bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of anti-angiogenic, anti-inflammatory and antinociceptive activity of coenzyme Q10 in experimental animals
Authors: Jung Hyun-Joo , Park Eun-Hee , Lim Chang-Jin 
Published: October 2010

AbstractObjectivesThis work aimed to assess some pharmacological activities of coenzyme Q10 (CoQ10) in animal experimental models.MethodsThe chick chorioallantoic membrane assay was used to evaluate anti-angiogenic activity of CoQ10. Anti-inflammatory activity of CoQ10 was confirmed using two animal models of inflammation. These were the vascular permeability and air pouch models, models of acute and sub-acute inflammation, respectively. Antinociceptive activity was assessed by the acetic acid-induced abdominal constriction response.Key findingsCoQ10 dose-dependently displayed inhibition of chick chorioallantoic membrane angiogenesis. In the acetic acid-induced vascular permeability model in mice, CoQ10 at 50, 100 and 200 mg/kg reduced vascular permeability from 0.74 ± 0.01 (A590) to 0.67 ± 0.01 (P &lt; 0.01), 0.46 ± 0.02 (P &lt; 0.01) and 0.30 ± 0.01 (P &lt; 0.01), respectively. In the carrageenan-induced inflammation in the air pouch, CoQ10 was able to diminish exudate volume, the number of polymorphonulcear leucocytes and nitrite content in the air pouches. CoQ10 at 25, 50 and 100 mg/kg significantly reduced acetic acid-induced abdominal constriction in mice from 27.0 ± 2.00 (number of abdominal constrictions) to 17.7 ± 0.33 (P &lt; 0.01), 9.3 ± 0.67 (P &lt; 0.01) and 1.3 ± 0.33 (P &lt; 0.01), respectively, suggesting a strong antinociceptive activity.ConclusionsCoQ10 possessed considerable anti-angiogenic, anti-inflammatory and antinociceptive activity, possibly via down-regulating the level of nitric oxide, which partly supported its use as a dietary supplement and in combination therapy.
Quercetin and naringenin transport across human intestinal Caco-2 cells
Authors: Chabane Meriem Nait , Ahmad Abraham Al , Peluso Jean , Muller Christian D , Ubeaud-Séquier Geneviève 
Published: October 2010

AbstractObjectivesFlavonoids are phenolic compounds found in most edible fruits and vegetables. Previous studies have demonstrated their biological and beneficial effects on human health. However, their bioavailability and, in particular, their intestinal absorption mechanism have not yet been clearly identified. The aim of our work was to quantify and to characterize in vitro the nature of the transport of two flavonoids distinguished by their physicochemical and pharmacological properties: quercetin, a flavan-3-ol, and naringenin, a flavanone.MethodsDifferentiated and polarized Caco-2 human intestinal epithelial cell lines were used for this purpose.Key findingsIn our experimental conditions, quercetin and naringenin were poorly absorbed by Caco-2 cells. Quercetin was absorbed by passive diffusion and a pH-dependent mechanism mediated by the organic anion transporting protein B (OATP-B). It was not a multidrug resistance associated protein (MRP)1 substrate, but was substrate of the MRP2 efflux transporter and not P-glycoprotein (P-gp). Intestinal permeability from the apical to the basolateral side was higher for naringenin than for quercetin, which was partly explained by naringenin's physicochemical characteristics. Naringenin, partially absorbed by passive diffusion, was also an ATP-dependent transport substrate mediated by MRP1, but was not an OATP-B substrate. However, naringenin was secreted via active P-gp and MRP2 efflux transporters.ConclusionsThe contribution of ATP-dependent efflux transporters (MRP2 and P-gp) to the permeability of these compounds in the apical side could explain their low bioavailability. In conclusion, knowledge of the absorption mechanism of these two flavonoids was used to determine the intake level that has a beneficial effect on human health and their putative role in food—drug interactions.
Rubus sanctusprotects against carbon tetrachloride-induced toxicity in rat isolated hepatocytes: isolation and characterization of its galloylated flavonoids
Authors: Badr Amira M , El-Demerdash Ebtehal , Khalifa Amani E , Ghoneim Asser I , Ayoub Nahla A , Abdel-Naim Ashraf B 
Published: October 2010

