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.     

Hypoglycaemic and hypolipidaemic effects of fractions from kolaviron, a biflavonoid complex from Garcinia Kola in streptozotocin-induced diabetes mellitus rats

In the search for natural hypoglycaemic agents as alternatives to synthetic ones that are expensive and not easily accessible, and to justify the use of Garcinia kola seeds in traditional African medicine to treat diabetes, the hypoglycaemic and hypolipidaemic effects of fractions from kolaviron (KV) (a Garcinia kola seed extract) were investigated in normal and streptozotocin (STZ)-diabetic rats. KV, a biflavonoid complex from Garcinia kola seed, was separated by thin-layer chromatography into three fractions; Fraction I (FI), Fraction II (FII) and Fraction III (FIII) with RF values of 0.48, 0.71 and 0.76, respectively. In normoglycaemic rats, KV, FI and FII administered at a dose of 100 mg kg(-1) body weight elicited significant (P < 0.05) hypoglycaemic activity within 4 h of oral administration. Precisely, KV, FI and FII decreased blood glucose levels of normoglycaemic rats by 66%, 50% and 61%, respectively, when compared with controls 30 min after oral administration of the extracts. In hyperglycaemic rats, KV, FI and FII significantly (P < 0.05) reduced blood sugar levels in STZ-diabetic rats within 4 h of oral administration. Furthermore, KV alone produced a significant (P < 0.05) anti-diabetic effect from day 3 to day 7 of oral intubation of STZ-diabetic rats. In addition, the extracts showed favourable effect on the plasma lipid profile of STZ-diabetic rats, and also decreased significantly (P < 0.05) the STZ-induced increase in the activity of microsomal glucose-6-phosphatase and lipid peroxidation (LPO) products. This study confirms the anti-diabetic and hypolipidaemic effects of KV in STZ-diabetic rats. These observed effects of KV are attributed to two of its fractions, FI and FII, with RF values of 0.48 and 0.71, respectively.     

Anti-oxidant mechanisms of kolaviron: studies on serum lipoprotein oxidation, metal chelation and oxidative membrane damage in rats

1. In the present study, we have examined the ability of kolaviron, a natural biflavonoid from Garcinia kola seeds, to prevent the susceptibility of rat serum lipoprotein to undergo oxidative modification in vitro and ex vivo. In addition, its ability to chelate metal ions and mitigate iron/ascorbate-induced damage to microsomal lipids was investigated. 2. Lipoprotein resistance to copper-induced oxidation was highly improved in rats treated with kolaviron (100 mg/kg) for 7 days, as demonstrated by a significant increase in lag time compared with control. A significant (P < 0.05) decrease in area under the curve (AUC) and slope of propagation was observed in kolaviron-treated rats compared with control. Conjugated dienes formed after 240 min of lipoprotein oxidation were markedly decreased in kolaviron-treated rats compared with controls. Malondialdehyde concentrations were significantly reduced in the serum lipoproteins of kolaviron-treated rats with an attendant significant increase in the total anti-oxidant activity compared with control. 3. In vitro, kolaviron (10-60 micromol/L) inhibited the Cu2+-induced oxidation of rat serum lipoprotein in a concentration-dependent manner. Kolaviron, at 20 and 60 micromol/L, produced 48 and 87% inhibition of oxidation of lipoprotein, respectively. Compared with control, kolaviron, at 10 and 20 micromol/L, resulted in 29 and 47% decreases in AUC, respectively. In addition, kolaviron (10 micromol/L) elicited a 53% increase in lag time, whereas 40 and 60 micromol/L kolaviron produced 38 and 88% decreases in slope, respectively. 4. Kolaviron effectively prevented microsomal lipid peroxidation induced by iron/ascorbate in a concentration-dependent manner. Kolaviron at the highest dose tested (90 micromol/L) had a significant chelating effect on Fe2+ (78%). 5. In conclusion, our data demonstrate that kolaviron protects against the oxidation of lipoprotein, presumably by mechanisms involving metal chelation and anti-oxidant activity, and, as such, may be of importance in relation to the development of atherosclerosis.     

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.     

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.     

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.     

