Anticancer activity of Saussurea lappa extract by apoptotic pathway in KB human oral cancer cells

Abstract

Context: Saussurea lappa Dence (Compositae) is used as a traditional herbal medicine to treat abdominal pain and tenesmus in East Asia. Current studies have shown that S. lappa has anticancer activity in divergent of cancer cells. However, the effects of S. lappa on oral cancer and its mechanisms of action have yet to be elucidated.

Objective: To explore its potential chemotherapeutic effects and mechanism of cell growth inhibition on human oral cancer cells.

Materials and methods: The dried roots of S. lappa were used in this study. Cell viability of KB cells was evaluated by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay after treatment with 30?µg/ml of methanol extract from the dried roots of S. lappa. To understand whether its effect on cell death is related with apoptosis pathway, we performed DNA fragmentation assay, western blot, caspase activity assay and fluorescence-activated cell sorting (FACS) analysis.

Results: Treatment of S. lappa extract onto KB cells reduced cell viability significantly with an IC₅₀ value of 30?µg/ml. The formation of a DNA ladder was observed starting at the 24?h treatment. In western blotting analysis, the S. lappa extract induced the proteolytic processing of caspase-3, -9 and poly (ADP-ribose) polymerase, a significant increase of Bax and marked reduction of Bcl-2. We also confirmed the activation of caspase-3/-7 in living KB cells by fluorescence microscopy.

Conclusion: These results suggested that S. lappa extract inhibited cell proliferation through the apoptosis pathway in KB human oral cancer cells.     

Two Novel Phenolic Triterpenes from Tripterygium Wilfordii

Abstract

Two novel phenolic triterpenes were isolated from Tripterygium wilfordii Hook. f., their structures were identified to be 2,3-dihydroxy-1,3,5(10),8-tetra-ene-6α-(2′-hydroxyethyl)-24-nor-D:A-friedooleanane-29-oic acid 1, named triptotin F, and 2,3-dihydroxy-1,3,5(10),8-tetraene-6β-(2′-hydroxyethyl)-24-nor-D:A-friedooleanane-29-oic acid 2, named triptotin G on the basis of spectroscopic studies.     

Hepatoprotective effects of cod liver oil against sodium nitrite toxicity in rats

Abstract

Context: Exposure to high levels of nitrites for a prolonged time have adverse health effects on several organs especially the liver due to oxidative properties. Meanwhile, cod liver oil has been reported to ameliorate organ dysfunction in animal models that involve oxidative stress.

Objective: Examine the impact of dietary cod liver oil on sodium nitrite-induced liver damage.

Materials and methods: Thirty-two adult male Sprague-Dawely rats were daily treated with sodium nitrite (80?mg/kg) in presence or absence of cod liver oil (5?ml/kg). Morphological changes were assessed in liver sections. Oxidative stress and antioxidant markers were measured in serum and liver homogenates. Liver samples were used for measurements of MCP-1, DNA fragmentation and mitochondrial function.

Results: The hepatoprotective effect of cod liver oil was proved by significant reduction of elevated liver enzymes and normal appearance of hepatocytes. Cod liver oil significantly reduced hepatic malondialdehyde, hydrogen peroxide and superoxide anion (224.3?±?18.9?nmol/g, 59.3?±?5.1 and 62.5?±?5.1?µmol/g, respectively) compared with sodium nitrite (332.5?±?25.5?nmol/g, 83.1?±?8.1 and 93.9?±?6.5?µmol/g, respectively). Cod liver oil restored hepatic cytochrome c oxidase activity after 38% reduction by sodium nitrite. Furthermore, cod liver oil significantly reduced hepatic MCP-1 (79.8?pg/mg) and DNA fragmentation (13.8%) compared with sodium nitrite (168.7?pg/mg and 41.3%, respectively).

Discussion and conclusion: Cod liver oil ameliorates sodium nitrite induced hepatic impairment through several mechanisms including attenuation of oxidative stress, blocking MCP-1, reactivation of mitochondrial function and reduction of DNA fragmentation.     

Quantitation of nanoparticle accumulation in flow using optimized microfluidic chambers

Abstract

Background: The vascular cell adhesion molecule-1 (VCAM-1) targeting peptide sequence, VHPKQHR, is a promising moiety for targeting atherosclerosis through incorporation into nanoparticles such as dendrimers and liposomes.

