铈盐治疗烧伤的有关药学性质探讨

本文比较了硝酸铈、氯化铈、乙酸铈等三种铈盐的抑菌作用,半数致死量(LD_(50)),抗炎作用及动物烧伤的治疗观察。认为铈盐能够提高治疗烧伤的疗效,其主要原因是抗炎作用,其次有杀菌和其它辅助作用。提出以铈盐与杀菌药物配合使用,是治疗烧伤的较好的配伍方式。

分光光度测定萝芙木生物碱：药物中利舍平的测量

萝芙木植物的提取物可用来治疗某些疾病，其药学性质主要来源于吲哚生物碱。萝芙木植物中的吲哚生物碱主要有两类，它们是类利舍平吲哚生物碱和类育亨宾吲哚生物碱。类利舍平吲哚生物碱中的有效成分主要是利舍平和瑞西那明。

超氧化物歧化酶的化学修饰进展

超氧化物歧化酶是生物体内能清除超氧阴离子自由基的一类重要酶,具有重要的生理功能和广泛的应用前景。化学修饰的方法可以提高其稳定性,改善酶的药学性质。本文简要综述了超氧化物歧化酶活性部位酪氨酸,组氨酸的化学修饰;重点综述了生物活性物质,药用辅料,二酶缀合物对非活性部位的化学修饰,以及相关病理研究。评价了这些修饰反应的特点和结果 ,并对其研究前景进行了展望。

Study on Kinetic Characteristics of Alliinase

[Objective] The kinetic characteristics of alliinase was studied to select the optimum reaction performance. [Method] Alliinase activity was measured to analysis the influence of temperature, pH, substrate concentration and metal iron. [Result] Alliinase was an enzyme with thermal instability. Its optimum reaction temperature was 29℃ and pH value was 6.1. The Vmax was 0. 439 IU/mg and Km was 0.483 mmol/L by using natural extract as substrate. Alliinase activity was activated when the K^＋ , Mg^2＋ , Na^＋ and Cd^2＋ existed and alliinase activity was inhibited when Cu^2＋ existed. [Condusion] Results showed that the kinetic characteristics of alliinase supply the academic foundation for development and application of garlic medical products.

Pharmaceutical Characteristics of Daunorubicin Stealth Liposomes

This report studied on pharmaceutical characteristics of the stealth liposome containing dau-norubicin (DNR). The shape, size, entrapment efficiency and stability of the daunorubicin stealth liposomes (DNRSL) were examined. Visible spectrophotometry and the HPLC method were established for determination of the DNR in the DNRSL. The release of DNR from DNRSL in HBS (pH 7.5) and rat serum at 37 oC were examined. The results showed that the DNRSL had high entrapment efficiency (>85%), small size and slow release.

PROSTAMIDES ANANDAMIDE CYCLOOXY- GENASE-2 METABOLITES: METABOLISM AND TRANSPORT STUDIES

The prostamides (prostaglandin-ethanolamides) are produced from the action of cyclooxygenase-2 (COX-2) on anandamide. So far prostamide E2, D2 and F2alpha and their synthetic analog Bimatoprost have been described, but little has been reported on their metabolism and pharmacology, except that they do not appear to activate prostanoid or cannabinoid receptors. These studies were performed to determine if prostamides exhibit simi-

Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase

AIM： To identify the proportion, causes and the nature of drug-induced liver injury （DILI） in patients with no- tably elevated alanine aminotransferase （ALT）. METHODS： All the inpatients with ALT levels above 10 times upper limit of normal range （ULN） were ret- rospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT eleva- tions were examined for each patient, including bili- ary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed usingthe Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors. RESULTS： A total of 129 cases with ALT 〉 i0 ULN were identified. Hemodynamic injury （n = 46, 35.7%）, DILl （n = 25, 19.4%） and malignancy （n = 21, 16.3%） were the top three causes of liver injury. Peak ALT val- ues were lower in DILI patients than in patients with hemodynamic injury （14.5 5.6 ULN vs 32.5 ：I： 30.7 ULN, P = 0.001）. Among DILI patients, one （4%） case was classified as definite, 19 （76%） cases were clas- sified as probable and 5 （20%） as possible according to the ClOMS scale. A hepatocellular pattern was ob- served in 23 （92%） cases and mixed in 2 （8%）. The extent of severity of liver injury was mild in 21 （84%） patients and moderate in 4 （16%）. Before discharge, 10 （40%） patients were recovered and the other 15 （60%） were improved. The improved patients tended to have a higher peak ALT （808 ＋ 348 U/L vs 623 ＋ 118 U/L, P = 0.016） and shorter treatment duration before discharge （8 ＋ 6 d vs 28 ~ 12 d, P = 0.008） compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILl. Antibacterials were the most common agents causing DILI in 8 （32%） cases, followed by glucocorticoids in 6 （24%） cases. Twenty-four （96%） cases received treatment of DILl with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs （e.g., glycyr- rhizinate）, antioxidants （e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin）, polyene phospha- tidyl choline and herbal extracts （e.g., protoporphyrin disodium and silymarin）. Diagnosis of DILl was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgi- cal wards had a higher risk of missed diagnosis in dis- charge letter [odds ratio （OR） 32.7, 95%CI （2.8-374.1）,CONCLUSION： DILI is mostly caused by use of anti- bacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT 〉 10 ULN. DILI is underdiagnosed frequently.

Effect of monocyte chemoattractant protein-1 on chemotactic gene expression by macrophage cell line U937

Objective: To study the chemotactic superfamily genes expression profiling of macrophage line U937 treated with monocyte chemoattractant protein-1 (MCP-1) using gene chip technique. Methods: Total RNA from macrophage line U937 (as control) and U937 with MCP-1 was extracted, made reverse transcript to cDNA and tested with gene expression chip HO2 human. Results: Some chemotactic-related gene expressions were changed in all analyzed genes. Regulated upon activation, normal T cell expressed and secreted (RANTES) was up-regulated over 2-fold and 7 chemotactic-related genes (CCR2, CCR5, CCL16, GROβ, GROγ, IL-8 and granulocyte chemotactic protein 2) were down-regulated over 2-fold in MCP-1 treated U937 cells at mRNA level. Conclusion: MCP-1 can influence some chemokines and receptors expression in macrophage in vitro, in which MCP-1 mainly down-regulates the chemotactic genes expression of those influencing neutrophilic granulocyte (GROβ, GROγ, IL-8 and granulocyte chemotactic protein 2). Another novel finding is that it can also down-regulate the mRNA level of CCR5, which plays a critical role in many disorders and illnesses.

Tetrandrine inhibits migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes through down-regulating the expressions of Rac1, Cdc42, and Rho A GTPases and activation of the PI3K/Akt and JNK signaling pathways

Tetrandrine （Tet）, the main active constituent of Stephania tetrandra root, has been demonstrated to alleviate adjuvant-induced arthritis in rats. The present study was designed to investigate the effects of Tet on the migration and invasion of rheumatoid arthritis fibroblast-like synovioeytes （RA-FLS） and explore the underlying mechanisms. By using cultures of primary FLS isolated from synoviums of RA patients and cell line MH7A, Tet （0.3, 1 μmol L-1） was proven to significantly impede migration and invasion of RA-FLS, but not cell proliferation. Tet also greatly reduced the activation and expressions of matrix degrading enzymes MMP-2/9, the expression of F-actin and the activation of FAK, which controlled the morphologic changes in migration process of FLS. To identify the key signaling pathways by which Tet exerts anti-migration effect, the specific inhibitors of multiple signaling pathways LY294002, Triciribine, SP600125, U0126, SB203580, and PDTC （against PI3K, Akt, JNK, ERK, p38 MAPK and NF-kB-p65, respectively） were used. Among them, LY294002, Triciribine, and SP600125 were shown to obviously inhibit the migration of MH7A cells. Consistently, Tet was able to down-regulate the activation of Akt and JNK as demonstrated by Western blotting assay. Moreover, Tet could reduce the expressions of migration-related proteins Rho GTPases Rac 1, Cdc42, and RhoA in MH7A cells. In conclusion, Tet can impede the migration and invasion of RA-FLS, which provides a plausible explanation for its protective effect on RA. The underlying mechanisms involve the reduction of the expressions of Racl, Cdc42, and RhoA, inhibition of the activation of Akt and JNK, and subsequent down-regulation of activation and/or expressions of MMP-2/9, F-actin, and FAK.

