Two new isoquinoline alkaloids from Corydalis hendersonii / 中国中药杂志

Corydalis hendersonii(CH) is a Tibetan folk medicine with the functions of clearing heat, detoxifying, cooling blood, checking diarrhea, and lowering blood pressure. It is often used to treat high altitude polycythemia, vasculitis, peptic ulcer, and diarrhea. Nine compounds were separated from the ethanol extract of CH by silica gel, ODS, Sephadex LH-20 chromatography and semi-preparative HPLC. Their structures were identified as hendersine H(1),hendersine I(2), dehydrocheilanthifoline(3), protopine(4), izmirine(5), 6,7-methylenedioxy-1(2H)-isoquinolinone(6), icariside D_2(7), ethyl 4-(β-D-glucopyranosyloxy)-3-methoxybenzoate(8), 3-hydroxy-4-methoxybenzoic acid(9), respectively, by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 1 and 2 are new isoquinoline alkaloids, and compounds 7-9 are reported the first time for Corydalis. The hypoglycemic model of H9c2 cardiomyocytes and the inflammatory model of H9c2 cardiomyocytes induced by conditional supernatant were employed to determine the activities of the above compounds. The results showed that 20 μmol·L~(-1) compound 1 had a protective effect on H9c2 cardiomyocytes and 10 μmol·L~(-1) compounds 4 and 5 inhibited H9c2 cardiomyocyte inflammation induced by conditional supernatant.

Characterization and identification of alkaloids in Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex based on UHPLC-IM-Q-TOF-MS / 中国中药杂志

A strategy combining collision cross section(CCS) prediction and quantitative structure-retention relationship(QSRR) model for quinoline and isoquinoline alkaloids was established based on UHPLC-IM-Q-TOF-MS and applied to Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex. The strategy included the following three steps.(1) The molecular features were extracted by the "find features" algorithm.(2) The potential quinoline and isoquinoline alkaloids were screened by filtering the original characteristic ions extracted from Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex by the established CCS vs m/z prediction interval.(3) According to the retention time of candidate compounds predicted by QSRR model, the chemical constituents were identified in combination with the characteristic fragment ions and pyrolysis law of secondary mass spectrometry. With the strategy, a total of 80 compounds were predicted, and 15 were identified accurately. The strategy is effective for the identification of small analogs of traditional Chinese medicine.

Research progress on medicinal resources of Coptis and its isoquinoline alkaloids / 中国中药杂志

Coptidis Rhizoma is a common Chinese medicinal in clinical practice,with the effects of clearing heat,drying dampness,purging fire,and removing toxin. All the medicinal plants of Coptis can be used for clinical treatment,but some species are endangered due to resource destruction and difficulty in planting. The dominant medicinal components in Coptidis Rhizoma are isoquinoline alkaloids. There are various methods for the analysis and detection of alkaloids,such as LC-MS,HPLC,and TLC,among which LC-MS is the most widely applied. Different plants of Coptis vary in the kind and content of alkaloids. C. chinensis,C. deltoidea,C. teeta,C. chinensis var. brevisepala,C. omeiensis,C. quinquefolia,and C. quinquesecta mainly contain berberine,palmatine,coptisine,jatrorrhizine,and columbamine,five effective alkaloid components. Plant isoquinoline alkaloids( PIAs) have strong pharmacological activity but are difficult to prepare. The application of synthetic biology of PIAs will be helpful for the clinical application of PIAs. This paper reviews the research progress on biological resources of Coptis species and structures of alkaloids as well as analysis methods and synthetic biology for isoquinoline alkaloids in the medicinal plants of Coptis in recent years,which will facilitate the protection of Coptis medicinal resources and the application and development of alkaloids.

A new antiviral isoquinoline alkaloid from Thalictrum glandulosissimum / 中国中药杂志

A new isoquinoline alkaloid(1) has been isolated from the whole plant of Thalictrum glandulosissimum by using various chromatographic techniques, including silica gel, sephadex, MCI-gel resin, and RP-HPLC, and its structure was determined as 1-(6-hydroxy-7-methylisoquinolin-1-yl) ethantone by physicochemical properties and spectroscopic data. This compound was evaluated for anti-tobacco mosaic virus(TMV) activity. The results showed that it had prominent anti-TMV activity with inhibition rates of 28.4%. This rate was closed to that of positive control.

Daclatasvir Plus Asunaprevir Dual Therapy for Chronic HCV Genotype 1b Infection: Results of Turkish Early Access Program

Abstract: Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. Aim. To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. Material and methods. Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. Results. Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. Conclusions. Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.

