Hypolipidemic effects of Sophora flavescens and its constituents in poloxamer 407-induced hyperlipidemic and cholesterol-fed rats

In this study, we investigated the hypolipidemic effects of Sophora flavescens in poloxamer 407-induced hyperlipidemic and cholesterol-fed rats. The MeOH extract and 4 fractions of S. flavescens were administered at doses of 250 and 100 mg/kg body weight, respectively, once a day for 3 d to the poloxamer 407-induced hyperlipidemic rats. Serum lipid levels such as total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) were markedly elevated in the poloxamer 407-induced hyperlipidemic control rats, while lipid levels were significantly decreased in the rats administered the MeOH extract or 4 fractions of S. flavescens. In addition, serum high-density lipoprotein-cholesterol (HDL-C) was reduced in the poloxamer 407-induced hyperlipidemic control rats. However, oral administration of both the MeOH extract and 4 fractions significantly increased HDL-C levels. Of the tested fractions, the EtOAc fraction showed the strongest lipid-lowering effect, as well as a high antiatherogenic potential with atherogenic index (A.I.) values of less than 1.92. We also investigated the hypolipidemic effects of the main compounds of the EtOAc fraction, kurarinol and kuraridinol, using the hyperlipidemic and hypercholesterolemic animal models. Here, elevated TC, TG, and LDL-C levels in the poloxamer 407-induced hyperlipidemic and cholesterol-fed rats were significantly reduced after oral administration of the compounds, and HDL-C levels had a significant increase. Furthermore, A.I. values were lowered by administering kurarinol and kuraridinol. In particular, kuraridinol exhibited stronger protective activities against hyperlipidemia than kurarinol. These results suggest that S. flavescens and its constituents may be effective cholesterol-lowering agents and useful for preventing hypercholesterolemic atherosclerosis.     

Tyrosinase inhibitors isolated from the edible brown alga<Emphasis Type="Italic">Ecklonia stolonifera</Emphasis>

Extracts from seventeen seaweeds were determined for tyrosinase inhibitory activity using mushroom tyrosinase with L-tyrosine as a substrate. Only one of them, Ecklonia stolonifera OKAMURA (Laminariaceae) belonging to brown algae, showed high tyrosinase inhibitory activity. Bioassay-guided fractionation of the active ethyl acetate (EtOAc) soluble fraction from the methanolic extract of E. stolonifera, led us to the isolation of phloroglucinol derivatives [phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5)]. Compounds 1 approximately 5 were found to inhibit the oxidation of L-tyrosine catalyzed by mushroom tyrosinase with IC50 values of 92.8, 126, 33.2, 177, and 2.16 microg/mL, respectively. It was compared with those of kojic acid and arbutin, well-known tyrosinase inhibitors, with IC50 values of 6.32 and 112 microg/ mL, respectively. The inhibitory kinetics analyzed from Lineweaver-Burk plots, showed compounds 1 and 2 to be competitive inhibitors with Ki of 2.3x10(-4) and 3.1x10(-4) M, and compounds 3 approximately 5 to be noncompetitive inhibitors with Ki of 1.9x10(-5), 1.4x10(-3) and 1.5x10(-5) M, respectively. This work showed that phloroglucinol derivatives, natural compounds found in brown algae, could be involved in the control of pigmentation in plants and other organisms through inhibition of tyrosinase activity using L-tyrosine as a substrate.     