Purpose: We aim to develop VCAM-1-targeted nanoparticles that effectively accumulate on the endothelium under shear conditions and to develop robust microfluidic chambers able to house sufficient cells for flow cytometric measurements.

Methods: Carboxyfluorescein-labeled monomeric VHP-peptide, tetrameric VHP-dendrimers (bisbidentate or radial architecture, with or without N-terminal acetylation) and VHP-peptide liposomes were prepared. Human umbilical vein endothelial cells were treated with nanoparticles under 0 or 2.9 dyne/cm² shear, and particle binding was quantified. Flow chambers cured at various temperatures, with or without glass backings were fabricated, characterized for deformation and applied in experiments.

Results: Although liposomes accumulated with highest efficiency, dendrimers also demonstrated specific binding. N-terminal acetylation significantly reduced dendrimer binding, and despite shorter movement range, bisbidentate dendrimers outperformed radial dendrimers, suggesting multiple epitope presence within its estimated arm-span of 57?Å. Under shear, while liposome binding increased 300%, dendrimer binding to cells decreased 65%. Through higher temperature curing and glass backing insertion, polydimethylsiloxane flow chambers maintaining rectangular cross-section with aspect-ratio as low as 1:111 were achieved.

Conclusion: Optimized dendrimers and liposomal nanocarriers specifically accumulated onto cells within microfluidic chambers.     

Does multi-parity affect the size of the ascending thoracic aorta in women: a prospective cohort study

Objective: Aortic dissection is an uncommon and potentially fatal complication of pregnancy; however, the association of the number of pregnancies with the indexed and absolute size of the ascending aorta in patients without aortic aneurysm or connective tissue disorders is not well elucidated.

Research design and methods: In this prospective observational study, women aged 18–80 years old undergoing transesophageal echocardiography in a university-affiliated echocardiography laboratory between 1 January 2015 and 1 September 2015 were enrolled. Indexed and absolute sizes of ascending aorta at the levels of annulus, root, sinotubular junction (STJ), proximal and arch were measured. Patients were grouped according to their gravida number into three classes (class I: ≤3, class II: 4–7, class III: ≥7).

Results: Of 653 screened patients, 437 women were included (38.9% gravida class I, 44.3% gravida class II and 16.7% gravida class III). In univariate analysis, the number of pregnancies correlated with indexed diameters of the root (p?<?.001), STJ (p?<?.001) and the proximal ascending aorta (p?<?.001). Meanwhile, the number of pregnancies neither correlated with the annular diameter nor with the arch (p?=?.070 and p?=?.154, respectively). In multivariate analyses, the gravida class was among the independent predictors of the root size along with age, aortic insufficiency and the presence of congestive heart failure.

Conclusion: Gravida class was an independent predictor of aortic size at levels of the root, STJ and the proximal ascending aorta. The largest increase was observed at the level of the aortic root.     

Curcumin attenuates fructose-induced vascular dysfunction of isolated rat thoracic aorta rings

Context: Consumption of high fructose is associated with metabolic abnormalities, insulin resistance, and hypertension. It is not known whether this hypertensive effect of fructose is related to metabolic abnormalities or due to the direct effect of fructose on blood vessels.

Objective: Here, we investigated the direct effect of fructose on rat isolated aorta and the possible protective effect of curcumin.

Materials and methods: The isolated rat thoracic aorta rings were used to measure the contractile responses to different concentrations of both phenylephrine and KCl, and the relaxant response to acetylcholine (Ach). The effect of curcumin (1?µM) alone or in combination with tempol (1?mM), a superoxide dismutase mimetic agent, and N-{[3(amino-methyl)-phenyl]-methyl} ethanimidamide dihydrochloride (1400?W), a specific inducible nitric oxide synthase (iNOS) inhibitor, (1?µM) on fructose-treated aorta was compared. The aortic rings were incubated with different treatments for 60?min before starting the experiment. Changes in the intracellular calcium in response to KCl and nitric oxide levels were also measured.

