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Non-physiological shear stress (NPSS) and thrombin have two distinct mechanisms for activating platelets. NPSS in mechanically assisted circulation (MAC) devices can cause platelet dysfunction, e.g., by shedding its key receptors. In addition, patients with heart failure have increased levels of thrombin generation, which may further affect the NPSS-induced platelet dysfunction, resulting in device-associated complications. This study aimed to assess the combined effect of NPSS and thrombin in platelet activation, expression of adhesion receptors on the platelet surface, and alterations of platelet aggregation. Fresh human blood from healthy donors was divided into two groups; one group was treated by adding 0.01 U/mL thrombin, and another group not treated with thrombin served as a control comparison. They were then pumped through a novel blood shearing device which produces similar shear stress conditions to those in the MAC devices. Three levels of NPSS (i.e., 75, 125, and 175 Pa) with a 1.0 s exposure time were selected for the shearing conditions. Expression of platelet activation markers (PAC-1, activated GPIIb/IIIa and CD62P, platelet surface P-selectin) were investigated along with the shedding of platelet receptors (GPIb, GPIIb/IIIa, and GPVI), generation of platelet microparticles, and Phosphatidylserine (PS)-positive platelets detected by flow cytometry. Platelet aggregation (induced by collagen/ristocetin) was measured by Lumi-aggregometry. Platelet receptors were shed after exposure to NPSS showing a positive correlation with the level of shear stress. The generation of platelet microparticles and PS-positive platelets also increased with greater NPSS. Elevated NPSS decreased the platelet aggregation capacity. Platelet activation level increased with greater NPSS. Being treated by thrombin can further exacerbate these characteristics under same level of NPSS, except that platelet activation level drastically dropped after the exposure to 175 Pa NPSS in the thrombin-treated blood. After being treated by thrombin, platelets became more susceptible to NPSS, resulting in more receptor shedding, platelet microparticles, and PS-positive platelets, thus limiting platelet aggregation capacity after exposure to NPSS. Platelet activation, in terms of PAC-1 and P-selectin, is an interim status competing between the expression and shedding of these makers/receptors. When platelets have reached a saturation level of activation, exposure to excessive NPSS can potentially impair activation. [ABSTRACT FROM AUTHOR]

Infusion of genetically modified dendritic cells (DC) expressing immunosuppressive molecules is a potential therapy for organ rejection. IL-12p70, a cytokine produced mainly by DC and macrophages, consists of two subunits, p40 and p35. IL-12p70 is an activator of T cells, while the IL-12p40 subunit serves as a natural antagonist for IL-12p70 action. The primary aim of this study was to evaluate the effect of IL-12p40 gene-modification on both the T-cell stimulatory activity of immature DC (imDC) and their ability to prolong cardiac allograft survival. IL-12p40 gene-modified imDC (DC-p40) exhibited a phenotype characteristic of imDC and displayed impaired T-cell allostimulatory ability in vitro. However, to our surprise, for murine vascularized heterotopic heart transplantation (HHT), administration of donor-derived DC-p40 7 days prior to transplantation did not prolong allograft survival but instead significantly exacerbated cardiac allograft rejection. Further study showed that DC-p40 augmented NK cell activity both in vitro and in vivo and enhanced interferon-gamma (IFN-γ) production in vivo, which might be due to the increased IL-23 production by DC-p40. Our data suggested that although IL-12p40 gene-modified immature DC can induce T cell hyporesponsiveness in vitro, their ability to activate NK cells and induce IFN-γ production counterbalances this, exacerbating cardiac allograft rejection. The unexpected effects of DC-p40 limit their value in promoting allograft survival in vivo and likely reflect the complexity of IL-12p40 biology. [Copyright &y& Elsevier]

