Effects of Buyang Huanwu Decoction on Intestinal Barrier, Intestinal Flora, and Trimethylamine Oxide in Rats with Heart Failure / 中国结合医学杂志

OBJECTIVE@#To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects.@*METHODS@#Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*RESULTS@#In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05).@*CONCLUSION@#BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.

Bioactive neolignans and lignans from the roots of Paeonia lactiflora / 中国天然药物

Two new neolignans and one new lignan (1-3) were obtained from the roots of Paeonia lactiflora. Their structures were unambiguously elucidated based on extensive spectroscopic analysis, single-crystal X-ray crystallography, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 was a racemic mixture and successfully resolved into the anticipated enantiomers via chiral-phase HPLC. Compound 3 demonstrated moderate inhibitory activity against human carboxylesterase 2A1 (hCES2A1) with an IC50 value of 7.28 ± 0.94 μmol·-1.

Anti-anaphylactic potential of benzoylpaeoniflorin through inhibiting HDC and MAPKs from Paeonia lactiflora / 中国天然药物

Guided by cell-based anti-anaphylactic assay, eighteen cage-like monoterpenoid glycosides (1-18) were obtained from the bioactive fraction of P. lactiflora extract. Among these, compounds 1, 5, 6, 11, 12, 15, and 17 significantly reduced the release rate of β-HEX and HIS without or with less cytotoxicity. Furthermore, the most potent inhibitor benzoylpaeoniflorin (5) was selected as the prioritized compound for the study of action of mechanism, and its anti-anaphylactic activity was medicated by dual-inhibiting HDC and MAPK signal pathway. Moreover, molecular docking simulation explained that benzoylpaeoniflorin (5) blocked the conversion of L-histidine to HIS by occupying the HDC active site. Finally, in vivo on PCA using BALB/c mice, benzoylpaeoniflorin (5) suppressed the IgE-mediated PCA reaction in antigen-challenged mice. These findings indicated that cage-like monoterpenoid glycosides, especially benzoylpaeoniflorin (5), mainly contribute to the anti-anaphylactic activity of P. lactiflora by dual-inhibiting HDC and MAPK signal pathway. Therefore, benzoylpaeoniflorin (5) may be considered as a novel drug candidate for the treatment of anaphylactic diseases.

Construction and application of pharmacophore model of human carboxylesterase 2 inhibitors / 中国中药杂志

According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 μmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.

A new lignan glucoside from root of Paeonia lactiflora / 中国中药杂志

A new lignan glucoside,(+)-fragransin A_2-4-O-β-D-glucopyranoside(1), has been isolated from the dry root of Paeonia lactiflora by column chromatography on silica gel, Sephadex LH-20, and MCI-gel resin, as well as preparative RP-HPLC. The structure of the new compound was elucidated by spectroscopic data analysis(MS, UV, IR, CD, 1 D and 2 D NMR) and chemical method. Compound 1 showed moderate inhibition against lipopolysaccharide induced nitric oxide production in RAW264.7 macrophages, with an IC_(50) value of 21.3 μmol·L~(-1).

Discovery of cytochrome P450 enzymes-inhibiting components in traditional Chinese medicine / 中国中药杂志