Results and discussion: Fructose strongly increased the contractile response of aortic rings to both phenylephrine and KCl (E_max was increased by 147.3% and 150.5%, respectively) but it did not affect the relaxant response to Ach. Curcumin significantly decreased the hyper responsiveness of arterial rings to both vasopressors (for phenylephrine, E_max decreased from 147.3% in fructose incubated aorta to 81%, and for KCl, E_max decreased from 150.5% in fructose-incubated aorta to 77.24% respectively). Curcumin also reduces the intracellular calcium level (85% reduction in intracellular calcium). A 1400?W was the only agent that potentiates the effect of curcumin.

Conclusion: Fructose has a direct deleterious effect on aortic vascular reactivity. Curcumin can partially protect against fructose-induced impairment in vascular contractility via an antioxidant effect and reduction of elevated intracellular calcium.     

Combretum lanceolatum flowers ethanol extract inhibits hepatic gluconeogenesis: an in vivo mechanism study

Context Ethnopharmacological studies have demonstrated that plants of the Combretum genus presented antidiabetic activity, including Combretum lanceolatum Pohl ex Eichler (Combretaceae).

Objective This study investigated the hepatic mechanisms of action of C. lanceolatum flowers ethanol extract (ClEtOH) related to its antihyperglycaemic effect in streptozotocin-diabetic rats.

Materials and methods Male Wistar rats were divided into normal (N) and diabetic control (DC) rats treated with vehicle (water); diabetic rats treated with 500?mg/kg metformin (DMet) or 500?mg/kg ClEtOH (DT500). After 21 d of treatment, hepatic glucose and urea production were investigated through in situ perfused liver with l-glutamine. Changes in the phosphoenolpyruvate carboxykinase (PEPCK) levels and in the activation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-signalling intermediates were also investigated.

Results Similar to DMet, DT500 rats showed a reduction in the rates of hepatic production of glucose (46%) and urea (22%) in comparison with DC. This reduction was accompanied by a reduction in the PEPCK levels in liver of DT500 (28%) and DMet (43%) when compared with DC. AMPK phosphorylation levels were higher in the liver of DT500 (17%) and DMet (16%) rats. The basal AKT phosphorylation levels were increased in liver of DT500 rats, without differences in the insulin-stimulated AKT phosphorylation and in the insulin receptor levels between DC and DT500 rats.

Discussion and conclusion The antidiabetic activity of ClEtOH can be attributed, at least in part, to inhibition of hepatic gluconeogenesis, probably due to the activation of both AMPK and AKT effectors and reduction in the PEPCK levels.     

In vitro and in vivo antimutagenic effects of DIG,a herbal preparation of Berberis vulgaris,Taraxacum officinale and Arctium lappa,against mitomycin C

DIG, a liquid herbal preparation made from a mixture of diluted mother tinctures of Berberis vulgaris, Taraxacum officinale and Arctium lappa, was assessed for its antimutagenic properties against mitomycin C. The micronucleus assay on Chinese hamster ovary (CHO)-K1 cells was used to evaluate the in vitro anticlastogenic activity of DIG compared to those of separately diluted mother tinctures. The micronucleus assay was performed on mouse erythrocytes and the comet assay was performed on mouse liver, kidney, lung, brain and testicles to assess the protective effects of DIG (0.2 and 2 % at libitum) against an intraperitoneal injection of mitomycin C (1 mg Kg^?1) in mice. DIG exerted a powerful anticlastogenic activity, under both pretreatment and simultaneous treatment conditions as assessed by the micronucleus assay in CHO-K1 cells. Its protective activity was greater than that observed for each mother tincture. DIG reduced micronuclei levels in mouse erythrocytes and suppressed >80 % of DNA strand breaks in the liver, kidney, lung, brain and testicles of mice exposed to mitomycin C.

     

Baohuoside-I suppresses cell proliferation and migration by up-regulating miR-144 in melanoma

Context: Baohuoside-I was reported to induce apoptosis in non-small-cell lung cancer and inhibit the growth of multiple myeloma cells. The antitumour potential of baohuoside-I has not been demonstrated in melanoma yet.

Objective: To investigate the potential antitumour activity of baohuoside-I against melanoma and elucidate its underlying molecular mechanism.

Materials and methods: Cell viability was evaluated by MTT assay. The malignant invasion capacity was measured with trans-well assay. The relative expression change of microRNAs was profiled with microarray. TargetScan was utilized for prediction of target gene of miR-144. Regulatory effect of miR-144 on SMAD1 was determined by dual luciferase reporter assay. Endogenous SMAD1 protein in response to ectopic expression of miR-144 was determined by immunoblotting. Xenograft mice were employed to evaluate antitumour potential of baohuoside-I (25?mg/kg by tail intravenous injection every two days) in vivo.

