Mechanisms for the hepatoprotective action of kolaviron: studies on hepatic enzymes, microsomal lipids and lipid peroxidation in carbontetrachloride-treated rats.

The present work examines the protective mechanisms of a biflavonoid fraction of an extract from Garcinia kola seeds, kolaviron, in rats treated with carbontetrachloride (CCl(4)). CCl(4)administered at a dose of 1.2 g kg(-1), three times a week for 2 weeks, significantly depressed the activities of microsomal aniline hydroxylase, aminopyrine N -demethylase, ethoxyresorufin O -demethylase and p -nitroanisole O -demethylase. Kolaviron (200 mg kg(-1)), administered for 14 days consecutively, inhibited (P<0.001) the CCl(4)mediated decrease in the activities of these enzymes by 60, 65, 55, and 63%, respectively. Kolaviron reduced the CCl(4)increase in the cholesterol/phospholipid ratio. Similarly, kolaviron attenuated the toxic onslaught imposed by CCl(4)on 5'nucleotidase, glucose 6-phosphatase (microsomal marker enzymes) and malondialdehyde formation by 41, 54 and 77%, respectively. Kolaviron elicited 168% and 234% increases in the activity of UDP-glucuronosyl transferase and glutathione S -transferase. Simultaneous administration of kolaviron with CCl(4)modulated the effect of CCl(4)on the activities of these enzymes. On the basis of the above data, it can be postulated that kolaviron exerts its protective action against carcinogen-induced liver damage, first, by acting as an in vivo natural antioxidant and, second, by enhancement of drug-detoxifying enzymes.     

Hepatoprotection of D-galactosamine-induced toxicity in mice by purified fractions from Garcinia kola seeds

The hepatoprotective effect of a biflavonoid complex, kolaviron, and its fractions from Garcinia kola seeds, together with the possible mechanisms involved was investigated in mice intoxicated with a single dose of D-galactosamine (GalNH(2)). Likewise, the ability of vitamin E to attenuate the toxicity was examined. Kolaviron, was separated by thin-layer chromatographic technique into three fractions; Fraction I, Fraction II and Fraction III with RF values of 0.48, 0.71 and 0.76, respectively. Pretreatment with kolaviron, fraction I and fraction II at a dose of 100 mg/kg for seven consecutive days before challenge with a single dose of GalNH(2) (800 mg/ kg) significantly (P<0.05) decreased serum alanine (ALT) and aspartate (AST) aminotransferases by 67%, 70%, 71% and 39%, 35%, 46%, respectively over GalNH(2)-only intoxicated mice. Vitamin E elicited respectively 65% and 39% reduction in the GalNH(2)-induced increase in the activities of these enzymes. In addition, pretreatment with kolaviron and fraction II significantly (P<0.05) decreased the activity of microsomal gamma-glutamyl transferase (gamma-GT) by 42% and 46%, respectively. Administration of kolaviron to GalNH(2)-intoxicated mice also restored glucose-6-phosphatase to level that was comparable to the control (P<0.05). These extracts except fraction III prevented the accumulation of serum and microsomal lipid peroxidation products, and also prevented the depletion of reduced glutathione (GSH) levels in the liver of GalNH(2)-intoxicated mice. Kolaviron, fraction I and fraction II at a dose of 100 mg/kg caused an induction of glutathione-S-transferase (GSH transferase) and uridyl glucuronosyl transferase (UDPGT) activities by 31%, 34%, 35% and 29%, 65%, 56%, respectively. GalNH(2)-induced toxicity was essentially prevented as indicated by a liver histopathologic study of liver slices from mice pretreated with kolaviron, fraction I and fraction II. This study shows that treatment with kolaviron, fraction I and fraction II (purified fractions from Garcinia kola) appeared to enhance the recovery from GalNH(2)-induced hepatotoxicity, and that the fractions I and II may therefore be responsible for the observed antihepatotoxic effect of kolaviron. This protection may be due to the ability of these extracts to induce the expression of phase II drug metabolizing enzymes.     