AbstractObjectivesRubus sanctus Schreb., known from the Bible as ‘holy thorn bush’, grows wild in Egypt. Rubus sanctus aqueous alcoholic extract (RE) contains a complicated phenolic mixture (ellagitanins, flavonoids and caffeic acid derivatives). In this study, the phytochemical investigation of the plant was re-evaluated. Herein, we report on the isolation and identification of three galloylated flavonoids, namely kaempferol-3-O-(6″-O-galloyl)-4C1-β-d-galactopyranoside, quercetin-3-O-(6″-O-galloyl)-4C1-β-d-galactopyranoside and myricetin-3-O-(6″-O-galloyl)- C1-β-d-galactopyranoside for the first time from the Rubus genus. We further aimed at evaluating the potential protective effects of RE against carbon tetrachloride (CCl4)-induced toxicity in isolated rat hepatocytes.MethodsBased on an initial concentration-response experiment, a concentration of 100 μg/ml was selected to investigate the hepatoprotective activity of RE.Key findingsPretreatment with RE afforded protection as indicated by counteracting CCl4-induced cell death, and reduced glutathione depletion. In addition, RE ameliorated CCl4-induced enzyme leakage by 40% for lactate dehydrogenase, 30% for alanine aminotransferase and 20% for aspartate aminotransferase as compared with CCl4-treated cells. Moreover, RE counteracted CCl4-induced lipid peroxidation and inhibited spontaneous lipid peroxidation in the control group.ConclusionsIn conclusion, RE protects against CCl4-induced toxicity in isolated rat hepatocytes.
Central nervous system effects of the essential oil of the leaves of Alpinia zerumbet in mice
Authors: De Araújo Fernanda Yvelize Ramos , Silva Maria Izabel Gomès , Moura Brinell Arcanjo , De Oliveira Gersilene Valente , Leal Luzia Kalyne A Moreira , Vasconcelos Silvânia Maria Mendes , Viana Glauce Socorro Barros , De Moraes Manoel Odorico , De Sousa Francisca Cléa Florenço , Macêdo Danielle Silveira 
Published: October 2010

Abstract

Objectives
Alpinia zerumbet, known in Brazil as colônia, is popularly used as a diuretic, antihypertensive, anti-ulcerogenic and sedative. Based on this, we have investigated the central effects of the essential oil isolated from A. zerumbet leaves.

Methods
Mice were treated once with 50 or 100 mg/kg of the essential oil, intraperitoneally, 30 min before being submitted to behavioural models of: locomotor activity (open-field), catalepsy, anxiety (elevated plus maze), depression (forced swimming test and tail suspension tests) as well as apomorphine-induced stereotypy.

Key findings
Results showed a dose-related decrease on locomotor activity and apomorphine-induced stereotypy. There was a decrease to the order of 55% of the grooming behaviour with both doses studied. The essential oil 100 mg/kg increased cataleptic activity (167%) and the immobility time in the forced swimming and tail suspension tests. Pretreatment with haloperidol (0.2 mg/kg, i.p.) alone also decreased locomotion, increased cataleptic activity and immobility time in the tail suspension test. No alterations in the elevated plus maze test were registered.

Conclusions
The essential oil of A. zerumbet leaves had depressant and possible antipsychotic activity, since it could reverse the stereotypy induced by apomorphine, presenting effects comparable with those obtained with haloperidol treatment.
Raphanus sativusextract prevents and ameliorates zearalenone-induced peroxidative hepatic damage in Balb/c mice
Authors: Salah-Abbès Jalila Ben , Abbès Samir , Haous Zohra , Oueslati Ridha 
Published: October 2010

AbstractObjectivesRaphanus sativus (radish) is a species of crucifer, which includes widely consumed vegetables, distributed in Asia, Africa and Europe. It is a rich source of bioactive molecules including anthocyanins, glucosinolates, isothiocyanates and other flavonoids, and miscellaneous phenolic substances. We have evaluated the hepatoprotection of R. sativus extract against zearalenone, an estrogenic mycotoxin initiating hepatotoxicity in male Balb/c mice.MethodsAnimals were divided into seven treatment groups and treated orally each day for twenty eight days as follows: a control, an olive oil group, group I, group II, and group III treated with radish extract alone (5, 10 and 15 mg/kg, respectively), group IV treated with zearalenone (40 mg/kg), and group V treated with zearalenone plus the lowest dose of radish extract.Key findingsAdministration of zearalenone alone resulted in significant decreases in the levels of alkaline phosphatase, lactate dehydrogenase, alanine and aspartate aminotransferases in the liver, suggesting hepatic damage. Moreover, a marked increase in the level of lipid peroxide and concomitant decrease of glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, glutathione-S-transferase, RNA and DNA concentrations were also observed in the liver tissue of zearalenone-treated mice. Co-treatment with R. sativus extract plus zearalenone succeeded in reversing the condition back to normal levels for all studied parameters.ConclusionsBy itself R. sativus extract did not show any toxic effects and could be considered as a potent hepatoprotectant.
Effect of dimethylnitrosamine-induced liver dysfunction on the pharmacokinetics of 5-fluorouracil after administration of S-1, an antitumour drug, to rats
Authors: Yoshisue Kunihiro , Kanie Shohei , Nishimura Takako , Chikamoto Junko , Nagayama Sekio 
Published: October 2010

