Construction of photo-induced zinc-doped carbon dots based on drug-resistant bactericides and their application for local treatment.

In this project, we propose a highly effective photosensitizer that breaks through drug-resistant bacterial infections with zinc-doped carbon dots. By passing through the membrane of drug-resistant bacteria, the photosensitizers produce ROS in bacteria under the action of blue light to directly kill bacteria, so as to realize the antibacterial local treatment of drug-resistant bacteria. The experiment firstly uses an efficient one-step hydrothermal method to prepare zinc-doped red-light CDs as photosensitizers, in which zinc metal was doped to improve the optical properties of the CDs. Then we try first to use EDTA as a second-step attenuator for preparing CDs to obtain photosensitizers with high-efficiency and low toxicity. In vitro cytotoxicity tests, bacterial effect tests, and in vivo animal experiments have also demonstrated that this antibacterial method has great potential for clinical translation, with a bactericidal efficiency of up to 90%. More notably, we used this antibacterial regimen seven times repeatedly to simulate the bacterial resistance process, with a bactericidal efficiency of up to 90% every time. The result indicated that S. aureus did not develop resistance to our method, showing that our method has the potential to break through drug-resistant bacterial infections as an alternative to antibiotic candidates.

ß-Cyclodextrin and diatomite immobilized in sodium alginate biosorbent for selective uranium(VI) adsorption in aqueous solution.

The separation and enrichment of uranium from various resources such as seawater is of great significance to the sustainable development of nuclear energy. Therefore, there is an urgent need to develop an adsorbent with low cost and easy availability, simple preparation process, and environment friendly. In this work, we used inexpensive natural polymer material (sodium alginate) and natural adsorbents (ß-cyclodextrin and diatomite) to prepare a novel biosorbent ß-cyclodextrin/sodium alginate/diatomite (CSD) hydrogel beads for uranium adsorption by a simple method. The results of FTIR, XRD, SEM, EDX and XPS characterization proved that the CSD were prepared. Static adsorption experiments showed that pH, contact time, initial concentration of U(VI) and temperature has significant impact on the adsorption capacity of CSD. Adsorption fitted the pseudo-second-order kinetic model and Langmuir model and the adsorption mechanism is chemical adsorption. In the presence of other metal ions (Cu2+, Mg2+, Ca2+, Na+, K+), CSD has obvious selectivity for uranium(VI) adsorption. In addition, the elution and reusability studies show that CSD has excellent reusability. Overall, CSD is an inexpensive, green preparation, efficient, and environment friendly biosorbent with obvious selectivity for U(VI). It has potential application in U(VI) enrichment from seawater or salt lake water.

Serum short-chain fatty acids and its correlation with motor and non-motor symptoms in Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) is associated with enteric nervous system dysfunction and gut microbiota dysbiosis. Short-chain fatty acids (SCFAs), derived from gut microbiota, are supposed to anticipate PD pathogenesis via the pathway of spinal cord and vagal nerve or the circulatory system. However, the serum concentration of SCFAs in PD patients is poorly known. This study aims to investigate the exact level of SCFAs in PD patients and its correlation with Parkinson's symptoms. METHODS: 50 PD patients and 50 healthy controls were recruited, and their demographic and clinical characteristics were collected. The serum concentration of SCFAs was detected using a gas chromatography-mass spectrometer. SCFAs were compared between PD and control groups. The correlation between serum SCFAs and Parkinson's symptoms and the potential effects of medications on the serum SCFAs was analyzed. RESULTS: Serum propionic acid, butyric acid and caproic acid were lower, while heptanoic acid was higher in PD patients than in control subjects. However, only the serum level of propionic acid was correlated with Unified Parkinson's Disease Rating Scale (UPDRs) part III score (R = -0.365, P = 0.009), Mini-mental State Examination (MMSE) score (R = -0.416, P = 0.003), and Hamilton Depression Scale (HAMD) score (R = 0.306, P = 0.03). There was no correlation between other serum SCFAs and motor complications. The use of trihexyphenidyl or tizanidine increased the serum concentration of propionic acid. CONCLUSIONS: Serum SCFAs are altered in PD patients, and the decrease of serum propionic acid level is correlated with motor symptoms, cognitive ability and non-depressed state. Thus, the gut microbial-derived SCFAs potentially affect Parkinson's symptoms through the blood circulation. Propionic acid supplementation might ameliorate motor and non-motor symptoms of PD patients, although clinical trials are needed to test this hypothesis.

