Toonanoronoids A-E, five new limonoids from Toona ciliata var. yunnanensis.

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.

[Comparative proteomic profiling of hippocampi in mice treated with Jingui Shenqi Pills and Liuwei Dihuang Pills].

The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.

A Strategy for Screening the Lipid-Lowering Components in Alismatis Rhizoma Decoction Based on Spectrum-Effect Analysis.

Alismatis Rhizoma decoction (ARD), comprised of Alisma plantago-aquatica subsp. orientale (Sam.) Sam and Atractylodes macrocephala Koidz. at a ratio of 5 : 2, is a classic traditional Chinese medicine (TCM) formula with successful clinical hypolipidemic effect. This paper aimed to explore the major bioactive compounds and potential mechanism of ARD in the treatment of hyperlipidemia on the basis of spectrum-effect analysis and molecular docking. Nine ARD samples with varying ratios of the constituent herbs were prepared and analyzed by UPLC-Q-TOF/MS to obtain the chemical spectra. Then, the lipid-lowering ability of the nine samples was tested in an oleic acid-induced lipid accumulation model in human hepatoma cells (HepG2). Grey relational analysis and partial least squares regression analysis were then performed to determine the correlation between the chemical spectrums and lipid-lowering efficacies of ARD. The potential mechanisms of the effective compounds were investigated by docking with the farnesoid X receptor (FXR) protein. The results indicated that alisol B 23-acetate, alisol C 23-acetate, and alisol B appeared to be the core effective components on hyperlipidemia in ARD. Molecular docking further demonstrated that all three compounds could bind to FXR and were potential FXR agonists for the treatment of hyperlipidemia. This study elucidated the effective components and potential molecular mechanism of action of ARD for treating hyperlipidemia from a perspective of different compatibility, providing a new and feasible reference for the research of TCM formulas such as ARD.

Self-Sufficient and Highly Efficient Gold Sandwich Upconversion Nanocomposite Lasers for Stretchable and Bio-applications.

Multifunctional lanthanide-doped upconversion nanoparticles (UCNPs) have spread their wings in the fields of flexible optoelectronics and biomedical applications. One of the ongoing challenges lies in achieving UCNP-based nanocomposites, which enable a continuous-wave (CW) laser action at ultralow thresholds. Here, gold sandwich UCNP nanocomposites [gold (Au1)-UCNP-gold (Au2)] capable of exhibiting lasing at ultralow thresholds under CW excitation are demonstrated. The metastable energy-level characteristics of lanthanides are advantageous for creating population inversion. In particular, localized surface plasmon resonance-based electromagnetic hotspots in the nanocomposites and the huge enhancement of scattering coefficient for the formation of coherent closed loops due to multiple scattering facilitate the process of stimulated emissions as confirmed by theoretical simulations. The nanocomposites are subjected to stretchable systems for enhancing the lasing action (threshold ∼ 0.06 kW cm-2) via a light-trapping effect. The applications in bioimaging of HeLa cells and antibacterial activity (photothermal therapy) are demonstrated using the newly designed Au1-UCNP-Au2 nanocomposites.

Electroacupuncture Is Effective for Peripheral Facial Paralysis: A Meta-Analysis.

OBJECTIVE: To explore the status of electroacupuncture (EA) among other treatments for peripheral facial paralysis (PFP). METHODS: Randomized controlled trials comparing EA with other treatments that met the eligibility criteria published in databases were included. The differences were observed and quantified through the risk ratio (RR) for dichotomous outcomes and the standardized mean difference (SMD) for continuous outcomes. Then, their 95% confidence intervals (CI) were recorded. RESULTS: Twenty-three studies involving 1985 participants were included. META-analysis results showed that EA was better than manual acupuncture for PFP (RR: 1.16, 95% CI 1.11 to 1.22, for responding rate; SMD: 2.26, 95% CI 0.15 to 4.37, for facial nerve function) and current promoted recovery (RR: 1.21, 95% CI 1.15 to 1.27, for responding rate; SMD: 2.87, 95% CI 1.16 to 4.58, for facial nerve function). When combined with other treatments, EA improved their effectiveness (RR: 1.19, 95% CI 1.12 to 1.28, responding rate; SMD: 1.85, 95% CI 0.67 to 3.03, facial nerve function). CONCLUSION: Patients with PFP received EA (used separately or combined with other treatments) resulting in a better prognosis. However, the quality of evidence was very low-to-moderate. Considering the poor quality of evidence, we are not very confident in the results. We look forward to more research and update results in the future and improve the evidence quality.