Kolaviron modulates cellular redox status and impairment of membrane protein activities induced by potassium bromate (KBrO(3)) in rats.

In this study, we examined the modulatory effects of kolaviron, a biflavonoid from Garcinia kola seeds on the antioxidant defense mechanisms, cellular redox status and oxidative stress in the kidney and liver of rats pretreated with potassium bromate (KBrO(3)) intragastrically as a single dose of 300 mg kg(-1)weight for 4 weeks. Treatment of rats with KBrO(3)resulted in an insignificant difference (P> 0.05) in body weight compared to controls. However, a significant increase in kidney/body weight ratio (P< 0.001) was observed in rats treated with KBrO(3)while liver/body weight ratio was not affected. KBrO(3)depressed the activities of superoxide dismutase, glutathione peroxidase and catalase (P< 0.001) in the kidney but not in the liver. Kolaviron (200 mg kg(-1)body weight) administered three times a week for 4 weeks inhibited the decrease mediated by KBrO(3)of these enzymes in the kidney by 29, 88 and 45%, respectively. Similarly, kolaviron reduced the KBrO(3)-induced decrease in the activities of gamma -glutamyltransferase and microsomal Ca(2+)ATPase by 73 and 63% in the kidney. In addition, the extract elicited a 27 and 25% decrease in the KBrO(3)-induced increase in malondialdehyde and lipid hydroperoxide formation in the kidney. Kolaviron also attenuated the KBrO(3)-decreased activities of glucose 6-phosphatase, 5 prime prime or minute nucleotidase and alkaline phosphatase (membrane enzymes) by 72, 57 and 25% respectively. The results of the present investigation indicate the antioxidative effect of kolaviron, a natural antioxidant, on drug-induced kidney toxicity. Kolaviron may therefore intervene in the cellular redox status and depression of membrane protein activities caused by KBrO(3)and other environmental carcinogens in the kidney.     

Chemoprevention of 2-acetylaminofluorene-induced hepatotoxicity and lipid peroxidation in rats by kolaviron--a Garcinia kola seed extract.

The effect of kolaviron, a mixture of Garcinia biflavonoid 1 (GB1), Garcinia biflavonoid 2 (GB2) and kolaflavanone, used in the treatment of various ailments in southern Nigeria on hepatotoxicity and lipid peroxidation induced by 2-acetylaminofluorene (2-AAF) in rats was investigated. The ability of butylated hydroxyanisole (BHA) to attenuate the toxic effect of 2-AAF was also examined. Kolaviron administered orally to rats at a dose of 100mg/kg body weight twice a day for 1 week before challenge with 2-AAF (200mg/kg feed) and continuously for 3 weeks at a single dose of 200mg/kg body weight reversed the 2-AAF-mediated decrease in final body weight and relative organ weights, especially the liver. BHA was administered at a dose of 7.5g/kg feed to the animals for 4 weeks. The extract decreased significantly the 2-AAF-mediated increase in the activity of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase and ornithine carbamyl transferase by 58%, 62%, 60% and 67%, respectively. BHA elicited respectively 55%, 63%, 57% and 65% reduction in the 2-AAF induced-increase in the activities of these enzymes. Histological examination of the liver slices correlated with the changes in serum enzyme alterations. Similarly, kolaviron decreased the 2-AAF reduction of 5'-nucleotidase and glucose-6-phosphatase activities by 63% and 60%, respectively while BHA elicited 59% and 61% decrease in the activities of these enzymes. Simultaneous administration of kolaviron with 2-AAF inhibited microsomal lipid peroxidation as assessed by the thiobarbituric acid reacting substances (TBARS) formation by 66%. BHA produced a 64% reduction in TBARS formation. In the present study, kolaviron appears to act as an in vivo natural antioxidant and an effective hepatoprotective agent and is as effective as BHA.     

