OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (1-5), and 7 known analogs (6-12). The separation of enantiomer mixtures 1-5 to 1a/1b-5a/5b was achieved using a chiral column with acetonitrile-water mixtures as eluents. The planar structures of 1-2 were previously undescribed, and the chiral separation and absolute configurations of 3-5 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.
Lignans/isolation & purification* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Molecular Structure ; Plant Extracts/pharmacology* ; Illicium/chemistry* ; Cyclooxygenase 2/immunology* ; Interleukin-6/immunology* ; Nitric Oxide/metabolism* ; Cell Line ; Tumor Necrosis Factor-alpha/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Lipopolysaccharides

OBJECTIVE To prepare venlafaxine hydrochloride and fluoxetine hydrochloride multiplayer tablets by stereolithography （SLA） 3D printing technology， and to conduct its quality evaluation and in vitro release investigation. METHODS Using venlafaxine hydrochloride/fluoxetine hydrochloride， photopolymerization monomer PEGDA 400， porogen PEG 300， photoinitiator TPO and light absorber citrine as formulation， SLA 3D printer technology was employed to prepare venlafaxine hydrochloride and fluoxetine hydrochloride multiplayer tablets， with outer diameter of 10 mm， inner diameter of 5 mm， and thickness of 6 mm. Moreover， the tablets’ appearance， three-dimensional dimensions， weight uniformity， drug content， internal structural characteristics and in vitro release characteristics were all investigated. RESULTS The multilayer tablets had good printing formability， smooth and round edges， and uniform size and thickness； the outer diameter， inner diameter and thickness were （10.06±0.26）， （4.94±0.06）， （5.80±0.12） mm （RSD＝2.58%， 1.21%， 2.07%，n＝20）， and the weight difference all met the requirements. The contents of venlafaxine hydrochloride and fluoxetine hydrochloride were （7.96±0.09） and （11.26±0.46） mg/tablet， respectively. The results of X-ray diffraction and scanning electron microscopy characterization showed that the two drug molecules in the multilayer film existed in an amorphous structure； after the dissolution of the venlafaxine hydrochloride layer， a clear pore structure was formed， while the fluoxetine hydrochloride layer did not show any pore structure. According to the release curve， 24 h accumulative release rates of venlafaxine hydrochloride layer and fluoxetine hydrochloride layer were（91.88±0.94）% and （106.25±1.28）%， which were in line with Rigter-Peppas release model. CONCLUSIONS This study successfully prepared venlafaxine hydrochloride and fluoxetine hydrochloride multilayer tablets using SLA 3D printing technology； the multilayer tablets have the advantages of excellent printing formability， which are in line with Rigter-Peppas release model.

Objective To investigate the effects of ursolic acid and rhynchophylline in Uncariae Ramulus Cum Uncis on human hepatoma HepG2 cells; To discuss its antihepatoma mechanism. Methods Culture the human hepatoma HepG2 cells with 50, 25, 12.5, 6.25 μmol/L ursolic acid, rhynchophylline for 24, 48, 72 hours respectively. 1%DMSO was set as negative control group. CCK-8 based cytotoxicity assay was used to detect the growth of HepG2. Acridine orange fluorescent staining was used to observe human hepatoma HepG2 cells cultured with 50 μmol/L ursolic acid, rhynchophylline and 1%DMSO for 48 hours were observed. Results Ursolic acid significantly acted as a disincentive to the growth of HepG2 cells, which was in positive correlation with time and concentration. Inhibited effect by rhynchophylline on HepG2 cell proliferation was weaker than ursolic acid. Pathological observation showed that most of the cells in rhynchophylline group showed cell shrinkage, dense pulp coating and nuclear staining edge set, and most of the cells in the ursolic acid group showed apoptosis late changes, such as nuclear cleavage and apoptotic bodies. Conclusion Ursolic acid and rhynchophyllinein Uncariae Ramulus Cum Uncis can inhibit the proliferation of HepG2 cells and can induce apoptosis.

Objective To investigate the effect of Biling Zhidai Tablets(BZT) on monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1)and tumor necrosis factor-alpha(TNF-α)levels as well as hemorheology of rats with sequela of pelvic inflammatory diseases(SPID). Methods One hundred Wistar rats were randomly divided into normal control group , sham-operation group , model group , BZT group(0.54 g·kg-1·d-1)and Fuke Baidai Tablets group(0.225 g·kg-1·d-1), 20 rats in each group . The rats of the model group, BZT group and Fuke Baidai Tablets group were given mechanical damage plus injection of mixed bacteria to induce SPID. After modeling for 2 weeks, the latter three groups were given intragastric administration of the medicine for 21 days. The uterine swelling rate, the serum levels of MCP-1, ICAM-1, TNF-α as well as hemorheological indexes of rats in various groups were detected. Results The uterine swelling rate in BZT group and Fuke Baidai Tablets group was significantly decreased as compared with that of the model group, and the uterine swelling inhibition rate of BZT group was higher than that of Fuke Baidai Tablets group (P<0.01). The levels of MCP-1, ICAM-1 and TNF-α of BZT group and Fuke Baidai Tablets group were significantly decreased as compared with those of the model group, and the effect of BZT group was better than t hat of Fuke Baidai Tablets group, the differences being statistically significant(P<0.05or P<0.01). The indexes of hemorheology in BZT group were significant improved as compared with Fuke Baidai Tablets group, and the improvement in BZT group was superior to that in Fuke Baidai Tablets group (P<0.05 or P<0.01). Conclusion B ZT e xert certain therapeutic effect on treating SPID rats, and the mechanism is related with the relief of swelling of uterus, decrease of serum MCP-1, ICAM-1 and TNF-αlevels and improvement of the indexes of hemorheology.

Objective To investigate high risk human papillomavirus(HR-HPV)prevalence among married women in Beijing and to study the high risk flactors.nethods During March 2007 to September 2008.a total of 6185 married women sampled from 137 communities in 12 districts were screened bv HR-HPV DNA test and cytogical test.The interview was carried out with unified questionnaires.The databage was set up and twice entered in EpiDam 3.0.After checked up,the data were analyzed in SPSS 15.0.Results (1) The HR-HPV infection rate was 9.89%.The HR-HPV infection rate of the city zone,the suburb and the exurb were 9.34%,10.51% and 9.51% (P>0.05).The HR-HPV infection rate of the native and the oudander were 9.53%,11.30% (P<0.05).(2) The age distribution of HR-HPV infection was that the rate was around 10% among 25 to 44 age groups,which was the highest(11.21%) in 30 to 34 age group;then the rate was descended as the age raising,the rate of 50 to 54 age group was the lowest(7.78%).(3) Multiple logistic regression showed that the related risk factors of HR-HPV infection mainly included 1000 RMB and above of family income per person per month.possessing more than 1 sexual partner of her husband,outlander and hish levels of education.(4) The prevalence of cervical intraepithelial neoplasia(CIN)in HR-HPV positive group wag significantly higher than that in HR-HPV negative group(29.76% vs 3.32%,P<0.01).Conclusions(1)The HR-HPV infection rate among aged 25 to 54 years was 9.9% and there was no significant difference in area distribution.(2)The hish risk population which should strengthen screening was the married bearing-age women with high level of family income,outlander,high levels of education and her husband possessing more than 1 sexual partner.(3)HR-HPV infection is the main risk factor for CIN and cervical cancer.while does not provide a causal relationship with them.The high risk population should be checked regularly to understand the development of HR-HPV infection and CIN incidence.