Results: Baohuoside-I significantly inhibited proliferation (45?±?4% reduction in M14 and 35?±?3% reduction in MV3 at 24?h) and migration (70?±?4% reduction in M14 and 72?±?3% reduction in MV3) in melanoma cells. Mechanistically, baohuoside-I up-regulated miR-144 expression levels (3?±?0.2-fold). Silence of miR-144 reversed the inhibition of baohuoside-I in melanoma. We have identified that SMAD1 was the novel target of miR-144. Moreover, baohuoside-I suppressed melanoma in vivo (52?±?8% reduction in xenograft tumour size at day 20).

Conclusions: Our data suggested significant antitumour potential of baohuoside-I against melanoma both in vitro and in vivo, which warrants further laboratory investigation and clinical trial.     

Hepatoprotective effect of peony total glucosides and the underlying mechanisms in diabetic rats

Context: Total glucosides of peony (TGP), compounds extracted from the dried roots of Paeonia lactiflora Pall, have been reported to have anti-inflammatory and antioxidative activities. However, the protective effect of TGP on liver injury and the underlying mechanisms remains unknown in diabetic rats.

Objectives: Current study investigates prevention of liver injury by TGP in diabetic rats and its mechanism was related to the inhibition of endoplasmic reticulum stress (ERS).

Materials and methods: Fifty adult male rats were randomly divided into: Normal group, diabetic group, TGP (50, 100 and 200?mg/kg/day) treatment groups (n?=?10 per group). At the end of the 8th week, the liver was removed for biochemical and histological examinations.

Results: Compared with the diabetic group, administration of TGP at doses of 50, 100 and 200?mg/kg significantly prevented the increase of hepatic fibrosis score (ED₅₀ 139.4?mg/kg). Compared with diabetic group, TGP at doses of 50, 100 and 200?mg/kg showed an inhibition on the increased macrophage infiltration. MCP-1 and TNF-α mRNA and protein expression were significantly increased in diabetic group compared with normal group; TGP administration caused significant reduction of high levels of MCP-1 and TNF-α mRNA as well as protein levels. Also, TGP at all doses showed an inhibition on the increased GRP78 levels, p-Perk levels and p-Eif2α levels in liver from diabetic group.

Discussion and conclusions: Our results indicate that TGP has potential as a treatment for diabetic liver injury attenuating liver lipid accumulation and inflammation as well as ERS induced by diabetic condition.     

Centella asiatica enhances hepatic antioxidant status and regulates hepatic inflammatory cytokines in type 2 diabetic rats

Context: Neutralizing the over-activation of oxidative stress and inflammation remains an important goal in the management of type 2 diabetes mellitus (T2DM). Centella asiatica (L.) Urban (Apiaceae) (CA) has been used in traditional folklore in Africa and Asia to treat various ailments including diabetes.

Objective: We investigated the hepatic antioxidant and anti-inflammatory potential of methanol extract of CA leaves in T2DM.

Materials and methods: T2DM was induced in male Sprague-Dawley rats with 10% fructose in drinking water for 14?days followed by a single intraperitoneal injection of streptozotocin (40?mg/kg b.wt). Hepatic oxidant/antioxidant status was assessed by measuring the concentrations of malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), Trolox equivalent antioxidant capacity (TEAC), reduced glutathione (GSH) and activities of glutathione S-transferase (GST) and glutathione peroxidase (GPX). The concentrations of cytokines IL-1β, IL-4, IL-6, IL-10, MCP-1 and TNF-α in the liver were determined.

Results: Diabetes increased MDA formed (47%) and reduced FRAP (20%), TEAC (15%), GSH levels (32%), significantly; decreased GST and GPX activities in the liver and elevated levels of cytokines studied. Treatment of diabetic rats with 500?mg/kg b.wt CA for 14?days decreased MDA (44%); elevated FRAP (15%) and GSH (131%) levels and increased the activities of GST and GPX by 16%. Hepatic concentrations of IL-1β, MCP-1 and TNF-α in DCA group were reduced to 68%, 75% and 63% of DC values, respectively.