Background: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Swertia bimaculata (Sieb. et Zucc.) Hook. Thoms.ex Clarke, a glabrous or procumbent perennial herb, is a traditional herb medicine. Swertiamarin, a secoiridoid glycoside, is a representative ingredient in this medical plant crude extract and shows antidiabetic and antihyperlipidaemic activities and protective effect against hepatic injury.Purpose: The present study aimed to determine whether swertiamarin can attenuate NAFLD in fructose-fed mice.Methods: Healthy male mice freely drank water containing 10% fructose for 12 consecutive weeks, whereas animals in those swertiamarin tested groups received different doses of swertiamarin (25, 50 and 100 mg/kg) by intragastric administration once a day from the ninth week to the twelfth week.Results: At the end of the experiment, fructose-fed mice administrated with swertiamarin showed low levels of serum glucose, triglycerides, uric acid, alanine aminotransferase and aspartate transaminase. Histological examinations suggested the alleviation of hepatic ballooning degeneration and steatosis by swertiamarin treatment. Moreover, swertiamarin administration mitigated hepatic oxidative stress along with decreases of hepatic pro-inflammation cytokines, which was associated with decrease of hepatic xanthine oxidase (XO) activity and enhancements of anti-oxidant defense system enzymes, as well as activation of nuclear factor E2-related factor 2 (Nrf2) in fructose-fed mice. In addition, swertiamarin down-regulated expression of sterol-regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1) in liver of fructose-fed mice.Conclusion: The present study demonstrates that swertiamarin alleviates NAFLD and metabolic alterations in fructose-fed mice. [ABSTRACT FROM AUTHOR]

Alantolactone and isoalantolactone isolated from many species of plants are a pair of positional isomers of C C bond. Previously, alantolactone and isoalantolactone have been proved to be good lead compounds for future anticancer agent development. Similarity of their molecular structures increases the separation difficulty for these two isomers on a conventional C 18 column. Silver perchlorate (AgClO 4 ) as mobile phase additives with RP-HPLC for improving the separation was developed for rapid determination of the positional isomers in Inula racemosa Hook.f. The effects of the concentration of silver perchlorate on the separation of the analytes were investigated. The composition of acetonitrile and water containing 5.0% silver perchlorate in a 65:35 (v/v) ratio was used as mobile phase, in which they were well separated within a short period of time on the C 18 column. The method was successfully applied to determine them in an extract of Inula racemosa Hook.f. root. Silver perchlorate in mobile phase can efficiently improve the separation of the positional isomers and could be applied to rapidly determinate their content in this plant. [ABSTRACT FROM AUTHOR]

Based on classical drug design theory, a novel series of gentiopicroside derivatives was designed and synthesized. All synthesized compounds were then biologically evaluated for their inhibition of influenza virus and anti-HCV activity in vitro . Some of the gentiopicroside derivatives, such as 11a , 13d and 16 showed interesting anti-influenza virus activity with IC 50 at 39.5 μM, 45.2 μM and 44.0 μM, respectively. However, no significant anti-HCV activity was found for all of gentiopicroside derivatives. The preliminary results indicate that modification of the sugar moiety on gentiopicroside was helpful for enhancing the anti-influenza activities. Our works demonstrate the importance of secoiridoid natural products as new leads in the development of potential antiviral inhibitors. [ABSTRACT FROM AUTHOR]

Silver ion chromatography, utilizing columns packed with silver ions bonded to silica gel, has proved to be an invaluable technique for the analysis of some positional isomers. In this work, silver ion chromatography by combination with online heart-cutting LC-LC technique for the preparative separation of two sesquiterpenes positional isomers from a natural product was investigated. On the basis of the evaluation that silver ion content impacts on the separation, the laboratory-made silver ion columns, utilizing silica gel impregnated with 15% silver nitrate as column packing materials, were used for peak resolution improvement of these two isomers and the preparative separation of them in heart-cutting LC-LC. The relationship among the maximal sample load, flow rate and peak resolution in the silver ion column were optimized, and the performance of the silver ion column was compared with conventional C 18 column and silica gel column. Based on the developed chromatographic conditions, online heart-cutting LC-LC chromatographic separation system in combination with a silica gel column and a silver ion column that was applied to preparative separation of these two isomers from a traditional Chinese medicine, Inula racemosa Hook.f., was established. The results showed that the online heart-cutting LC-LC technique by combination of a silica gel column and a silver ion column for the preparative separation of these two positional isomers from this natural plant was superior to the preparative separation performed on a single-column system with C 18 column or silica gel column. [ABSTRACT FROM AUTHOR]

