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Computerized detection is a promising method for monitoring adverse drug events (ADEs); however, this method is currently in its infancy and is a new area of exploration in China. This study aimed to develop a computerized ADE alarm and assessment system to help pharmacists effectively detect, assess, and analyze possible ADEs in patients in China.Based on the clinical characteristics of these adverse drug events, we designed combined multiparameters as ADE alert rules to be assembled into detection configurations. We also developed system function modules by extracting data from the People's Liberation Army (PLA) general hospital information system (electronic medical records). Positive predictive values were calculated for the alert.Five function modules were created in this platform: automatic screening, assisted evaluation, risk characteristic analysis, report generation into SRS (spontaneous reporting system), and a dictionary database. Four ADE alert configurations were set in our ADE alarm and assessment system: drug-related thrombocytopenia, anemia, liver injury, and kidney injury. The positive predictive values of the 4 monitored ADEs were approximately 44.4% to 95.8%.An automatic ADE screening system was established for hospitalized patients in Chinese medical institutions. Compared with previous studies, combined drug-event alerts and a system-assisted assessment interface performed better than alerts based only on laboratory values. Furthermore, this platform's assisted-layered evaluation and risk factor analysis functions could save considerable time for professionals and improve early prevention of potentially serious ADEs. To date, this system has been applied in 10 large-scale medical institutions.

Background Fluoroquinolone-related hepatotoxicity is rare but serious and is attracting increasing attention. We explored the incidence, clinical features and risk factors of acute liver injury associated with fluoroquinolone use. Materials and methods Based on the Adverse Drug Events Active Surveillance and Assessment System that we developed, we carried out a case-control study by enrolling patients who were hospitalized and received fluoroquinolones to treat or prevent infections at the Chinese People's Liberation Army General Hospital from Jan 2016 to Dec 2017. The incidence of fluoroquinolone-induced acute liver injury was estimated, and logistic regression was used to reveal the risk factors of this adverse reaction. Results We found that 17,822 patients received fluoroquinolones, and 13,678 of them met the inclusion criteria. A total of 91 patients developed acute liver injury after receiving the medication, and 369 controls were matched to these patients. The overall incidence of fluoroquinolone-induced acute liver injury in the Chinese population is approximately 6-7 cases per 1,000 individuals annually. Multivariate logistic regression analysis showed that older age slightly decreased the risk of hepatotoxicity (OR, 0.98; 95% CI, 0.96-0.99). The male sex (OR, 2.19; 95% CI, 1.07-4.48), alcohol abuse (OR, 2.91; 95% CI, 1.39-6.11) and hepatitis B carrier status (OR, 2.38; 95% CI, 1.04-5.48) increased the risk of liver injury. Concurrent use of cephalosporins or carbapenems was also associated with an increased risk. Conclusion Increased risk of fluoroquinolone-related hepatotoxicity may be associated with youth, the male sex, alcohol abuse, hepatitis B carrier status and the concurrent use of cephalosporins or carbapenems.

This study aims at investigating the radioprotective effect of ethanol extract from Ji-Xue-Teng (JXT,Spatholobus suberectus) on radiation-induced hematopoietic alteration and oxidative stress in the liver. Mice were exposed to a single acuteγ-radiation for the whole body at the dose of 6.0 Gy, then subjected to administration of amifostine (45 mg/kg) or JXT (40 g crude drug/kg) once a day for 28 consecutive days, respectively. Bone marrow cells and hemogram including white cells, red cells, platelet counts, and hemoglobin level were examined. The protein expression levels of pJAK2/JAK2, pSTAT5a/STAT5a, pSTAT5b/STAT5b, and Bcl-2 in bone marrow tissue; levels of reactive oxygen species (ROS); and the activity of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum and liver tissue were determined. At the end of the experiment, the effect of JXT on cell viability and G-CSF and G-CSFR levels in NFS-60 cells were tested by CCK-8 assay, ELISA, and flow cytometry. The results showed that the mice exposed toγ-radiation alone exhibited a typical hematopoietic syndrome. In contrast, at the end of the 28-day experiment, irradiated mice subjected to oral administration of JXT showed an obvious improvement on blood profile with reduced leucopenia, thrombocytopenia (platelet counts), RBC, and hemoglobin levels, as well as bone marrow cells. The expression of pJAK2/JAK2, pSTAT5a/STAT5a, and Bcl-2 in bone marrow tissue was increased after JXT treatment. The elevation of ROS was due to radiation-induced toxicity, but JXT significantly reduced the ROS level in serum and liver tissue, elevated endogenous SOD and GSH-PX levels, and reduced the MDA level in the liver. JXT could also increase cell viability and G-CSFR level in NFS-60 cells, which was similar to exogenous G-CSF. Our findings suggested that oral administration of JXT effectively facilitated the recovery of hematopoietic bone marrow damage and oxidative stress of the mice induced byγ-radiation.