Combined therapy with daclatasvir plus asunaprevir for chronic hepatitis C genotype 1b: a case report / 南方医科大学学报

The combination therapy with daclatasvir and asunaprevir can achieve a high sustained viral response rate against hepatitis C virus (HCV) genotype 1, but so far this regimen has not been reported in the treatment of Chinese patients with chronic hepatitis C (CHC) genotype 1b. Here we report a case of CHC genotype 1b in a 44-year-old female chinese patient who was treated with this regimen for 24 weeks. The patient showed sustained viral response after the treatment and was clinically cured. During the treatment, the patient experienced a transient elevation of serum total bilirubin accompanied by lowered hemoglobin fluctuating between 100 and 110 g/L.

Effects 'of β3 adrenoceptors on the contractility of rat thoracic aorta smooth muscle and the mechanism / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effect of β₃adrenoceptors (β₃-AR) activation on rat thoracic aorta smooth muscle contractility and the possible related mechanism.</p><p><b>METHODS</b>The endothelium removed thoracic aorta was pre-contracted with 30 mmol/L KCl physiological saline solution (PSS). Then the tension of the thoracic aorta was recorded in presence of BRL37344 (BRL) to determine the action of β₃-AR. The tension of the thoracic aorta was also recorded in the presence of Propranolol (PRA), SR59230A (SR), L-NNA, H-89 and Iberiotoxin (IBTX) respectively to reveal the underling mechanism of β₃-AR activation on rat vascular smooth muscle. Immunohistochemistry was adopted to confirm the existence and the distribution of β₃-AR in rat thoracic aorta.</p><p><b>RESULTS</b>The results showed that: (1) The thoracic aorta was relaxed by β₃-AR activation, with a relaxation percentage of (10.59 ± 0.79). (2) β₃-AR was expressed in both endothelial and smooth muscle layer in thoracic aorta sections of rats. (3) PRA did not block the effect of BRL on the thoracic aorta. The relaxation actions of BRL could be antagonized by pre-incubating the thoracic aorta with SR. (4) L-NNA (a NOS inhibitor) and H-89 (a PKA inhibitor) reversed the relaxation effect of BRL on vascular smooth muscle. (5) The effect of BRL was decreased after application of Ibriotoxin (IBTX), a large conductance calcium dependent potassium channel blocker.</p><p><b>CONCLUSION</b>The results confirmed that activation of β₃-AR led to relaxation of thoracic aorta smooth muscle. The relaxation action of β₃-AR on smooth muscle of rat thoracic aorta was related to activation of NOS and PKA signaling pathway. Large conductance Ca²⁺-K⁺ channels were involved in the relaxation action of β₃-AR activation on rat thoracic aorta smooth muscle.</p>

Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection

BACKGROUND/AIMS: The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. METHODS: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. RESULTS: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. CONCLUSIONS: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.

Hemodynamic responses during and after multiple sets of stretching exercises performed with and without the Valsalva maneuver

OBJECTIVE: This study investigated the acute hemodynamic responses to multiple sets of passive stretching exercises performed with and without the Valsalva maneuver. METHODS: Fifteen healthy men aged 21 to 29 years with poor flexibility performed stretching protocols comprising 10 sets of maximal passive unilateral hip flexion, sustained for 30 seconds with equal intervals between sets. Protocols without and with the Valsalva maneuver were applied in a random counterbalanced order, separated by 48-hour intervals. Hemodynamic responses were measured by photoplethysmography pre-exercise, during the stretching sets, and post-exercise. RESULTS: The effects of stretching sets on systolic and diastolic blood pressure were cumulative until the fourth set in protocols performed with and without the Valsalva maneuver. The heart rate and rate pressure product increased in both protocols, but no additive effect was observed due to the number of sets. Hemodynamic responses were always higher when stretching was performed with the Valsalva maneuver, causing an additional elevation in the rate pressure product. CONCLUSIONS: Multiple sets of unilateral hip flexion stretching significantly increased blood pressure, heart rate, and rate pressure product values. A cumulative effect of the number of sets occurred only for systolic and diastolic blood pressure, at least in the initial sets of the stretching protocols. The performance of the Valsalva maneuver intensified all hemodynamic responses, which resulted in significant increases in cardiac work during stretching exercises. .