Aims Aucubin, an iridoid glycoside, was isolated from seeds of Eucommia ulmoides Oliver. This study was aimed to evaluate the protective effect of aucubin against ethanol-induced gastric mucosal injury in mice. Materials and methods Mice were orally administrated with aucubin (20, 40 and 80 mg/kg) for 3 consecutive days. On the 3rd day, the mice of gastric mucosal injury were induced with 70% ethanol after the last administration of aucubin. Gastric tissue of mice were submitted for evaluating the severity of gastric mucosal injury. The protective effect of aucubin was evaluated by the gastric ulcer index and histological examinations and determining the levels of inflammatory cytokines, oxidative stress and some gastric mucosal protection factors. Key findings Prophylactic oral administration of aucubin decreased gastric ulcer indexes and histological scores. A significant decrease of myeloperoxidase (MPO) activity and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were observed in aucubin administrated groups. In addition, mice administrated with aucubin increased glutathione (GSH) and heat shock protein-70 (HSP-70) levels and superoxide dismutase (SOD) activity, as well as normalized the levels of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and cyclooxygenase-1 (COX-1) in gastric tissue of mice. Significance The findings of this study demonstrated that aucubin shows protective effect against ethanol-induced acute gastric mucosal injury through its anti-inflammatory and anti-oxidant effects. Furthermore, aucubin enhanced gastric mucosal protection by up-regulation of HSP-70 level and normalization of EGF, VEGF and COX-1 levels. [ABSTRACT FROM AUTHOR]

A sensitive and credible high performance liquid chromatography hyphenated to mass spectrometry (HPLC–MS/MS) was established to quantify the concentration of gracillin in rat plasma. The plasma samples were subjected to a direct protein precipitation process with acetonitrile as a precipitant in a single-step. Ginsenoside Rb 1 was selected as an internal standard (IS). The chromatographic separation of analyte and IS were carried out on an Inersil ODS-3 C 18 column (250 × 4.6 mm, 5 μm) with a binary solvent system containing acetonitrile and 0.1% formic acid in water at a flow rate of 1 mL min −1 under a gradient elution mode. Mass spectrometric detection was performed on a triple quadrupole tandem mass spectrometer by the multiple reaction monitoring (MRM) mode to examine the precursor-to-daughter ion transitions of 1110.3 → 948.2 for IS and 886.1 → 739.9 for gracillin, respectively, in a positive electrospray ionization mode. The calibration curve showed a promising linearity over a concentration range of 0.065–800 ng mL −1 with a better regression coefficient of r 2 = 0.9960. The intra- and inter-day precisions (as relative standard deviation) of the assay at three quality control levels were all less than 3.48%, while the intra- and inter-day accuracies (as relative error) ranged from −8.43% to 9.74%, whose data were within the acceptable limits. The mean extraction recoveries of analyte from rat plasma were all more than 74.11%, and no notable matrix effect was observed. Stability experiments revealed that gracillin remained stable throughout the analytical procedure under various stored conditions. The above validated method was successfully used to investigate the pharmacokinetic behaviors of gracillin orally administrated to rats at three proportion doses. The pharmacokinetic analysis would pave the way for understanding the pharmacological actions and provide a meaningful foundation for further development and application in preclinical and clinical use of gracillin in the near future. [ABSTRACT FROM AUTHOR]

The aim of the current research is to investigate the cerebral-protection of protodioscin on a transient cerebral ischemia-reperfusion (I/R) model and to explore its possible underlying mechanisms. The rats were preconditioned with protodioscin at the doses of 25 and 50 mg kg −1 prior to surgery. Then the animals were subjected to right middle cerebral artery occlusion (MCAO) using an intraluminal method by inserting a thread (90 min surgery). After the blood flow was restored in 24 h via withdrawing the thread, some representative indicators for the cerebral injury were evaluated by various methods including TTC-staining, TUNEL, immunohistochemistry, and Western blotting. As compared with the operated rats without drug intervening, treatment with protodioscin apparently lowered the death rate and improved motor coordination abilities through reducing the deficit scores and cerebral infarct volume. What’s more, an apparent decrease in neuron apoptosis detected in hippocampus CA1 and cortex of the ipsilateral hemisphere might attribute to alleviate the increase in Caspase-3 and Bax/Bcl-2 ratio. Meanwhile, concentrations of several main pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in the serum were also significantly suppressed. Finally, the NF-κB and IκBa protein expressions in the cytoplasm of right injured brain were remarkably up-regulated, while NF-κB in nucleus was down-regulated. Therefore, these observed findings demonstrated that protodioscin appeared to reveal potential neuroprotection against the I/R injury due to its anti-inflammatory and anti-apoptosis properties. This therapeutic effect was probably mediated by the inactivation of NF-κB signal pathways. [ABSTRACT FROM AUTHOR]