Effect of linezolid is associated with hematocytopenia. A possible relationship between oxidative stress and hematologic toxicity has also been discussed. This present study was performed to determine the effect of oral administration of linezolid on hematological and oxidative parameters in rats. Rats were divided into five groups of 20 each. Drugs were given for a 15-day period. Control rats were vehicle treated. In the second and third groups, linezolid (50 and 125 mg kg(-1)) was given to rats twice a day (100 and 250 mg kg(-1) per day) orally by gavage. The fourth group was given diet supplement that contained 250 mg kg(-1) Vitamin E. The fifth group was given 125 mg kg(-1) linezolid twice a day along with Vitamin E supplement. Blood cell counts (red blood cell (RBC), white blood cell (WBC) and platelet) were measured every 5 days. Enzymatic antioxidant activities, lipid peroxidation and free radical production were performed at the end of 15th day. The results showed that linezolid induces a decrease of WBC, RBC and platelet numbers in rat blood and enzymatic activities of superoxide dismutase and catalase in rat serum in a dose-dependent manner. While the content of malondialdehyde and nitric oxide was significantly increased in rats serum compared with the control group, Vitamin E supplement could partially reverse the above changes without affecting the control group. The results suggest that linezolid has effect on decreasing hemocyte level in rats, and oxidative stress may be one of the major causative factors. Antioxidant may prove to be a useful therapeutic option in the reversal of hematologic effects induced by linezolid.

The aim of this study was to explore whether the ethanolic extract of Ardisia gigantifolia rhizomes (AGB-5), a traditional herbal medicine from China, could affect the proliferation of human breast adenocarcinoma (MCF-7) cells in vitro and to explore the antitumor effects of AGB-5 in BALB/c mice engrafted with MCF-7 cells. The results showed that AGB-5 markedly inhibited the proliferation of MCF-7 cells with an IC50 value of 11.89±1.12 µg/mL, increased the S phase and decreased the G2/M phase without influence on G1 phase. MCF-7 cells treated with AGB-5 presented a dose-dependent increase of apoptosis compared with the control group. AGB-5 also significantly increased the activity of caspase-3 and -9 in a dose-dependent manner in MCF-7 cells. Furthermore, in an in vivo model, AGB-5 reduced tumor volume, brought back the red blood cell (RBC) and white blood cell (WBC) count near to normal value, enhanced superoxide dismutase and catalase level of MCF-7 bearing mice. This is the first study to verify the antitumor activity of A. gigantifolia in vivo. The results suggest that AGB-5 may have potential beneficial effects against human breast adenocarcinoma.

Thirteen 13,28-epoxy triterpenoid saponins were isolated from Ardisia gigantifolia stapf. and one potential anti-tumor saponin was methanolysised by H2SO4 to afford four new compounds. The seventeen compounds were evaluated for their anti-proliferative activity on A549, HCT-8 and Bel-7402 cells. The structure-activity relationship analysis indicated that the incorporation of =O group at C-16, L-rhamnose at R(5) and acetyl group at OH-6 of the D-glucose lead to a significant increase of the cytotoxic activity on A549 and HCT-8 but significant reduction of the cytotoxic activity on Bel-7402 cells. The synthesized saponins losing 13,28-epoxy and CHO at C-30, losed their cytotoxicities on A549 and HCT-8 cells, suggesting that the two moieties play an essential role for activity. 3β-O-α-L-rhamnopyranosyl-(1→3)-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranosyl-(1→4)-[β-D-glucopyranosyl-(1→2)]-α-l-arabinopyranoside-16α-hydroxy-13,28-epoxy-oleanane (2) showed better inhibitory activity to Bel-7402 (IC50 0.86 μM) than that of 5-FU (IC50 8.30 μM), which indicate that five saccharide and methyl moiety at C-30 are important for anti-proliferative activity. The activities of saponins 15>14, 17>16, suggested that the configuration of 28,30-epoxy is preferable to be 30(R) rather than 30(S) on Bel-7402 cells. Further molecular mechanism studies of saponins 1 and 2 were carried out on the cell cycle distribution of Bel-7402 cells.

