Hepatoprotective activity of cis-(trans)-emodin-emodin dianthrone from Polygonum multiflorum Thunb / 药学学报

The cis-emodin-emodin dianthrone (compound 1) and trans-emodin-emodin dianthrone (compound 2) were extracted from Polygonum multiflorum Thunb. The protective effect and mechanism of compound 1 and compound 2 (emodin-emodin dianthrones) on acute liver injury induced by concanavalin A (ConA) in ICR mice was first investigated. The results indicated that emodin-emodin dianthrones at 1 mg·kg-1 significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level (P < 0.05). Emodin-emodin dianthrones also improved liver histopathological damage in liver-injured mice. The level of Bcl-2-associated X protein (Bax) mRNA in liver was significantly reduced by 1 mg·kg-1 of emodin-emodin dianthrones, while the level of B-cell lymphoma-2 (Bcl-2) mRNA expression was significantly increased (P < 0.05). The protective activity of compounds 1 and 2 against hepatocyte injury was further evaluated by hydrogen peroxide (H2O2)-induced hepatocyte injury. Compounds 1 and 2 significantly inhibited H2O2-induced hepatocyte injury and reduced the levels of ALT, AST, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in cell culture. Compounds 1 and 2 also significantly improved the cell survival rate and decreased H2O2-induced oxidative stress in hepatocytes. Compound 1 (0.5 µmol·L-1) significantly increased the enzymatic activity of superoxide dismutase (SOD) in hepatocytes (P < 0.01), and 0.5 µmol·L-1 of compound 2 significantly decreased the intracellular reactive oxygen species (ROS), increased SOD enzyme activity, and glutathione (GSH) content (P < 0.01). Compounds 1 and 2 at 0.5 µmol·L-1 also inhibited hepatocyte apoptosis by increasing the protein expression ratio of Bcl-2/Bax (P < 0.05) and decreasing the protein expression ratio of cleaved caspase-3 and pro caspase-3 (P < 0.05). This study indicates that the emodin-emodin dianthrones from Polygonum multiflorum Thunb. have liver-protective activity. Compounds 1 and 2 exerted hepatoprotective effects by inhibiting apoptosis and oxidative stress. The study provides an important material basis for the hepatoprotective effect of commonly used amounts of Polygonum multiflorum Thunb.

New phenolic constituents obtained from Polygonum multiflorum / 中草药·英文版

Objective: To isolate the phenolic compounds obtained from the dried roots of Polygonum multiflorum and investigate their pharmacological activities. Methods: The chemical constituents were isolated and purified by combining them with a macroporous resin (DM-8), MCI gel, and Sephadex LH-20 and by performing ODS column chromatography. Their structures were elucidated by 1D and 2D NMR analyses, as well as mass spectrometry. The isolated compounds were evaluated to determine their hepatoprotective and α-glucosidase inhibitory activities in vitro. Results: Two phenolic compounds, namely, polygonimitin E (1) and polygonimitin F (2), were isolated from the dried roots of P. multiflorum. Compound 2 (10 µmol/L) only showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage. Unfortunately, these two compounds exhibited no α-glucosidase inhibitory activity. Conclusion: Compounds 1 and 2 were new compounds. Compound 2 could be one of the potential hepatoprotective constituents of P. multiflorum.

Study on potential hepatotoxicity of rhein in Rhei Radix et Rhizoma based on liver metabolism / 中国中药杂志

The bilirubin metabolism mediated by the phase Ⅱ metabolizing enzyme UGT1A1 in the liver was evaluated to study the potential hepatotoxicity risk based on investigation on the inhibitory effect of rhein and its metabolites on the UGT1A1 enzyme in Rhei Radix et Rhizoma. Firstly, in vitro liver microsomes incubation was used to initiate the phase Ⅱ metabolic reaction to investigate the inhibitory effect of rheinon UGT1A1 enzyme. Secondly, the phase Ⅰ and phase Ⅱ metabolic reactions were initiated to investigate the hepatotoxicity risk of rhein metabolites. It was found that the rhein and its phase Ⅱ metabolites had no significant inhibitory effect on UGT1A1 enzyme, but its phase Ⅰ metabolites significantly reduced UGT1A1 enzyme activity. Based on the metabolites analysis, it is speculated that the rhein phase Ⅰ metabolite rheinhydroxylate and its tautomers have certain hepatotoxicity risks, while the toxicity risk induced by the prototype and phase Ⅱ metabolites of rheinglucoside, rheinglucuronic acid and rhein sulfate is small.