Conclusions: The antioxidant and anti-inflammatory properties of CA may protect tissues such as the liver from diabetes-induced oxidative damage.     

The dipeptidyl peptidase-4 inhibitor alogliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis

Objectives: The potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin improves glycemic control in patients with type 2 diabetes through incretin hormone-mediated increases in both α- and β-cell responsiveness to glucose. In this study, the efficacy and safety of alogliptin in type 2 diabetic patients undergoing hemodialysis (HD) were evaluated.

Methods: A prospective, open-label study of 30 patients (male/female: 24/6; mean age: 69.7 ± 1.7 years) with type 2 diabetes who were undergoing HD without insulin injection therapy was conducted. Patients were administered 6.25 mg/day alogliptin and efficacy and safety were determined by monitoring clinical and laboratory parameters during the 48-week study period.

Results: After 48 weeks, alogliptin had decreased postprandial plasma glucose levels from 212 ± 8 mg/dL baseline to 156 ± 7 mg/dL, hemoglobin A1c levels from 7.1 ± 0.2% baseline to 6.3 ± 0.2% and glycated albumin (GA) levels from 25.6 ± 0.6% baseline to 20.7 ± 0.4% (all p < 0.0001). Alogliptin efficacy did not differ according to median age or body mass index, but the GA reduction was significantly greater in the antidiabetic agents-naïve group. The magnitude of GA reduction was baseline GA-dependent, being greater at higher baseline GA levels. No serious adverse effects, such as hypoglycemia or liver impairment, were observed in any patient.

Conclusion: Alogliptin as monotherapy or in combination with other oral antidiabetic agents improved glycemic control and was generally well tolerated in patients with HD over a 48-week period.     

Dihydromyricetin improves vascular hyporesponsiveness in experimental sepsis via attenuating the over-excited MaxiK and KATP channels

Context: Dihydromyricetin (DMY) has oxidation resistance, anti-inflammatory and free radical scavenging capabilities. The preventive effects of DMY for vascular hyporeactivity remain unclear.

Objective: This study investigates the preventive effects of DMY in vascular hyporeactivity.

Materials and methods: The experimental sepsis was induced by transvenous administration of lipopolysaccharide (LPS) to Sprague–Dawley (SD) rats. DMY-treated rats received daily administration of DMY, 5?μg/kg dissolved in DMSO through the tail vein for 7?days. The invasive mean arterial pressure (MAP) of the caudal ventral artery was measured. Dose-response curves for norepinephrine (NE, doses from 10^?9 to 10^?6?M) were obtained in isolated thoracic aorta in a cumulative manner. The function of MaxiK and K_ATP channels were investigated using whole-cell patch clamp recording. The Elisa was adopted to measure the serum concentration of NO, MDA, 3-NT, IL-1β and TNF-α.

Results: The increased MAP in septic rats induced by vasopressor agents was smaller than that in control rats. However, the % of increased MAP induced by vasopressor agents was raised by DMY injection (NE: 20.4?±?8.495 vs. 15.16?±?5.195%; AVP: 14.05?±?2.459 vs. 9.583?±?2.982%, p??6?M) in vitro. was increased by 51% in LPS?+?DMY group compared with that in LPS?+?Con group (2.74?±?0.81 vs. 1.82?±?0.92?g, p?ATP channel blocker) pretreatment, instead of 4-aminopyridine (4-AP) and BaCl₂, could diminish the DMY-induced improvement of vasoconstrictor hyporeactivity (ChTX: 73.2?±?11.8 vs. 71.8?±?13.5%; Glib: 63.1?±?12.5 vs. 58.1?±?13.7%, p?>?0.05). DMY blunted the highly sensitized MaxiK and K_ATP channels of arterial smooth muscle cells isolated from the thoracic aorta of LPS rats. DMY decreased the serum level of NO, MDA, IL-1β and TNF-α, which had increased in LPS rats.

Discussion and conclusions: Our results indicate that DMY administration ameliorated the impaired contractility of the rat aorta in experimental sepsis. Such an effect is mediated by normalization of the over-excited MaxiK and K_ATP, channels possibly via oxidative stress inhibition.     

Antioxidative burst and hepatoprotective effects of ethanol root extract of Hippocratea africana against paracetamol-induced liver injury

Abstract

Context: Hippocratea africana (Willd.) Loes. ex Engl. (Celastraceae) root is used traditionally as an antipoison or antidote to treat liver diseases.