To study the anti-radiation effect and mechanism of ethanol extracts from Spatholobus suberectus and its active component catechin, ICR mice were exposed to 6Gy irradiation and randomly divided into normal group, model group, positive control group (amifostine, 43.6 mg•kg⁻¹, iv 30 min before irradiation), SSD group (10, 20, 40 g•kg⁻¹) and catechin group (50, 100, 200 mg•kg⁻¹). The mice were administered the appropriate drugs once a day after irradiation for 28 consecutive days. Blood samples were collected from the tail end and the number of peripheral blood cells was counted before irradiation and on day 1, 3, 7, 14, 21 and 28 using a microcell counter. Changes of thymus and spleen index of mice on day 7 were observed. The serum SOD, GSH-Px activity and MDA level were detected by the colorimetric method. The colony forming ability of bone marrow hematopoietic progenitor cells on day 7 was detected by semi solid culture method. The HE staining was adopted to observe the pathological changes. The apoptosis of bone marrow cells was detected by flow cytometry. The expression of cleaved caspase-3 and Bax of bone marrow cells were measured separately by western-blotting and immunohistochemistry method. SSD and catechin can both significantly revert the irradiated-induced decline in hematological parameters (RBC, WBC, PLT, Hb), improve thymus and spleen index, significantly enhance serum SOD and GSH-Px activity and decrease the MDA level. The proliferation and differentiation of hematopoietic progenitor cells in bone marrow were promoted, the apoptosis of bone marrow cells was significantly up-regulated and the expression of cleaved caspase-3 and Bax was significantly reduced in SSD and catechin group. SSD and catechin have significant anti-radiation effect and its mechanism may be related to hematopoietic promoting, antioxidant and anti-apoptotic effects.

Background: Diabetes is a metabolic disorder caused by oxidative stress and inflammation. JianYuTangKang (JYTK), as a potential Chinese integrative medicine, is an antioxidant used in Chinese medicine with potential anti-inflammatory properties. Objectives: The present randomized clinical trial was carried out to evaluate the effects of JYTK on oxidative stress and inflammation in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: The parallel, randomized, double-blinded, placebo-controlled clinical trial included 150 newly diagnosed T2DM patients receiving metformin treatment (1.5 g/day), some of whom also received JYTK (4.5 g/day) in tablet form. The control group received 4.5 g/day placebo plus 1.5 g/day metformin. Body mass index (BMI), fasting plasma glucose, urinary albumin-to-creatinine ratio, and complete blood count as well as antioxidant and inflammation indices such as tumor necrosis factor (TNF)- α, interleukin (IL)-6, superoxide dismutase (SOD), malonaldehyde (MDA), glutathione peroxidase (GPX), and high sensitivity C-reactive protein (hs-CRP) levels were assessed at baseline and at different time points during the treatment. Results: All 112 patients, including 59 in the treatment group (JYTK + metformin) and 52 controls (metformin only) completed the 26-week clinical trial. JYKT plus metformin treatment increased IL-6 (36.4 ± 11.5 ng/L; P < 0.05), TNF-α (17.5 ± 11.3 vs. 22.5 ± 12.9 ng/L; P < 0.05), and MDA (1.9 ± 0.9; P < 0.05) levels compared to the control (2.2 ± 0.6 mM/mL), whereas total SOD level decreased (98.1 ± 30.4 vs. 78.5 ± 29.3 U/mL; P < 0.05). There were no changes in GPX and hs-CRP levels. There were no adverse effects associated with JYTK treatment. Conclusions: JYTK combined with metformin improves some antioxidant indices (SOD and MDA), and decreases inflammation in patients with T2DM, suggesting that it can reduce the risk of diabetic complications.

The neuroprotective effects of 3,6′-disinapoyl sucrose (DISS) from Radix Polygala against glutamate-induced SH-SY5Y neuronal cells injury were evaluated in the present study. SH-SY5Y neuronal cells were pretreated with glutamate (8 mM) for 30 min followed by cotreatment with DISS for 12 h. Cell viability was determined by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTT) assay, and apoptosis was confirmed by cell morphology and flow cytometry assay, evaluated with propidium iodide dye. Treatment with DISS (0.6, 6, and 60 μmol/L) increased cell viability dose dependently, inhibited LDH release, and attenuated apoptosis. The mechanisms by which DISS protected neuron cells from glutamate-induced excitotoxicity included the downregulation of proapoptotic gene Bax and the upregulation of antiapoptotic gene Bcl-2. The present findings indicated that DISS exerts neuroprotective effects against glutamate toxicity, which might be of importance and contribute to its clinical efficacy for the treatment of neurodegenerative diseases.