miR-34a-5p suppresses the invasion and metastasis of liver cancer by targeting the transcription factor YY1 to mediate MYCT1 upregulation.

BACKGROUND: In recent years, microRNAs (miRNAs) are reported to act as molecular biomarkers for cancer diagnosis, treatment, and prognosis (including liver cancer) and to be involved in the development and progression of cancer and other physiological and pathological changes. However, the role of miR-34a-5p in liver cancer is still largely unknown. METHODS: In our study, the expression of miR-34a-5p in liver cancer tissues and HCC cell lines was detected by qRT-PCR. The CCK-8, scratch wound-healing motility and Transwell assays were used to evaluate the effect on cell proliferation, migration and invasion. The expression of YY1, E-cadherin, N-cadherin and vimentin was analysed by western blotting. The dual luciferase assay was performed to confirm whether YY1 is a target of miR-34a-5p. The combination of YY1 and MYCT1 was detected by chromatin immunoprecipitation (ChIP) assay. RESULTS: The results showed that miR-34a-5p was downregulated in liver cancer tissues and HCC cell lines. Overexpression of miR-34a-5p inhibited the proliferation, migration and invasion of liver cancer cells. YY1 was a direct target of miR-34a-5p, and the expression of YY1 could reverse the influence of miR-34a-5p on the proliferation, migration and invasion of liver cancer cells. YY1 inhibited MYCT1 expression by directly binding to its promoter region, and knockdown of MYCT1 reversed the influence of miR-34a-5p on the proliferation, migration and invasion of liver cancer cells. CONCLUSION: Our results suggest that miR-34a-5p could inhibit the invasion and metastasis of hepatoma cells by targeting YY1-mediated MYCT1 transcriptional repression.

A pharmacokinetics study of orally administered higenamine in rats using LC-MS/MS for doping control analysis.

According to WADA guidelines, the presence of Higenamine (HG) in urine should not be ≥10 ng/mL. HG is widely found in materials used in Chinese herbal medicines as well as food and additives. This paper is the first method wherein a rat model has been used to evaluate the pharmacokinetics of orally administered HG by LC-MS/MS and would be helpful in doping control analysis. The method was found to be linear over a concentration range of 0.5(lower limit of quantification, LLOQ)-500 ng/mL for plasma and 0.5(LLOQ)-1000 ng/mL for urine. The values for intra- and inter-day accuracy and precision did not deviate by >12.25% for HG in plasma and 5.87% in urine. Extraction recoveries of HG were 70.30-86.71% from plasma and 74.93%-79.29% from urine. HG was stable in plasma and urine after the extraction process and when exposed to different storage conditions. The findings of this study could provide some reference value for the assessment of HG misuse and for the control of intake and external application of HG-related materials (foods and medicinal herbs). Our key findings are that high levels of external application or oral administration of HG-rich materials may lead to a positive urine test for HG in athletes.

[Determination of 63 compounds illegally added in tea, substitute tea and beverage foods by ultra-high performance liquid chromatography-tandem mass spectrometry].