The aim of the present study is to explore the potential cerebroprotection of diosgenin against the transient focal cerebral ischemia-reperfusion (I/R) injury and its possible underlying mechanisms. The diosgenin at two dose levels, namely 100 and 200 mg kg −1 , was intragastrically administrated once daily for 7-day period prior to the surgery. Then, the rats were subjected to middle cerebral artery occlusion (MCAO) using the intraluminal thread for 90 min. After 24 h reperfusion, several diagnostic indicators were evaluated and all animals were sacrificed to harvest their brains and blood for subsequent biochemical analyses. The results indicated that diosgenin treatment significantly inhibited the death rate and improved the impaired neurological functions along with neurological deficit scores and cerebral infarct size as compared with the rats exposed to I/R insult without agents administration. The increase in the number of apoptotic cells determined by TUNEL in the hippocampus CA1 and cortex was also apparently attenuated in the diosgenin treatment group, which was closely correlated with suppression of Caspase-3 activity and Bax/Bcl-2 ratio. In addition the elevated concentrations of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in blood serum of the I/R treated rats were reduced almost to their normal level. Further results obtained from the Western blotting analysis revealed that the protein expression of IκBα in the injured brain was up-regulated, while the p65 subunit of NF-κB was down-regulated in nucleus after the treatment. Collectively, this neuroprotection of diosgenin against I/R injury may be attained through its anti-apoptosis, anti-inflammation and intervening the NF-κB signal pathway properties. Due to the satisfactory findings, diosgenin might be a powerful therapeutic agent to combat the similar disease in future clinic. [ABSTRACT FROM AUTHOR]

Taurocholate is a natural conjugated bile acid. The aim of this study was to evaluate the anti-inflammatory effect of taurocholate in TNBS-induced ulcerative colitis in mice. The colitis were induced by rectal administration of TNBS. After 24 h, the experimental animals were treated with sulfasalazine (SASP, 500 mg/kg/day) and taurocholate (20, 40 and 60 mg/kg) for 7 consecutive days. The anti-inflammatory effects of taurocholate for colitis were assessed by body weight, colonic weight and length, macroscopic scores, and histopathological examinations. In addition, the colonic tissue levels of myeloperoxidase (MPO) activity, interleukin (IL)-1β, interferon (IFN-γ) and tumour necrosis factor-α (TNF-α) were also determined to assess the effect of taurocholate. Compared with the model group, treatment with taurocholate (20, 40 and 60 mg/kg) significantly inhibited the body weight loss, improved colonic weight and length, and decreased macroscopic and histopathological scores. Furthermore, the activity accumulation of MPO and the colonic tissue levels of IL-1β, IFN-γ and TNF-α were also decreased by administration of taurocholate. All the findings of this study suggested that taurocholate has the anti-inflammatory effect in ulcerative colitis in mice and indicated it as a good candidate to treat inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is a chronic nonspecific inflammatory disease of unknown cause. The aim of this study was to evaluate the anti -inflammatory effect of tauroursodeoxycholate in 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in mice. After the induction of colitis for 24 h, the mice were administrated orally with tauroursodeoxycholate (20, 40 and 60 mg/kg) and sulfasalazine (500 mg/kg) by gavage for 7 consecutive days. The inhibition effects were evaluated by the body of weight change, survival rate, macroscopical and histological evaluations. Besides, myeloperoxidase (MPO) activity, interleukin (IL)-1β, interferon (IFN)-γ and tumour necrosis factor-α (TNF-α) in colon tissue were also determined by enzyme-linked immunosorbent assay. Treatment with different doses of tauroursodeoxycholate (20, 40 and 60 mg/kg) significantly improved the body weight change, decreased the macroscopic and histopathological scores. Compared with the model group, the accumulation of MPO activity, the colonic tissue levels of IL-1β, IFN-γ and TNF-α were significantly reduced in the tauroursodeoxycholate treated groups. Moreover, tauroursodeoxycholate assuaged the symptoms of colitis. These results suggested that tauroursodeoxycholate has an anti -inflammatory effect in TNBS-induced ulcerative colitis in mice. [ABSTRACT FROM AUTHOR]