A new 2,3-dioxoflavonoid from the aerial part of Hypericum perforatum / 药学学报

Phytochemical study of the aerial parts of Hypericum perforatum L. resulted in the isolation of an undescribed compound, which was identified as Rel-(2S,3R)-2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2-methoxy-3-(2-oxopropyl)chroman-4-one (1) by spectroscopic methods including UV, IR, HR-ESI-MS, 1D and 2D NMR spectra. Compound 1 is a new 2,3-dioxo-flavone with an acetonyl moiety, rarely found in nature. In addition, a plausible biogenetic pathway of 1 was proposed in this article.

Study on hepatotoxicity of physcion based on liver metabolism in vitro / 中国中药杂志

To evaluate the hepatotoxicity risks of physcion on the basis of the bilirubin metabolism mediated by glucuronidation of UDP-glucuronosyltransferases 1A1(UGT1A1 enzyme). The monomers were added into the rat liver microsomes to test the hepatotoxicity by using bilirubin as UGT1A1 enzyme substrate, with apparent inhibition constant K_i as the evaluation index. Liver microsome incubation in vitro was adopted to initiate phase Ⅱ metabolic reaction and investigate the inhibitory effect of physcion. Then the phase Ⅰ and Ⅱ metabolic reactions were initiated to investigate the comprehensive inhibition of metabolites and prototype components. The results showed that when only the phase Ⅱ reaction was initiated, physcion directly acted on the UGT1A1 enzyme in a prototype form, exhibited weak inhibition and the inhibition type was mixed inhibition; When the phase Ⅰ and Ⅱ reactions were initiated simultaneously, the inhibitory effects of physcion on UGT1A1 enzyme became strong and the inhibition type was mixed inhibition, suggesting that physcion had phase Ⅰ and Ⅱ metabolic processes, and the metabolites had strong inhibitory effect on UGT1A1 enzyme. This experiment preliminarily proved that the metabolites of physcion may be the main components to induce hepatotoxicity.

Prediction of potential drug interactions of apigenin based on molecular docking and in vitro inhibition experiments / 中国中药杂志

The purpose of this study was to investigate the effect of apigenin on UGT1 A1 enzyme activity and to predict the potential drug-drug interaction of apigenin in clinical use. First,on the basis of previous experiments,the binding targets and binding strength of apigenin to UGT1 A1 enzyme were predicted by computer molecular docking method. Then the inhibitory effect of apigenin on UGT1 A1 enzyme was evaluated by in vitro human liver microsomal incubation system. Molecular docking results showed that apigenin was docked into the active region of UGT1 A1 enzyme protein F,consistent with the active region of bilirubin docking,with moderate affinity. Apigenin flavone mother nucleus mainly interacted with amino acid residues ILE343 and VAL345 to form hydrophobic binding Pi-Alkyl. At the same time,the hydroxyl group on the mother nucleus and the amino acid residue LYS346 formed an additional hydrogen bond,which increased the binding of the molecule to the protein. These results suggested that the flavonoid mother nucleus structure had a special structure binding to the enzyme protein UGT1 A1,and the introduction of hydroxyl groups into the mother nucleus can increase the binding ability. In vitro inhibition experiments showed that apigenin had a moderate inhibitory effect on UGT1 A1 enzyme in a way of competitive inhibition,which was consistent with the results of molecular docking. The results of two experiments showed that apigenin was the substrate of UGT1 A1 enzyme,which could inhibit the activity of UGT1 A1 enzyme competitively,and there was a risk of drug interaction between apigenin and UGT1 A1 enzyme substrate in clinical use.

In vitro release and in situ gastrointestinal absorption of evodiamine butyryl derivative-loaded solid lipid nanoparticles / 中国药理学通报