肌萎缩侧索硬化患者低密度脂蛋白的氧化敏感性

目的测定肌萎缩侧索硬化（ALS）患者血中低密度脂蛋白（LDL）体外氧化延迟时间的变化。方法根据EL Escorial诊断标准选取ALS 19例,其中男15例,女4例,并与19例年龄、影响因素等相当的健康成人相对照。以铜氧化共轭双烯法测定血中LDL体外氧化延迟时间。结果 ALS组血中LDL体外氧化延迟时间较对照组明显减低,分别为（59.32±8.65）min与（83.16±8.37）min,差异有统计学意义（P〈0.05）。结论增高的氧化压力与降低的抗氧化能力在ALS的发病机制中具有一定的作用,提示有效的抗氧化治疗可能对控制疾病的发展及改善预后具有一定的临床意义。     

Possible anti-atherogenic effect of kolaviron (a Garcinia kola seed extract) in hypercholesterolaemic rats

1. The hypolipidaemic effect of kolaviron, a mixture of Garcinia biflavonoid 1 (GB1), Garcinia biflavonoid 2 (GB2) and kolaflavanone, used in the treatment of various ailments in southern Nigeria, was investigated in rats. The ability of Questran (Bristol-Myers Squibb, Hounslow, UK), a hypolipidaemic therapeutic drug, to attenuate hypercholesterolaemia in rats was also examined. 2. In order to assess the hypolipidaemic effect of this extract in experimental animals, thiobarbituric acid-reactive substances (TBARS), cholesterol, phospholipid, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and triglyceride levels were determined in the plasma and liver. 3. Cholesterol administered orally to rats at a dose of 30 mg/0.3 mL five times a week for 8 consecutive weeks resulted in a significant increase (P<0.001) in the relative weight of the heart of hypercholesterolaemic animals compared with control. However, cotreatment with kolaviron and Questran ameliorated the cholesterol-induced enlargement of the heart. Kolaviron (100 and 200 mg/kg) elicited 88.5 and 87.4% reductions, respectively, in plasma cholesterol levels of pretreated animals compared with the cholesterol-fed group. In addition, kolaviron produced a significant decrease (P<0.05) in post-mitochondrial fraction (PMF) cholesterol levels in treated animals compared with untreated hypercholesterolaemic animals. Similarly, Questran significantly decreased (P<0.05) the cholesterol-induced increase in plasma cholesterol levels compared with untreated hypercholesterolaemic animals. In addition, (100 and 200 mg/kg) significantly (P<0.05) decreased plasma LDL-C levels by over 70% in treated animals compared with untreated hypercholesterolaemic animals. Similarly, kolaviron significantly decreased (P<0.05) PMF LDL-C levels by over 60% in treated animals compared with untreated hypercholesterolaemic animals. 4. The significantly (P<0.05) higher values of plasma and PMF triglycerides obtained in cholesterol-fed animals compared with control animals were unaltered following cotreatment with kolaviron and Questran. In the present study, there was a significant decrease (P<0.05) in plasma formation of malondialdehyde in kolaviron- and Questran-treated animals compared with untreated hypercholesterolaemic animals. 5. The results of the present study demonstrate that kolaviron exerts a hypocholesterolaemic effect and reduces the relative weight of the heart in cholesterol-fed animals. This reduction and the favourable lipid profile indicate a possible anti-atherogenic property of the extract.     

Commonly consumed and naturally occurring dietary substances affect biomarkers of oxidative stress and DNA damage in healthy rats.

