The hepatoprotective effects of Sedum sarmentosum extract and its isolated major constituent through Nrf2 activation and NF-κB inhibition.

BACKGROUND: Sedum sarmentosum, which is recorded in Chinese Pharmacopoeia, has been applied clinically to treat liver and gallbladder diseases. PURPOSE: This study aimed to explore the hepatoprotective effect of S. sarmentosum less polar extract (SSE) against ANIT-induced liver injury in rats, and the protective activity and mechanism of one major constituent isolated from this extract on D-GalN-induced human hepatic QSG7701 cell damage. METHODS: Rats were divided into groups and then administrated intragastrically with SSE at doses of 100, 200 and 400 mg/kg for 7 days. They were modeled in the experiments with ANIT (70 mg/kg) to induce liver injury after the sixth day administration. The levels of serum biochemical markers ALT, AST, ALP, GGT/γ-GT, DBiL, TBiL, ALB, TP, and bile flow rate, as well as the histopathology of the liver tissue were used as indices of liver damage and measured. The inflammatory response and oxidative stress were thought to be key contributors to ANIT-induced liver injury in rats. Therefore, the inflammatory mediators (TNF-α, IFN-γ, IL-4) and oxidative stress (ROS, SOD, GSH-PX) were measured in the serum and liver homogenates, respectively. Next, phytochemical research was performed to produce the main component, and the isolated compound was evaluated for its hepatoprotective activity against QSG7701 cell injured by D-GalN through the measurement of cell viabilities, ALT, AST, IL-1ß, TNF-α, IL-6, ROS, GSH-PX and SOD productions. Furthermore, the protein expression of the Nrf2 and NF-κB pathways were analyzed by western blotting. RESULTS: SSE had an obvious effect on the decreases of ALT, AST, ALP, GGT/γ-GT, DBiL and TBiL levels, the increases of ALB and TP levels in serum, and the ANIT-induced deceleration in bile flow for liver injury. Meanwhile, SSE pretreatment alleviated ANIT-induced liver pathological injuries exhibited by HE stain of the liver. Moreover, SSE significantly suppressed levels of pro-inflammatory cytokines TNF-α and IFN-γ, and elevated level of anti-inflammatory cytokine IL-4 in serum. SSE also attenuated oxidative stress by reducing ROS level and by enhancing antioxidative enzymes (SOD and GSH-PX) activities after ANIT administration in liver tissue. Further, the major compound shown in HPLC was isolated from SSE. Its structure was identified by the spectroscopic data analysis and comparison with literature values. The principal constituent had potent protective effect on D-GalN-induced QSG7701 cells damage in a dose dependent manner with survival rates of 58.2% and 69.5% at 10 µM and 20 µM, respectively. Its cytoprotective effect was associated with the reduction of ALT, AST, IL-1ß, TNF-α, IL-6 and ROS levels, and the elevation of GSH-PX and SOD productions in QSG7701 cells induced by D-GalN. Western blotting showed that this compound enhanced the expression of Nrf2, HO1, NQO1 and GCLC, and inhibited D-GalN-induced IκBα and NF-κB p65 phosphorylation. CONCLUSIONS: Current study showed that SSE treatment exerted a protective effect on ANIT-induced liver injury. The main compound δ-amyrone isolated from the extract was characterized as the effective component with hepatoprotective activity by promoting Nrf2 antioxidant defense and suppressing NF-κB inflammatory response.

A new isoflavanone from Ficus tikoua Bur.

A new isoflavanone compound, ficustikounone A (1), together with 22 known flavones, was isolated from Ficus tikoua Bur. The structures of these isolates were determined by UV, ECD, HRESIMS, 1D and 2D spectral analyses.

New isocoumarin and stilbenoid derivatives from the tubers of Sparganium stoloniferum (Buch.-Ham.).