Effects on splenic, hepatic, hematological, and growth parameters following high-dose poloxamer 407 administration to rats

The nonionic surfactant poloxamer 407, NF (PIuronic ^® F-127, NF) has previously been shown to produce marked hyperlipidemia in rats at a dose of 1.5 g/kg for greater than 96 h following a single intraperitoneal (i.p.) injection (Wout et al. J. Parenter. Sci. Technol., 46 (1992) 192–200). In an effort to characterize any potential toxicity of the polymeric vehicle to various organ systems in the rat following multiple i.p. injections, a dose of 0.33 g/kg per day (10% w/w solution) or 1.0 g/kg per day (30% w/w solution) of poloxamer 407 was administered once daily for 4 consecutive days. When compared to control (non-injected) animals, rats injected with 0.33 g/kg per day of poloxamer 407 did not show a significant (p > 0.05) increase or decrease in spleen, liver, or total body weight. A complete blood count (CBC) with a white blood cell (WBC) differential was performed on blood samples collected on day five from rats injected with poloxamer 407 at both doses. The CBC with WBC differentia] was conducted to assess any changes in the WBC count, percent lymphocytes (LY), percent monocytes (MO), percent granulocytes (GR), red blood cell (RBC) count, hemoglobin (HGB), percent hematocrit (HCT), and the mean corpuscular volume (MCV) following administration of poloxamer 407. Rats injected i.p. with a dose of 0.33 g/kgper day of poloxamer 407 for 4 days demonstrated a significant (p < 0.05) increase in the number of MO when compared to controls. Administration of 1.0 g/kg per day of poloxamer 407 to rats for 4 days demonstrated distinct splenomegaly when compared to non-injected control animals. In addition, a significant (p < 0.05) reduction in body weight and significant (p < 0.05) decrease in the percent LY, RBCs, HGB, and percent HCT were noted. Lastly, a significant (p < 0.05) increase in the number of WBCs and the percent MO was observed in this same group of rats. However, rats administered 1.0 g/kg per day of poloxamer 407 for 4 days were observed to have no detectable changes in the values of the MCV, the percent GR, or liver-to-body weight ratio when compared to control animals. Thus, repetitive i.p. injections of poloxamer 407 to rats at a dose of 1.0 g/kg per day for four days results in splenomegaly and a reduction in total body weight. Splenomegaly in rats administered poloxamer 407 at a dose of 1.0 g/kg per day resulted from red pulp expansion due to infiltration of macrophages which contained phagocytized lipids.     

Effect of phlorotannins isolated from Ecklonia cava on melanogenesis and their protective effect against photo-oxidative stress induced by UV-B radiation

In the present study, three kinds of phlorotannins, marine algal polyphenol, were isolated from a brown alga Ecklonia cava, and their inhibitory effect on melanogenesis as well as the protective effect against photo-oxidative stress induced by UV-B radiation was investigated. The effect on melanogenesis was evaluated via the inhibitory effects of tyrosinase and melanin synthesis. Among the phlorotannins, dieckol showed higher effect than that of the other phlorotannins in the both assays; especially the value of dieckol in the tyrosinase inhibition assay was relatively higher than that of a commercial tyrosinase inhibitor (kojic acid). The UV-B protection effect was evaluated via DCFH-DA, MTT, comet assays, and morphological changes in fibroblast. Intracellular ROS induced by UV-B radiation was reduced by the addition of phlorotannins and cell viability was dose-dependently increased. Moreover, dieckol demonstrated strong protective properties against UV-B radiation-induced DNA damage via damaged tail intensity and morphological changes in fibroblast. Hence, these results indicated that dieckol isolated from E. cava has potential whitening effects and prominent protective effects on UV-B radiation-induced cell damages, which might be used in pharmaceutical and cosmeceutical industries.     