The influence of black currant juice, Bowman-Birk protease inhibitor (BBI), kolaviron (a biflavonoid fraction of Garcinia kola seed), sugars, vitamin C and tert-butyl hydroperoxide on a wide range of biomarkers for oxidative stress, DNA damage and sugar or lipid metabolism has been investigated in male F 344 rats. The selected pro-oxidant control, tert-butyl hydroperoxide, significantly increased plasma and liver 2-amino-adipic semialdehyde (AAS), a marker of protein oxidation (p <0.05) whereas lipid oxidation assessed as malon dialdehyde (MDA) and DNA oxidation were not significantly increased. Feeding BBI also increased the level of oxidized protein in plasma and liver at the higher dose level (0.5%). No effect was observed at the lower dose level (0.25%), which even decreased lipid oxidation in plasma. BBI did not affect background levels of DNA strand breaks or oxidation (comets). In rats exposed to black currant juice, a statistically significant decrease in liver AAS and MDA was observed. This effect could not be explained by its content of sugars or of the known redox active constituent, vitamin C. The lowering effect of black currant juice on protein and lipid oxidation was similar in magnitude to that of the known liver protectant, kolaviron. In rats treated with kolaviron (200 mg/kg body weight), background AAS levels were significantly reduced in both plasma and liver whereas the effect on MDA only reached statistical significance in plasma. Kolaviron was the only extract tested which decreased oxidative damage to DNA in the liver. The erythrocyte antioxidant enzyme activities, catalase and glutathione peroxidase were decreased in rats treated with tert-butyl hydroperoxide (p <0.05) but were not affected by the other treatments. Black currant juice and sugars increased plasma triglyceride levels and black currant juice increased plasma cholesterol but neither of them nor any other treatment affected blood glucose, erythrocyte HbA1c or fructosamine. We conclude that markers of oxidative stress may be modified by several mechanisms after feeding rats with complex dietary factors and that both pro- and antioxidant effects may consequently be observed simultaneously after short-term feeding of antioxidant-rich foods, herb medicines, or known pro- and antioxidants.     

Kolaviron prevents carbendazim-induced steroidogenic dysfunction and apoptosis in testes of rats

The study evaluated the protective role of kolaviron (an isolated biflavonoid from the seed of Garcinia kola) and vitamin E in carbendazim-induced reproductive dysfunction in male rats. Adult male Wistar rats were orally exposed to carbendazim (200 mg/kg) singly or in combination with kolaviron (100 and 200 mg/kg). Exposure to carbendazim significantly decreased the activities of superoxide dismutase and catalase but markedly increased sialic acid concentration and lipid peroxidation in the testes of rats. Western blot analysis revealed that carbendazim treatment decreased the expression of steroid acute regulatory (StAR) protein and androgen binding protein (ABP) with concomitant decrease in activities of steroidogenic enzymes. Germ cell apoptosis in carbendazim-treated rats was confirmed by TUNEL assay. However, pretreatment with kolaviron and vitamin E restored the testicular antioxidant status and steroidogenesis and decreased apoptotic nuclei to near control level in carbendazim-treated rats. Kolaviron may prove useful in combating carbendazim-induced reproductive toxicity.     

Functional evidence for anti-oxidant action of fluvastatin on low-density lipoprotein using isolated macrophages and aorta

1. Fluvastatin has been reported to have not only a hypocholesterolaemic effect, but also a protective effect on low-density lipoprotein (LDL) from oxidation. We functionally evaluated the anti-oxidant effect of fluvastatin on oxidation of LDL by copper ions in vitro using mouse macrophages and rabbit aorta preparations. 2. After native LDL (N-LDL) from rabbit plasma had been pre-incubated in the presence or absence of fluvastatin (10 micromol/L) for 4 h, the N-LDL was mildly oxidized by incubation with 5 micromol/L CuCl2 for 5 h and two oxidized LDL, fluvastatin-pretreated (Flu-OxLDL) and -non-treated (OxLDL), were prepared. The level of thiobarbituric acid-reactive substances (TBARS) in Flu-OxLDL and OxLDL markedly increased compared with N-LDL. The degree of increment was significantly less in Flu-OxLDL than OxLDL. 3. When macrophages were incubated with Flu-OxLDL or OxLDL, the amount of cholesteryl ester that accumulated in the macrophages markedly increased compared with N-LDL. The degree of increment was significantly less in Flu-OxLDL than OxLDL. 4. Acetylcholine-induced endothelium-dependent relaxations in rabbit aortic rings were impaired in the presence of either Flu-OxLDL or OxLDL. The degree of impairment was significantly less in Flu-OxLDL. 5. The increased TBARS level, facilitated cholesteryl ester accumulation in macrophages and impaired endothelium-dependent relaxation elicited by OxLDL were not affected by simultaneous treatment with fluvastatin (10 micromol/L). 6. These findings indicate that fluvastatin can protect plasma LDL from oxidative modification and, thereby, prevent cholesterol accumulation in macrophages and endothelial dysfunction in blood vessels. This additional anti-oxidative effect of fluvastatin may be beneficial for preventing the progression of atherosclerosis.     