Reversal of stemness in multidrug-resistant hepatocellular carcinoma cells by SIS3 / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate whether SIS3, a specific inhibitor of Smad3 phosphorylation, can reverse the stemness of multidrug-resistant(MDR) hepatocellular carcinoma cells.</p><p><b>METHODS</b>MDR HCC Huh7.5.1/ADM cell lines were developed by exposing parental cells to stepwise increasing concentrations of ADM. CCK-8 assay was used to determine the cellular sensitivity of various anticancer drugs. Flow cytometry (FCM) was used to analyze the expression level of cancer stem cell marker CD133. Clone formation assay and mouse subcutaneous xenograft tumors were used to investigate the tumorigenicity in vitro and in vivo. Western blotting (WB) was used to analyze the changes of expressions of CD133, Smad3, Bcl-2, Bax and p-Smad3 in different conditions.</p><p><b>RESULTS</b>ADM treatment of HCC cells in vitro resulted in a development of subline, Huh7.5.1/ADM cells, with CSC phenotypes: stable MDR phenotype (besides ADMc Huh7.5.1/ADM cells were also more resistant to some other anticancer drugs including VCR, MMC and CTX ) (IC50: 0.215 ± 0.018 vs. 0.123 ± 0.004, 0.145 ± 0.009 vs. 0.014 ± 0.002, 1.021 ± 0.119 vs. 0.071 ± 0.006, 27.007 ± 1.606 vs. 1.919 ± 0.032) (unit: µg/ml) (P<0.05). Huh7.5.1/ADM cells enriched the cancer stem-like cell fraction (CD133-positive subpopulation) (76.06 ± 2.948% vs. 25.38 ± 4.349%) (P<0.05), had stronger tumorigenicity in vivo and colony formation ability, and activated the Smad3 activity. Inhibition of Smad3 activity by SIS3 decreased stemness of the Huh7.5.1/ADM cells: CD133-positive subpopulation (48.49 ± 2.304% vs. 76.06 ± 2.948%) (P<0.05); ADM IC50: (0.112 ± 0.019 vs. 0.215 ± 0.018), VCR IC50 (0.065 ± 0.013 vs. 0.145±0.009), MMC IC₅₀ (0.749 ± 0.121 vs. 1.021 ± 0.119), CTX IC50 (10.576 ± 1.248 vs. 27.007 ± 1.606) (unit: µg/ml) (P<0.05), and decreased tumorigenicity and colony formation ability.</p><p><b>CONCLUSION</b>SIS3 as a specific inhibitor of Smad3 signal is involved in the stemness of multidrug resistant hepatocellular carcinoma cells.</p>

Minimal endoscopic changes in non-erosive reflux disease / Alterações endoscópicas mínimas na doença do refluxo não erosiva

BACKGROUND: Gastroesophageal reflux disease is an increasingly common condition worldwide causing a considerable economic impact. More than half the patients with clinical symptoms of reflux disease display no mucosal erosions on esophagogastroduodenoscopy, making it impossible to confirm the diagnosis without further investigations. AIM: To evaluate the correlation between minimal endoscopic changes on white-light esophagogastroduodenoscopy (carditis, mucosal thickening and invisibility of vessels) and histologic changes observed in distal esophageal biopsies in a sample of patients with symptoms suggestive of reflux disease, and to verify the specificity of these symptoms for non-erosive reflux disease. METHODS: Retrospective, cross-sectional study based on information retrieved from a digital database at a Brazilian hospital for the period March-October, 2012. The sample consisted of previously untreated, non-smoking subjects aged >18 years with symptoms suggestive of reflux disease but no esophageal erosions, submitted to esophagogastroduodenoscopy and distal esophageal biopsy. RESULTS: The final sample included 23 subjects. The most frequently observed change was invisibility of vessels (n=21; 91.3%), followed by mucosal thickening (n=15; 65.2%) and carditis (n=5; 21.7%). The correlation coefficient between each variable and the anatomopathological diagnosis was 0.386 for body mass index, 0.479 for mucosal thickening, -0.116 for invisibility of vessels, 0.306 for carditis and 0.462 for hiatal hernia. CONCLUSION: All patients displayed minimal endoscopic changes on esophagogastroduodenoscopy, but only mucosal thickening revealed a moderately significant correlation with severity of esophagitis, although increased body mass index values and the presence of hiatal hernia were also associated. .