A specific high performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS method) was established for determining the concentration of protodioscin (PG) in rat plasma after intragastric administration of its standard form. Ginsenoside Rb 1 was selected as the internal standard (IS). The plasma sample was prepared using one-step deproteinization procedure by adding three parts of acetonitrile to precipitate proteins. The chromatographic separation was accomplished on an Inersil ODS-3 C 18 column (250 × 4.6 mm, 5 μm) with a mobile phase composed with acetonitrile and water containing 0.1% formic acid under a gradient elution mode at a flow rate of 1 mL min −1 . A 3:1 portion of the eluent after a microsplit was detected on a triple quadrupole tandem mass spectrometer coupled with electrospray ionization (ESI) in positive ion and multiple reaction monitoring (MRM) scanning modes. The mass transitions were selected as 888.1 → 1050.2 for PG and 948.2 → 1110.3 for IS, respectively. After careful validation, the plasma samples were always stable under different storage conditions. These analytical results rendered sensitive, selective, and reliable values by this established method which displayed high accuracy, adequate extracted recoveries, and almost negligible matrix effects. This method was applied to the pharmacokinetic studies on PG level in the rat plasma and its pharmacokinetic effect. The results of our studies suggest that the present method may be a useful tool for further clinical study of PG. [ABSTRACT FROM AUTHOR]

A simple, reliable and sensitive high-performance liquid chromatography tandem mass spectrometry method (HPLC–MS/MS) was established for simultaneous analyses of the following 5 steroid saponins in rat plasma after the single dose administration of total steroid saponins extracted from the rhizome of Dioscorea zingiberensis C.H. Wright for the first time. Protodioscin, huangjiangsu A, zingiberensis new saponin, dioscin, and gracillin were quantified using ginsenoside Rb 1 as the internal standard (IS). The plasma samples were pretreated by a single step acetonitrile-mediated protein precipitation. The chromatographic separation was performed on an Inersil ODS-3 C 18 column (250 mm × 4.6 mm, 5 μm) with the mobile phase composed of acetonitrile and water containing 0.1% formic acid under a gradient elution mode at 0.2 mL min −1 using a microsplit after the eluent from the HPLC apparatus. The quantification was accomplished on a triple quadrupole tandem mass spectrometer using the multiple reaction monitoring (MRM) in the positive ionization mode. The above five analytes were stable under sample storage and preparation conditions applied in the present study. The linearity, precision, accuracy, and recoveries of the analysis confirmed the requirements for quality-control purposes. After validation, this proposed method was successfully adopted to investigate the pharmacokinetic parameters of these five analytes. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: NKT cells comprise a rare, but important subset of T cells which account for ~0.2% of the total circulating T cell population. NKT cells are known to have anti-tumor functions and rapidly produce high levels of cytokines following activation. Several clinical trials have sought to exploit the effector functions of NKT cells. While some studies have shown promise, NKT cells are approximately 50% lower in cancer patients compared to healthy donors of the same age and gender, thus limiting their therapeutic efficacy. These studies indicate that baseline levels of activation should be assessed before initiating an NKT cell based immunotherapeutic strategy. Aim: The goal of this study was to develop a sensitive method to rapidly assess NKT cell function. Methods: We utilized artificial antigen presenting cells in combination with qPCR in order to determine NKT cell function in peripheral blood mononuclear cells from healthy donors and breast cancer patients. Results: We found that NKT cell activation can be detected by qPCR, but not by ELISA, in healthy donors as well as in breast cancer patients following four hour stimulation. Conclusion: This method utilizing CD1d-expressing aAPCs will enhance our knowledge of NKT cell biology and could potentially be used as a novel tool in adoptive immunotherapeutic strategies. [Copyright &y& Elsevier]