Kolaviron prevents ethylene glycol monoethyl ether-induced testicular apoptosis via down-regulation of stress proteins,Fas/Fas-L and caspases expressions in rats

Abstract

This study investigated the protective role of kolaviron, a natural antioxidant biflavonoid isolated from the seed of Garcinia kola, in ethylene glycol monoethyl ether (EGEE)-induced testicular dysfunction in male rats. Adult male Wistar rats were exposed to EGEE (200?mg/kg) separately or in combination with either kolaviron (100 or 200?mg/kg) or vitamin E (50?mg/kg) for 14 days. Immunoblot analysis revealed that EGEE exposure alone significantly increased stress-inducible proteins levels. The increased protein expression of active caspases, Fas and Fas-L, was accompanied by nuclear factor kappa B downregulation and elevation of cytosolic cytochrome c level in EGEE-treated rats. In addition, the observation from immunofluorescence staining was consistent with the increased TUNEL-positive nuclei in the testes of EGEE-treated rats. Kolaviron and vitamin E significantly inhibited induction of stress proteins and germ cell apoptosis in EGEE-treated rats. Overall, kolaviron by virtue of its antioxidant and anti-apoptotic properties prevented EGEE-induced reproductive toxicity in rats.     

Kolaviron,a Natural Antioxidant and Anti‐Inflammatory Phytochemical Prevents Dextran Sulphate Sodium‐Induced Colitis in Rats

The beneficial effects of kolaviron, a natural biflavonoid from the seeds of Garcinia kola, have been attributed mainly to its antioxidant and anti‐inflammatory effects. This study investigated these effects on dextran sulphate sodium (DSS)‐induced ulcerative colitis in rats. Sulfasalazine served as standard reference in this study. Kolaviron and sulfasalazine were separately co‐administered orally at 200 mg/kg and 500 mg/kg, respectively, to dextran sulphate sodium‐exposed rats for 5 days. The result indicated that kolaviron or sulfasalazine significantly prevented DSS‐induced body weight loss as well as the incidence of diarrhoea and bleeding in DSS‐exposed rats. Kolaviron suppressed the DSS‐mediated increase in colonic nitric oxide concentration and myeloperoxidase activity and significantly prevented the increase in inflammatory mediators, interleukin‐1β and tumour necrosis factor alpha, in the colon of DSS‐treated rats. The significant depletion in colonic antioxidant status in rats exposed to DSS alone was evident by marked reduction in colonic catalase and glutathione S‐transferase activities as well as glutathione content, leading to elevated hydrogen peroxide and lipid peroxidation levels. Histopathologically, DSS alone resulted in severe epithelial erosion, total absence of goblet cells, destruction of the crypts, necrotic and distorted glands, accompanied by marked cellular mononuclear cells infiltration. However, administration of kolaviron and sulfasalazine ameliorated DSS‐induced colitis by increasing the antioxidant status decreased hydrogen peroxide and lipid peroxidation levels and attenuated the adverse effect of DSS on colon architecture. In conclusion, the anti‐colitis effect of kolaviron is related to its intrinsic anti‐inflammatory and anti‐oxidative properties.     