The present study aimed to evaluate the radioprotective efficacy of green tea polyphenols and the component ingredients against irradiated-induced damage in mice and elucidate the underlying mechanisms. Green tea polyphenols (GTP 50, 50 and 100 mg/kg, p.o. daily) and its four individual components (25 and 50 mg/kg, p.o. daily) were administrated to the irradiated-injured mice for 21 days. The radioprotective effect on the hematopoietic system, serum cytokines, and endogenous antioxidant enzymes was studied. GTP 50 significant revert the irradiated-induced decline in hematological parameters (RBCs, WBCs, Hb), meanwhile, protected antioxidant defense system, as evidenced by decreased of serum lipid peroxidation (malonyldialdehyde) and elevation the antioxidant enzyme superoxide dismutase (SOD). Among the GTP components, catechin showed the best effect on elevation of hematological parameters, and epigallocatechin gallate showed the best antioxidant activity. Moreover GTP and its bioactive components (catechin, epigallocatechin and epigallocatechin-3-gallate) assisted in decreasing the leukocytopenia seen after whole mice irradiation and significantly reduced the elevated serum inflammatory cytokines (TNF-α, IL-1β, and IL-6). Green tea polyphenols have a potential to be developed as radioprotective agents against irradiated-induced toxicity. Furthermore the antioxidant and anti-inflammatory activities of GTP can be attributed to the interaction of the different components through multiple and synergistic mechanisms.

Objective The present study was designed to observe the effects of 3,6′-disinapoyl sucrose (DISS), an active oligosaccharide ester component obtained from the roots of Polygala tenuifolia Willd., on behavioral and biochemical aspects of depression induced by chronic mild stress (CMS) in rats. It is the first exploration of the possible association between DISS's antidepressant-like effects and biochemical markers of depression, and involved measuring monoamine oxidase (MAO) activity, cortisol levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels. Methods Rats were exposed to stressor once daily for consecutive 5 weeks. DISS and a positive control drug, fluoxetine, were administered via gastric intubation to once daily for consecutive 3 weeks from the third week. Key findings The results showed that rats subjected to CMS exhibit a reduction in sucrose intake. Conversely, brain MAO-A and MAO-B activity, plasma cortisol levels, and MDA levels were increased, while SOD activity was decreased following CMS exposures. DISS significantly inhibited MAO-A and MAO-B activity and blocked plasma elevated cortisol level, an indicator of the hypothalamic–pituitary–adrenal (HPA) axis. In addition, DISS increases SOD activity, inhibits lipid peroxidation, and lessens production of MDA. Conclusion These results suggest that DISS may possess potent and rapid antidepressant properties, which are mediated via MAO, the HPA axis and oxidative systems. These antidepressant actions make DISS a potentially valuable drug for the treatment of depression.

The purpose of this study was to investigate the radioprotective effects of tea polyphenols (TPs) in various combinations against radiation-induced damage in mice. Mice were divided into different groups: non-irradiated control, irradiated control, amifostine (43.6 mg/kg, i.v. 30 min before irradiation; positive control) and various combinations of tea polyphenols in different doses. The radioprotective effect on the haematopoietic system, serum cytokines and endogenous antioxidant enzymes were studied. TP50, containing approximately 50% of (-)-epigallochatechin-3-gallate in addition to other catechins, showed the greatest radioprotective effect against radiation-induced changes in haematological parameters (red blood cell count, white blood cell count and haemoglobin), and maintained the spleen and thymus indices unchanged (spleen or thymus weight/body weight × 1000). Tea polyphenols also significantly decreased radiation-induced lipid peroxidation (malondialdehyde levels), elevated endogenous antioxidant enzymes (superoxide dismutase) and reduced the serum cytokines which were elevated in radiation-induced toxicity. This evidence shows the potential of tea polyphenols, particularly in the combination found in TP50, as radioprotectors in mice, especially regarding recovery of the haematopoietic system, antioxidant potential activity and reduction of inflammatory cytokines. Copyright © 2011 John Wiley & Sons, Ltd.

The aim of this 26-week, double-blind, controlled clinical trial, was to compare the efficacy of monotherapy (metformin only) with combination therapy (Chinese medicine prescription JianYuTangKang [JYTK] plus metformin) on type 2 diabetes. All patients on metformin were randomized to receive authenticated JYTK (59 patients) or placebo JYTK (53 patients), 4.5g daily, for 26 weeks. Patients also received information regarding diet and exercise. Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1C) level, and a lipid profile were measured before, during, and after the treatment. The results of the treatment group (JYTK plus metformin) were noninferior to those of the control group (metformin plus placebo) at 8 and 18 weeks. After 26 weeks of treatment, FPG levels decreased to 6.1±1.0mmol/L in the treatment group and 7.0±1.5mmol/L in the control group (p

