods: Murine bone marrow cells were isolated and cultured in RPMI1640 complete medium in the presence of GM-CSF(20 ng/ml) for 8 days to induce differentiation of murine bone marrow cells to DC progenitors. Then these cells were treated with LPS(1 μg/ml) for 36 h which polarized immature DCs into mature DCs. Different concentrations of rmIL-17A(10 or 100 ng/ml) was added to the culture medium at different stages of BMDC differentiation and maturation. Co-stimulatory molecules expression on BMDC were analyzed by flow cytometry,and the culture supernatants were analyzed for IL-12p40 and IL-10 level by ELISA. Results:rmIL-17 could promote co-stimulatory molecules( CD40,CD80,CD86 and MHCⅡ) expression on BMDCs in a does-dependent manner,especially,the expression of CD40 and MHCⅡhad a significant increase in high concentration of rmIL-17A group;rmIL-17A was added while LPS induced maturation of BMDCs. CD40,CD80,CD86 and MHCⅡexpression on BMDC increased sharply in LPS plus rmIL-17A stimulation group,besides,CD86,MHCⅡ showed a higher level expression on BMDC with the increase of con-centration of rmIL-17A. Furthermore,secretion of IL-12p40 and IL-10 increased significantly in the group of DCs treated with LPS plus low concentration of rmIL-17 compared with the group without rmIL-17(P<0. 001). However,high concentration of rmIL-17A group showed significantly higher levels of IL-12p40(P<0. 001),but there was no difference in IL-10. Conclusion:IL-17A promotes the phe-notypic development of BMDC progenitors propagated in GM-CSF and cooperate with LPS to induce BMDC differentiation and matura-tion.