左卡尼汀通过增加UCP1和p-AKT的表达活化高脂血症大鼠棕色脂肪细胞的研究

目的探讨左卡尼汀对高脂喂养大鼠棕色脂肪的影响及其相关机制。方法将30只SD大鼠随机分为对照组、模型组和左卡尼汀低、中、高剂量(100、200、300mg/kg)组,每组各6只。每日ig给药,治疗12周后称重、处死大鼠,收集血清和棕色脂肪组织,检测血清相关生化指标,测定棕色脂肪组织中解偶联蛋白1(UCP1)和磷酸化AKT(p-AKT)的表达水平。结果与模型组相比,左卡尼汀100、200、300 mg/kg组的总胆固醇(TC)、三酰甘油(TG)明显降低,高密度脂蛋白胆固醇(HDL-C)明显升高(P0.05);左卡尼汀100、200 mg/kg组的体质量明显降低,棕色脂肪组织(BAT)质量、BAT质量/体质量明显升高(P0.05)。与模型组相比,左卡尼汀100、200mg/kg组BAT中UCP1RNA明显增加,差异有统计学意义(P0.05)。与模型组相比,左卡尼汀组100、200、300mg/kg组BAT中UCP1和p-AKT蛋白表达明显增加,差异有统计学意义(P0.05、0.01),且呈剂量相关性。结论左卡尼汀具有降脂和促进棕色脂肪活化的作用,这可能与其增加棕色脂肪组织中UCP1和p-AKT的表达有关。     

药食同源植物-葱（Allium fistulosum）种植物的研究进展

药食同源植物葱（Allium fistulosum）的化学成分复杂,主要的化学成分主要集中在黄酮类、甾体皂苷类、含硫类化合物等几部分。有较好的消除亚硝酸盐、抑制肿瘤细胞增殖、降血脂、防治非酒精性脂肪肝等作用。本文综述近年关于葱的化学成分及药理活性,为其进一步开发利用提供依据。     

The effect of dl-propranolol,d-propranolol and practolol on the hyperactivity induced in rats by prolonged isolation

Exploratory behaviour in an open field situation was found to be greatly increased in rats, isolated for 6–8 weeks, when compared with grouphoused controls. Propanolol, dl- and d- and practolol, 0.2–0.5 mg/kg reduced hypermotility, sniffing and rearing in isolated rats without affecting behaviour of group-housed rats. 20 mg/kg dl-propanolol was needed to reduce exploratory behaviour of group housed rats. Chlorpromazine reduced activity of isolated rats at a dose of 0.1 mg/kg, and group housed rats at 0.5–1 mg/kg. The action of propranolol does not appear to result from central receptor blockade because of the almost equal activity of d- and dl-propranolol. Since practolol was also active in this test, the effect of these drugs also does not appear to result from general C.N.S. depression. It is suggested that these compounds may reduce hyperactivity by diminishing an excessive release of central catecholamines.This work forms part of a Ph.D. Thesis by Z. Speiser to be submitted to Tel-Aviv University.     

The effect of p-chloroamphetamine on motility in rats after inhibition of monoamine synthesis,storage, uptake and receptor interaction

The effect of PCA on motility was investigated after s.c. injection to rats in a familiar cage. The doses 1, 2, 5 and 10 mg/kg induced increasing hypermotility. PCA 1 and 2 mg/kg produced various normal behavioral items, but 5 and 10 mg/kg induced mainly abnormal jerky locomotion and head movements.The effect of PCA 5 mg/kg was investigated in rats treated s.c. with various drugs affecting central monoamines. Pretreatment with the 5HT-synthesis inhibitor H 69/17 200 mg/kg, the tyrosinehydroxylase inhibitor H 44/68 250 mg/kg twice and reserpine 7.5 mg/kg inhibited PCA-hyperactivity. H 44/68 250 mg/kg once and the dopamine -hydroxylase inhibitor FLA 63 did not influence the effect of PCA.Simultaneous administration of imipramine 3.1 mg/kg, chlorimipramine 0.9 mg/kg, desipramine 26 mg/kg, amitriptyline 15 mg/kg, doxepine 1.8 mg/kg, chlorpromazine 0.1 mg/kg, haloperidol 0.01 mg/kg, spiramide 0.01 mg/kg and chlorpheniramine 3.9 mg/kg antagonized PCA-hypermotility. Protriptyline 50 mg/kg, clozapine 20 mg/kg and benztropine 10 mg/kg showed no PCA-antagonism.These results indicate that 5HT and DA release are involved in PCA-hyperactivity and that 5HT-membrane blockers inhibit uptake of PCA into brain 5HT neurons thus preventing 5HT release.     