A method based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of 63 compounds illegally added in tea, substitute tea, and beverage products. The samples were extracted by ultrasonic extraction using methanol, and the analytes were separated on the Thermo Acclaim RSLC C18 chromatographic column (100 mm×2.1 mm, 2.2 µm) by gradient elution using 5 mmol/L ammonium formate solution containing 0.1% (v/v) formic acid and 0.1% (v/v) formic acid acetonitrile as the mobile phase. The electrospray ion source was operated in the positive ion mode using the dynamic multi-reaction monitoring (dMRM) method, and the results were quantified by the external standard method. The correlation coefficients (R2) of the linear calibration curves were greater than 0.99 in the corresponding mass concentration ranges, and the limits of quantification (LOQs) for the analytes were 0.10-2.50 mg/kg. The average recoveries at three spiked levels ranged from 62.4% to 129.4%. The RSDs of the injection precision and the repeatability of samples were in the range 0.3%-9.6% (n=6). Thus, the proposed method is simple, rapid, accurate, reliable, and applicable for the detection of the illegal addition of antipyretic and analgesic affect compounds in tea, substitute tea and beverage food.

Design and Optimization of Sulfone Pyrrolidine Sulfonamide Antagonists of Transient Receptor Potential Vanilloid-4 with in Vivo Activity in a Pulmonary Edema Model.

Pulmonary edema is a common ailment of heart failure patients and has remained an unmet medical need due to dose-limiting side effects associated with current treatments. Preclinical studies in rodents have suggested that inhibition of transient receptor potential vanilloid-4 (TRPV4) cation channels may offer an alternative-and potentially superior-therapy. Efforts directed toward small-molecule antagonists of the TRPV4 receptor have led to the discovery of a novel sulfone pyrrolidine sulfonamide chemotype exemplified by lead compound 6. Design elements toward the optimization of TRPV4 activity, selectivity, and pharmacokinetic properties are described. Activity of leading exemplars 19 and 27 in an in vivo model suggestive of therapeutic potential is highlighted herein.

Graphene oxide encapsulated polyvinyl alcohol/sodium alginate hydrogel microspheres for Cu (II) and U (VI) removal.

In this work, a novel sodium alginate (SA)/polyvinyl alcohol (PVA)/graphene oxide (GO) hydrogel microspheres were prepared by a simple method. Sodium alginate was physically crosslinked by Ca2+; GO was encapsulated into the composite to strengthen the hydrogels; PVA played a significant role in well dispersing of GO in SA. The SA/PVA/GO (SPG) hydrogels were employed as an efficient adsorbent for removal of Cu (II) and U (VI) from aqueous solution. Batch experiments with the subject of the pH, initial metal ion concentration, competing ions and contact time were investigated. Structure characterization was successfully conducted by FTIR, SEM, EDX, BET and XPS. Furthermore, the sorption kinetics of Cu2+ and UO22+ followed pseudo-second order model and exhibited 3-stage intraparticle diffusion model. Equilibrium data were best described by Langmuir model and the obtained maximum adsorption capacities of SPG hydrogel microspheres for Cu2+ and UO22+ were 247.16 and 403.78 mg/g, respectively. The difference in adsorption capacity can be confirmed by the percentage of elements in EDX spectra and the intension of peak of elements in XPS spectra. The SPG sorbent exhibited excellent reusability after 5 adsorption-desorption cycles. All results suggested that the prepared adsorbents could be considered as effective and promising materials for removal of Cu (II) and U (VI) in wastewater.

Enhancement of Wound Healing by the Traditional Chinese Medicine Herbal Mixture Sophora flavescens in a Rat Model of Perianal Ulceration.