A new isocoumarin derivative 8,5'-dihydroxy-6'-methoxy-4-phenyl-5,2'-oxidoisocoumarin (1) and a new stilbenoid derivative methyl 5-hydroxy-2-(2-hydroxyphenyl)benzofuran-4-carboxylate (2) together with nine known compounds (3-11) were isolated from the tubers of Sparganium stoloniferum Buch.-Ham.. Another stilbenoid derivative (3) and a xanthone (4) were identified as new natural products and compounds 5-10 were obtained for the first time from the genus Sparganium. All their structures were elucidated by comprehensive spectroscopic analysis and comparison with available literature information.

Microwave coagulation/ablation in combination with sorafenib suppresses the overgrowth of residual tumor in VX2 liver tumor model.

OBJECTIVES: Our study is to evaluate the effect of thermal ablation on residual VX2 tumor tissue and the efficiency of sorafenib as an adjuvant therapy after insufficient microwave coagulation (MWC) on a rabbit VX2 liver tumor model. METHODS: Thirty-seven rabbits with orthotic VX2 liver tumors were randomly divided into MWC group (n=11), combination treatment group (n=14), and control group (n=12). The therapeutic efficacy was evaluated by contrast enhanced ultrasound (CEUS), magnetic resonance imaging (MRI), pathological and immunohistochemical examinations. Analysis of enhancement characteristics included enhancement level, pattern, and location. The necrotic degree of tumor was analyzed by semi-quantitative classification. The apparent diffusion coefficiency (ADC) was calculated using diffused weighted image (DWI). RESULTS: The tumor growth was accelerated in MWC group compared with control group and combination treatment group. A low metastasis rate was shown in combination treatment group compared with other two groups. The degree of necrosis in combination treatment group was greater than that in MWC group. The ADC value on DWI was higher compared with that of the control and MWC group, with statistical significance (P<0.05). With adjuvant therapy of sorafenib after insufficient ablation, the microvessel density (MVD) was lower than that of control group, whereas in MWC group the MVD was higher than that of control group, with statistical significance (P<0.05). CONCLUSION: Insufficient thermal ablation promotes residual tumor progression. While the adjuvant therapy of sorafenib serves as an effective way to suppress the overgrowth and neovascularization of residual tumor after insufficient thermal ablation.

Early treatment response to sorafenib for rabbit VX2 orthotic liver tumors: evaluation by quantitative contrast-enhanced ultrasound.

The aim of our study was to investigate the application of contrast-enhanced ultrasound (CEUS) and its quantification analysis for the prediction of early treatment response of sorafenib on rabbit VX2 liver tumor model. Rabbits were implanted VX2 tumor mass to establish a liver tumor model. Fourteen days after tumor implantation, rabbits presented with single liver tumor were randomly divided into two groups. Rabbits in treatment group were given by gavage once a day for 14 days with sorafenib suspension at a dose of 30 mg/kg, whereas rabbits in control group were given saline by gavage of the same volume. CEUS was performed before treatment and 3, 7, 14 days after treatment for the analysis of tumor size, enhancement pattern, and necrosis range. The time intensity curve (TIC) was used to obtain quantitative parameters of enhancement patterns. Before sorafenib administration, tumor volumes ranged from 0.24 to 0.75 cm(3) (mean 0.49 ± 0.18 cm(3)) in treatment group and 0.24 to 0.44 cm(3) (mean 0.30 ± 0.12 cm(3)) in control group. The dynamic enhancement patterns of tumors were homogeneous hyper-enhancement (n = 8), heterogeneous hyper-enhancement (n = 4), and peripheral rim-like enhancement (n = 2). All tumors of the treatment group presented with peripheral rim-like enhancement with large necrotic area after sorafenib administration, whereas tumors of the control group showed heterogeneous hyper-enhancement (n = 5) and peripheral rim-like enhancement (n = 2). There was a significant difference in area under the curve (AUC) before and after sorafenib treatment (P = 0.045). CEUS may be of value in the evaluation of early therapeutic response after sorafenib administration.

Coffee consumption and urologic cancer risk: a meta-analysis of cohort studies.