[Study on compatibility of active ingredients of Simiao Yongan Decoction in rats with in situ single-pass intestinal perfusion model].

To study the compatibility rule of Simao Yongan Decoction,the rat single pass intestinal perfusion model in situ was used in this study. On the basis of early research,the five kinds of anti-inflammatory active ingredients,i.e. chlorogenic acid,liquiritin,hyperoside,angoroside C and isochlorogenic acid C in Simao Yongan Decoction were selected as research objects. The contents of the above five actives compounds with various compatibility combinations and in different intestinal segment perfusates were determined by using the method of ultra-performance liquid chromatography-mass spectrometry( UPLC-MSn). The kinetic parameters of intestinal absorption of the five anti-inflammatory active ingredients were calculated,which could be used to evaluate the intestinal absorption of each component in different combinations. The results showed that the absorption parameters of liquiritin in ileum were highest in Glycyrrhizae Radix et Rhizoma single herb,while the absorption parameters of other four components in ileum and duodenum were highest in the compatible combinations. Among them,the absorption parameters of chlorogenic acid in ileum and duodenum were highest in the whole prescription compatibility; ischlorogenic acid C showed higher absorption levels in the whole prescription and the herb compatibility of Lonicerae Japonicae Flos-Scrophulariae Radix-Glycyrrhizae Radix et Rhizoma. However,the absorption levels of hyperoside and angoroside C in different compatibilities were quite different in ileum and duodenum. In this study,the intestinal absorption of five anti-inflammatory active ingredients in Simiao Yongan Decoction with different compatibility combinations was investigated,revealing that the absorption of active ingredients varied with the different compatibility combinations and different intestinal segments. At the same time,the above research also indicated that the absorption of active ingredients could be obviously promoted by the compatibility of compound prescriptions,laying a foundation for the research on the compatibility rule of Simiao Yongan Detection from the biological point of view.

New Cytotoxic Cycloartane Triterpenes from the Aerial Parts of Actaea heracleifolia (syn. Cimicifuga heracleifolia).

One new 15,16-seco-cycloartane triterpene (1: ), three new cycloartane triterpene glycosides (2: -4: ), and five known compounds (5: -9: ) were isolated from the aerial parts of Actaea heracleifolia. The chemical structures of these compounds were determined on the basis of NMR analysis, HRTOF-ESIMS data, and other spectroscopic methods. Selected compounds were evaluated for their cytotoxicity against human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) in vitro. Compounds 3: and 4: showed weak activity against the HL-60, A-549, and MCF-7 cell lines with IC50 values ranging from 21.34 to 36.98 µM.

[Effects of Long-term Fertilization Regimes on Microbial Biomass, Community Structure and Activity in a Paddy Soil].

Four paddy soils were collected in Ningxiang County, Hunan province. These used with different long-term fertilization regimes, including a control without fertilizer (CK), chemical fertilization with nitrogen, phosphate, and kalium (NPK), straw fertilization combined with NPK (ST), and manure fertilization combinedwith NPK (OM). Phospholipid fatty acid (PLFA) technology and MicrorespTM method were used to study the effect of long-term fertilization on soil microorganism abundance, community structure, and activity. Results showed that the abundance of bacteria, fungi, gram-negative (G-) bacteria, and gram-positive (G+) bacteria in the soil from the OM treatment was generally higher than for the other treatments; these levels were lower in the ST and NPK treatments and lowest in the CK treatment. The principal components analysis (PCA) of PLFA showed that the community structure of microorganisms in NPK, ST, and OM treatments was altered in comparison with that in CK, especially in the case of the ST and OM treatments. MicroRespTM results revealed that compared to the CK treatment (1.28 µg·h-1), soil microorganisms in the OM treatment had the highest average utilization rate of multiple carbon sources (1.81 µg·h-1), followed by ST (1.19 µg·h-1), CK (1.28 µg·h-1), and NPK (0.95 µg·h-1). Furthermore, different long-term fertilization regimes resulted in distinct carbon source preferences for the soil microorganisms and revealed a significant alteration in the microbial community. Conclusively, long-term fertilizer with straw or manure changes the microbial community and is a benefit for improving the biomass and activity of microorganism in rice paddy soils.

Cytotoxic 9,19-cycloartane triterpenes from the aerial parts of Cimicifuga yunnanensis.