3β-O-{α-L-Pyran rhamnose-(1→3)-[β-D-xylopyranose-(1→2)]-β-D-glucopyranose-(1→4)-[β-D-lucopyranose-(1→2)]-α-L-pyran arabinose}-cyclamiretin A (AG4) is a saponin component obtained from the Giantleaf Ardisia Rhizome (Rhizoma Ardisiae Gigantifoliae). The present study aimed to investigate the antitumor potential of AG4 and its possible mechanisms in human nasopharyngeal carcinoma cells (CNE). We exposed tumor cells to AG4 to investigate which cell line was the most sensitive to AG4. Cell viability was assessed using the MTT reduction assay, and the effects of AG4 on apoptosis, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), and cell cycle were detected using a flow cytometer; the glutathione, superoxide dismutase and malondialdehyde activities were measured using colorimetric methods. The relative expressions of Bax, Bad, Bid, Bcl-2, and Fas mRNA were calculated using the (Equation is included in full-text article.)comparative method by real-time PCR studies and protein was detected by western blotting. AG4 markedly inhibited the growth of CNE cells by decreasing cell proliferation, inducing apoptosis, and blocking the cell cycle in the S phase. The release of caspase-3, caspase-8, and caspase-9 was stimulated by AG4 in CNE, and the decreased proliferation induced by AG4 was blocked by the inhibitor of pan caspase (Z-VAD-FMK). Moreover, the MMP was decreased in AG4-treated cells, and AG4-induced cell apoptosis was accompanied by a rapid and lasting increase in ROS, which was abolished by N-acetyl-L-cysteine (NAC); glutathione, superoxide dismutase, and malondialdehyde were regulated by AG4. AG4 inhibited Bcl-2 mRNA and protein expression and stimulated Bax, Bad, Bid, Fas mRNA, and protein expression in CNE cultures, suggesting an effect at the transcriptional and protein level. In addition, both the FasL inhibitor (AF-016) and the Bcl-2 family inhibitor (GX15-070) could prevent the cell apoptosis induced by AG4. The findings suggested that AG4-induced apoptosis in CNE cells involved a death receptor pathway and a Bcl-2 family-mediated mitochondrial signaling pathway by decreasing the MMPs in an ROS-dependent manner and regulating genes and proteins relative to apoptosis; also, regulation of cell cycles may also play a role in the antitumor mechanism of AG4.

Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.

(20S*,24R*)-epoxy-9,19-cyclolanstane-3β,12β,16β,25-pentaol-3-O-β-d-xylopyranoside (BC1) is a kind of natural bioactive substance extracted from Beesia calthaefolia (Maxim.)Ulbr. This study was designed to evaluate the effects of BC1 on the proliferation of lymphocytes, phagocytosis of peritoneal macrophage, and cytokine secretion, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and the foot pad thickness index, which is beneficial for understanding the mechanism of BC1 on immunoregulation and anti-inflammation and also will benefit our further research. The proliferation of splenic lymphocyte induced by mitogen (concanavalin A or lipopolysaccharide (LPS)) was detected using the cell counting kit assay. The neutral red phagocytic test of macrophages was determined by colorimetric method. The gene and protein expressions of TNF-α and IL-1β were measured by real time RT-PCR and ELISA in serum, spleen, and lymphocytes, respectively. In vitro, our present study has shown that BC1 (31.25–250 μg/ml) could inhibit the proliferation of splenic lymphocyte and phagocytosis of macrophages, and inhibit the increased production of TNF-α and IL-1β in protein and gene levels. In mice, LPS could increase the gene and protein expressions of TNF-α and IL-1β, respectively, but BC1 (12.5–50 μg/kg) could recover the increased gene and protein expressions of TNF-α and IL-1β induced by LPS in the spleen and serum of mice. Treatment of arthritic rats with BC1 (1.5 mg/kg body weight) resulted in a significant reduction in foot pad thickness index and serum TNF-α level comparable to the indomethacin-treated arthritic rats, proving its anti-inflammatory effect. Thus, the function of immunoregulation of BC1 may be accomplished through modulating the gene and protein expressions of TNF-α and IL-1β.

Two new 9,19-cycloartane triterpenes (1, 2), together with three known compounds (3-5), were isolated from the whole plant of Beesia calthaefolia. Their structures were determined by the application of spectroscopic analyses and chemical methods. Compound 1 showed moderate anticomplement activity similar to that of the positive control (rosmarinic acid), while compounds 3 and 4 showed weak activity. The results suggest that 6'-O-(4″-hydroxy-3″-methoxy-benzoyl)-β-D-glucosyl of 9,19-cycloartane-type triterpenoids could be a structure that is essential for anticomplement activity.