Curcumin and kolaviron ameliorate di-n-butylphthalate-induced testicular damage in rats

The present study was carried out to evaluate the ameliorative effects of kolaviron (a biflavonoid from the seeds of Garcinia kola) and curcumin (from the rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced testicular damage in rats. Administration of DBP to rats at a dose of 2 g/kg for 9 days significantly decreased the relative testicular weights compared to the controls, while the weights of other organs remained unaffected. Curcumin or kolaviron did not affect all the organ weights of the animals. While only DBP treatment significantly increased the testicular malondialdehyde level and gamma-glutamyl transferase activity (gamma-GT), it markedly decreased glutathione level, the testicular catalase, glucose-6-phosphate dehydrogenase, superoxide dismutase, sperm gamma-GT activities and serum testosterone level compared to the control group. Data on cauda epididymal sperm count and live/dead ratio were not significantly affected in the DBP-treated rats. Alone, DBP treatment resulted in a 66% decrease in spermatozoa motility and a 77% increase in abnormal spermatozoa in comparison to control. DBP-treated rats showed marked degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes. The DBP-induced injuries in biochemical, spermatological parameters and histological structure of testis were recovered by treatment with kolaviron or curcumin. The pattern in the behaviour of these compounds might be correlated with their structural variations. Our results indicate that kolaviron and curcumin protect against testicular oxidative damage induced by DBP. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties and as such may prove useful in combating phthalate-induced reproductive toxicity.     

Chemoprotection of ethylene glycol monoethyl ether-induced reproductive toxicity in male rats by kolaviron, isolated biflavonoid from Garcinia kola seed

The present study investigated the protective effect of kolaviron, a biflavonoid from the seed of Garcinia kola, on ethylene glycol monoethyl ether (EGEE)-induced reproductive toxicity in male rats. The protective effect of kolaviron was validated using vitamin E, a standard antioxidant. EGEE was administered at a dose of 200 mg/kg. Other groups of rats were simultaneously treated with kolaviron (100 and 200 mg/kg) and vitamin E (50 mg/kg) for 14 days. EGEE treatment resulted in significant decrease in glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities but markedly increased the glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) activities in the testes. In the spermatozoa, administration of EGEE caused significant decrease in the activities of CAT, GPx, GST and LDH as well as in the level of GSH but significantly increased SOD activity with concomitant increase in hydrogen peroxide and malondialdehyde levels in both testes and spermatozoa. EGEE-exposed rats showed marked testicular degeneration with concomitant decrease in spermatozoa quantity and quality. Overall, EGEE causes reproductive dysfunction in rats by altering antioxidant systems in the testes and spermatozoa. Kolaviron or vitamin E exhibited protective effects against EGEE-induced male reproductive toxicity by enhancement of antioxidant status and improvement in spermatozoa quantity and quality.     

洛伐他汀对低密度脂蛋白损伤血管内皮的保护作用

目的：探讨洛伐他汀对低密度脂蛋白所致血管内皮功能损伤的保护作用及可能的机制．方法：一次性从大鼠舌下静脉注射天然低密度脂蛋白(n-LDL 4mg／kg),在舌下静脉注射n-LDL之前大鼠腹腔注射洛伐他汀(2或4mg／kg),每天一次,连续五天．注射n-LDL后48小时检测乙酰胆碱诱导的血管内皮依赖性舒张(EDR)及血清一氧化氮(N0)、丙二醛(MDA)的含量和超氧化物歧化酶(SOD)的活性．结果：一次注射n-LDL导致了EDR、血清NO水平及SOD活性明显降低,MDA的浓度明显增高。预先给予洛伐他汀能明显减轻LDL引起的EDR的抑制和血清NO水平及SOD活性的降低,减少MDA的生成,左旋硝基精氨酸(L-NNA)减弱洛伐他汀对血管内皮的保护作用．结论：洛伐他汀对LDL损伤的血管内皮具有保护作用,可能与保护内皮依赖性松弛因子和抗氧化作用有关。     

Tanshinone II A attenuates atherosclerotic calcification in rat model by inhibition of oxidative stress