Abstract: A concise and efficient synthetic route for preparation of four ganglioside GM3 analogues was described. The key step is a highly regioselective and stereoselective α-sialylation from a suitably protected glycoside acceptor with a sialyl xanthate to provide the sialo-oligosaccharide in good yield. The cytotoxic properties of the synthetic gangliosides were evaluated against normal human keratinocytes and human HCT116 and K562 cancer cells. Two of them exhibited good antiproliferative activity and displayed a better cytotoxicity against cancer cell than HaCaT normal cell. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Picrasma quassiodes (D. Don) Benn.(PQB) is used in folk medicines for the treatment of colds, upper respiratory infection, acute tonsillitis, acute gastroenteritis, bacillary dysentery and a variety of acute infectious diseases in Asia. Although recent reports indicate that PQB has antibacterial, and anti-inflammatory effects, its effects on colitis and its inhibitory mechanisms have not been previously reported. Aim of the study: To assess the effects and the mode of action of the extract of Picrasma quassiodes (D. Don) Benn.(PQB) on a model of colitis in mice induced by trinitrobenzene sulfonic acid (TNBS). Materials and methods: We induced mice colitis using TNBS/ethanol, then different doses of Picrasma quassiodes (D. Don) Benn.(PQB) extract (100, 200 and 400mg/kg/day) and sulfasalazine (500mg/kg/day) were administered by gavage for 7 days after the induction of colitis. The mice body weight, colonic wet weight, colonic lengths, myeloperoxidase (MPO) activity, macroscopic and histological colon injury were observed. Pro-inflammatory cytokines such as: tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were assayed by enzyme-linked immunoassay. The protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the colons were determined by immunohistochemical analysis. Results: PQB administration effectively prevented mice diarrhea, decreasing of the body weights, shortening of colon length and increasing of colon wet weight. Macroscopic and histological examinations also indicated that it was protected against colonic edema, ulceration and MPO activity elevation. Furthermore, PQB inhibited the abnormal secretions of pro-inflammatory cytokines, such as TNF-α and IL-8. Additionally, administration of PQB effectively inhibited COX-2 and iNOS protein expression. Conclusions: These results suggest that PQB has an anti-inflammatory effect on TNBS-induced colitis due to the down-regulations of the productions and expressions of inflammatory mediators, and that it may be a potential inflammatory bowel disease (IBD) drug candidate. [Copyright &y& Elsevier]