Synergistic effect of tincture of Crataegus and Mangifera indica L. extract on hyperlipidemic and antioxidant status in atherogenic rats

This study was designed to address the synergistic effect of tincture of Crataegus (TCR) and Mangifera indica L. (MNG) extracts on the lipid and antioxidant parameters in the development of aortic lesions in diet-induced atherosclerosis in rats. TCR, is an alcoholic extract made from the berries of Hawthorn, Crataegus oxyacantha with flavanoids as the main constituent. MNG, is an alcoholic extract made from the stem bark of Mangifera indica L. with polyphenols as the main constituent. Simultaneous oral administration of these two extracts (0.5 ml/100 g body weight) to rats fed with an atherogenic (4% cholesterol, 1% cholic acid, 0.5% thiouracil) diet prevented the elevation of lipids in the serum and heart and also caused a significant decrease in lipid accumulation in the liver and aorta reverting the hyperlipidaemic condition of these rats. These extracts significantly restored the activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione, thereby restoring the antioxidant status of the organism to almost normal levels. This effect could be attributed to the synergistic activity of flavonoids in TCR and polyphenols of MNG.     

Studies on protective effect of DA-9601,Artemisia asiatica extract, on acetaminophen- and CCI4-induced liver damage in rats

The hepatoprotective effect of DA-9601, a quality-controlled extract ofArtemisia asiatica, on liver damage induced by acetaminophen (APAP) and carbon tetrachloride (CCI₄) was investigated by means of serum-biochemical, hepatic-biochemical, and histopathological examinations. Doses of DA-9601 (10, 30, or 100mg/kg) were administered intragastrically to each rat on three consecutive days i.e. 48 h, 24 h and 2 h before a single administration of APAP (640 mg/kg, i.p.) or CCl₄ (2 ml/kg, p.o.). Four h and 24 h after hepatotoxin treatment, the animals were sacrificed for evaluation of liver damage. Pretreatment of DA-9601 reduced the elevation of serum ALT, AST, LDH and histopathological changes such as centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration dose-dependently. DA-9601 also prevented APAP- and CCl₄-induced hepatic glutathione (GSH) depletion and CCl₄-induced increase of hepatic malondialdehyde (MDA), a parameter of lipid peroxidation, in a dose-dependent manner. These findings suggest that pretreatment with DA-9601 may reduce chemically induced liver injury by complex mechanisms which involve prevention of lipid peroxidation and preservation of hepatic GSH.     

The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage

The aim of this study was to assess the possible protective effects of Nigella sativa (NS) and its constituent, thymoquinone (TQ) on ethanol-induced gastric mucosal damage in an experimental model. Forty male rats aged four months were divided into four groups (each group containing ten animals); the control group received physiologic saline (10 ml kg⁻¹) and the ethanol group had taken 1 ml (per rat) absolute alcohol by gavage. The third and fourth groups also received NS (500 mg kg⁻¹) and TQ (10 mg kg⁻¹) by gavage 1 h before alcohol administration, respectively. Both drugs (NS and TQ) could protect the gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index values. Gastric damage was confirmed histomorphometrically by significant increases in the number of mast cells (MC) and gastric erosions in ethanol treated rats. The NS treatment significantly decreased the number of MC and reduced the area of gastric erosions. Likewise, TQ treatment was also able to reduce the number of MC and the gravity of gastric mucosal lesions, but to lesser extent compared to NS. Gastric tissue histamine levels and myeloperoxidase activities were found to be increased in ethanol treated rats, and NS or TQ treatment reversed these increases. Results obtained from this study suggest that both drugs, particularly NS could partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects could be due to their antiperoxidative, antioxidant and antihistaminic effects.     