Aim To prepare evodiamine butyryl deriva-tive (EBD) and evodiamine butyryl derivative-loaded solid lipid nanoparticles (EBDLN), and study its re-lease in vitro,and to investigate its in situ gastrointesti-nal absorption. Methods EBD was prepared by a one-step synthetized method, and then EBDLN was prepared by a film dispersion method. Dynamic dialy-sis was used to evaluate drug release in vitro,and sin-gle-pass gastrointestinal perfusion was employed to study the gastrointestinal absorption of EDM,EBD and EBDLN. Results In identical release media, there were identical drug release tendencies of EBD and EB-DLN, but the release rate of EBDLN was faster than EBD. Compared with EDM and EBD, the Kavalues and Pappvalues of EBDLN in every perfusion segment increased significantly. The Kaof EBDLN in stomach, duodenum, jejunum, ileum and colon was 110.14-fold,56.70-fold,51.23-fold,45.70-fold and 127.23-fold of free EDM respectively. The Pappvalue of EB-DLN was 9.74-fold, 4.48-fold, 3.82-fold and 11.3-fold of that of free EDM. Conclusion EBDLN has sustained effect and can enhance the gastrointestinal absorption of EDM and EBD.

Evaluation of Protective Effects of Bioactive Phytochemicals Against Methotrexate in Salmonella typhimurium TA1535/pSK1002 Coupled with Micronucleus Assay / 生物医学与环境科学（英文）

We evaluated the antimutagenic effects of 10 kinds of bioactive phytochemicals and some phytochemical combinations against methotrexate (MTX)-induced genotoxicity by the umu test in Salmonella typhimurium TA1535/pSK1002 combined with a micronucleus assay. We observed that allicin, proanthocyanidins, polyphenols, eleutherosides, and isoflavones had higher antimutagenic activities than the other five types of bioactive phytochemicals. At the highest dose tested, MTX-induced genotoxicity was inhibited by 25%-75%. Kunming mice treated by MTX along with bioactive phytochemical combinations showed significant reduction in micronucleus induction and sperm abnormality rate (P<0.01). These results indicate that bioactive phytochemical combinations can be potentially used as new cytoprotectors.

A new lanostane-type triterpenoid from Cymbopogon citratus / 中国中药杂志

To study the chemical constituents of Cymbopogon citratus, isolation and purification of constituents were carried out on silica gel, Sephadex LH-20 and prepatative HPLC. The structures of the compounds were identified by physicchemical properties and spectral data analysis. Eight compounds were isolated and identified as 3beta-methoxy lanosta-9(11)-en-27-ol (1), 3beta-hydroxylanosta-9 (11)-en (2), (24S) -3beta-methoxylanosta-9(11), 25-dien-24-ol (3), 8-hydroxyl-neo-menthol (4), (2E)-3,7-dimethyl-2,7-octadiene-1, 6-diol (5), (+)-citronellol (6), 7-hydroxymenthol (7) and ethyl nonadecanoate(8). Compounds 1 is a new one. Compounds 2-3 are obtained from C. citratus for the first time.

The relationship between within-day drinking occasion and intake amount of water of primary and middle school students in four cities of China / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the number of drinking occasions per day and average amount consumed per drinking occasion of primary and middle school students in four cities of China, and understand the relationship among drinking occasion, average amount consumed per drinking occasion and total drinking water.</p><p><b>METHODS</b>A total of 5914 primary and middle school students from Beijing, Shanghai, Guangzhou and Chengdu were selected using multiple-stage random sampling method, and 5868 students completed the study from September to October in 2011. The detailed information of amounts and types of daily drinking water was recorded by subjects using a 24 hours measurement for seven consecutive days. Analysis of the relationship among drinking occasion, average amount consumed per drinking occasion and total drinking water was carried out.</p><p><b>RESULTS</b>The daily total drinking water of subjects was (1089 ± 540) ml; the daily number of drinking occasions was (4.7 ± 1.8) times, with 79.1% (4639/5868) of subjects reporting 6 or less drinking occasions. The amount consumed per drinking occasion was (239 ± 96) ml, plain water (231 ± 112) ml, and beverages (237 ± 112) ml. The number of drinking occasions of subjects was positively correlated with total drinking water (r = 0.614, P < 0.05), and negatively correlated with the average amount consumed per drinking occasion (r = -0.211, P < 0.05). Total drinking water and the average amount consumed per drinking occasion was positively correlated (r = 0.598, P < 0.05).</p><p><b>CONCLUSION</b>The number of drinking occasion of primary and middle school students more than 6 times was fewer in four cities of China, but the average amount of beverages consumed per drinking occasion was relatively more. With the increasing of drinking occasion, the average amount consumed per drinking occasion decreased, but total drinking water increased.</p>