BACKGROUND/AIM: Hemorrhoidectomy is often associated with significant postoperative complications that may result in slow wound healing. The traditional Chinese medicine (TCM) compound Sophora flavescens (CSF) has shown efficacy on many inflammatory disorders. The aim of the present study was to examine the efficacy of CSF on wound healing in a rat model of perianal ulceration. MATERIALS AND METHODS: A rat model of perianal ulceration was induced by subcutaneous injection of 75% glacial acetic acid. The animals with induced perianal ulcer received topical treatment of low, medium, and high doses of CFS twice daily. Potassium permanganate (PP); 0.02%) was given to the animals for comparison. Macroscopic and histological assessments of the ulcerated area were performed after treatment. The expression of pro-inflammatory cytokines prostaglandin E2 (PGE2) and interleukin-8 (IL-8) was detected by immunohistochemical analysis. RESULTS: Topical administration of medium- and high-dose CSF significantly enhanced perianal ulcer healing as compared to the untreated control (p<0.05). The macroscopic ulceration score was significantly reduced only in the high-dose CSF-treated group as compared to the control (p<0.01). All doses of CSF and PP ameliorated histological damages in the rats with induced perianal ulceration. High-dose CSF or PP significantly reduced the expression of PGE2 and IL-8 as compared to the control (p<0.01). No treatment-related toxicity was found in either the CSF- or the PP-treated mice. CONCLUSION: CSF enhances wound healing in a rat model of perianal ulceration. The inhibitory effect of CSF on pro-inflammatory cytokines PGE2 and IL-8 may be involved in the mechanism of enhanced wound-healing.

Fully-Automated High-Throughput NMR System for Screening of Haploid Kernels of Maize (Corn) by Measurement of Oil Content.

One of the modern crop breeding techniques uses doubled haploid plants that contain an identical pair of chromosomes in order to accelerate the breeding process. Rapid haploid identification method is critical for large-scale selections of double haploids. The conventional methods based on the color of the endosperm and embryo seeds are slow, manual and prone to error. On the other hand, there exists a significant difference between diploid and haploid seeds generated by high oil inducer, which makes it possible to use oil content to identify the haploid. This paper describes a fully-automated high-throughput NMR screening system for maize haploid kernel identification. The system is comprised of a sampler unit to select a single kernel to feed for measurement of NMR and weight, and a kernel sorter to distribute the kernel according to the measurement result. Tests of the system show a consistent accuracy of 94% with an average screening time of 4 seconds per kernel. Field test result is described and the directions for future improvement are discussed.

Therapeutic Efficacy of the Traditional Chinese Medicine Baishaoqiwu on TNBS-induced Colitis is Associated with Down-regulation of the TLR4/MyD88/NF-κB Signaling Pathway.

BACKGROUND/AIM: The traditional Chinese medicine Baishaoqiwu (BSQW) has been previously used to clinically treat inflammatory bowel diseases. However, the mechanisms of it's therapeutic efficacy remain unclear. The aim of this study was to examine the efficacy of BSQW on ulcerative colitis (UC) and the TLR4/MyD88/NF-κB signaling pathway in a rat model of colitis. MATERIALS AND METHODS: The colitis rat model was induced by anal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The animals with induced colitis were treated with BSQW at a dose of 13.2 mg/kg daily, p.o. Mesalazin was used as a positive control and was given to the animals with induced colitis at a dose of 420 mg/kg daily, p.o. The untreated animals with induced colitis and normal animals served as model controls and normal controls, respectively. Macroscopic and histological assessments were performed after treatment. The expression of MyD88, NF-κB P65 and TLR4 were determined by immunohistochemical analysis. RESULTS: Administration of BSQW or Mesalazin ameliorated TNBS-induced macroscopic and histological damage in the rats with induced colitis. The macroscopic score and total colitis index were significantly reduced in the BSQW- and Mesalazin-treated groups compared to the model control group (p<0.05). BSQW or Mesalazin significantly inhibited TNBS-induced expression of the TLR4, MyD88 and NF-κB P65 genes. No treatment-related toxicity was found in either the BSQW- or the Mesalazin-treated groups. CONCLUSION: Suppression of the TLR4/MyD88/NF-κB signaling pathway may be one of the mechanisms involved in the therapeutic efficacy of BSQW against UC.

Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma.

