OBJECTIVE:To optimize the matrix formula of Lanlian ertong qingre cataplasm. METHODS:Taking adhesion force,peel strength and sensory description as index,the ratio of matrix framework material(sodium polyacrylate-gan hydroxyl alu-minum-tartaric acid-glycerin) was optimized with orthogonal test. The single factor test was adopted to select adhesive and filler;the amount of penetrating agent azone was screened using the in vitro penetration amount of phillyrin. RESULTS:The best matrix ratio of Lanlian ertong qingre cataplasm was sodium polyacrylate-gan hydroxyl aluminum-tartaric acid-glycerin(4.0:0.8:0.4:15);PVP K-90 was used as adhesive,and bolus alba as filler;penetration enhancers azone accounted for 2.0%. Validation test showed, prepared cataplasm had good appearance,could stick on the 5th or the 6th ball;it's peel strength was 7.5 N;all RSDs of score were lower than 4%(n=3). CONCLUSIONS:The optimized matrix formula of Lanlian ertong qingre cataplasm is simple,stable and good in molding.

Animals ; Cold Temperature ; adverse effects ; Heart ; physiopathology ; Inflammation ; physiopathology ; Myocardium ; metabolism ; Oxidative Stress ; Particulate Matter ; adverse effects ; Rats

Cold Temperature ; Dinoprost ; analogs & derivatives ; urine ; Dust ; Humans ; Interleukin-6 ; urine ; Thromboxane B2 ; analogs & derivatives ; urine ; Weather

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; Colitis, Ulcerative/drug therapy* ; Colon ; Dextran Sulfate/therapeutic use* ; Drugs, Chinese Herbal ; Mice ; Molecular Docking Simulation ; Plasma

We have identified anti-inflammatory quality markers (Q-markers) of Jiangzhenxiang. The chemical components of Jiangzhenxiang were identified by mass spectrometry and the substances that contribute to its anti-inflammatory activity, their targets and signaling pathways were analyzed by network pharmacology to identify potential Q-markers of the anti-inflammatory action of Jiangzhenxiang. The potential Q-markers were verified by high performance liquid chromatography, and in vitro experiments verified the anti-inflammatory activity and the target of the potential Q-markers. The experimental scheme was approved the Guangxi University of Chinese Medicine Institutional Animal Ethical and Welfare Committee. The results show that 31 chemical components were identified by mass spectrometry from the Jiangzhenxiang extract. Through network pharmacological screening, 727 component targets, 422 disease targets and 110 targets including prostaglandin G/H synthase 2 (PTGS2) were obtained. These targets were mainly enriched in 498 biological processes including inflammatory response and response to lipopolysaccharide, with 101 pathways that included the TNF signaling pathway, toll-like receptor signaling pathway and others. Isorhamnetin, formononetin, naringenin, glycitein, ursolic acid and oleanolic acid were detected by high performance liquid chromatography. Jiangzhenxiang medicated serum and 6 components thereof could significantly reduce the content of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-α in RAW264.7 cells induced by lipopolysaccharide (P < 0.01 or P < 0.05). These six components are regarded as the potential anti-inflammatory Q-markers of Jiangzhenxiang. Isorhamnetin was screened and verified from the 6 potential Q-markers as an inhibitor of PTGS2 by molecular docking and in vitro cyclooxygenase 2 (COX-2) activity assay. The half-inhibitory concentration of isorhamnetin was 9.55 μmol·L^-1. In summary, extracts of Jiangzhenxiang showed significant in vitro anti-inflammatory actions. The anti-inflammatory mechanism of Jiangzhenxiang appears to be related to regulation of TNF signaling pathway and Toll-like receptor signaling pathway meditated by IL-6, RAC alpha serine/threonine protein kinase, PTGS2 and other targets. Isorhamnetin, formononetin, naringenin, glycitein, ursolic acid and oleanolic acid could be regarded as the Q-markers of Jiangzhenxiang. Isorhamnetin appears to act as a COX-2 inhibitor.

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.
Computational Biology ; Drugs, Chinese Herbal ; Humans ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Urinary Bladder Neoplasms/genetics*

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.
Polysorbates/chemistry* ; Flavonoids ; Pueraria ; Surface-Active Agents/chemistry* ; Ethanol ; Emulsions ; Particle Size ; Solubility

To develop a caregiver parenting behavior scale for children aged 2 to 6 years, and to verify its reliability and validity. This study recruited 1 350 caregivers of children aged 2 to 6 years. The item discrimination analysis and exploratory factor analysis were used to analyze the structure, dimensions and items of the scale. Homogeneity reliability, split-half reliability and test-retest reliability were used to analyze the reliability of the scale. Content validity and construct validity were used to analyze the validity of the scale. The results showed that the final scale contained 7 dimensions and 45 items. Cronbach's α coefficient of the total scale was 0.945; the coefficient of split half was 0.899; the test-retest reliability analysis showed that the correlation coefficients between the two tests were 0.893 (total score), 0.854 (social), 0.832 (language), 0.871 (gross motor), 0.893 (fine motor), 0.862 (cognitive), 0.832 (self-care), and 0.872 (sensory). The content validity analysis was carried out by two rounds of expert argumentation using Delphi expert consultation method. The Kendall coefficient of the items score in two rounds of Delphi expert consultation was 0.813 (P<0.01). The structure validity analysis showed that there were significant correlations between each dimension and the total scale, also between each dimension of the scale, and the extracted average variance values of each dimension was greater than the correlation coefficients between this dimension and other dimensions. In conclusion, the reliability and validity of the scale are qualified. It can be used as a tool to evaluate and guide the parenting behavior of caregivers of children aged 2 to 6 years.
Humans ; Child ; Caregivers/psychology* ; Reproducibility of Results ; Parenting ; Surveys and Questionnaires ; Factor Analysis, Statistical ; Psychometrics/methods*