The causes, conditions and correlated factors of Keshan disease / 中国地方病学杂志

Objective To explore the cause and epidemiologic characteristics of Keshan disease.Methods The cases observation method,epidemiologic methods,fungus-mycotoxin methods and the analytic chemistry methods were used in our studies.Results From the year 1973-1975,in serious endemic areas,fifteen families and one disease outbreak village were investigated,it was found that all patients and his family members had eaten a vast amount of mould millet or maize 4-12 months before onset of the disease; the millet samples collected from endemic areas were cultured and they werc found to be polluted mainly by fungus(20％ of all),the toxin was citreoviridin(CIT).The cause factor of Keshan disease entered into human body through grain but not drinking water,and the transmitting effect was not different with different grains,millet and maize transmit but wheat did not;according to data of endemic disease inspection,after 1990 no new cases of Keshan disease had been reported in the country,at the same time the CIT content in grain produced in endemic areas did not reduced so quickly.However,after 1983,the reform of agriculture promoted significantly the hygienic quality of grain which was considered to be a specific cause for the decreasing of Keshan disease threatening; Keshan disease was distributed on the narrow-long areas from Yunnan till Heilongjiang.These areas were the connection parts,between the cold west north high lands and the warm-moist east-south flatlands,a narrow-long region.The year mean temperature and humidity in endemic areas might be suitable for growing of fungus and production of its toxin ; of animal experiment,rats were feed with CIT contaminated grain every day 4 mg/kg(body weight) for 4-6 weeks,the necrosis of myocardium and cell mitochondria swelling,proliferation and damage were found,just like what had been seen in died cases of Keshan disease.Conclusions The cause of Keshan disease is CIT toxin,the endemic conditions are geographic climate suitable for growing of fungus and production of its toxin and bad hygienic situation of grain storage.Some discussion about the prevention mcthod was proceeding.

Studies on chemical constituents from Davidia involucrata var. vilmoriniana / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of Davidia involucrata var. vilmoriniana.</p><p><b>METHOD</b>The chemical constituents were isolated by column chromatography on silical gel and sephadex LH -20. Their structures were elucidated on the basis of spectral analysis and physical constants.</p><p><b>RESULT</b>Seven compounds were isolated from this plant and the structures of them were identified as 3, 4, 5-trihydroxybenzoic acid (1), ellagic acid (2), maleic acid (3), quercetin (4), quercetin-3-O-beta-D-galactoside (5), 2alpha, 3alpha, 19alpha, 23-tetrahydroxyurs-12-en-28-oic-acid-28-O-beta-D-glucopyranosyl ester (6), ethyl brevifolin carbosylate (7), respectively.</p><p><b>CONCLUSION</b>Compounds 1-7 were isolated from this plant for the first time.</p>

Syntenin: a novel PDZ domain-containing scaffolding protein associated with human melanoma metastasis / 中南大学学报(医学版)

Syntenin is overexpressed in multiple human cancers and is newly recognized as a novel regulator in melanoma metastasis. It functions as a scaffolding protein, via its two PDZ domains interacting with multiple transmembrane and cytoplasmic partners to regulate many of the major signaling pathways involved in various cellular processes, such as cell surface receptor clustering, protein trafficking, cytoskeleton remodeling, and activation of transcription factor, and results in the increased abilities for tumor cell growth, adhesion, angiogenesis, invasion and metastasis. The present article attempts to review the structure and functions of syntenin by summarizing our current knowledge on the interacting partners and diverse signaling pathways related to syntenin, and highlight the importance of syntenin as a new potential therapeutic target for the aggressive human melanoma.

Studies on chemical constituents of Artemisia rupestris (II) / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of Artemisia rupestris.</p><p><b>METHOD</b>The chemical constituents were isolated by column chromatography on silica gel, polyamide and Sephadex LH-20. Their structures were elucidated on the basis of spectral analysis.</p><p><b>RESULT</b>11 compounds have isolated from this plant, and the structure of them have identified as robinin (1), quercetin (2), linearin (3), luteolin (4), sucrose (5), tilianin (6), luteolin-7-glucoside (7), beta-D-3'-methoxy-4'-O-P-coumaroylglucoside (8), hirsutine (9), 3-(4-methoxy phenyl)-(E)-2-propenoic acid ethyl ester (10), rutin (11).</p><p><b>CONCLUSION</b>All this compounds have been isolated from this plant for the first time.</p>

