Effects of Rutin on Lipid Profile in Hypercholesterolaemic Rats

Abstract: Rutin (3, 3′, 4′, 5, 7‐pentahydrohyflavone‐3‐rhamnoglucoside) is a flavonoid of the flavonol type. Rutin is found in many plants and is also an important dietary constituent of food and plant‐based beverages. Rutin has several pharmacological properties including antioxidant and cardioprotective activities. Also, it was identified that rutin is the major low‐density lipoprotein (LDL) antioxidant compound of mulberry in an in vitro study. The effects of rutin were tested by using it as a supplement in a high‐cholesterol diet. Male rats were fed a high‐cholesterol diet (1 ml/100 g) for 4 weeks with rutin (10 or 100 mg/kg) or rutin 100 mg/kg and lovastatin supplementation to study the hypocholesterolaemic effects of rutin on plasma lipid levels, hepatic enzyme activity, and liver tissue. Feeding the animals a high‐cholesterol diet resulted in marked hypercholesterolaemia and increased the serum level of LDL cholesterol (LDL‐C). Rutin (at 100 mg/kg) alone or in combination with lovastatin significantly reduced the levels of total cholesterol, and LDL‐C and also markedly decreased liver enzymes and weight in animals with a high‐cholesterol diet. Our findings show that 100 mg/kg of rutin alone or with lovastatin supplementation lowered liver weight and enzymes as well as plasma total cholesterol and LDL. The hepatic histopathological results reflect the correlation of rutin and lovastatin combination with both liver weight and the levels of plasma total cholesterol and LDL‐C. These results indicate that rutin in combination with lovastatin has increased anti‐hypercholesterolaemic effects in an animal model.     

Effects of guggulsterone isolated from Commiphora mukul in high fat diet induced diabetic rats

Sedentary lifestyle, consumption of energy-rich diet, obesity and longer lifespan are some of the major reasons for the rise of metabolic disorders like type II diabetes, obesity, hypertension and dyslipidemia among people of various age groups. High fat diet induced diabetic rodent models resembling type II diabetic condition in human population were used to assess the anti-diabetic and hypolipidemic activity of guggulsterone (isolated from Commiphora mukul resin). Four groups of rats were fed high fat diet, for 16 weeks. On feeding the normal rats with fat rich diet they showed increased serum glucose, cholesterol and triglyceride levels along with increase in insulin resistance significantly (p < 0.05) in comparison to control animals. Different biochemical parameters like GTT, glycogen content, glucose homeostatic enzymes (like glucose-6-phosphatase, hexokinase), insulin release in vivo and expression profiles of various genes involved in carbohydrate and lipid metabolism clearly demonstrated the hypoglycemic effect of this extract. Guggulsterone demonstrated a differential effect with a significantly improved PPARγ expression and activity in in vivo and in vitro conditions, respectively. However, it inhibited 3T3-L1 preadipocytes differentiation in vitro. The results presented here suggest that the guggulsterone has both hypoglycemic and hypolipidemic effect which can help to cure type II diabetes.     

Preventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress in male Wistar rats

High intake of dietary fructose exerts a number of adverse metabolic effects. The aim of the present study was to investigate whether aqueous extract of Tinospora cordifolia stem (TCAE) alleviates high-fructose diet-induced insulin resistance and oxidative stress in rats. High-fructose diet (66% of fructose) and TCAE (400 mg/kg/day) were given simultaneously for a period of 60 days. Fructose fed rats showed hyperglycemia, hyperinsulinemia, hypertriglyceridemia, impaired glucose tolerance and impaired insulin sensitivity (P < 0.05). TCAE treatment prevented the rise in glucose levels by 21.3%, insulin by 51.5%, triglycerides by 54.12% and glucose–insulin index by 59.8% of the fructose fed rats. Regarding liver antioxidant status, fructose fed rats showed higher values of lipid peroxidation (91.3%), protein carbonyl groups (44%) and lowered GSH levels (42.1%) and, lowered activities of enzymatic antioxidants, while TCAE treatment prevented all these observed abnormalities. In conclusion, our data indicate the preventive role of T. cordifolia against fructose-induced insulin resistance and oxidative stress; hence this plant could be used as an adjuvant therapy for the prevention and/or management of chronic diseases characterized by hyperinsulinemia, hypertriglyceridemia, insulin resistance and aggravated antioxidant status.     