Effect of Morinda officinalis capsule on osteoporosis in ovariectomized rats

AIM:To explore the therapeutic effects of Morinda officinalis capsules(MOP) on osteoporosis in ovariectomized rats.METHOD:Six-month-old female Sprague–Dawley rats were induced for postmenopausal osteoporosis(PMOP) by bilateral ovariectomy and divided into seven groups as follows:sham-operated group,ovariectomized(OVX) control group,OVX treated with xianlinggubao(XLGB)(270 mg·kg-1·d-1),OVX treated with alendronate sodium(ALN)(3 mg·kg-1·d-1),and OVX treated with Morinda officinalis capsule(MOP) of graded doses(90,270 and 810 mg·kg-1·d-1) groups.Oral treatments were administered daily on the 4th week after ovariectomy and lasted for 12 weeks.The bone mineral density was evaluated by dual-energy X-ray absorptiometry.The tartrate-resistant acid phosphatase(TRAP),alkaline phosphatase(AKP),and osteocalcin(OC) levels in the serum and plasma were determined by standard colorimetric and enzyme immunoassays methods.Bone biomechanical properties and morphological parameters were analyzed by three-point bending test and histomorphometry respectively.RESULTS:Morinda officinalis capsules at all doses were able to significantly prevent the OVX-induced loss of bone mass due to diminishing serum AKP and TRAP levels while elevating OC level in the plasma.Morinda officinalis capsules also enhanced the bone strength and prevented the deterioration of trabecular microarchitecture.CONCLUSION:Morinda officinalis capsules possess potent anti-osteoporotic activity in OVX rats which could be an effective treatment for postmenopausal osteoporosis.

Tongqiao Huoxue Decoction ameliorates learning and memory defects in rats with vascular dementia by up-regulating the Ca^(2+)-CaMKII-CREB pathway

The present study was aimed at determining the effects of Tongqiao Huoxue Decoction （TQHXD） on the Ca2＋-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia （VD）. The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g.kg-1 per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II（CaMKII）, protein kinase A（PKA）, cAMP-response element binding protein（CREB）, and three N-methyl-D-aspart^c acid receptor subunits （NR1, NR2A, and NR2B）. Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity （P 〈 0.05 and P 〈 0.01 vs the model group, respectively）. The treatment with 6.02 and 12.04 g.kg-1 of TQHXD significantly up-regulated the Ca2＋-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling oathwavs.

Simultaneous quantification of ten constituents of Xanthoceras sorbifolia Bunge using UHPLC-MS methods and evaluation of their radical scavenging, DNA scission protective, and α-glucosidase inhibitory activities

The present study was designed to investigate the bioactive constituents ofXanthoceras sorbifolia in terms of amounts and their antioxidant, DNA scissiou protection, and ct-glucosidase inhibitory activities. Simultaneous quantification of 10 X. sorbifolia constituents was carried out by a newly established ultra-high performance liquid chromatography-quadrupole mass spectrometry method （UHPLC-MS）, The antioxidant activities were evaluated by measuring DPPH radical scavenging and DNA scission protective activities. The a-glucosidase inhibitory activities were investigated by using an assay with a-glucosidase from Bacillus Stearothermophilus and disaccharidases from mouse intestine. We found that the wood ofX. sorbifolia was rich in phenolic compounds with the contents of catechin, epicatechin, myricetin, and dihydromyricetin being 0.12-0.19, 1.94-2.16, 0.77-0.91, and 6.76-7.89 mg.g-1, respectively. The four constituents strongly scavenged DPPH radicals （with ECs0 being 4.2, 3.8 and 5.7 μg-mL-1, respectively） and remarkably protected peroxyl radical-induced DNA strand scission （92.10%, 94.66%, 75.44% and 89.95% of protection, respectively, at a concentration of 10 μmol.L-1）. A dimeric flavan 3-ol, epigallocatechin-（4β→8, 2β→O-7）-epicatechin potently inhibited a-glucosidase with an IC50 value being as low as 1.2 μg.mL1. The established UHPLC-MS method could serve as a quality control tool for X. sorbifolia. In conclusion, the high contents of antioxidant and α-glucosidase inhibitory constituents in X. sorbifolia support its use as complementation of other therapeutic agents for metabolic disorders, such as diabetes and hypertension.