With the widespread use of traditional Chinese medicine(TCM) and the integration of TCM and western medicine, drug-drug interaction(DDI) is considered as a major cause of therapeutic failures and side effects. Cytochrome P450 enzymes(CYPs) are responsible for large number of drug metabolism. CYP3 A4 and CYP2 D6, two important CYP isoforms, are responsible for about 80% drug metabolism of CYPs super family. The inhibition of CYPs is likely to be the most common factor leading to adverse DDI. Therefore, it is of great significance to predict potential CYP3 A4 and CYP2 D6 inhibitors to prevent the DDI. A fast and low-cost me-thod for calculating and predicting CYP inhibiting components was established in this paper, namely support vector machine(SVM) and molecular docking technology which are used to predict and screen drugs. Firstly, 12 qualitative models of two targets were established by using SVM, and the optimal model was selected to predict the compounds in traditional Chinese medicine database(TCMD). Then, molecular docking technology was used to establish docking model. By analyzing the key amino acids involved in drug-target interactions and combining with SVM model, potential inhibitors of CYP3 A4 and CYP2 D6 were found. From the computational results, astin D and epiberberine exhibited inhibition effect on CYP3 A4 and CYP2 D6, respectively. Astin D was only found in astins family from Aster tataricus, while epiberberine was considered to be the active constituent of Coptidis Rhizoma. Therefore, for the risk of DDI, extra attention should be paid to the source of these potential inhibitors, Asteris Radix et Rhizoma and Coptidis Rhizoma. This computational method provides technical support for discovering potential natural inhibitors of CYPs from Chinese herbs by using SVM and molecular docking model, and it is also helpful to recognize the CYPs-mediated DDI existing in TCM, providing research ideas for further pharmacovigilance of integrated therapy.

Three new polyoxygenated bergamotanes from the endophytic fungus Penicillium purpurogenum IMM 003 and their inhibitory activity against pancreatic lipase / 中国天然药物

Purpurolides D-F (1-3), three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system, were isolated from the endophytic fungus Penicillium purpurogenum IMM 003. Their structures were unambiguously elucidated based on extensive spectroscopic data analyses, C NMR chemical shifts calculations coupled with the DP4+ probability method, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 1-3 showed significant inhibitory activity against pancreatic lipase (PL). The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.

Changes in autophagy during maturation and differentiation of Hepa1-6 cells induced by all-trans retinoic acid / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of different concentrations of all-trans retinoic acid (ATRA) on the maturation, differentiation and autophagy of Hepa1-6 cells.</p><p><b>MONTHOD</b>Hepa1-6 cells were treated with 0.1, 1, and 10 µmol/L ATRA, and the changes in the expressions of hepatic specific markers were detected using real-time PCR and Western blotting. Indocyanine green (ICG) and periodic acid-schiff (PAS) staining was used to assess the functional maturation of Hepa1-6 cells, and the cell-cell junction and autophagy were observed under transmission electron microscopy to determine the optimal concentration of ATRA for treatment. The expressions of autophagy-related markers in the cells were detected using Western blotting, and confocal microscopy was used to observe the autophagic flow in the cells transfected with ptfLC3 plasmid.</p><p><b>RESULTS</b>Compared with the control cells, the hepatocytes treated with ATRA showed a concentration-dependent decrease in AFP expression and increase in the expressions of ALB, CK18, TAT and ApoB. ICG and PAS staining revealed significantly increased number of positive cells after ATRA treatment. Following ATRA treatment, the cells exhibited obviously increased tight junctions, cytoskeleton and number of autophagosomes under transmission electron microscopy. ATRA treatment resulted in significantly increased the expressions of autophagy-related markers LC3-II, Beclin-1, RAB7 and P62 and also an increased ratio of LC3-II/LC3-I(P<0.05). Confocal microscopy revealed obviously increased green and red spots in the cells after ATRA treatment.</p><p><b>CONCLUSION</b>ATRA can induce the maturation and differentiation and enhance the level of autophagy in Hepa1-6 cells.</p>

Study on structural conversion of dihydrochelerythrine in different solvents / 中国中药杂志

Dihydrochelerythrine was isolated from the ethanol extract of Corydalis yanhusuo by chromatographic and recrystallization techniques. To our knowledge, this is the first report that dihydrochelerythrine was found to be unstable. The NMR, HPLC, and LC-MS were applied to monitor the structural conversion process of dihydrochelerythrine. The results showed that when dissolved in polar deuteration solvent (e.g., DMSO-₆ & MeOD), dihydrochelerythrine is directly converted to chelerythrine gradually. However, if used non-polar reagent (e.g.,CD₂Cl₂), the sample of dihydrochelerythrine undergoes the formation of pseudobase, chelerythrine, and bimolecular ether then followed by oxidation to oxychelerythrine as the major final product. Which leads to this phenomenon maybe is that the C-6 in dihydrochelerythrine is highly reactive to nucleophiles, and is easily converted to different derivatives in different solvents attributed to the solvent effect. This finding will contribute to the extraction and isolation, bioactivity screening, and quality evaluation of medicinal materials containing dihydrochelerythrine and other similar derivatives.