Coconut kernel protein in diet protects the heart by beneficially modulating endothelial nitric oxide synthase,tumor necrosis factor-alpha,and nuclear factor-kappaB expressions in experimental myocardial infarction

Previous studies conducted in our laboratory revealed that coconut kernel protein has a significant cardioprotective effect on isoproterenol-induced myocardial infarction in rats. In the present study, we explored the possible protective mechanism of coconut kernel protein during acute myocardial infarction. Coconut kernel protein (50 mg/100 g) was administered to Sprague-Dawley rats orally for 45 days. Isoproterenol (20 mg/100 g) was injected subcutaneously at an interval of 24 hours twice to induce myocardial infarction. Myocardial infarction was confirmed by the abnormal activities of cardiac marker enzymes in serum. Activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase were decreased (p < 0.05) in the heart of isoproterenol-treated rats, whereas pretreatment with coconut kernel protein increased (p < 0.05) these activities. An improved antioxidant status in these rats was further confirmed by the increased level of reduced glutathione and decreased level of lipid peroxidation products. Nitric oxide synthase (NOS) activity in the heart and nitrite level in blood were increased (p < 0.05) in coconut kernel protein-treated rats administered with isoproterenol compared to isoproterenol control rats. Coconut protein pretreatment upregulated the expression of endothelial nitric oxide synthase (eNOS), whereas expressions of nuclear factor-kappaB (NF-κB) and tumor necrosis factor-alpha (TNF-α) were downregulated in isoproterenol-treated rats. These findings suggest that the protective effects of coconut kernel protein may be mediated in part through upregulation of nitric oxide production, antioxidant mechanisms, and its ability to inhibit TNF-α and NF-κB activation.     

Hesperidin attenuates altered redox homeostasis in an experimental hyperlipidaemic model of rat

Diets rich in saturated fats and cholesterol contribute to the incidence of hyperlipidaemia. An altered lipid profile is a major factor responsible for the development of CVD. Male Wistar rats were fed with a high-fat diet (HFD) (suspension (w/v) of 0.5% cholesterol, 3% coconut oil and 0.25% cholic acid for 30 days) to induce an experimental hyperlipidaemic model. High-fat diet fed rats were also supplemented with hesperidin (100 mg/kg body weight). The present study reports reactive oxygen species (ROS) production, oxidative stress parameters: malondialdehyde (MDA), protein carbonyl (PCO), oxidation of plasma protein (AOPP), and advance glycation end products (AGEs); antioxidant defence parameters: ferric reducing ability of plasma (FRAP), reduced glutathione (GSH), Paraoxonase-1 (PON-1), plasma membrane redox system (PMRS); general biochemical parameters: triglyceride, cholesterol, serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT), fasting insulin, fasting glucose, homeostatic model assessment–insulin resistance (Homa-IR) index, and inflammatory biomarkers: interleukin (IL)-6 and tumour necrosis factor (TNF)-α. Experimental hyperlipidaemia was found to be associated with significantly higher body weight (27.58%), cholesterol (140%), triglyceride (190%), and fasting glucose level (37%). Reactive oxygen species production (67%), MDA (28.9%), AOPP (31.42%), PCO (58.53%), and PMRS (156%), inflammatory markers, cytokines IL-6 and TNF-α, were elevated and GSH (50%), PON 1 (37.07%), and FRAP (26.58%) activity were significantly (P < .05) lower in the high-fat diet group. Hesperidin supplementation protected HFD-fed rats from oxidative damage. Our findings indicate that the supplementation of hesperidin provides protection against redox imbalance induced by hyperlipidaemia in rats.     