OBJECTIVES: Controversial results were reported among several epidemiologic studies on the relationship between coffee consumption and urologic cancer risk. We, therefore, conducted this meta-analysis to clarify these associations. METHODS: Electronic databases including Pubmed, Embase and Cochrane library were searched between January 1966 and August 2013 for eligible studies. Pooled relative risk (RR) and its 95 % confidence interval (CI) were calculated. All P values are two tailed. RESULTS: Thirteen cohorts were eligible for inclusion. As to prostate cancer (PCa), significant reverse association was found among highest versus none/lowest analysis with acceptable heterogeneity (RR 0.86, 95 % CI 0.79-0.95; I(2) 25 %, P value for heterogeneity: 0.221). A pooled RR which assessed advanced PCa was 0.73 (with 95 % CI 0.50-1.07), and a slight stronger reverse association was found in fatal PCa. However, a slight insignificant reverse association, basing on 8 studies with 9 outcomes, was found in dose-response analysis (RR 0.98, 95 % CI 0.93-1.03). For kidney and bladder cancer, insignificant associations were found in both highest versus none/lowest analyses and dose-response analyses. CONCLUSIONS: Our findings suggest that coffee consumption may reduce the risk of PCa. No associations were found with both bladder and kidney cancer. Further well-designed large-scaled cohort studies are warranted to provide more definitive conclusions.

[Medical statistics in the late Qing dynasty].

Chinese medical statistics basically went through three stages in the Late Qing Dynasty. The early stage was individual behavior of missionary doctors. In the early 16(th) century, western countries began to collect materials about medicine and public health in China. After the Opium War in 1840, more missionaries came to China and more doctors engaged in medical information collection and statistics. In 1860s, the western countries stole the customs power control from the Qing's government and the systematization process of statistics began. The process, content, method and time of statistics were improved. In the 20(th) century, modernity of medicine became the scale for a country's self-management qualification. Statistics was needed by the Qing government and relevant medical administration was established. During this process, they carried out this activity with different purposes according to the different participants. But from the point of influence, medical statistics promoted the spread and development of western medicine in China. They were also helpful to the perfection of medical research and public health system in China.

A new indoloquinazoline alkaloidal glucoside from the nearly ripe fruits of Evodia rutaecarpa.

A new indoloquinazoline alkaloidal glucoside, rutaecarpine-10-O-ß-D-glucopyranoside (1), together with one known alkaloidal glycoside namely rutaecarpine-10-O-rutinoside (2) was isolated from the nearly ripe fruits of Evodia rutaecarpa (Juss.) Benth.. Their structures were elucidated on the basis of extensive spectroscopic methods.

Cytotoxic phorbol esters of Croton tiglium.

Chemical investigation of the seeds of Croton tiglium afforded eight new phorbol diesters (three phorbol diesters, 1-3, and five 4-deoxy-4α-phorbol diesters, 4-8), together with 11 known phorbol diesters (nine phorbol diesters, 9-17, and two 4-deoxy-4α-phorbol diesters, 18 and 19). The structures of compounds 1-8 were determined by spectroscopic data information and chemical degradation experiments. The cytotoxic activities of the phorbol diesters were evaluated against the SNU387 hepatic tumor cell line, and compound 3 exhibited the most potent activity (IC50 1.2 µM).

A novel sensitive detection platform for antitumor herbal drug aloe-emodin based on the graphene modified electrode.

This paper has presented a novel strategy to carry out direct and sensitive determination of antitumor herbal drug aloe-emodin in complex matrices based on the graphene-Nafion modified glassy carbon (GN/GC) electrode. This proposed modified electrode showed good electrochemical response towards aloe-emodin (AE). Compared with the multiwall carbon nanotubes (MWCNTs) modified electrode, the GN/GC electrode has the advantages of higher sensitivity and lower cost. Under the optimized conditions, the calibration curve for AE concentration was linear in the range from 5 nmol/L to 1 µmol/L with the detection limit of 2 nmol/L. In addition, the practical analytical performance of the GN/GC electrode was examined by evaluating the selective detection of AE in natural aloe extracts and human urine samples with satisfied recovery. Therefore, the GN/GC electrode may hold great promise for fast, simple and sensitive detection and biomedical analysis of AE in complex matrices.