Abstract: Ethnopharmacologica relevance: Picrasma quassiodes (D. Don) Benn. (PQB) is a widely used herbal medicine used for gastroenteritis, snakebite, infection and hypertension in China. The aim of the study was to investigate the possible antihypertensive mechanisms on spontaneously hypertensive rats (SHR) of the extract from Picrasma quassiodes (D. Don) Benn. Materials and methods: In the in vivo study, extract from Picrasma quassiodes (D. Don) Benn. at the dose of 50, 100, 200mg/kg and captopril (12.5mg/kg) were administrated to different group of SHR rats by gavage for six consecutive weeks after the blood pressures were firstly measured. At the end of the study, rats serum nitric oxide (NO) was measured by the nitrate reductase method; superoxide dismutase (SOD) and malondialdehyde (MDA) activities were measured by the colorimetric method; the expression of aorta endothelial nitric oxide synthase (eNOS) was measured by immunohistochemical analysis. Results: The results showed that the oral administration of PQB could lower the systolic blood pressure (SBP) of SHR rats. In addition, the serum level of NO in SHR treated with PQB (100 and 200mg/kg) was increased dramatically (P<0.05, P<0.01), but administration with captopril had no significant effect. The expression of aorta eNOS was markedly increased when treated with PQB. The serum SOD levels were increased with treatment of PQB (100 and 200mg/kg; P<0.05, P<0.01). All the effects of these parameters were comparable to that of the SHR control group. Conclusions: Our results disclosed that PQB is effective to lower blood pressure of SHR, its antihypertensive effect is probably associated with lowering oxidative stress by reducing SOD activity, preserving endothelial function and increasing the expression of eNOS to regulate NO and directly relax artery. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Tibetan medicine get used to use the flowers of Gentiana straminea Maxim. to cure inflammation of stomach and intestines, hepatitis, cholecystitis, etc. The flowers of Gentiana macrophylla Pall. have been traditionally treated as an anti-inflammatory agent to clear heat in Mongolian medicine. In traditional Chinese medicine, Gentiana macrophylla Pall. and Gentiana straminea Maxim. have also been used under the name “Gentianae Macrophyllae Radix” and prescribed for the treatment of pain and inflammatory conditions. Aim of study: The present study evaluated the pharmacological effects of two species of “Radix Gentianae Macrophyllae” in experimental inflammation and pain models, and determined the chemical compounds that may correlate with their pharmacological activities. The comparison is needed to identify whether the two related plants can be used interchangeably. Materials and methods: We evaluated the pharmacological effects of the flowers of Gentiana macrophylla Pall. and Gentiana straminea Maxim. in experimental inflammation and pain models. An HPLC-MS method was developed to analyze the chemical composition. The effects of Gentiana macrophylla Pall. and Gentiana straminea Maxim. on the p65 and p50 phosphorylation were examined by immunblotting. NF-κB transcriptional activity was measured using the luciferase assay, in vitro kinase assay and Griess reaction. Results: The extracts of Gentiana macrophylla Pall. and Gentiana straminea Maxim. possessed significant antinociceptive and anti-inflammatory activities. Flavonoids, secoiridoid glycosides and triterpines were determined in the extracts and may be the basis of the observed pharmacological effects. Nuclear translocation of p65, p50 and NF-κB transcriptional activity induced by LPS were suppressed by Gentiana macrophylla Pall. and Gentiana straminea Maxim. Conclusion: The results clearly demonstrated that the chemical composition and pharmacological activities of the two herbs were similar, which support the interchangeability among the two herbs when using them in folk medicine. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Er-Zhi-Wan (EZW), a classic Chinese formulation, which contains Fructus Ligustri Lucidi (FLL) and Herba Ecliptae (HE). EZW is widely used to prevent and treat various kidney diseases for its actions of nourishing the kidney and strengthening tendon and bone. Although recent reports indicate that EZW restrains osteoclastic bone resorption, its effects on the protection against define OVX-induced bone loss in mature rats have not been systematically investigated. Materials and methods: Sixty 3-month-old female Sprague–Dawley rats were randomly assigned into sham-operated group (Sham) and five OVX subgroups, OVX with vehicle (OVX); OVX with Estradiol Valerate (EV, 0.4mg/kg body weight/day); OVX with EZW of graded doses (9.0, 4.5, or 2.25g/kg/day). Daily oral administration of EV and EZW on 5th week for 26 weeks. Bone turnover markers (Serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), osteocalcin (OCN), deoxypyridinoline (DPD)), other parameters, including serum calcium (S-Ca), serum phosphorus (S-P), urine calcium (U-Ca), phosphorus (U-P), and bone mineral density (BMD) of the femur, 4th lumbar vertebra and tibia, bone biomechanical properties and trabecular microarchitecture parameters were measured. Results: Administration of EZW could significantly prevent ovariectomy-induced bone loss, biomechanical reduction, deterioration of trabecular microarchitecture and the body weight gain without affecting the weight of the uterus, and increased S-Ca, S-P levels, decreased level of bone turnover markers and U-Ca, U-P levels in ovariectomized rats. Conclusion: The present study indicated that EZW had a definite antiosteoporotic effect without hyperplastic effect on uterus, and it might be a potential alternative medicine for treatment of postmenopausal osteoporosis. [Copyright &y& Elsevier]