Six new 9,19-cycloartane triterpenes (1-6) were isolated from the aerial parts of Cimicifuga yunnanensis. The new chemical structures were determined by extensive analyses of 1D and 2D NMR spectroscopy. Compounds 1 and 2 are the first 9,19-cycloartane triterpenes characterized by CH3-18 shifting from C-13 to C-12 in the Cimicifuga spp. The evaluation of inhibition activity against human HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines indicated that compounds 1-6 showed different levels of cytotoxic activities with IC50 values ranging from 1.2 to 27.8 µm.

Purgative components in rhubarbs: adrenergic receptor inhibitors linked with glucose carriers.

Rhubarbs and their extractives have been used as cathartic for many years. There have been numerous breakthroughs in the pharmacological research of the drug. However, as the key point of the mechanism, the targets of the effective components still remain unclear. In this paper, with an in vitro system of isolated intestine, we found that both the rhubarb extractives and the anthraquinone derivatives can antagonize the adrenaline effectively. Furthermore, computer based docking provided the binding model of the anthraquinone derivatives and adrenergic receptor. Then, based on the results of the small intestinal promotion and purgative effect experiments in vivo, we built an "inhibitor-carrier" hypothesis to elucidate the mechanism of rhubarb. This work provided key massages for the pharmacological research of rhubarb, such a common and active medicinal plant, and might be of help for the development of new purgative drugs.

Mesenchymal stem cells alleviate TNBS-induced colitis by modulating inflammatory and autoimmune responses.

AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by measuring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-ß). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by down-regulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4(+)CD25(+)Foxp3(+) regulatory T cells (TGF-ß, IL-10, Foxp3) with a suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). CONCLUSION: MSCs are key regulators of immune and inflammatory responses and may be an attractive candidate for cell-based therapy of IBD.

[Study on the diet quality and its relative effect factors among rural residents, using the Chinese Diet Balance Index (CDBI) in Hanzhong, Shaanxi province].

OBJECTIVE: To evaluate the diet quality and the relative factors among rural residents in Hanzhong, Shaanxi province. METHODS: A cross-sectional survey on dietary status together with a semi-quantitative food frequency questionnaire were conducted on rural residents aged from 18 to 80 in Hanzhong of Shaanxi in 2010. Diet quality was evaluated by using the Chinese Diet Balance Index (CDBI) scoring and evaluating system. Linear regression models were developed to identify factors that influencing the status of under/over intake. RESULTS: 2748 rural residents were investigated with the average daily intake of grains, beans, heavily salted vegetables, plant oil, nuts and salt. Results showed that they were higher than average level of Chinese rural residents' (P < 0.01). 80% of the residents having their daily intake of grains, oil and salt exceeded, while animal food, diary food, egg, vegetable and fruits were lower (P < 0.01) than the RNIs. However, there was under intake noticed to some extent in some areas. The average values of DBI_LBS and DBI_HBS were 22.8 and 9.8. The proportions of moderate under intake (20 < DBI_LBS ≤ 40) and moderate over intake (10 < DBI_HBS ≤ 20) were 62.6% and 48.0%. The main factors that influenced the dietary under-intake were education level, fortune index, hypertension, physical activity, and time to watch television. The main factors that affected the over-intake of diet were sex, age, number of family numbers, intensity of labor, time to sleep, smoking and drinking habits. CONCLUSION: The main diet problem among the rural residents was under-dietary-intake, with over-intake to some extents, suggesting that it was necessary to strength the specific intervention program, to improve the diet quality in the residents of Hanzhong area.

[Effect of abdominal needling in treating post-cardiosurgical operational gastrointestinal dysfunction].

OBJECTIVE: To evaluate the clinic effect of abdominal needling (AN) on post-cardiosurgical operational gastrointestinal dysfunction. METHODS: Sixty patients were equally assigned to two groups, the AN group and the control group. AN applied on the AN group was conducted by needling at Xiawan (Ren 10), Qihai (Ren 6), Qipang, Guanyuan (Ren 4), Qixue, Shuifen (Ren 9), Tianshu (St. 25) and Daju (St. 27), starting from the first day after operation, once every day with the needle retained time of 20 min, 5 days as one therapeutic course. The control group was treated with the conventional post-operational measurement with intravenous injection of 20 mg Omeprazole once a day, for 3 successive days. The score on symptoms as anorexia, weakness, abdominal distension, constipation, laziness to speak, nausea and vomiting, weakened borborygmus, pale-yellow complexion and edema, etc. , were observed. RESULTS: The symptom scores in the aspects of anorexia, weakness, abdominal distension, constipation, weakened borborygmus, nausea and vomiting in the AN group were significant difference when compared with before treatment and the control group (P <0.01). After treatment the improvement in the control group only showed in weakness and pale-yellow complexion (P <0.01). Observation on gastric emptying showed that 24 h gastric paresis occurred in 17 patients (56.7%) of the AN group, and 22 (73.3%) of the control group; the 24 h and 72 h barium residue (strip) in the AN group was 10.60 +/- 4.61 and 8.53 +/- 4.08 respectively, while in the control group 17.07 +/- 3.99 and 15.83 +/- 4.19; the 24 h, 72 h gastric emptying rate in the former was (47.00 +/- 23.07) % and (57.33 +/- 20.37) %, and in the latter (14.67 +/- 19.95) % and (20.83 +/- 20.97) %, all showed significant difference between them (P <0.05 or P <0.01). Levels of motilin in the two groups after operation were decreased showing significant difference in comparison with before operation (P < 0.01), and AN group was raised after teratment, also showing significant difference between groups (P <0.01). CONCLUSION: AN can strengthen gastrointestinal peristalsis, promote gastrointestinal emptying, recover quickly gastrointestinal hormone to the normal range. Besides, it is safe and effective, with no pain or only slight pain, easy in locating the acupoint accurately, standard prescription, high compliance of patients, and convenient for clinical operating, therefore, it is worthy of spreading in clinical practice.