BACKGROUND: Extranodal NK/T-cell lymphoma (ENKL) is an aggressive hematological malignancy associated with Epstein-Barr virus (EBV) infection. It is often resistant to conventional chemotherapy and has a poor prognosis. Icaritin, a compound derived from Chinese herbal medicine, Herba Epimedii, has been reported to exert antitumor effects on a variety of cancer cell lines. In the present study, we investigated the cytotoxic effects of Icaritin on the two EBV-positive ENKL cell lines SNK-10 and SNT-8, along with the underlying molecular mechanisms. METHODS: ENKL cell lines SNK-10 and SNT-8 were exposed to different concentrations of Icaritin for the indicated time. Treated cells were analyzed for cell proliferation, cell cycle, and cell apoptosis. Phosphorylation of Stat3 and Akt proteins in signaling pathways and the EBV-encoded LMP1 proteins were measured by Western blot. Expression of EBV genes was assessed by Real-Time PCR. RESULTS: Our results showed that Icaritin dose-dependently inhibits ENKL cell proliferation and induces apoptosis and cell cycle arrest at G2/M phase. Additionally, Icaritin upregulates Bax, downregulates Bcl-2 and pBad, and activates caspase-3 and caspase-9. The anti-proliferative and pro-apoptotic effects of Icaritin are likely mediated by inhibition of Stat3 and Akt pathways through LMP1 downregulation. Importantly, Icaritin induces EBV lytic gene expression in ENKL cells, and the combination of Icaritin and the antiviral drug ganciclovir (GCV) is more effective in inducing ENKL cells apoptosis than Icaritin or GCV alone. CONCLUSIONS: These findings indicate that EBV-targeted approaches may have significant therapeutic potential for ENKL treatment.

Astragaloside IV ameliorates renal fibrosis via the inhibition of mitogen-activated protein kinases and antiapoptosis in vivo and in vitro.

Apoptosis of renal tubular cells plays a crucial role in renal fibrosis. Astragaloside IV (AS-IV), a compound extracted from Radix Astragali, has been shown to inhibit renal tubular cell apoptosis induced by high glucose, but its role in preventing chronic renal fibrosis as well as the underlying molecular mechanisms involved still remain obscure. In this study, human kidney tubular epithelial cells induced by transforming growth factor-ß1 (TGF-ß1) were used to investigate the protective role of AS-IV in antifibrosis. As an in vivo model, mice subjected to unilateral ureteral obstruction (UUO) were administered AS-IV (20 mg/kg) by intraperitoneal injection for 7 days. AS-IV significantly alleviated renal mass loss and reduced the expression of α-smooth muscle actin, fibronectin, and collagen IV both in vitro and in vivo, suggesting that this compound functions in the inhibition of renal tubulointerstitial fibrosis. Furthermore, transferase-mediated dUTP nick-end labeling assay results both in vivo and in vitro showed that AS-IV significantly attenuated both UUO and TGF-ß1-induced cell apoptosis and prevented renal tubular epithelial cell injury in a dose-dependent manner. Western blotting results also revealed that the antiapoptotic effect of AS-IV was reflected in the inhibition of caspase-3 activation, which might be mediated primarily by the downregulation of mitogen-activated protein kinase effectors phospho-p38 and phospho-c-Jun N-terminal kinase. These data infer that AS-IV effectively attenuates the progression of renal fibrosis after UUO injury and may have a promising clinical role as a potential antifibrosis treatment in patients with chronic kidney disease.

Salvianolic acid B possesses vasodilation potential through NO and its related signals in rabbit thoracic aortic rings.