Abstract: Ulcerative colitis is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and up-regulation of pro-inflammatory cytokines. The aim of this study is to evaluate the effect of taurohyodeoxycholic acid (THDCA) isolated from Pulvis Fellis Suis on acute ulcerative colitis model induced by trinitrobenzene sulfonic acid (TNBS) in mice. The efficacy of THDCA was studied by macroscopical and histological scoring systems as well as myeloperoxidase (MPO) activity. Serum levels, including tumor necrosis factor (TNF)-α and interleukin (IL)-6 were assayed by enzyme-linked immunoassay. The expression of cyclooxygenase (COX)-2 in the colons was assessed by immunohistochemical analysis. Treatment with THDCA in doses of 25, 50 and 100mg/kg/day and sulfasalazine in a dose of 500mg/kg/day used as reference for 7 consecutive days after the induction of colitis, significantly decreased colonic MPO activity, TNF-α, IL-6 serum levels and the expression of COX-2 in colon compared with TNBS induced ulcerative colitis model group. Moreover, THDCA attenuated the macroscopic colonic damage and the histopathological changes induced by TNBS. All the effects of these parameters were comparable to that of the standard sulfasalazine, especially at the highest dose level. The results suggested that THDCA from Pulvis Fellis Suis has a protective effect in TNBS-induced ulcerative colitis which might be due to its anti-inflammatory activities, and that it may have therapeutic value in the setting of inflammatory bowel disease. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Pulvis Fellis Suis is used in folk medicines to treat intestinal diseases, acute pharyngitis, whooping cough and asthma in China. Although several reports indicate that Pulvis Fellis Suis display diverse biological activities, such as antibacterial, anti-inflammatory and anti-infusorian effects, its effects on ulcerative colitis have not been previously explored. Aim of the study: The purpose of the present study is to assess the anti-inflammatory effect of Pulvis Fellis Suis (PFS) extract in acute ulcerative colitis model induced by trinitrobenzene sulfonic acid (TNBS) in mice. Materials and methods: Different doses of Pulvis Fellis Suis extract (100, 200 and 400mg/kg/day) and sulfasalazine (500mg/kg/day) were administered by gavage for 7days after the induction of colitis with TNBS. The efficacy of PFS was studied by macroscopical and histological scoring systems as well as myeloperoxidase (MPO) activity. Serum levels, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assayed by enzyme-linked immunoassay. The expression of cyclooxygenase (COX)-2 in the colons was assessed by immunohistochemical analysis. Results: Treatment with PFS significantly attenuated macroscopic damage as compared with TNBS (P <0.01). Histological analysis showed that PFS improved the microscopic structure and preserved some areas of the colonic mucosa structure. In addition, administration of PFS effectively inhibited COX-2 protein expression and MPO activity accumulation. TNF-α and IL-6 levels were also diminished dose-dependently (P <0.05, P <0.01), and IL-6 level obtained had no significant results by small dose of PFS. All the effects of these parameters were comparable to that of the standard sulfasalazine, especially at the highest dose level. Conclusions: We have shown for the first time that PFS has an anti-inflammatory effect in TNBS-induced ulcerative colitis which might be related to the reduction of up-regulated TNF-α and IL-6 production, and that it may have therapeutic value in the setting of inflammatory bowel disease (IBD). [Copyright &y& Elsevier]

Maturation of dendritic cells (DC) is critical for efficient antigen presentation and initiation of an immune response. Interferon-γ (IFN-γ) is an important Th1 cytokine. In this study, we investigated the role of IFN-γ in DC maturation using either IFN-γ receptor deficient- or IFN-γ overexpression-models. We showed that immature DC generated in vitro from bone marrow (BM) progenitor cells produced low level of IFN-γ. After LPS stimulation, DC produced more IFN-γ, and IFN-γ productions were at comparable levels among C57BL/6 mice-derived DC (C57BL/6 DC), wild-type 129 mice-derived DC (129 DC) and IFN-γ receptor deficient 129 mice-derived DC (IFN-γR-/-DC). We found that IFN-γR-/-DC exhibited decreased expression of CD54, CD86, reduced capacity to secrete IL-1β and IL-12p70, and impaired capacity to stimulate alloreactive T cells and to drive Th1 differentiation. Transfection of IFN-γ gene into DC promoted DC to express higher CD40, CD54, CD80, CD86, CCR7 and I-Ab, secrete more IL-1β and IL-12p70, and more potently activate both CD4 and CD8 T cells. These data suggest that IFN-γ signaling pathway is important for the maturation of DC in an autocrine fashion. [Copyright &y& Elsevier]