傣百解醇提物调控趋化素表达发挥对非酒精性脂肪肝大鼠治疗作用

目的 研究傣百解醇提物对非酒精性脂肪肝大鼠的治疗作用,并探讨其调控趋化素（Chemerin）及其受体（CMKLRI）表达的作用机制。方法 高脂饲料喂养8周建立非酒精性脂肪肝（NAFLD）大鼠模型,验证造模成功后改普通饲料喂养,并随机分为模型组、非诺贝特胶囊组（阳性药,0.2 g/kg）和傣百解醇提物低、高（2.6、4.5 g/kg）剂量组,每组10只,给药组每天ig给药1次,连续4周;对照组大鼠一直饲予普通饲料,对照、模型组给予等体积纯水。最后1次给药后大鼠禁食不禁水12 h,腹主动脉取血收集血清,于全自动生化分析仪上测定血清总胆固醇（TC）、三酰甘油（TG）、游离脂肪酸（FFA）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、空腹血糖（FBG）水平;ELISA法检测血清空腹胰岛素（FINS）的浓度;计算胰岛素敏感指数（ISI）和胰岛素抵抗指数（HOMA-IR）。取肝组织进行HE染色,光学显微镜下观察肝组织病理学改变。实时荧光定量PCR（qRT-PCR）法检测肝组织Chemerin及CMKLRI mRNA表达水平。结果 与模型组比较,傣百解醇提物高、低剂量组血清TC水平均显著降低（P<0.05）,低剂量组HDL-C含量显著升高（P<0.05）;各剂量组HOMA-IR水平均降低,其中高剂量组差异显著（P<0.05）;各剂量组ISI均有所升高,但作用均无统计学差异;高、低剂量组肝脏脂质沉积等病理学改变有所改善;各剂量组Chemerin及CMKLRI mRNA表达均有所下调,其中高剂量组下调Chemerin mRNA表达作用显著（P<0.05）。结论 傣百解醇提物对大鼠NAFLD具有降低LDL-C、升高HDL-C含量、降低HOMA-IR水平和保肝作用,其作用机制可能与下调chemerin mRNA表达有关。     

Effects of d-amphetamine on temporal and spatial discrimination in rats

Rats were trained to lever-press for food reinforcers on a multiple schedule that had a fixed-interval (FI) and a differential reinforcement of low rate (DRL) component. Illumination of a stimulus light above the right-hand lever indicated that responses on this lever would be reinforced according to a FI 60-s schedule while responses on the left-hand lever were without programmed consequences. However, when the light above the left-hand lever was illuminated only responses on this lever were reinforced according to a DRL 15-s schedule. When the behaviour of the subjects had been brought under schedule control so that characteristic patterns of FI and DRL responding were emitted and there were relatively few responses on the incorrect levers, the effects of several doses of d-amphetamine (0.25, 0.5, 1.0, and 2.0 mg/kg) were assessed. The drug increased preference for responding on the right-hand lever. Thus, as dosage increased performance tended towards a constant high rate of responding on the right-hand lever throughout a session, with a much lower response rate on the left-hand lever. This result emphasises that the behavioural effects of drugs depend not only on patterns of ongoing behaviour but also on the context in which this behaviour occurs.     

Effects of naltrexone,andd-amphetamine,and their interaction on the stimulus control of choice behavior of rats

The hypothesis that endogenous opioid peptides modulate attentional processes was tested. The effects of the opioid antagonist naltrexone (NALT),d-amphetamine (AMP), and their interaction were investigated in rats trained in a two-choice task in which the position of a short-duration light served as a cue for food-reinforced responses. NALT (0.25, 1.0, 5.0, and 10.0 mg/kg) produced no significant changes in performance (accuracy, choice latency, and food retrieval time). As predicted, AMP induced dose-dependent biphasic effects. Low doses of AMP (0.25 and 0.5 mg/kg) significantly enhanced accuracy, decreased choice latency, and lengthened food retrieval time; 1.25 mg/kg AMP disrupted accuracy, increased choice latency, and further lengthened food retrieval time. The combination of NALT (0.25, 1.0, and 10.0 mg/kg) and subthreshold doses of AMP (0.07 and 0.1 mg/kg) had no effect on performance except for an increase in food retrieval time with 10.0 mg/kg NALT, whereas the combination of NALT and moderate doses of AMP (0.5 and 1.0 mg/kg) disrupted accuracy, increased choice latencies, and lengthened food retrieval time. These results do not support the hypothesis that endogenous opioid peptides play a vital role in attentional processes or that opioid antagonists may be useful in the treatment of attentional deficit disorders.     