Gingival vascular damage in atherosclerotic rabbits: Hydroxytyrosol and squalene benefits

Cardiovascular alterations and periodontal disease have been associated, although cardiovascular disease treatments have not yet been tested against periodontal alterations. We investigated effects of squalene, hydroxytyrosol and coenzyme Q₁₀ on gingival tissues of rabbits fed on an atherosclerotic diet. Forty-eight rabbits were distributed in six groups. Control group was fed on standard chow for 80 days. The rest were fed with an atherogenic diet for 50 days. After that, a group was sacrificed and the rest were subjected for another extra 30 days on commercial chow alone or supplemented with coenzyme Q₁₀, squalene or hydroxytyrosol. Atherosclerotic rabbits had higher fibrosis and endothelial activation and lower cellularity in gingival mucosa than controls (P < 0.05). Hydroxytyrosol reduced endothelial activation (P < 0.05) and squalene additionally decreased fibrosis (P < 0.05). Results suggest that gingival vascular changes after the atherosclerotic diet have been reversed by hydroxytyrosol and squalene, natural products from the minor fraction of virgin olive oil.     

Long-term feeding of red algae (Gelidium amansii) ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model

This study was designed to investigate the effect of Gelidium amansii (GA) on carbohydrate and lipid metabolism in rats with high fructose (HF) diet (57.1% w/w). Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1) control diet group (Con); (2) HF diet group (HF); and (3) HF with GA diet group (HF + 5% GA). The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC) and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model.     

Potential of long-term dietary administration of rosemary in improving the antioxidant status of rat tissues following carbon tetrachloride intoxication

In this study, 24 Wistar rats were allocated to 4 groups of 6 animals each. Groups 1 and 2 were fed a basal diet, while groups 3 and 4 were fed the basal diet supplemented further with ground rosemary at 1% level. Following 6-weeks feeding, groups 2 and 4 were injected 1 ml CCl₄/kg bw and after six hours all animals were sacrificed. Results showed that feeding rosemary before CCl₄ treatment resulted in decline (P < 0.05) of the increased aspartate transaminase, alanine transaminase and alkaline phosphatase activities and increase (P < 0.05) of the reduced cholesterol and triacylglycerols in serum. It also decreased (P < 0.05) lipid peroxidation and increased (P < 0.05) the reduced hydroxyl anion radical and hydrogen peroxide scavenging activities in serum, liver, kidney and heart tissues. In addition, it increased (P < 0.05) the reduced ABTS radical cation and the superoxide anion scavenging activities in all tissues except in heart and in kidney and heart tissues, respectively. These results suggest that dietary rosemary has the potential to become a promising functional food component.     

Effects of conjugated linoleic acid supplementation on blood lipids and adiposity of rats fed diets rich in saturated versus unsaturated fat

Conjugated linoleic acid (CLA) may decrease adiposity and improve blood lipid profiles under some conditions. The goal of this study was to determine the effects of CLA supplementation on blood lipid profiles and adiposity of rats fed a diet containing a primarily saturated fat versus a diet containing a primarily unsaturated fat. Twenty-eight male Sprague-Dawley rats were randomly assigned to one of four diets containing coconut oil, coconut oil with CLA, corn oil or corn oil with CLA. After 28 days, blood was collected and serum concentrations of total cholesterol (TC), HDL-cholesterol (HDL-C), and triacylglycerols (TG) were assessed. Food intake, body weights, and epididymal fat pads were measured. No significant differences (p>0.05) were noted among groups for amount of food consumed, weight gained, food efficiency ratio or serum TG concentrations. TC concentrations were lower (p<0.05) in the CLA-supplemented rats that were fed coconut oil but not those consuming corn oil. Serum HDL-C was lower (p<0.05) in rats consuming corn oil but was not significantly different (p>0.05) for CLA supplemented groups. Epididymal fat pads weighed significantly more (p<0.05) in the coconut oil fed group compared to the corn oil fed group, but there was no significant difference (p>0.05) between the corn oil and coconut oil + CLA group. Overall, this study suggests that CLA is more beneficial for control of blood lipids and adiposity when supplemented to a diet rich in saturated versus unsaturated fat.     