Anti-inflammatory and anti-arthritic effects of Guge Fengtong Formula: in vitro and in vivo studies

Rheumatoid arthritis （RA） is the most common inflammatory arthritis and a major cause of disability. Presently, the clinical therapeutic medicines for inflammatory and arthritic diseases are unsatisfactory due to severe adverse effects or ineffectiveness. The Guge Fengtong formula （GGFT）, containing the standardized extracts of Dioscoreae Nipponicae Rhizoma, Spatholobi Caulis, and Zingiberis Rhizoma, has long been used for RA treatment in China. However, the detailed anti-inflammatory and anti-arthritic activity of GGFT has not been reported so far. In the present work, we aimed to evaluate the anti-inflammatory and anti-arthritic effects of GGFT using three in vivo animal models and tried to uncover the underlying mechanism of action in RAW 264.7 macrophages. The obtained results indicated that GGFT significantly attenuated ear edema, decreased carrageenan-induced paw edema, reduced the ar- thritis score, and reversed the weight loss of the complete Freund＇s adjuvant （CFA）-injected rats. Additionally, decrease in synovial inflammatory infiltration and synovial lining hyperplasia in the joints and decline of inflammatory factors （TNF-α and IL-1β） in the serum were observed in the GGFT-treated rats. In lipopolysaccharide-activated RAW264.7 macrophages, GGFT reduced the produc- tion of NO, PGE2, and IL-6 and inhibited the expression of iNOS, COX-2, and NF-kB. Our results demonstrated that GGFT possessed considerable anti-inflammatory activity and had potential therapeutic effects on adjuvant induced arthritis in rats, providing experi- mental evidences for its application in the treatment of RA and other inflammatory diseases.

Chemical profiling of Jinqi Jiangtang tablets by HPLC-ESI-Q-TOF/MS

AIM： To profile the chemical constituents in Jinqi Jiangtang tablets. METHOD： Based on the chromatographic retention behavior, fragmentation patterns of chemical components, and published lit- eratures, a high-performance liquid chromatography coupled with electrospray ionization quadrnpole time-of-flight tandem mass spectrometry （HPLC-ESI-Q-TOF/MS） method was established to characterize and identify components in Jinqi Jiangtang tablets. RESULTS： A total of 52 chemical compounds, including eight iridoid glycosides, seven phenolic acids, twelve alkaloids, six fla- vonoids, and nineteen saponins, were identified in Jinqi Jiangtang tablets. CONCLUSION： The established method could serve as a powerful tool for structural characterization and quality control of this Chinese herbal preparation.

Preparation and quality assessment of high-purity ginseng total saponins by ion exchange resin combined with macroporous adsorption resin separation

AIM： To prepare high-purity ginseng total saponins from a water decoction of Chinese ginseng root.METHOD： Total saponins were efficiently purified by dynamic anion-cation exchange following the removal of hydrophilic impurities by macroporous resin D101. For quality control, ultrahigh-performance liquid chromatography with a charged aerosol detector （CAD） was applied to quantify marker components. The total saponin content was estimated by a colorimetric method using a vanillin-vitriol system and CAD response. RESULTS： D201, which consisted of a cross-linked polystyrene matrix and -]N＋（CI-13）3 functional groups, was the best of the four anion exchange resins tested. However, no significant difference in cation exchange ability was observed between D001 （strong acid） and D 113 （weak acid）, although they have different functional groups and matrices. After purification in combination with D101, D201, and D 113, the estimated contents of total saponins were 107% and 90% according to the colorimetric method and CAD response, respectively. The total amount of representative ginsenosides Re, Rd, Rgl, and compound K was approximately 22% based on ultrahigh-performance liquid chromatography-CAD quantitative analysis. CONCLUSION： These findings suggest that an ion exchange resin, combined with macroporous adsorption resin separation, is a promising and feasible purification procedure for neutral natural polar components.