AIM: We have previously proved that oxidized low-density lipoprotein (oxLDL), a proatherogenic lipoprotein, plays a pivotal role in the development of atherosclerotic calcification (AC). The present study was performed to investigate whether tanshinone II A (TS II A), an anti-oxidant which has been shown to inhibit in vitro oxidation of LDL, has the effects to inhibit AC in rat model and by which, if any, mechanisms. METHODS: Rat AC model was induced by excessive vitamin D(2) (VD) and high cholesterol diet (HCD), which was proven to be successful histopathologically and biochemically. RESULTS: Administration of AC rats with TS II A (35, 70 mg/kg) dose-dependently attenuated the AC pathological changes, meanwhile reduced the vessel contents of lipid and calcium. However, TS II A had no effects on serum levels of lipids, calcium and 25-OH VD. Further studies revealed that TS II A decreased serum concentration of oxLDL, reduced the superoxide anion production and malondialdehyde (MDA) in vessel. In addition, TS II A increased vessel Cu/Zn SOD activity, upregulated vessel mRNA and protein expression of Cu/Zn SOD. CONCLUSION: The results suggested that TS II A significantly attenuated the AC in rat model, which might be attributed to its inhibition of oxLDL production independent of the serum levels of lipids, calcium and 25-OH VD, and that increasing of Cu/Zn SOD activity as well as mRNA and protein expression by TS II A might protect LDL against oxidation induced by superoxide anion in vessel.     

Hypocholesterolaemic effects of an ethanol precipitate of Kabosu juice in stroke-prone spontaneously hypertensive rats fed a cholesterol-free diet

1. We have previously identified strong inhibitory effects of Kabosu (Citrus sphaerocarpa Hort.) juice precipitate (KJP) on cholesterol elevation in stroke-prone spontaneously hypertensive rats (SHRSP) fed a cholesterol diet. In the present study, to elucidate the hypocholesterolaemic mechanism, we examined the effect of dietary KJP on lipid metabolism by using SHRSP fed a cholesterol-free diet. 2. Compositions of the experimental diet containing 10% KJP powder were adjusted to those of the control diet. Seven-week-old male SHRSP were fed control or experimental diet for 2 weeks with free access to the diet and water. 3. Serum levels of cholesterol, phospholipid and triglyceride of the KJP group were significantly reduced, which was due to decreases in the very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions. 4. Serum concentrations of apolipoproteins A-I and E (apoA-I and E) of the KJP group were significantly lower than those of the control group, whereas no significant differences were observed in serum apoB and apoA-IV between the two groups. 5. In liver, there were no significant differences in the contents of lipids or relative liver weight between the two groups. The activity of microsomal cholesterol 7alpha-hydroxylase of the KJP group tended to increase, whereas that of microsomal acyl-coenzyme A : cholesterol acyltransferase was significantly reduced, compared with the control group. 6. These results indicate that dietary KJP produces reductions of serum lipid levels, which are due to reductions in VLDL, apoE HDL and apoA-I HDL, and may promote catabolism and excretion of hepatic cholesterol in SHRSP fed a cholesterol-free diet.     

Effect of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside on lipoprotein oxidation and proliferation of coronary arterial smooth cells

To investigate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), a compound extracted from the root of Polygonum multiflorum Thunb, on lipoprotein (LDL and VLDL) oxidation, proliferation and nitric oxide (NO) content of coronary arterial smooth cells (CASMCs) induced by LDL, VLDL, ox-LDL and ox-VLDL. The oxidation level of lipoprotein was determined by thiobabituric acid (TBA) method and agarose gel electrophoresis. The proliferative degree was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) method. The NO content was assayed by nitrate reductase method. (1)THSG (0.1 - 100 mumol L(- 1)) could dose-dependently prevent lipoprotein from oxidation induced by Cu(2 + ) and CASMCs. (2)THSG (0.1 - 100 micromol L(- 1)) inhibited porcine CASMCs proliferation elicited by LDL, VLDL, ox-LDL and ox-VLDL. (3)THSG (0.1 - 100 micromol L(- 1)) counterpoised the decrease of NO content in CASMCs evoked by LDL, VLDL, ox-LDL and ox-VLDL. As compared with control, it was found that the threshold concentration of THSG, which significantly exerted the actions mentioned above, were at the concentration of 1 micromol.L(- 1) (P < 0.01). In conclusion, THSG possesses the antagonistic effects on oxidation of lipoprotein, proliferation and decrease of NO content of CASMCs, which partially explain the mechanism of anti-atherosclerosis of Polygonum multiflorum Thunb.     