Salviae miltiorrhizae, a traditional Chinese medicine, is widely used in the treatment of cardiovascular and cerebrovascular diseases. Salvianolic acid B is identified as one of the most important water-soluble active ingredients in Salviae miltiorrhizae and associated with the activation of Ca(2+) channel of cytomembrane. But the further mechanism of action was not very clearly. In our study, we investigated the vasodilation activity of salvianolic acid B using the isolated thoracic aortic rings from Japanese white rabbit. Salvianolic acid B significantly released the contraction of the isolated thoracic aortic rings induced by phenylephrine and CaCl(2) while had no effects on the aortic rings with KCl stimulated. Different with Di-ao-xin-xue-kang capsule, salvianolic acid B caused an increase of Ca(2+) in cytoplasm from not only activation of Ca(2+) channel in cytomembrane but also release of endogenous Ca(2+). Then, a series of endogenous Ca(2+) inhibitors were pretreated to explore the mechanism of salvianolic acid B, and the results provided further evidences that salvianolic acid B causes intracellular calcium release in ryanodine receptors-dependent manners. Moreover, combining l-arginine (l-Arg) with salvianolic acid B promoted the vasodilation activity suggesting a relationship with nitric oxide (NO). To further investigated its mechanism, both guanylate cyclase (GC) inhibitor and NO Synthase inhibitor were used and demonstrated to block vasodilation activity of the aortic rings. Our findings reveal a NO-sGC-cGMP signals dependence mechanism of salvianolic acid B on its vasodilation activity which provide an evidence for its subsequent application in clinic.

The protein kinase SnRK2.6 mediates the regulation of sucrose metabolism and plant growth in Arabidopsis.

In higher plants, three subfamilies of sucrose nonfermenting-1 (Snf1)-related protein kinases have evolved. While the Snf1-related protein kinase 1 (SnRK1) subfamily has been shown to share pivotal roles with the orthologous yeast Snf1 and mammalian AMP-activated protein kinase in modulating energy and metabolic homeostasis, the functional significance of the two plant-specific subfamilies SnRK2 and SnRK3 in these critical processes is poorly understood. We show here that SnRK2.6, previously identified as crucial in the control of stomatal aperture by abscisic acid (ABA), has a broad expression pattern and participates in the regulation of plant primary metabolism. Inactivation of this gene reduced oil synthesis in Arabidopsis (Arabidopsis thaliana) seeds, whereas its overexpression increased Suc synthesis and fatty acid desaturation in the leaves. Notably, the metabolic alterations in the SnRK2.6 overexpressors were accompanied by amelioration of those physiological processes that require high levels of carbon and energy input, such as plant growth and seed production. However, the mechanisms underlying these functionalities could not be solely attributed to the role of SnRK2.6 as a positive regulator of ABA signaling, although we demonstrate that this kinase confers ABA hypersensitivity during seedling growth. Collectively, our results suggest that SnRK2.6 mediates hormonal and metabolic regulation of plant growth and development and that, besides the SnRK1 kinases, SnRK2.6 is also implicated in the regulation of metabolic homeostasis in plants.

[Comprehensive research and evaluation of chlorogenic acid allergy].

OBJECTIVE: The non-allergy of chlorogenic acid was demonstrated by the study result of allergy with different purity of chlorogenic acid and comprehensive analysis of literature. METHOD: The allergies of different samples, which contained the different purity of chlorogenic acid extracts, chlorogenic acid for injection, interior solution of dialysis, external solution of dialysis, post-term chlorogenic acid for injection and chlorogenic acid for injection with degradation, were validated with active systemic anaphylaxis and passive cutaneous anaphylaxis on rats and guinea pigs respectively. The range of molecular weight of macromolecular remains after dialysis were identified by LC-MS. RESULT: Allergic reactions were happened in dialysis isolated macromolecular substances, which were identified by LC-MS, and lower purity extracts (purity of chlorogenic acid < or = 40%), while the reactions were not happened in isolated micromolecular substances and high purity samples (purity of chlorogenic acid > or = 92%). CONCLUSION: Macromolecules in lower purity of chlorogenic acid extracts were relative closely to the allergen causing anaphylaxis, but not the chlorogenic acid, which was demonstrated according to the study result and analysis of literatures home and abroad.

Cost-effectiveness study comparing imatinib with interferon-alpha for patients with newly diagnosed chronic-phase (CP) chronic myeloid leukemia (CML) from the Chinese public health-care system perspective (CPHSP).