Antidiabetic and aldose reductase activities of biflavanones of Garcinia kola

Kolaviron, a mixture of C-3/C-8 linked biflavonoids obtained from Garcinia kola produces significant hypoglycaemic effects when administered intraperitoneally to normal and alloxan diabetic rabbits at a dose of 100 mg kg-1. The fasting blood sugar in normoglycaemic rabbits was reduced from 115 mg/100 mL to 65 mg/100 mL after 4 h. In alloxan diabetic rabbits, the blood sugar was lowered from 506 mg/100 mL to 285 mg/100 mL at 12 h. The hypoglycaemic effects have been compared with those of tolbutamide. Kolaviron inhibited rat lens aldose reductase (RLAR) activity, with an IC50 value of 5.4 x 10(-6). The significance of these findings in the potential use of kolaviron as an antidiabetic agent is discussed.     

Morphological and biochemical investigation into the possible neuroprotective effects of kolaviron (Garcinia kola bioflavonoid) on the brains of rats exposed to vanadium

In this study, the morphological and biochemical susceptibility of the rat brain to vanadium, in the form of sodium metavanadate, and the comparative ameliorative effect of Garcinia kola and kolaviron (G. kola extract), was examined. Brain regions examined were the cerebrum, cerebellum, hippocampus and the olfactory bulb. We showed that vanadium administration caused cellular vacuolation, congestion, and Purkinje cell degeneration and a marked reduction in myelin tracts. Biochemical tests revealed increased lipid peroxidation induced by vanadium, which was ameliorated with the administration of G. kola and kolaviron. Vanadium administration caused an increase in thiobarbituric acid-reactive substances (TBARS) in the cerebrum and hippocampus, whereas the administration of kolaviron resulted in a reduction of the TBARS level by 65.7 and 80%, respectively, in the regions aforementioned. Also, the administration of kolaviron resulted in an increased activity of superoxide dismutase (61.24%) in all brain regions assessed, when compared with the group administered vanadium alone. Results obtained from this study led to the conclusion that kolaviron reduces vanadium-induced oxidative stress in the brain.     

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.     

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.     

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.     

In vitro antioxidant and free radical scavenging activities of Garcinia kola seeds

Garcinia kola Heckel – a tropical plant which grows in moist forest, has found wide applications in traditional medicine especially in the West and Central African sub-region. The seeds have been demonstrated to possess numerous bioactivities but research is highly limited on the link between its fractions and the bioactivities. In this work, the methanolic extract of Garcinia kola seeds was subjected to silica gel column chromatography into five fractions ME1–ME5 and the free radical scavenging activities and antioxidant potentials were determined for each fraction using various in vitro models. The ME4 fraction possessed the greatest activities. It was also demonstrated that the ME4 fraction strongly inhibited nitric oxide production in lipopolysaccharide activated macrophage U937 cells. Chromatographic fractionation and spectroscopic analysis of the ME4 fraction revealed the presence of four compounds namely garcinia biflavonoids GB1 and GB2, garcinal and garcinoic acid. These findings show that these four compounds are partly responsible for the great antioxidant potential of Garcinia kola seeds. This gives further evidence to the nutraceutical and pharmaceutical potential of Garcinia kola.     

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.     

Antitumor constituents ofPolyporus giganteus

To investigate antitumor constituents of higher fungi, the carpophores ofPolyporus giganteus Pers. ex. Fr. (81 g, dry weight) which were collected in Indiana, U.S.A. were examined for antitumor activity. Two protein-bound polysaccharide fractions (I and II) were prepared from the hot water extract and one fraction (III) from the 0.1 N NaOH extract of the carpophores. The antitumor effect of each fraction was tested against sarcoma 180 implanted subcutaneously in female ICR mice. Of three fractions, Fraction II showed 85.2% inhibition ratio at the dose of 20 mg/kg/day for 10 days and was named gigantan. Gigantan was found to contain 59% polysaccharide and 27% protein. Its polysaccharide moiety was a heteroglycan that consisted of mainly glucose (89.3%), galactose (7.7%), manose (2.0%) and fructose (1.0%).     