RACIONAL: Doença do refluxo gastroesofágico é condição cada vez mais comum em todo o mundo causando impacto econômico considerável. Mais da metade dos pacientes com sintomas clínicos da doença não apresentam erosões endoscópicas da mucosa, o que torna impossível confirmar o diagnóstico sem outras investigações. OBJETIVO: Avaliar a correlação entre mudanças mínimas endoscópicas em endoscopia digestiva alta de luz branca (cardite, espessamento da mucosa e invisibilidade de vasos) e as alterações histológicas observadas em biópsias distais de uma amostra de pacientes com sintomas sugestivos de doença do refluxo, e para verificar a especificidade desses sintomas para a doença não-erosiva. MÉTODOS: Estudo retrospectivo, transversal, com base em informações obtidas a partir de uma base de dados digital em um hospital brasileiro no período de março/outubro de 2012. A amostra foi composta por indivíduos não tratados previamente, não fumantes, >18 anos, com sintomas sugestivos de doença do refluxo, mas sem erosões esofágicas submetidos à endoscopia digestiva alta e biópsia de esôfago distal. RESULTADOS: A amostra final incluiu 23 indivíduos. A alteração mais frequente foi invisibilidade dos vasos (n=21; 91,3%), seguido por espessamento de mucosa (n=15; 65,2%) e cardite (n=5; 21,7%). O coeficiente de correlação entre cada variável e o diagnóstico anatomopatológico foi 0,386 para o índice de massa corporal, 0,479 para espessamento de mucosa, -0,116 para a invisibilidade de vasos, 0,306 para carditis e 0,462 para hérnia hiatal. CONCLUSÃO: Todos os pacientes apresentaram alterações endoscópicas mínimas, mas apenas espessamento da mucosa revelou correlação moderadamente significativa com a gravidade da esofagite, apesar do aumento dos valores no índice de massa corporal e da presença de hérnia hiatal também estarem associados. .

Chemical constituents of the roots of Macleaya microcarpa and activation efficacy of benzophenanthridine alkaloids for the transcription of xbp1 gene / 药学学报

Ongoing study on the chemical constituents of the roots of Macleaya microcarpa led to the isolation of eight compounds of derivatives of triterpenes and organic acids in addition to some previously identified benzophenanthridines. The eight compounds were identified by spectroscopic methods as well as comparison with literature values as 1-oxo-2, 22 (30)-hopandien-29-oic acid (1), 3-oxo-12-oleanen-30-oic acid (2), 3α-hydroxy-12-oleanen-30-oic acid (3), 3β-hydroxy-12-oleanen-30-oic acid (4), ferulic acid (5), ferulic acid 4-O-β-D-glucoside (6), 3-O-feruloylquinic acid (7), and methyl 3-O-feruloylquinate (8). Of which, 1 is a new triterpenoid of hopanes and 2-8 are isolated from M microcarpa for the first time. In order to discover natural active compounds as potential agents of anti-ulcerative colitis (UC), an in vitro drug high-throughput screening model targeted x-box-binding protein 1 (xbp1) was employed to evaluate the activity of the major chemical constituents of M microcarpa. The result confirmed that two dihydrobenzophenanthridines, dihydrosanguinarine (9) and dihydrochelerythrine (10), showed a certain activity on activating the transcription of xbpl, a transcription factor (TF) associated with the occurrence, development, and potential treatment of UC, with their relative activating ratios being 1.76 and 1.77 times, respectively, as compared with control group.

Palonosetron versus granisetron in combination with aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer / 부인종양

OBJECTIVE: There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. METHODS: We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. RESULTS: When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). CONCLUSION: The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

Metoclopramida e ondansetrona alteram o bloqueio neuromuscular induzido por mivacurio? - um estudo randomizado / Do metoclopramide and ondansetrone alter mivacurium-induced neuromuscular blockade? - a randomised trial / La metoclopramida y la ondansetrona alteran el bloqueo neuromuscular inducido por mivacurio? - un estudio aleatorizado