Tocolytic effect of parecoxib, a new parenteral cyclo-oxygenase-2-specific inhibitor, on the spontaneous and prostaglandin-induced contractions of rat isolated myometrium

1. The present study was undertaken to elucidate the effects of parecoxib, a novel cyclo-oxygenase (COX)-2 inhibitor, on spontaneous and prostaglandin-induced contractions of uterine smooth muscle. 2. Non-pregnant adult Wistar rats were decapitated and dissected to isolate myometrial strips. The tissue was mounted in 5 mL organ baths filled with Krebs' solution that was maintained at 37 degrees C and bubbled continuously with a mixture of 95% O(2)-5% CO(2) to give pH 7.4. Contractions were recorded through transducers for isometric tension recording. The dose-dependent effects of parecoxib on contractility were quantified by changes in the mean amplitude, frequency and area under the contractile curve (AUC; percentage of control conditions) of the isometric tension recordings, averaged over 5 min intervals. Statistical analyses were performed using ANOVA. 3. Application of parecoxib (50-900 micromol/L) caused dose-dependent decreases in mean amplitude, mean frequency and mean AUC of both spontaneous and prostaglandin-induced contractions. Mean percentage inhibition of the AUC of spontaneous contractions was found to be 29, 56, 74 and 84% in the presence of 50, 150, 300 and 600 micromol/L parecoxib, resepctively (n = 8). In the case of prostaglandin (PG) F(2alpha)-induced contractions, 100, 300, 600 and 900 micromol/L parecoxib resulted in a 27, 43, 61 and 73% inhibition, respectively (n = 9). Moreover, pretreatment with parecoxib (600 micromol/L) reduced the responsiveness and maximum contractility to PGF(2alpha) compared with non-treated strips. 4. The data from the present study indicate, for the first time, that parecoxib inhibits spontaneous and prostaglandin-induced contractions of rat myometrium in vitro. These results raise the possibility that parecoxib may be of therapeutic use in the management of preterm labour and dysmenorrhoea.     

U937泡沫细胞中细胞间粘附分子—1的表达及欧芹素乙的抑制作用

目的：研究在人类单核细胞系U937泡沫细胞中,细胞间粘附分子－1（ICAM－1）的表达水平,观测欧芹素乙（欧前胡内酯,imperatorin,IMP)对ICAM－1表达的抑制作用。方法：将U937细胞与80mg/L氧化低密度脂蛋白孵育48h,建立U937泡沫细胞模型,在培养基中预加入不同浓度的IMP（0,25,50,100μmol/L）,采用Western blotting检测ICAM－1的蛋白表达;采用Northern blotting检测ICAM－1的mRNA水平。结果：泡沫细胞中ICAM－1的表达显著高于正常U937细胞。ICAM－1的蛋白和mRNA水平分别是正常U937的15和10倍。经IMP50和100μmol/L预处理后,泡沫细胞中ICAM－1的高表达被显著抑制。当IMP浓度达到100μmol/L时,ICAM－1的蛋白水平降低了79％,mRNA水平降低了74％。结论：经氧化低密度脂蛋白孵育后,U937泡沫细胞中ICAM－1呈现高表达,IMP能显著抑制这种表达。     

瑞香素对血清脂质及脂蛋白胆固醇含量的影响

瑞香素(daphnetin)系瑞香科植物长白瑞香(Daphne koreana Nakai)中的有效单体,化学结构为7,8-二羟基香豆素,并已由长春春城制药厂人工合成。药理实验证明有扩张冠状血管、增加冠脉流量,改善心肌代谢作用,并有抑制实验性“关节炎”及兴奋垂体—肾上