Effect of feeding blended and interesterified vegetable oils on antioxidant enzymes in rats

The present study was undertaken to evaluate the effect of feeding blended and interesterified oils prepared using coconut oil (CNO) with rice bran oil (RBO) or sesame oil (SESO), with a polyunsaturated/saturated (P/S) ratio of 0.8-1.0, on oxidative stress and endogenous antioxidant system. Feeding blended oils resulted in significantly increased hepatic lipid peroxide levels in rats given blended oil CNO + RBO or CNO + SESO by 1.3 and 1.6-fold, respectively compared to rats fed diet containing CNO. The lipid peroxide level in erythrocyte membrane also increased in rats fed blended oil compared to rats fed with CNO. Rats fed interesterified oils prepared from these blended oils also showed increased lipid peroxide level compared to rats given CNO diet, however it was not significantly different from rats fed with their respective blends. There was a significant increase in the activity of endogenous antioxidant enzymes super oxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase after feeding blended and interesterified oils. The activities of Na⁺/K⁺-ATPase and Ca²⁺/Mg²⁺-ATPase were increased in rats fed blended and interesterified oils. These results indicated that the P/S ratio of dietary fat is an important factor in determining the oxidative stress, activity of endogenous antioxidant enzymes and activity of membrane bound enzymes.     

Antidiabetic and antidyslipidemic activities of Cuminum cyminum L. in validated animal models

The ethanolic extract of seeds of Cuminum cyminum (C.c) was found to improve glucose tolerance to the tune of around 18.3% (P < 0.01) in normal rats and shows around 17.7% (P < 0.01) and 17.1% fall on blood glucose levels at 0–300 and 0–1440 min, respectively, on streptozotocin-induced diabetic rats at an oral dose of 250 mg/Kg body weight. The extract has also been found to improve around 26.7% (P < 0.01) glucose intolerance on 14th day post treatment in high fructose fed streptozotocin-induced diabetic rats. The extract was also found to have antidyslipidemic activity as evident by 21.04% (P < 0.01) decline in serum triglycerides, 22.7% (P < 0.01) decline in total serum cholesterol, and 16.9% of decline in serum LDL-C, respectively, along with 12.2% (P < 0.05) increase in serum HDL-C on high fat diet fed male Syrian golden hamster. The extract was also found inhibitory to eye lens aldose reductase (EC 1.1.1.21) with IC₅₀ value of 7.07 μg/ml as compared to the standard AR inhibiting compound Quercetin which showed IC₅₀ 2.35 μg/ml. The extract was also found inhibitory to α-glucosidase with IC₅₀ value of 100 μg/ml as compared to known drug Acarbose which showed IC₅₀ of around 25 μg/ml.     

The influence of polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and its metabolite—dichlorodiphenyldichloroethylene (DDE) on mRNA expression for NP-I/OT and PGA, involved in oxytocin synthesis in bovine granulosa and luteal cells

The effect of polychlorinated biphenyls (PCBs) congeners (PCB 77, PCB 126, PCB 153) and their technical mixture—Aroclor (Ar) 1248, as well as dichlorodiphenyltrichloroethane (DDT) and its metabolite—dichlorodiphenyldichloroethylene (DDE; two individual isomers p,p′- and o,p′- or their mixture, 95% and 5%, respectively) at the dose of 10 ng/ml each, on the gene expression of (a) oxytocin (OT) precursor—neurophysin–oxytocin (NP-I/OT) and (b) peptidyl glycine-α-amidating mono-oxygenase (PGA), the terminal enzyme in the pathway of OT synthesis, was studied. Granulosa cells from follicles >1 cm in diameter, collected on days 19–21 of estrous cycle, and luteal cells from corpora lutea (CL) collected on days 8–12 of the estrous cycle were used. The cells were incubated (6 h) with these xenobiotics and the expression of NP-I/OT and PGA genes was determined. All PCBs increased (P < 0.05) NP-I/OT gene expression in granulosa cells. Similarly, all PCBs but PCB 126 increased (P < 0.05) PGA gene expression in these cells. DDT and DDE increased (P < 0.05) gene expression of NP-I/OT in granulosa cells, while gene expression of PGA in these cells was stimulated (P < 0.05) by DDE only. The mRNA expression for NP-I/OT and PGA in luteal cells was increased (P < 0.05) by PCB 77 and PCB 153. Both DDE isomers and mixture also stimulated (P < 0.05) of NP-I/OT mRNA expression, while increase (P < 0.05) of PGA mRNA expression was elicited by incubation of these cells with DDE mixture and Ar 1248.Obtained data suggest that PCBs, DDT and DDE can affect the mRNA expression for NP-I/OT and PGA in bovine granulosa and luteal cells.     