Chemical constituents from water-soluble extract of dry roots of Paeonia lactiflora / 中国中药杂志

Nineteen compounds were isolated from the water-soluble extract of the dry roots of Paeonia lactiflora by using various chromatographic techniques. Their structures were identified by MS， NMR and other spectroscopic analysis as paeoniflorin(1)， 4--ethylpaeoniflorin(2)， 2'--benzoylpaeoniflorin(3)， benzoylpaeoniflorin(4)， 4"-hydroxy-benzoyloxypaeoniflorin(5)， moudanpioside C(6)， 6'--benzoyl-4"-hydroxy-3"-methoxy-paeoniflorin(7)， paeoniflorin B(8)， 6--benzoylalbiflorin(9)， secoisolariciresinol (10)， (+)-lyoniresinol(11)， dihyrodehydrodiconiferyl alcohol(12)， ()-threo-7，9，9'-trihydroxy-3，3'-dimethoxy-8--4'-neolignan(13)， (+)-neo-olivil (14)， [()-5-methyl-2，3-dihydro-1-benzofuran-3-yl]methanol(15)， 5-hydroxy--hydroxymethyl-6-methyl-2，3-dihydrobenzofuran(16)， (+)-()-2-hydroxy-1-(4-methoxyphenyl)-1-propan-1-one(17)， (+)-(2)-1-(4-hydroxy-3-methoxyphenyl)-2-propanol(18)， (+)-()-()-4-hydroxy-2-nonenoic acid(19). Compounds 15 and 18 are new natural products， while compounds 10， 11， 13， 14， 17 and 19 are isolated from the genus Paeonia for the first time.

Chemical constituents from Fusarium redolens, the endophytic fungus from Edgeworthia chrysantha / 药学学报

A new phomapyrone derivative (1), and 9 known compounds were isolated from the ethyl acetate fraction of solid fermentation of Fusarium redolens, the endophytic fungus from Edgeworthia chrysantha, by using various isolation techniques such as Sephadex LH-20, MCI GEL and Semi pre-HPLC, etc. Their structures were identified by spectroscopic analysis, including MS, UV, CD, specific rotation, IR, 1D and 2D NMR, as (+)-7S-4-deoxy-9-hydroxyphomapyrone C (1), uracil (2), uridine (3), 2'-deoxyuridine (4), adenosine (5), 2'-deoxyadenosine (6), cordysinin B (7), ergosterol (8), ergosta-5α, 8β-epidioxy-6, 22-dien-3β-ol (9), and (22E, 24S)-3α-hydroxy-24-methylcholesta-5, 8, 22-trien-7-one (10).

Application of support vector machine approach in studying nephron toxicity of Chinese medicinal materials / 中国中药杂志

On the basis of web databases, 111 compounds with nephrotoxicity and 90 compounds without nephrotoxicity were collected as data set of nephrotoxicity discrimination model, 39 compounds with tubular necrosis and 39 compounds without tubular necrosis were collected as data set of tubular necrosis discrimination model. The 6 122 molecular descriptors, including physicochemical, charge distribution and geometrical descriptors were calculated to characterize the molecular structure of the above-mentioned compounds. CfsSubsetEval valuation method and BestFirst-D1-N5 searching method were used to select molecular descriptors. Two models with high accuracy were built based on the support vector machine (SVM) approach, respectively. Accuracy, sensitivity, specificity and matthew's correlation coefficient of the two models were all above 70%. By using 22 nephrotoxicity compounds of Chinese medicine, the nephrotoxicity discrimination model was further verified with an accuracy of 72.73%. Using the tubular necrosis discrimination model, 10 potential compounds which can cause tubular necrosis were screened from the positive results of nephrotoxicity discrimination model, 6 of them have been verified by literatures. The results demonstrated that the discrimination models can be applied to screen nephrotoxic compounds from Chinese medicinal materials, and they also offer a new research idea for the further studies on the mechanism of nephrotoxicity.