Experiência: Objetivamos investigar os efeitos de metoclopramida e ondansetrona no bloqueio neuromuscular por mivacúrio. Métodos: Foram incluídos no estudo 75 pacientes ASA I-II, com idades entre 18 e 65 anos e agendados para cirurgia eletiva necessitando de intubação traqueal. Os pacientes receberam metoclopramida 10 mg, ondansetrona 4 mg ou salina normal 5 mL; grupo M, grupo O e grupo SN (n = 25) respectivamente. Antes da anestesia, os medicamentos em estudo foram administrados em um volume de 5 mL. O nível de colinesterase plasmática foram obtidos antes e 5 minutos depois da administração dos medicamentos em estudo e 5 minutos depois da administração de mivacúrio. Os tempos até o início e os níveis T25, T75, T25-75 e T90 foram comparados entre si, tendo sido investigadas as diferenças entre cada paciente. Depois de registrar T90, o estudo foi terminado, tendo início a cirurgia. Resultados: O tempo até o início foi significativamente mais breve no Grupo M versus os outros dois grupos. O tempo até o início no Grupo O foi significativamente mais breve versus grupo SN. No grupo M, T25, T75, T90 e os índices de recuperação foram significativamente maiores versus Grupo NS (p < 0,001). No Grupo O, T25 e T75 foram maiores versus Grupo NS (p < 0,01 e p < 0,05,respectivamente). No Grupo M, T75, T90 e índices de retorno da anestesia foram significativamente maiores versus Grupo O (p < 0,001, p < 0,01, p < 0,001, respectivamente). Nos Grupos M e O, os níveis plasmáticos de colinesterase diminuíram significativamente (p < 0,001). Depois da administração dos medicamentos em estudo e de mivacúrio. Houve também redução na colinesterase plasmática no Grupo NS 5 minutos após a administração de mivacúrio (p < 0,001). ...

Background: We aimed to investigate the effects of metoclopramide and ondansetrone on mivacurium neuromuscular blockade. Methods: Seventy five, ASA I-II patients, aged 18-65 and scheduled for elective surgery requiring tracheal intubation were included in the study. The patients received metoclopramide 10 mg, ondansetrone 4 mg or normal saline 5 mL; group M, group O, group NS (n = 25), respectively. Before anesthesia study drugs were administered in a volume of 5 mL. The level of plasma cholinesterase were obtained before and 5 minutes after the administration of study drugs and5 minutes after the administration of mivacurium. Onset time, T25, T75, T25-75, T90 levelswere compared with each other and differences between each patients were investigated. After recording T90, the study was terminated and surgery was started. Results: Onset time was significantly shorter in group M, than the other two groups. Onset time in group O was significantly shorter than in group NS. In Group M T25, T75, T90 and recovery indices were significantly greater than in Group NS (p < 0.001). In Group O T25, T75 were greater than Group NS (p < 0.01 and p < 0.05, respectively). In Group M T75, T90 and emergence indices were significantly higher than Group O (p < 0.001, p < 0.01, p < 0.001, respectively). In Groups M and O, plasma cholinesterase levels decreased significantly (p < 0.001) after administration of study drugs and mivacurium. Plasma cholinesterase also was reduced in Group NS 5 minutes after the administration of mivacurium (p < 0.001). Conclusion: Ondansetrone is believed to be more reliable agent than metoclopramide when used with mivacurium. .

Derivatization of berberine based on its synergistic antifungal activity with fluconazole against fluconazole-resistant Candida albicans / 药学学报

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.

Isolation of endophytic fungi from Macleaya cordata and screening of sanguinarine-producing strains / 中国中药杂志

Endophytic fungi were isolated from Macleaya cordata growing in Dabie Mountain by agar-block method, and then the endophytic fungi were grouped into different types based on their morphological characteristics, and thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) were employed to determine whether the metabolic substances contained sanguinarine or not, and then preliminarily identified by morphological method. The results showed that the leaves hosted the largest number of endophytes (96 isolates) followed by the stems (57 isolates) and finally the roots (28 isolates), respectively. Based on morphological characteristics the endophytic fungi were grouped into 26 types in our study. TLC and HPLC results showed that there was sanguinarine in the metabolic substances of BLH 51 strain. According to the morphological characteristic, the BLH 51 strain was identified as Fusarium proliferatum. All these indicated that the medicinal plant M. cordata harbors abundant endophytes, which could be a new source for the search of active secondary metabolites.