OBJECTIVE: Imatinib, a breakthrough oral molecular-targeted therapy, has demonstrated durable responses and significant survival advantage compared with interferon-based treatment. This study compares imatinib with interferon in newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) patients from the Chinese public health-care system perspective (CPHSP). METHODS: One-year cost responder and lifetime cost-utility analyses were conducted, respectively. Complete cytogenetic response was used to define a responder. Direct medical costs were included. Response rates as well as survival estimates were obtained from published literature. RESULTS: The cost per responder for interferon was close to 20 times higher than that for imatinib. The cost per additional responder was RMB36,545. The incremental cost-effectiveness ratio (ICER) comparing imatinib with interferon was RMB73,674 (95% confidence interval RMB67,712-RMB79,637) per quality-adjusted life-year. CONCLUSION: In newly diagnosed CML-CP, the cost per responder for patients treated with imatinib is much lower than that for patients treated with interferon. In the cost-utility analysis, the ICER is below the cost-effectiveness threshold recommended by the World Health Organization for developing countries. Therefore, imatinib is more cost-effective than interferon from the CPHSP.

Development of potent and selective small-molecule human Urotensin-II antagonists.

This work describes the development of potent and selective human Urotensin-II receptor antagonists starting from lead compound 1, (3,4-dichlorophenyl)methyl{2-oxo-2-[3-phenyl-2-(1-pyrrolidinylmethyl)-1-piperidinyl]ethyl}amine. Several problems relating to oral bioavailability, cytochrome P450 inhibition, and off-target activity at the kappa opioid receptor and cardiac sodium channel were addressed during lead development. hUT binding affinity relative to compound 1 was improved by more than 40-fold in some analogs, and a structural modification was identified which significantly attenuated both off-target activities.

[Water-soluble chemical constituents of Swertia davidi Franch].

AIM: To study the active constituents of Swertia davidi Franch. METHODS: Column chromatographies on silica gel, Sephadex LH-20 and Diaion-201 et al. were used to isolate and purify the chemical components. Their structures were identified by UV, IR, MS, NMR and 2D-NMR. RESULTS: These compounds were elucidated as 8-O-beta-D-glucopyranosyl-1, 3, 5-trihydroxyxanthone (I), 5-O-beta-D-glucopyranosyl-1, 8-dihydroxy-3-methoxyxanthone (II), 5-O-beta-D-glucopyranosyl-1, 3, 8-trihydroxyxanthone (III) and swertamarin (IV). CONCLUSION: Compound III is a new xanthone glucoside. The other compounds were isolated from this plant for the first time.

Electrophysiologic effects of SB-237376: a new antiarrhythmic compound with dual potassium and calcium channel blocking action.

Combined potassium and calcium channel blocking activities are suggested to be the basis for antiarrhythmic efficacy with low proarrhythmic risk. The electrophysiologic effects of SB-237376 were investigated in single myocytes and arterially perfused wedge preparations of canine or rabbit left ventricles. The concentration-dependent prolongation of action potential duration (APD) and QT interval by SB-237376 was bell-shaped and the maximum response occurred at 1-3 microM SB-237376 inhibited rapidly activating delayed rectifier K current (I(Kr) ) with an IC50 of 0.42 microM and use-dependently blocked L-type Ca current (I (Ca,L) ) at high concentrations. The SB-237376 (3 microM) induced phase-2 early afterdepolarizations (EADs) in five of six rabbit wedge preparations but none of six canine wedge preparations. This is probably due to larger increases of APD, QT interval, and transmural dispersion of repolarization (TDR) in rabbits than dogs. Based on the drug effects on QT interval, TDR, and EAD in rabbit ventricular wedge preparations, a scoring system predicted lower proarrhythmic risk for SB-237376 than for dl-sotalol, a specific I blocker. In conclusion, SB-237376 increases APD, QT interval, and TDR mainly by I (Kr) inhibition. These effects are self-limited due to SB-237376-induced I(Ca,L) blockade at high concentrations, which may explain its lower proarrhythmic risk than dl-sotalol.