[Effect of andrographolide on QS regulating virulence factors production in Pseudomonas aeruginosa].

OBJECTIVE: To investigate the effect of andrographolide on virulence factors production in Pseudomonas aeruginosa. METHOD: Growth rate, pyocyanin, proteolytic activity and elastase activity were measured with or without the presence of andrographolide. The effect of andrographolide on pyocyanin production, proteolytic activity and elastase activity in PAO-JP2 was investigated simultaneously. RESULT: The andrographolide did not affect the growth of PAO1 in planktonic culture. The production of pyocyanin, proteolytic activity and elastase activity were significanthy suppressed in P. aeruginosa cultures grown in the presence of andrographolide. However, these effects were not observed in PAO-JP2. CONCLUSION: The inhibiting effect of andrographolide on virulence factors production in P. aeruginosa may play a role in its anti-infection activity.

[Determination of isoimperatorin and osthol in ganmao yixiaoshi capsule by RP-HPLC].

OBJECTIVE: To develop a method for the determination of isoimperatorin and osthol in Ganmao Yixiaoshi capsule by RP-HPLC. METHOD: The chromatographic conditions included Hypersil C18 column and the mobile phase consisting of a mixture of acetonitrile-water (42.5:57.5). The detection wavelength was at 320 nm. RESULT: The calibration curve was linear over the concentration range of 0-0.3975 microg for isoimperatorin and 0-0.3825 microg for osthol respectively. The correlation coefficient was r = 0.9999 and r = 0.9997. The average recovery of isoimperatorin was 98.1% and that of osthol was 99.8%. CONCLUSION: The method sensitive, simple and accurate for the determination of isoimperatorin and osthol concentrations in Ganmao Yixiaoshi capsule.

[Intervention of xuezhikang on patients of acute coronary syndrome with different levels of blood lipids].

OBJECTIVE: To observe the intervention of Xuezhikang (XZK) on patients of acute coronary syndrome (ACS) with different levels of blood lipids. METHODS: Adopting the double blind randomized controlled method, 105 patients of ACS were divided into two groups. The 53 patients in the treated group, 26 with normal blood lipids (NBL) and 27 with hyperlipemia (HL) were treated with conventional western medicine plus XZK 1.2 g per day for 12 weeks. The 52 patients in the control group, 25 with NBL and 27 with HL, were treated with conventional western medicine alone. Besides, a healthy control group consisted of 40 subjects was set up. The changes of brachial arterial endothelium-dependent diastolic function (FMD) before and after treatment was observed, the changes of blood levels of nitric oxide (NO), endothelin-1 (ET-1), C-reactive protein (CRP) and lipids were also recorded. RESULTS: Before treatment, FMD value and serum NO level were lower and ET-1 and CRP levels in ACS patients were higher than those in the healthy subjects, and a significant correlation existed between CRP, NO and FMD with LDL-C. After treated for 12 weeks, FMD value and serum NO level increased, levels of ET-1 and CRP decreased significantly in the treated group, showing significant difference to those in the control group (P < 0.05, P < 0.01). Serum levels of TC, TG and LDL-C in the treated group lowered significantly. HDL-C level in patients with HL increased significantly while in those with NBL, it showed a trend of increasing but with no statistical significance. CONCLUSION: Applying XZK in ACS patients in early stage, either with NBL or with HL, could improve the endothelial function, antagonize inflammatory response to stabilize the atheromatous plaque.