AbstractObjectivesThe anti-tumour agent S-1 comprises tegafur (a prodrug of 5-fluorouracil; 5-FU), gimeracil (2-chloro-2,4-dihydroxypyridine (CDHP); a competitive inhibitor of 5-FU metabolism) and oteracil potassium. The effect of hepatic dysfunction induced by dimethylnitrosamine (DMN) on the pharmacokinetics of 5-FU after administration of S-1 to rats was investigated.MethodsS-1 (5 mg/kg) was administered intravenously and orally to rats with DMN-induced liver dysfunction. Plasma concentrations of S-1 components and 5-FU were measured by HPLC and LC/MS-MS. Blood tests and in-vitro enzymatic investigations were also conducted.Key findingsDMN treatment induced hepatic dysfunction and decreased the conversion of tegafur to 5-FU in the liver without altering renal function or dihydropyrimidine dehydrogenase activity. Following intravenous administration of S-1, the blood concentration-time profiles of CDHP were similar between control rats and rats with hepatic dysfunction, but the half-life of tegafur was significantly prolonged. The maximum plasma concentration (Cmax) of 5-FU was significantly reduced and the area under the blood concentration-time curve (AUC) was reduced by 22%. Following oral administration, the Cmax of tegafur, 5-FU and CDHP were significantly decreased and half-lives significantly increased. Hepatic dysfunction had a less pronounced effect on the AUC of 5-FU (13.6% reduction).ConclusionsThe pharmacokinetic profiles of tegafur, 5-FU and CDHP were altered by changes in the elimination rate of tegafur induced by a decrease in the conversion of tegafur to 5-FU. However, hepatic dysfunction had less of an effect on the AUC of 5-FU, which correlates with anti-tumour effect, after the oral administration of S-1.
Inhibitory effects of 1,3-thiazine derivatives on melanogenesis
Authors: Ha Sang Keun , Koketsu Mamoru , Lee Minjae , Moon Eunjung , Kim Sung-Hoon , Yoon Tae-Jin , Kim Sun Yeou 
Published: October 2010

Abstract

Objectives
The aim of this study was to identify a novel skin-depigmenting agent from synthetic 1,3-thiazine derivatives.

Methods
We investigated the inhibitory effects of six kinds of 1,3-thiazine derivative on melanogenesis by examining their effects on tyrosinase activity and melanin biosynthesis in melan-a cells and the zebrafish model.

Key findings
Of the six compounds, 4-hydroxy-2,6-dimethyl-5,6-dihydro-4H-1,3-thiazine (TZ-6) had the strongest anti-melanogenic effects in cultured melan-a cells (30.4% inhibition at 100 μM). In addition, TZ-6 exhibited an inhibitory effect on mushroom and cellular tyrosinase. Based on the results of Western blotting, TZ-6 reduced the expression of tyrosinase at 100 mM. Additionally, TZ-6 reduced body pigmentation and inhibited tyrosinase activity in the zebrafish model.

Conclusions
The results have provided useful information for the development of a skin whitening agent.
Gastroprotective effect and cytotoxicity of abietane diterpenes from the Chilean LamiaceaeSphacele chamaedryoides(Balbis) Briq.
Authors: Areche Carlos , Schmeda-Hirschmann Guillermo , Theoduloz Cristina , Rodríguez Jaime A 
Published: October 2010