Three new cycloartane triterpenoids (1–3) and two known compounds (4, 5) were isolated from the whole plant of Beesia calthaefolia. Their structures were elucidated by 1D and 2D NMR, HRESIMS and optical rotation spectral data. All isolates were investigated for their inhibitory effects on the classical pathway of the complement system. Among them, compound 4 showed stronger inhibitory activity (IC50 136.7 μM) than positive control (Rosmarinic acid, IC50 181.8 μM) while compounds 2 and 3 were moderately active with IC50 value of 206 μM and 200.9 μM. Chemical compound studied in this article: Rosmarinic acid (PubChem CID: 5281792).

A new triterpenoid saponin, named 3-O-β-d-glucopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 2)-[α-l-rhamnopyranosyl-(1 → 3)]-β-d-glucopyranosyl-(1 → 4)-[β-d-glucopyranosyl-(1 → 2)]-α-l-arabinopyranosyl-3β,16α,28,30-tetrahydroxy-olean-12-ene (1), along with four known triterpenoids (2–5), was isolated from the rhizomes of Ardisia gigantifolia. Their structures were elucidated by spectroscopic methods. Compounds 1–4 showed cytotoxic activity against Hela, EJ, BCG, and HepG-2 cell lines. The percentage of early apoptotic cells after treatment with 1 was significantly increased compared with control cells (p

The inhibitory action and the possible mechanism of anticancer compound Sanguinarine (SAN) on vascular endothelial growth factor (VEGF) in human mammary adenocarcinoma cells MCF-7 were evaluated in this study. We exposed MCF-7 to SAN for 24 h, then cell viability was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Human VEGF was measured using a paired antibody quantitative ELISA kit, relative expression of VEGF mRNA was calculated using the real-time PCR studies, and the effect of SAN on the reactive oxygen species (ROS) level was detected by the flow cytometer. Treatment with SAN remarkably inhibited growth of MCF-7 cells and induced cell apoptosis. We found that VEGF release was stimulated by subtoxic concentrations of SAN and inhibited by high dose of SAN, SAN-evoked VEGF release was mimicked by low concentration of H2O2, and SAN-regulated VEGF inhibition was accompanied by increasing of ROS; these changes were abolished by antioxidant. High concentration of SAN inhibited VEGF mRNA expression in MCF-7 cultures, suggesting an effect at transcriptional level, and was also abolished by antioxidant. The present findings indicated that the regulation of VEGF expression and release from MCF-7 cells were possibly through reactive oxygen species evoked by SAN.

A series of piperine derivates (1–19) have been designed, synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. It is worth noting that most of the small amine moieties substituted on the piperidine ring proved to be potent and selective inhibitors of MAO-B rather than of MAO-A. 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid n-propyl amide (3) showed the greatest MAO-B inhibitory activity (IC50(MAO-B) = 0.045 μM) and good selectivity (IC50(MAO-A) = 3.66 μM). The conjugated double bond and carbonyl group of piperine are proved to be an essential feature for piperine and related alkylamides to exhibit MAO-inhibitory activity. Binding mode of the titled compounds was predicted using FlexX algorithm. The design and optimization of novel small molecule monoamine oxidase inhibitors will be guided by the results of this report.

The constituents of the ethanol extract from the root of Polygala tenuifolia Willd. (Polygalaceae) were investigated for antioxidant activity in senescence-accelerated mice. Consequently, two relevant samples were obtained, a fraction separated by macroporous resin (YZ-OE), and a major pure crystal of 3,6'-disinapoyl sucrose (DISS). Based on HPLC-ESI-MS analysis, the most constituents in the YZ-OE fraction from the extract of P. tenuifolia were oligosaccharide esters. The antioxidant activities of these two samples were evaluated using the accelerated senescence-prone, short-lived mice (SAMP) in vivo. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased significantly in SAMP mice fed oligosaccharide esters (YZ-OE 50 mg/kg) and its constituents (DISS 50 mg/kg). However, the content of malondialdehyde (MDA) was increased in the blood and liver of SAMP mice. But when given YZ-OE, it could be decreased, by 44.3% and 47.5%, respectively, compared with the SAMP model. Results from the analyses indicated that the oligosaccharide esters (YZ-OE) from roots of P. tenuifolia had a high in vivo antioxidant activity.