Effects of chlordiazepoxide,ripazepam and d-amphetamine on conditioned acceleration of timing behaviour in rats

The lever-pressing behaviour of three rats was maintained by a schedule in which food reinforcement was obtained by any response which was emitted at least 15 s after the previous response (DRL 15 s). When performance on this schedule had stabilised, the animals were presented intermittently with 1-min periods of a white noise stimulus, the termination of which was accompanied by the delivery of a mild electric footshock. This procedure led to reliable increases in response rates during the stimulus although responding at other times continued to be appropriate to the DRL 15-s schedule. Administration of the benzodiazepine chlordiazepoxide (1, 3, 10, 17 and 30 mg/kg) and of ripazepam (1, 3, 10, 30 and 56 mg/kg), a non-benzodiazepine reported to have anxiolytic properties, increased response rates on the DRL baseline while decreasing the acceleration of responding produced by the preshock stimulus. Baseline response rates were also increased by d-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg) and at the higher doses this drug completely abolished the accelerated responding during the preshock stimulus. Although the effects of chlordiazepoxide and ripazepam are consistent with the suggestion that these drugs may attenuate the behavioural effects of aversive stimuli, in this experiment the behavioural effects of d-amphetamine were similar in many respects.     

Age-related differences in the effects of d-amphetamine and illumination on fixed-interval responding of rats

The effects of d-amphetamine (0.0, 0.4, and 0.8 mg/kg) on fixed-interval responding in light and dark sensory conditions were examined in rats that were 25, 100, and 200-days-old at the beginning of the experiment. In the youngest and oldest groups, the drug increased responding in light more than in dark. The drug increased responding of the middle age group in the light, but decreased operant rates in the dark. These data appear to support the notion that d-amphetamine reduces the effects of ambient light on behavior in rats.     

Antiallergic effect of the root of <Emphasis Type="Italic">Paeonia lactiflora</Emphasis> and its constituents paeoniflorin and paeonol

The root of Paeonia lactiflora PALL (PL, Family Paeoniaceae) has been used frequently as an antipyretic and anti-inflammatory agent in traditional medicines of Korea, China and Japan. To evaluate antiallergic effect of PL, we isolated its main constituents, paeoniflorin and paeonol, and evaluated in vivo their inhibitory effects against passive cutaenous anaphylaxis (PCA) reaction induced by IgE-antigen complex and scratching behaviors induced by compound 48/80. PL, paeoniflorin and paeonol potently inhibited PCA reaction and scratching behaviors in mice. Paeoniflorin exhibited the most potent inhibition against scratching behaviors and the acetic acid-induced writhing syndrome in mice. Paeonol most potently inhibited PCA reaction and mast cells degranulation. These findings suggest that PL can improve IgE-induced anaphylaxis and scratching behaviors, and may be due to the effect of its constituents, paeoniflorin and paeonol.     

Chemical constituents of Acanthus ilicifolius L. and effect on osteoblastic MC3T3E1 cells

A new coumaric acid derivative called acancifoliuside (1) and six known compounds as acteoside (2), isoacteoside (3), acanthaminoside (4), (+)-lyoniresinol 3a-O-beta-glucopyranoside (5), (-)-lyoniresinol (6), and alpha-amyrin (7), were isolated from the methanolic extract of the leaves of Acanthus ilicifolius L. (Acanthaceae). Their structures were determined by spectroscopic methods and a comparison with the spectral data reported in the literature. The effects of the compounds on the function of osteoblastic MC3T3-E1 cells were tested. Compounds 2, 3, and 5 (30 microM) increased the growth and differentiation of osteoblasts significantly (P<0.05), indicating that A. ilicifolius leaves may help prevent osteoporosis.