Ethanolic extract of dandelion(Taraxacum mongolicum) induces estrogenic activity in MCF-7 cells and immature rats

Plants of the genus Taraxacum, commonly known as dandelions, are used to treat breast cancer in traditional folk medicine. However, their use has mainly been based on empirical findings without sufficient scientific evidence. Therefore, we hypothesized that dandelions would behave as a Selective estrogen receptor modulator （SERM） and be effective as hormone replacement therapy （HRT） in the postmenopausal women. In the present study, in vitro assay systems, including cell proliferation assay, reporter gene assay, and RT-PCR to evaluate the mRNA expression of estrogen-related genes （pS2 and progesterone receptor, PR）, were performed in human breast cancer cells. Dandelion ethanol extract （DEE） significantly increased cell proliferation and estrogen response element （ERE）-driven luciferase activity. DEE significantly induced the expression of estrogen related genes such as pS2 and PR, which was inhibited by tamoxifen at 1 gmol L-1. These results indicated that DEE could induce estrogenic activities mediated by a classical estrogen receptor pathway. In addition, immature rat uterotrophic assay was carried out to identify estrogenic activity of DEE in vivo. The lowest concentration of DEE slightly increased the uterine wet weight, but there was no significant effect with the highest concentration of DEE. The results demonstrate the potential estrogenic activities of DEE, providing scientific evidence supporting their use in traditional medicine.

Chemical investigation of the roots of Polygala sibirica L.

AIM:To investigate the chemical constituents of the roots of Polygala sibirica L.(Polygalaceae) METHOD:The isolation was performed by solvent extraction and various chromatographic techniques,including silica gel,Sephadex LH-20,ODS,semi-preparative HPLC,and preparative TLC.The chemical structures were elucidated based on extensive spectroscopic analysis,including HR-ESI-MS and 1D- and 2D-NMR spectroscopic data.RESULTS:A total of sixteen compounds,including five xanthones(5,7–10),five saccharide esters(1,3,4,12,13),two flavonoids(14,16),two triterpenoids(11,15),one phenylpropanoid(6),and one benzophenone glycoside(2) were isolated.Their structures were determined as sibiricose A7(1),sibiriphenone A(2),polygalatenoside A(3),polygalatenoside C(4),lancerin(5),3,4,5-trimethoxycinnamic acid(6),6-hydroxy-1,2,3,7-tetramethoxyxanthone(7),1,3,7-trihydroxy-2-methoxyxanthone(8),onjixanthone II(9),1,2,3,6,7-pentamethoxyxanthone(10),presenegenin(11),3'-O-3,4,5-trimethoxycinnamoyl-6-O-4-methoxy benzoyl sucrose(12),tenuifoliside C(13),5,3'-dihydroxy-7,4'-dimethoxyflavonol-3-O-β-D-glucopyranoside(14),tenuifolin(15),and rhamnetin 3-O-β-D-glucopyranoside(16).CONCLUSION:Compounds 1 and 2 are two new compounds from P.sibirica.

Evaluation and SAR analysis of the cytotoxicity of tanshinones in colon cancer cells

AIM:This study was designed to evaluate the anti-cancer actions of tanshinone I and tanshinone IIA,and six derivatives of tanshinone IIA on normal and cancerous colon cells.Structure activity relationship(SAR) analysis was conducted to delineate the significance of the structural modifications of tanshinones for improved anti-cancer action.METHOD:Tanshinone derivatives were designed and synthesized according to the literature.The cytotoxicity of different compounds on colon cancer cells was determined by the MTT assay.Apoptotic activity of the tanshinones was measured by flow cytometry(FCM).RESULTS:Tanshinone I and tanshinone IIA both exhibited significant cytotoxicity on colon cancer cells.They are more effective in p53+/+ colon cancer cell line.It was also noted that the anti-cancer activity of tanshinone I was more potent and selective.Two of the derivatives of tanshinone IIA(N1 and N2) also exhibited cytotoxicity on colon cancer cells.CONCLUSIONS:The anti-colon cancer activity of tanshinone I was more potent and selective than tanshinone IIA,and is p53 dependent.The derivatives obtained by structural modifications of tanshinone IIA exhibited lower cytotoxicity on both normal and colon cancer cells.From steric and electronic characteristics point of view,it was concluded that structural modifications of ring A and furan or dihydrofuran ring D on the basic structure of tanshinones influences the activity.An increase of the delocalization of the A and B rings could enhance the cytotoxicity of such compounds,while a non-planar and small sized D ring region would provide improved anti-cancer activity.