AbstractObjectivesThe aim of this report was to isolate, identify and assess the gastroprotective effect and cytotoxicity of abietane diterpenes from the Chilean medicinal plant Sphacele chamaedryoides (Balbis) Briq. (Lamiaceae).MethodsThe isolated compounds were identified by spectroscopic means. The gastroprotective effect of the compounds was studied on the HCl/EtOH-induced gastric lesions model in mice. The cytotoxicity of the compounds was assessed on human normal lung fibroblasts (MRC-5) and gastric adenocarcinoma cells (AGS).Key findingsFrom the aerial parts of the plant, five phenolic and five p-quinone abietanes, the sesquiterpene spathulenol and two flavonoids were obtained. The main diterpene from the plant was carnosol (7). Lansoprazole at 20 mg/kg reduced gastric lesions by 64.7% (P &lt; 0.01), being statistically similar to carnosol at doses of 10 and 20 mg/kg; the percent lesion reduction with 7 at 5 mg/kg was 49.3%. At a single oral dose of 5 mg/kg, the diterpenes bearing a p-quinone moiety −6,7-dehydroroyleanone (1), royleanone (2), 7,20-epoxyroyleanone (3), taxoquinone (5) and horminone (6) - presented a gastroprotective effect of 54.4, 70.8, 65.0, 35.8 and 52.7%, respectively. Of the C-7 hydroxy derivatives, the activity was much lower for the 7β-OH isomer. The phenolic diterpenes 7 and 7-oxo-11,12,14-trihydroxy-8,11,13-abietatrien-20-al (8) inhibited gastric lesions by 49.3 and 53.0%, respectively. Royleanone (2), 7,20-epoxyroyleanone (3), horminone (6), 8 and spathulenol proved to be cytotoxic with IC50 values in the range of 11–67 μM. The selective cytotoxicity of compounds 1 (IC50: 61 and 366 μM) and 5 (IC50: 310 and 27 μM) against AGS cells and fibroblasts, respectively, merit additional studies.ConclusionsAll the abietanes obtained from S. chamaedryoides present either one or two phenolic OH groups, a quinone system, or both. Several compounds present in the plant showed higher gastroprotective effect than lansoprazole. The cytotoxic effect of most compounds was found at fairly high concentrations and lacked cell specificity. Further studies are required using different tumour cell lines and viability/proliferation assays to assess the specificity of the isolated compounds. The selective cytotoxicity of compounds 1 and 5 against AGS cells and fibroblasts, respectively, merit additional studies.
Huang-Lian-Jie-Du-Tang exerts anti-inflammatory effects in rats through inhibition of nitric oxide production and eicosanoid biosynthesis via the lipoxygenase pathway
Authors: Zeng Huawu , Liu Xiaohua , Dou Shengshan , Xu Wen , Li Na , Liu Xiaojun , Zhang Weidong , Hu Zhenlin , Liu Runhui 
Published: October 2010

AbstractObjectivesHuang-Lian-Jie-Du-Tang (HLJDT) is a traditional Chinese medicine with a long history of anti-inflammatory use, but its pharmacological effects have not been thoroughly investigated. This study aimed to evaluate the anti-inflammatory activity of HLJDT in vivo and in vitro.MethodsThe carrageenan rat air pouch model was used to investigate the anti-inflammatory action of HLJDT after oral administration. Moreover, we exploited a modified method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique to assay the effects of HLJDT on arachidonic acid metabolites.Key findingsOur data demonstrate that oral administration of HLJDT significantly inhibited the inflammatory responses in carrageenan-injected rat air pouches, and also significantly reduced the production of nitric oxide (NO) and leukotriene B4 (LTB4) in vivo, without any influence on biosynthesis of cyclooxygenase (COX)-derived eicosanoids. Similar behaviour of HLJDT was also observed by using calcium ionophore A23187-stimulated peritoneal macrophages, where HLJDT markedly inhibited eicosanoids derived from different lipoxygenases. The NO production and the mRNA expression of inducible nitric oxide synthase (iNOS) and chemotactic factors (CCL3, CCL4, CCL5 and CXCL2) were also inhibited by HLJDT in RAW 264.7 macrophages stimulated by lipopolysaccharide.ConclusionsOur data revealed, for the first time, that HLJDT could inhibit biosynthesis of eicosanoids derived from different lipoxygenases. Also, HLJDT may exert its anti-inflammatory effects by its suppression on eicosanoid generation, NO production and gene transcription of chemotactic factors, which supports its effectiveness in the treatment of inflammatory diseases.
Pharmacokinetics of drugs in rats with diabetes mellitus induced by alloxan or streptozocin: comparison with those in patients with type I diabetes mellitus
Authors: Lee Joo H , Yang Si H , Oh Jung M , Lee Myung G 
Published: October 2010