泽泻汤对高血脂症小鼠降血脂作用有效部位的实验研究

目的：研究泽泻汤及其3个组分对实验性高血脂症小鼠血脂的调节作用,研究泽泻汤降血脂作用的有效部位。方法：泽泻汤水提取制备总提物,总提物依次以100％、50％甲醇提取制备泽泻汤组分Ⅰ、组分Ⅱ和残渣部分组分Ⅲ。采用高脂饲料喂养雄性昆明小鼠建立高血脂症模型,观察泽泻汤及其3个组分对小鼠体重、血清总胆固醇（TC）,甘油三酯（TG）含量、肝肾系数及肝组织超氧化物歧化酶（SOD）、丙二醛（MDA）含量的影响。结果：泽泻汤总提物及其各组分能不同程度的降低高脂血症小鼠的体重、肝肾系数,改善肝组织MDA、SOD水平;泽泻汤总提物和组分Ⅰ在给药4周时显著降低小鼠血清TC水平,组分Ⅱ和组分Ⅲ无此作用;给药2周和4周,泽泻汤总提物及3个组分均能降低TG水平,组分Ⅰ在给药4周时降低TG的作用最为显著。结论：泽泻汤及其各组分能改善小鼠高脂血症,其有效部位为组分Ⅰ,而组分Ⅱ、Ⅲ作用较弱。     

Synthesis of low-phenylalanine polypeptides

Low-phenylalanine-peptides for dietotherapy of phenylketonuria (PKU) were prepared from soybean protein isolate. Soluble fraction of soybean protein isolate was hydrolysed by α-chymotrypsin then followed by carboxypeptidase-A. Molecular weight distribution and amino acid analysis were made on the resultant polypeptides. The chymotrypsin hydrolysate was divided into two fractions, Fraction I (molecular weight > 2500) and Fraction II (molecular weight between 1000 and 2500). The phenylalanine content of Fraction I (3.1%) was lower than that of Fraction II (5%), indicating the nonuniform distribution of phenylalanine in soybean protein. Carboxypeptidase hydrolysis of Fraction I further reduced the phenylalanine concentration to 2.3%, approximately half of the original concentration in soybean protein isolate.     

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.     

Venom of the Australian rough-scaled snake, Tropidechis carinatus: lethal potency and electrophysiological actions

A series of experiments to define the lethal potency (LD50) and electrophysiological properties of the venom of the Australian Rough-scaled Snake (Tropidechis carinatus) are described. Crude pooled venom contains at least five fractions which were separated using liquid chromatography and high pressure liquid chromatography techniques (Fractions I-V). LD50 studies are reported using each of these fractions, with data for both adult and neonatal mice. Fraction I (mol. wt greater than 100,000) was essentially non-toxic. Fraction IV (mol. wt less than or equal to 10,000) and Fraction V (mol. wt less than 1,000) were potent toxic components with LD50'S (s.c. injection; fraction in 0.1% bovine serum albumin and 0.85% saline; neonatal mice) of 0.04 mg/kg and 0.06 mg/kg respectively. LD50'S for the whole crude venom were similar in both adult and neonatal mice. Electrophysiological studies using a Bulbring preparation (rat isolated phrenic nerve-hemidiaphragm) indicated that Fractions I, IIa and IIb were inactive. Fraction IV (mol. wt less than or equal to 10,000) caused rapid neuromuscular blockade which appeared to be irreversible. Neurophysiological experiments with a rat isolated extensor digitorum longus muscle preparation suggested that the major toxic activity of the whole venom resides in Fractions III and IV, and that both of these fractions have presynaptic and postsynaptic action.     

Antihyperlipidemic activity of Ichnocarpus frutescens in triton WR-1339-induced and high-fat diet animals

Context: Ichnocarpus frutescens (L.) R.Br. (Apocynaceae) is used to treat diabetes and hyperlipidemia in folk medicine.

Objective: The crude methanol extract and fractions of I. frutescens were investigated for antihyperlipidemic effect.

Materials and methods: Fresh leaves of I. frutescens were extracted with methanol and fractionated with hexane, benzene, ethyl acetate, acetone, and methanol. The active acetone fraction was subfractionated, which resulted in active fraction 3. The antihyperlipidemic effects of the methanol extract and fractions of I. frutescens were studied in triton WR-1339-induced and high-fat diet (HFD) obese animals. Further, lipid absorption and excretion were studied.

Results and discussion: The methanol extract significantly reduced total cholesterol (TC) by 29.63% and triglyceride (Tg) by 51.10% at 400?mg/kg in triton WR-1339-induced animals and significantly reduced TC (27.81%) and Tg (37.03%) at 400?mg/kg in HFD animals. Fraction 3 showed significant reduction in TC (25.03%) and Tg (58.05%) at 200?mg/kg. Feeding of HFD consisting 3% of fraction 3 increased feces weight and Tg level in mice. Fraction 3, showed significant decrease in plasma Tg level at the second hour, after oral administration of the lipid emulsion to rats.

Conclusion: The observed properties apparently validate the folk medicinal use of this plant in amelioration of hyperlipidemia.