YZ-50 is an active fraction obtained from the root of Polygala tenuifolia Willd. (Polygalaceae) extract and it has been reported previously to exert beneficial effects on mental health in depressed sufferers, however, its mechanism of action remains unresolved. This study utilized the chronic mild stress (CMS) model of depression in Sprague-Dawley rats to evaluate the effects of YZ-50 on depressive behaviors. Furthermore, we tested the hypothesis that the capacity of YZ-50 to reverse the harmful effects of CMS is relative to the hypothalamo-pituitary-adrenal (HPA) system and brain-derived neurotrophic factor (BDNF) in the hippocampus. Repeated administration of YZ-50 for 28 days at the doses of 140 and 280 mg/kg in CMS, YZ-50 reversed the CMS-induced changes in sucrose consumption, plasma corticosterone levels and open field activity. In addition, CMS significantly decreased hippocampal BDNF mRNA levels. However, YZ-50 counteracted a decrease in hippocampal BDNF mRNA caused by CMS. In conclusion, YZ-50 reversed the harmful effects of CMS on mood and behaviors in rats and it possesses an antidepressant property that is at least in part mediated by the neuroendocrine and neuropropective systems, and it is likely that the HPA system plays an important role in this process.

The purpose of this study was to investigate the radioprotective effects of tea polyphenols (TPs) in various combinations against radiation-induced damage in mice. Mice were divided into different groups: non-irradiated control, irradiated control, amifostine (43.6 mg/kg, i.v. 30 min before irradiation; positive control) and various combinations of tea polyphenols in different doses. The radioprotective effect on the haematopoietic system, serum cytokines and endogenous antioxidant enzymes were studied. TP50, containing approximately 50% of (-)-epigallochatechin-3-gallate in addition to other catechins, showed the greatest radioprotective effect against radiation-induced changes in haematological parameters (red blood cell count, white blood cell count and haemoglobin), and maintained the spleen and thymus indices unchanged (spleen or thymus weight/body weight × 1000). Tea polyphenols also significantly decreased radiation-induced lipid peroxidation (malondialdehyde levels), elevated endogenous antioxidant enzymes (superoxide dismutase) and reduced the serum cytokines which were elevated in radiation-induced toxicity. This evidence shows the potential of tea polyphenols, particularly in the combination found in TP50, as radioprotectors in mice, especially regarding recovery of the haematopoietic system, antioxidant potential activity and reduction of inflammatory cytokines.

This manuscript is intended to explore and establish a management system and working model which can maximise the development of clinical pharmacy in China. With a study of a series of documents about clinical pharmacists issued by China Ministry of Health and practical experience in clinical pharmacist training, the authors have reached the conclusion that the management system and working model of clinical pharmacist in China can be realized by making a standard work flow chart and series of standard registration forms, pharmaceutical and practical manuals and clinical pharmacy information support system, with features of the hospital and the specialty of clinical pharmacy.

3,6'-Disinapoyl sucrose (DISS) is the active oligosaccharide ester component from roots of Polygala tenuifolia, and its antidepressant effects was found in the forced swimming test (FST) and tail suspension test (TST). We aimed to study the antidepressant effects of DISS in the chronic unpredictable mild stress (CMS) model in rats and explore the underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis. We found that when subjected to the chronic stress protocol for 28 days, animals showed reduced sensitivity to reward and abnormality in the HPA axis. DISS (10 or 20 mg/kg, i.g.) improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT, ACTH and CRH levels in the CMS-treated rats. In addition, DISS enhanced the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) mRNA. These results indicated that the antidepressant effects of DISS in chronically stressed animals might relate to the modulating effects on the HPA axis, which might be an important mechanism for its antidepressant effect.

OBJECTIVE To evaluate the effect of abducens orthosis combined with walker on developmental dysplasia of the hip (DDH). METHODS A total of 126 patients (224 hips) with DDH aged 6-36 months in Xiangya Hospital was randomly divided into 2 groups: an orthosis combined with walker group and an improved hip frog cast fixation group. Seventy patients (130 hips) were treated by the orthosis combined with walker and 56 patients (94 hips) were treated by the improved hip frog cast fixation. We compared the effect and complications of the 2 groups. RESULTS The fineness rates of the orthosis combined with walker group and the improved hip frog cast fixation group were 89.2% and 90.4%, respectively, with no significant difference (P>0.05). The rate of femoral head osteonecrosis in the orthosis combined with walker group was significantly lower than that in the improved hip frog cast fixation group (1.5% vs. 5.3%,P

Radix Polygalae (“Yuan Zhi”, the roots of Polygala tenuifolia Willd., YZ) is an important herb used in traditional Chinese medicine to mediate depression. The present study was designed to verify the antidepressant effects of the standardized YZ ethanol extract (YZE) and its four fractions YZ-30, YZ-50, YZ-70 and YZ-90 on the tail suspension (TST) and forced swimming test (FST). Furthermore, the standardization of the fractions obtained from the separation procedures was carried out by high-performance liquid chromatography (HPLC)-fingerprint. The YZ-50 fraction (Oligosaccharide esters –enriched, oral (200 mg/kg) showed a significant anti-immobility like effects. The data of YZ-50 on the corticosterone-induced injure of SH-SY5Y human neuroblastoma cell indicated that YZ-50 may have biological effects on neuroprotection. Proliferation of cell lines was assessed by dimethylthiazoldiphenyltetrazoliumbromide (MTT) and 5-bromo-2′-deoxyuridine (BrdU) incorporation assays. It was found that YZ-50 and its two bioactive compounds, 3,6′-di-o-sinapoyl-sucrose (DISS) and tenuifoliside A(TEA) showed protection activities in SY5Y cells from the lesion. By using bioassay-screening methods, our results indicate that the presence of oligosaccharide esters such as DISS and TEA in this herb may be responsible for the cytoprotective activity effects.