Objective: To evaluate antioxidative burst and hepatoprotective potentials of H. africana against paracetamol-induced liver injury in rats.

Materials and method: Antioxidative burst activity of the extract (1–100?µg/ml) in whole blood, neutrophils and macrophages was investigated using a luminol/lucigenin-based chemiluminescence assay. The hepatoprotective effect of the extract (200–600?mg/kg) was evaluated by the assay of liver function parameters, antioxidant enzymes and histopathological studies of the liver. GC-MS analyses of hexane and dichloromethane fractions were also carried out.

Results and discussion: The root extract/fractions exerted pronounced inhibition of oxidative burst activity in whole blood, neutrophils (intracellular and extracellular) and macrophages (3.04–99.70%). The administration of the root extract caused significant (p?<?0.05–0.001) reduction of high levels of liver enzymes (AST, ALT and ALP), total cholesterol, direct and total bilirubin as well as elevation of serum levels of total protein, albumin and antioxidant enzymes (SOD, CAT, GPx and GSH). Histology of the liver sections of extract and silymarin-treated animals showed reductions in the pathological features compared to the paracetamol-treated animals. The chemical pathological changes were consistent with histopathological observations suggesting a marked hepatoprotective effect of the root extract of H. africana. The GC-MS analysis revealed some pharmacologically active compounds.

Conclusion: The results show that the root extract of H. africana has hepatoprotective potential probably due to its antioxidative burst activity.     

基于网络药理学和分子对接方法探讨雷公藤对狼疮性肾炎的效毒作用机制

目的基于网络药理学和分子对接方法探讨雷公藤治疗狼疮性肾炎的效毒作用机制。方法通过TCMSP、Uniprot、STITCH等数据库查询雷公藤的化合物分子及其主要靶点,并与狼疮性肾炎相关基因做对比,获得药物靶点与疾病相关的共有基因,构建药物与疾病之间的网络关系。通过String数据库获取潜在作用靶标之间的相互作用关系,利用Cytoscape软件构建中药-成分-疾病网络。运用Clusterprofiler程序分别进行GO基因富集分析和KEGG通路富集分析。结果从雷公藤中筛选得到44个候选活性成分,包括雷公藤甲素、雷公藤多苷、雷公藤红素等;潜在作用靶标228个,其中治疗靶标152个,毒性靶标76个。GO富集分析结果显示,治疗靶标主要与细菌来源分子的反应(response to molecule of bacterial origin)、对脂多糖的反应(responsetolipopolysaccharide)、胞浆钙离子浓度的正调控(positiveregulationofcytosoliccalciumion concentration)等有关。治疗狼疮性肾炎的相关基因参与通路共125条,具有潜在不良反应的相关基因通路共130条。分子对接结果表明,5α-benzoyl-4α-hydroxy-1β, 8α-dinicotinoyl-dihydro-agarofuran、triptofordin B1、triptofordinine A2与SYK有较好的结合性。结论基于网络药理学方法和分子对接挖掘雷公藤对狼疮性肾炎治疗靶点和毒性靶点、治疗作用通路和毒性作用通路,为研究雷公藤对狼疮性肾炎效毒作用机制提供了新的研究方法。     

The role of artichoke leaf tincture (Cynara scolymus) in the suppression of DNA damage and atherosclerosis in rats fed an atherogenic diet

Context: Polyphenols and flavonoids in artichoke leaf tincture (ALT) protect cells against oxidative damage.

Objectives: We examined ALT effects on deoxyribonucleic acid (DNA) damage and lipid profiles in rat plasma and gene expression in rat aorta [haemeoxygenase-1 (HO1), haemeoxygenase-2 (HO2), NADPH oxidase 4 (NOX-4), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)].

Materials and methods: Eighteen male Wistar albino rats were divided into three groups (n?=?6/group): The control group (CG) was fed with standard pellet chow for 11 weeks; the AD group was fed for a similar period of time with pellet chow supplemented with 2% cholesterol, 3% sunflower oil and 1% sodium cholate. The ADA group was fed with pellet chow (for 1 week), the atherogenic diet (see above) for the following 4 weeks and then with ALT (0.1?mL/kg body weight) and atherogenic diet for 6 weeks. According to HPLC analysis, the isolated main compounds in ALT were chlorogenic acid, caffeic acid, isoquercitrin and rutin.