Effect of berberine, liensinine and neferine on HERG channel expression / 中国中药杂志

<p><b>OBJECTIVE</b>Immunofluorescence and Western blot methods were adopted for qualitative and quantitative detections of the effect of different concentrations of berberine, liensinine and neferine on the expression of stable transfection in HERG potassium channel in HEK-293 cells, as well as the effect of different concentrations of berberine on protein expression of Ikr channel in cardiac muscular tissues, in order to investigate the anti-arrhythmic mechanism of berberine, liensinine and neferine.</p><p><b>METHOD</b>Western blot method was used to detect protein expression of HERG channel in HERG-HEK cells. Immunofluorescence method as well as confocal laser microscope were used to detect the effect of different concentrations of berberine, liensinine and neferine on protein expression of HERG channel. Western blot method was used to detect the effect of different concentrations of berberine on protein expression of Ikr channel in cardiac muscular tissues as well as the effect of berberine, liensinine and neferine on protein expression of stable transfection in HERG potassium channel in HEK-293 cells.</p><p><b>RESULT</b>Western blot experiment manifested that stable transfection of HEK293 cells containing HERG genes could increase protein expression of HERG channel. Berberine (10, 30 micromol x L(-1)) remarkably inhibited protein expression of HERG channel in HERG-HEK cells (P < 0.01). Berberine (10, 20 mg x kg(-1)) also inhibited protein expression of Ikr channel in rat ventricular tissues (P < 0.05). Liensinine (3, 10, 30 micromol x L(-1)) increased protein expression of HERG channel in HERG-HEK cells (P < 0.05). Neferine showed no effect on protein expression of HERG channel in HERG-HEK cells.</p><p><b>CONCLUSION</b>The stably transfection of HERG-HEK cells can increase protein expression of HERG channel. Berberine shows inhibitory effect on protein expressions of in vitro HERG-HEK cells and Ikr channel in rat ventricular tissues. Liensinine improves protein expression of HERG channe in HERG-HEK cells. Neferine shows no effect on protein expression of HERG channel.</p>

Forskolin inhibits spontaneous contraction of gastric antral smooth muscle in rats / 生理学报

The aim of the present study was to investigate the effects of cyclic adenosine monophosphate (cAMP) on rat gastric antral circular smooth muscle function. Forskolin, a direct activator of adenylyl cyclase (AC), was used to observe the influences of cAMP. Multi-channel physiological recorder was used to record spontaneous contraction activity of gastric antral circular muscle from Wistar rats. And ELISA method was used to detect the change of cAMP production in perfusate. The results showed that forskolin concentration-dependently suppressed the amplitude and frequency of the spontaneous contraction of the gastric antral muscle, and lowered the baseline of contraction movement significantly. Forskolin concentration-dependently increased the production of cAMP in the perfusate, which showed a significant negative correlation with the contraction amplitude of gastric antral ring muscle. The inhibitory effect of forskolin on spontaneous contraction activity of rat gastric antral circular muscle could be blocked by cAMP-dependent protein kinase (PKA) inhibitor H-89. These results suggest forskolin increases cAMP production and then activates PKA pathway, resulting in the inhibition of the spontaneous contraction activity of rat gastric antral circular smooth muscle.

Postoperative nausea and vomiting [PONV]: a cause for concern

Postoperative nausea and vomiting [PONV] has been a cause for concern, not only for the anesthesiologist but also for the patients. It is troublesome and may cause many untoward physiological consequences. Various authors have studied risk factors associated with it and management strategies, but the results have been confusing. Many new drugs have been developed for preventing and treating PONV, including ondansetron and palonosetron, and the research for the more effective and safe anti-emetic drug continues. This editorial compliments an original article being published in this issue of 'Anesthesia, Pain and Intensive Care' on the same topic

prospective, randomized, double-blind, comparative study of the efficacy of intravenous ondansetron and palonosetron for prevention of postoperative nausea and vomiting

Palonosetron is a second generation 5-Hydroxytryptamine-3 receptor antagonist with longer half life and higher receptor binding affinity than Ondansetron. To assess the efficacy and safety profile of intravenous palonosetron compared to the ondansetron for prevention of post-operative nausea and vomiting [PONV] under general anesthesia. A prospective, randomized, placebo-controlled, double-blind study was conducted in 90 patients aged 20-60 years, undergoing major surgeries. Group I [n=30] received placebo injection; Group II [n=30] received inj. ondansetron 8 mg and Group III [n=30] received inj. palonosetron 0.075 mg IV. In the operating room, the study drugs were given IV in equal volume of 4ml, before inducing the patients. In postoperative period each patient was observed for retching, nausea and/or vomiting at 30 min; and then at 1, 2, 6, 12 and 24 hours. Any side effects intra-operatively and post-operatively were recorded. The number of patients, who remained vomiting free in the first 24 hours after surgery was 56.6%, 80% and 86% in the placebo, Ondansetron and Palonosetron groups respectively. The difference with placebo was highly significant for ondansetron [p < 0.05], and highly significant for palonosetron [p=0.009]. The difference in vomiting between Ondansetron and Palaonosetron was not significant but the incidence of nausea was significantly less common in the Palonosetron group than the Ondansetron group [16.7% vs. 43.4%, p=0.006]. We conclude that the second generation 5-HT3 antagonist, palonosetron is significantly more effective against PONV than ondansetron. It has a particularly more pronounced and prolonged effect on postoperative nausea