AbstractObjectivesIn rats with diabetes mellitus induced by alloxan (DMIA) or streptozocin (DMIS), changes in the cytochrome P450 (CYP) isozymes in the liver, lung, kidney, intestine, brain, and testis have been reported based on Western blot analysis, Northern blot analysis, and various enzyme activities. Changes in phase II enzyme activities have been reported also. Hence, in this review, changes in the pharmacokinetics of drugs that were mainly conjugated and metabolized via CYPs or phase II isozymes in rats with DMIA or DMIS, as reported in various literature, have been explained. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized in the kidney, and that were excreted mainly via the kidney or bile in DMIA or DMIS rats were reviewed also. For drugs mainly metabolized via hepatic CYP isozymes, the changes in the total area under the plasma concentration–time curve from time zero to time infinity (AUC) of metabolites, AUCmetabolite/AUCparent drug ratios, or the time-averaged nonrenal and total body clearances (CLNR and CL, respectively) of parent drugs as reported in the literature have been compared.Key findingsAfter intravenous administration of drugs that were mainly metabolized via hepatic CYP isozymes, their hepatic clearances were found to be dependent on the in-vitro hepatic intrinsic clearance (CLint) for the disappearance of the parent drug (or in the formation of the metabolite), the free fractions of the drugs in the plasma, or the hepatic blood flow rate depending on their hepatic extraction ratios. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized via the kidney in DMIA or DMIS rats were dependent on the drugs. However, the biliary or renal CL values of drugs that were mainly excreted via the kidney or bile in DMIA or DMIS rats were faster.SummaryPharmacokinetic studies of drugs in patients with type I diabetes mellitus were scarce. Moreover, similar and different results for drug pharmacokinetics were obtained between diabetic rats and patients with type I diabetes mellitus. Thus, present experimental rat data should be extrapolated carefully in humans.
Development of an original method to study drug release from polymeric nanocapsules in the skin
Authors: Weiss-Angeli Valeria , Bourgeois Sandrine , Pelletier Jocelyne , Guterres Silvia Stanisçuaski , Fessi Hatem , Bolzinger Marie-Alexandrine 
Published: October 2010

Abstract

Objectives
This study aimed to investigate the distribution and release profile in the skin of a lipophilic model molecule, octylmethoxycinnamate (OMC), loaded in poly(ε-caprolactone) nanocapsules (NC) by the Franz cell method.

Methods
Nanocapsules were formulated in a hydroxyethylcellulose gel and compared to the same gel containing 5% of free OMC as control. A new extraction method was used to discriminate the OMC still entrapped in the NC from free OMC released in the skin strata. The OMC extraction from the skin was performed using acetonitrile, which broke the NC, or isopropyl myristate, which kept the NC intact.

Key findings
When isopropylmyristate was used to determine the OMC released from NC, the results showed that more than 80% of the OMC was released from the NC at the skin surface after 6 h, whereas only 30% was released in the stratum corneum and epidermis.

Conclusions
It is suggested that the mechanism of release is different at the surface and in viable skin, probably due to the different local environments surrounding the NC. The small amount of OMC that reached the dermis was no longer encapsulated, suggesting that the NC did not reach the dermis. The viable epidermis seemed to be the limiting barrier against NC diffusion into the skin.
Geranylgeranylacetone preconditioning may attenuate heat-induced inflammation and multiorgan dysfunction in rats
Authors: Zhao Yong-Qi , Gao Jun-Tao , Liu Shou-Hong , Wu Yan , Lin Mao-Tsun , Fan Ming 
Published: October 2010

Abstract

Objectives
Geranylgeranylacetone, an acyclic isoprenoid, is a non-toxic inducer of heat shock protein (HSP)70. HSP70 overproduction is associated with heat tolerance in rats. This study aimed to investigate whether geranylgeranylacetone preconditioning of rats reduced heat-induced inflammation and multiple organ dysfunction.

Methods
Anaesthetised rats were given vehicle or geranylgeranylacetone (800 mg/kg) orally. After 48 h they were exposed to ambient temperature of 43°C for 70 min to induce heatstroke. Another group of rats kept at room temperature were used as normothermic controls.

Key findings
Vehicle-treated rats all succumbed to heat stress; their survival time was 25 ± 4 min. Pretreatment with geranylgeranylacetone significantly increased survival time to 92 ± 15 min. Compared with normothermic controls, all vehicle-treated heatstroke rats displayed hepatic and renal dysfunction (e.g. increased plasma levels of serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase) and active inflammation (e.g. increased plasma and brain levels of interleukin-1β, tumour necrosis factor-α and interleukin-6). These heat-stress response indicators were all significantly suppressed by geranylgeranylacetone pretreatment. In addition, the plasma and brain levels of interleukin-10 (an anti-inflammatory cytokine) and brain levels of HSP70 were significantly increased after geranylgeranylacetone preconditioning during heatstroke.

Conclusions
Geranylgeranylacetone preconditioning attenuates heat-induced inflammation and multiorgan dysfunction in rats.