The aim of this study was to investigate (1) whether Rhodobryum roseum, a traditional Chinese medicine used to treat cardiac disease, can protect myocardium damage due to isoproterenol-induced injury, (2) whether the cardioprotective effect of the R. roseum extract is related to its antioxidant activity, and (3) to identify the active components of R. roseum using the oxidant-mediated injury in cardiomyocytes. R. roseum was extracted with 95% EtOH (RE-95), 50% EtOH (RE-50) and water (Re-H2O) and the rats were treated orally for 11 days at doses of 250 mg and 63 mg/kg respectively after cardiac necrosis was induced by administering ISO subcutaneously at a dose of 85 mg/kg body weight. Levels of marker enzymes (LDH, GOT and CK) were assessed in serum whilst the antioxidant parameters, superoxide dismutase (SOD), and malondialdehde (MDA) were assayed in heart homogenate. Significant myocardial necrosis, depletion of endogenous antioxidants and an increase in serum levels of marker enzymes was observed in ISO-treated animals when compared with the normal animals. The RE-50 elicited a significant cardioprotective effect by lowering the levels of serum marker enzymes, lipid peroxidation (MDA). To extend this work, we sought to investigate the antioxidant effects of the components of R. roseum, using the neonatal rat cardiomyocytes model of H2O2-induced oxidant injury. Among the four major components, piperine and methyl piperate significantly reduced the medium level of CK and LDH at a variety of dosages. Moreover, piperine and methyl piperate significantly attenuated 2',7'-dichlorofluorescein (DCF) fluorescence by 63.9% and 52.6%, respectively. The present findings demonstrate that the cardioprotective effects of extracted R. roseum in ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation of the membranes. Moreover, its components piperine and methyl piperate exert significant protectective effects on cardiac myocytes.

BACKGROUND Hematopoietic growth factor (HGF) is indispensable to hematopoiesis in the body. The proliferation and differentiation of hematopoietic cells must rely on the existence and stimulation of HGF. This study investigated the effect of catechin, an active component extracted from Spatholobus suberectus Dunn (SSD), on bioactivity of granulocyte-macrophage colony-stimulating activity (GM-CSA), burst-promoting activity (BPA) and megakaryocyte colony-stimulating activity (MK-CSA) in spleen condition medium (SPCM) of mice to clarify the hematopoietic mechanism of catechin and SSD. METHODS Spleen cells of mice were separated and spleen condition medium (SPCM) was prepared from spleen cell culture. Bone marrow cells of mice were separated and cultured in a culture system including 10% (v/v) SPCM (induced by catechin in vivo or ex vivo) for 6 days. Granulocyte-macrophage colony forming units (CFU-GM), erythrocyte burst-colony-forming units (BFU-E) and megakaryocyte colony-forming units (CFU-Meg) formation were employed to assay the effects of different treatment on the bioactivity of GM-CSA, BPA and MK-CSA in SPCM. RESULTS SPCM induced by 100 mg/L catechin ex vivo could promote the growth of CFU-GM, BFU-E and CFU-Meg, which indicated that catechin could stimulate the production of GM-CSA, BPA and MK-CSA in SPCM. SPCM prepared at the fourth day of spleen cell culture showed the best stimulating activity. The bioactivity of GM-CSA, BPA and MK-CSA in the SPCM prepared after intraperitoneally injecting catechin into mice was also increased. The number of CFU-GM, BFU-E and CFU-Meg gradually increased as the dose of catechin increased and the time of administration prolonged. CFU-GM, BFU-E and CFU-Meg of the high-dose catechin group were significantly higher than those of the control group (P < 0.01) and reached the maximum at the seventh day after administration. CONCLUSIONS This study suggests that catechin extracted from the active acetic ether part of Spatholobus suberectus Dunn can regulate hematopoiesis by inducing bioactivity of GM-CSA, BPA and MK-CSA in SPCM of mice. This may be one of the mechanisms for the hematopoietic-supportive effect of catechin and Spatholobus suberectus Dunn.