Results: Normalized HO-1 [0.11 (0.04–0.24)] and MCP-1 [0.29 (0.21–0.47)] mRNA levels and DNA scores [12.50 (4.50–36.50)] were significantly lower in the ADA group than in the AD group [0.84 (0.35–2.51)], p?=?0.021 for HO-1 [0.85 (0.61–3.45)], p?=?0.047 for MCP-1 and [176.5 (66.50–221.25)], p?=?0.020 for DNA scores. HO-1 mRNA was lower in the ADA group than in the CG group [0.30 (0.21–0.71), p?=?0.049].

Conclusions: Supplementation with ALT limited the effects of the atherogenic diet through reduced MCP-1 expression, thereby preventing oxidative damage.     

Liver function assessment by indocyanine green plasma disappearance rate in patients with intra-abdominal hypertension after “non-hepatic” abdominal surgery

Background and objective: Liver function assessment in patients with intra-abdominal hypertension (IAH) after major abdominal surgery is complex and often confounding. Elevated intra-abdominal pressure (IAP) often occurs after major abdominal surgery, and is associated with decreased abdominal blood flow and organ dysfunction, and it could cause abdominal compartment syndrome (ACS), which is a life-threatening condition. Plasma disappearance rate (PDR) of indocyanine green (ICG) and ICG retention rate after 15?min (R15) were used to evaluate liver function and as a prognostic parameter after major abdominal surgery.

Methods: In this prospective/observational study, 51 patients were followed in the surgical intensive care unit after major abdominal surgery (operation of the small and large intestine, stomach, pancreas, spleen, or resection of the abdominal aorta), 29 had IAH. The PDR-ICG and R15 were analyzed 24?h after surgery concurrently with IAP, APP, bilirubin, AST, ALT, prothrombin time, albumin, cardiac index, arterial lactate, oxygen delivery, MAP (mean arterial pressure), APACHE II (acute physiology and chronic health evaluation), SOFA (sequential organ failure assessment), and SAPS II (simplified acute physiology score). IAH has been defined as a peak intra-abdominal pressure (IAP) value of ≥12?mmHg, at a minimum, as two standardized measurements obtained 1–6?h apart.

Results: The PDR-ICG measured 24?h after surgery was not different among groups (20.95% [SD?=?10.34] vs 25.40% [SD?=?7.42]), p?=?.094. ICG R15 was significantly higher in patients with IAH, 11.10% [SD?=?13.82] vs 8.30 [SD?=?11.46], p?p?Conclusions: The results suggest that PDR/ICG and ICG R15 are useful dynamic tests for evaluation of complex liver function and survival prediction after major abdominal surgery in patients with IAH.     

Immunostimulatory and Anti-inflammatory Polysaccharides from Tripterygium wilfordii.: Comparison with Organic Extracts

Abstract

The organic extracts of Tripterygium wilfordii. Hook F. (Celastraceae) have been used in the treatment of inflammatory and autoimmune diseases for many years in China, although they also possess significant toxicity. These extracts are anti-inflammatory and immunosuppressive in nature, suppressing lipopolyscacharide (LPS)-stimulated upregulation of NF kappa B gene expression. In the current study, an ethyl acetate (EA) extract and a crude hot water soluble polysaccharide (PS) fraction from T. wilfordii. were compared. Both fractions were effective in reducing LPS-stimulated NO accumulation in cultured RAW 267.4 macrophages in a dose-dependent manner (IC₅₀ values of 1.7 and 32.1 μ g/mL for EA and PS, respectively). The LC₅₀ of EA (19.8–22.3 μ g/mL) was significantly greater than that of PS, which exhibited no apparent cytotoxicity toward either macrophages or EAhy 926 endothelial cells (up to 10 mg/mL). We also showed that PS was able to stimulate NO production by untreated macrophages in a dose-dependent manner. Thus, depending on the experimental condition of cultured macrophages, a crude PS fraction of T. wilfordii. may exhibit immunostimulatory or anti-inflammatory effects. This unique property, together with its relatively low level of toxicity, supports further investigation of its role in diseases in which inflammation and immunomodulation are critical.