The incidence of dementia among elderly people in Xi' an, China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the incidence of dementia among elderly people in Xi'an and its related risk factors.</p><p><b>METHODS</b>Subjects that had been studied on the prevalence of dementia were follow-up, and the incidence of dementia, Alzheimer disease (AD) , and vascular dementia (VD) were counted by person-years. The clinical diagnosis on dementia,AD and VD were based upon the 3rd Edition of Diagnostic and Statistical of Manual of Mental Disorder, Revised version (DSM-III-R) and NINCDS-ADRDA criteria.</p><p><b>RESULTS</b>2197 subjects of non-dementia being identified in 1998, were re-surveyed in 2001. Out of them, 47 new cases of dementia including 37 cases of AD and 8 cases of VD were identified, with an annual incidence rates of dementia, AD and VD as 0.68%, 0.54% and 0.12% among those of 55 years and over and 0.89%, 0.69% and 0.17% in 65 years and over, respectively. Analysis from single factor logistic regression showed that age and education but not gender were closely related to the occurrence of AD. On the contrary, age, hypertension and stroke were closely related to the occurrence of VD.</p><p><b>CONCLUSION</b>The incidence of dementia in the "Xi' an cohort" was similar to that being reported from other countries. AD and VD were an age-related diseases but education seemed to have had great protective effect while lack of formal education served as risk factor to AD.</p>

Clinical analysis of badly necrotic pyogenic infection in cervical part with pneumatosis of vomica / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To analyze the clinical character, diagnosis and treatment of badly necrotic pyogenic infection in cervical part with pneumatosis of vomica.</p><p><b>METHODS</b>The clinical character, diagnosis and treatment of badly necrotic pyogenic infection in cervical part with pneumatosis of vomica of 46 cases were investigated retrospectively.</p><p><b>RESULTS</b>Lateral and bilateral neck infection cases were 38 and 8 respectively. 30 cases formed primary pyogenic infection in cervical part with pneumatosis of vomica, and 16 did from adjacent sites. Besides the characters of the acute infection, gas storage in deep cervical part abscess was notable. CT and B Ultrasonic examination provided useful informations such as sizes, shapes, capacity, extents of abscess and the relationship between the abscess and vessel or vital organ. Diagnosis puncture and germiculture were performed before and after operation. The results showed that 25 of 46 cases were infected by staphylococcus or streptococcus, and 21 cases did by other bacterium. Exploration and drainage treatments were performed. All cases were cured except 2 died.</p><p><b>CONCLUSION</b>Diagnostic puncture, CT and/or B Ultrasonic examination are essential for diagnosis and presurgical planning. Germiculture provides reliable evidence for finding pathogeny and therapy. The most possibilities of pyogenic infection with pneumatosis of vomica in cervical part are the action of aerogenic bacterium, infection both in cervical part and chest or swallowing movement of pharynx.</p>

The management of thyroid well-differentiated carcinoma invading the upper aerodigestive tract / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the management and prognosis of thyroid well-differentiated carcinoma invading the upper aerodigestive tract.</p><p><b>METHODS</b>A retrospective analysis of the management was performed done 62 patients with thyroid well-differentiated carcinoma invading the upper aerodigestive tract. The main method of surgery was shaving excision, and the other means including partial thyrochondrectomy, total laryngectomy, sleeve tracheal resection, sternocleidomastoid myoperiosteal flap and myodermal flap reconstruction, or simply palliative excision. Some patients received postoperative radioactive isotope therapy and radiotherapy. All patients were followed-up for 2 to 15 years with an average of 6.5 years.</p><p><b>RESULTS</b>The best curative effect was proved in the patients with local invasion, with the lumen uninvolved and their locoregional control rate was 100.0% (17/17). And the second choice was in patients with more extensive involvement of the upper aerodigestive tract structures. For them, extensive surgical management was done attempting to remove all gross disease followed by reconstruction, their locoregional control rate was 87.5% (7/8). And the third place was designated to patients with local invasion for which shaving excision was performed even though minor residual disease was left, their locoregional control rate was 55.6% (5/9). The poorest result went to simple palliative excision. For 17 patients with minor residual tumor, the locoregional control rate of those who were given postoperative radioactive isotope therapy was significantly higher than those without.</p><p><b>CONCLUSION</b>According to the limits and degree of invasion in the upper aerodigestive tract by thyroid well-differentiated carcinoma, different ways of surgery is indicated. For patients with residual disease, radioactive isotope therapy should be used to improve the result and life quality. Advanced lesions should be given postoperative radio therapy.</p>