Application of support vector machine in screening neurotoxic compounds from traditional Chinese medicine / 中国中药杂志

In this study, based on web database, 324 neurotoxic compounds and 234 non-neurotoxic compounds were selected as a data set for neurotoxicity discriminative model. 6 122 molecular descriptors, including charge distribution, physicochemical and geometrical descriptors,were calculated to characterize the molecular structure of neurotoxic compounds. The combination of Cfs Subset Evaluation and Best First-D1-N5 searching was used to select molecular descriptors. A discrimination model with high accuracy was built based on the support vector machine (SVM) approach. Meanwhile, the model accuracy, sensitivity and specificity were all above 80%. Besides, 30 traditional Chinese medicine compositions with neurotoxicity were set as external validation to further verify the model accuracy,with anaccuracy of 73.333%. Using the model, 13 potential neurotoxic compounds were screened from Sophorae subprostrate Radix,4 of them were verified by literatures. The results demonstrated that the discrimination model can be applied to screen neurotoxic compounds from Chinese medicinal materials.

Subcutaneous implantation of tissue-engineered heart valve leaflets in nude mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the viability of tissue-engineered heart valve leaflets prepared with cell-polymer constructs in nude mice.</p><p><b>METHODS</b>Sheep endothelial cells and smooth muscle cells/fibroblasts were seeded on patches of PHA and implanted subcutaneously in athymic mice (BALB/C). The cell-polymer constructs were harvested 12, 14, 21 and 28 days after implantation.</p><p><b>RESULTS</b>Fourteen days after implantation, the cell-polymer constructs exhibited similar color with the autologous tissues, and HE staining showed more numerous cells in the implant. At 28 days following implantation, muscular fibers were formed in the cell-polymer constructs. V-G staining showed positive collagen staining in the implant at 12 days after implantation, while the control implants retrieved 28 days after implantation did not show extensive tissue formation or muscular fiber formation.</p><p><b>CONCLUSION</b>The cell-polymer constructs can survive in vivo and has the potential to grow into autologous valve leaflets in the nude mice.</p>

Clinical analysis of gastrointestinal bleeding after cardiac surgery / 中华外科杂志

<p><b>OBJECTIVE</b>To explore early diagnosis, treatment and prevention of gastrointestinal (GI) bleeding after cardiac surgery.</p><p><b>METHODS</b>In the last 13 years, cases complicated with GI bleeding after cardiac surgeries were analyzed retrospectively.</p><p><b>RESULTS</b>Fourty-four GI bleeding occurred post-operatively in (6 +/- 3) d. The mortality was 23% (10/44). Thirty-eight were located in upper GI tract, of them 26 underwent conservative therapy while 4 died of other than GI bleeding cause; six underwent laparotomy while 1 and 3 died of septicemia and multi-organ failure respectively; six underwent gastric endoscopic hemostasis by electrocautery or clipping the bleeding vessel while all survived. Six were located in lower GI tract, and 2 of them underwent laparotomy without finding bleeding section and died of multi-organ failure. By multivariable logistic regression analysis, deaths were highly related to the post-operative ventilator-dependence, acute renal insufficiency, intra-aortic balloon pump (IABP) assisting and laparotomy.</p><p><b>CONCLUSION</b>The mortality of GI bleeding after cardiac surgeries is very high, early gastrointestinal endoscopic examination and minimally invasive intervention can treat this complication more effectively. GI bleeding must be prevented whenever complicating post-operative ventilator-dependence, acute renal insufficiency, and IABP assisting after cardiac surgery.</p>