Antioxidant and lipid peroxidation activities in rats fed with Aspergillus carbonarius carotenoid

Effect of feeding partially saturated canthaxanthin (PSC), purified from Aspergillus carbonarius mutant, was studied using four groups of female albino rats (n = 6) for 4 weeks. While the control group received basal diet ad libitum, Groups I, II and III were fed with basal diet containing 50, 100 and 250 ppm PSC, respectively. PSC feeding did not cause any significant changes in food intake and there was no gain in body weight either. PSC included in the diet significantly decreased cholesterol in blood. There was 44.75% and 60.54% decrease in LDL-cholesterol in rats fed with 50 and 100 ppm carotenoid. Hepatic ascorbic acid content increased by 44.59% in rats fed with 50 ppm PSC. Dietary PSC at 250 ppm lowered lipid peroxides by 19.49%. Activities of antioxidant enzymes, glutathione transferase and catalase were significantly higher in serum and liver of PSC fed rats compared to the controls. The results suggested that PSC feeding can induce hypocholesterolmic and antioxidant properties in rats.     

Effects of oleanolic acid and maslinic acid on hyperlipidemia

In the present study, we examined the therapeutic effects of pentacyclic triterpenes, oleanolic acid (OA) and maslinic acid (MA), on hyperlipidemia in a high‐cholesterol diet model. Hyperlipidemia was induced in male Sprague‐Dawley rats by feeding with a high‐cholesterol diet (HCD) for 30 days. MA and OA were supplemented (100 mg/kg body wt/day) during the last 15 days. The levels of serum total cholesterol (TC), triglyceride (TG), high‐density lipoprotein‐cholesterol (HDL‐C), and low‐density lipoprotein‐cholesterol (LDL‐C) increased in hyperlipidemic rats. An apparent increase in the expression of Acyl‐CoA cholesterol acyltransferase (ACAT) mRNA was seen in HCD‐fed rats. The activities of hepatic marker enzymes that serve as indices of cellular injury were also altered in HCD‐fed rats. Treatment with triterpenes modulated the abnormalities induced by hyperlipidimia. Lipid accumulation was decreased in histological findings. Elevated hepatic glycogen content (P<0.05) in triterpene groups was observed compared with HCD‐fed groups. Furthermore, ACAT gene expression was suppressed compared with hyperlipidemia‐induced groups without triterpenes. It can be concluded that triterpene treatment possesses therapeutic effects on diet‐induced hyperlipidemia by inhibiting the intestinal absorption and storage of cholesterol. Drug Dev Res 68:261–266, 2007. © 2007 Wiley‐Liss, Inc.     

款冬花水提物对肥胖小鼠糖脂代谢的影响

目的 研究款冬花水提物对肥胖小鼠血脂血糖的调节作用。方法 采用化学方法对款冬花水提物成分进行鉴定；用紫外可见分光光度法测定款冬花水提物中总萜的含量；将小鼠随机分为空白组，模型组，奥利司他组以及款冬花水提物低、中、高剂量组，空白组给予普通饲料喂养，其余各组采用高脂高糖饲料喂养制备肥胖动物模型，边造模边给药45 d。实验结束后，检测血清中甘油三酯(triglyceride，TG)、胆固醇(cholesterol，CHO)、高密度脂蛋白胆固醇(high density lipoprotein-C，HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein-C，LDL-C)、葡萄糖(glucose，GLU)、糖化血清蛋白(glycosylated serum protein，GSP)含量，采用苏木素-伊红(HE)和油红O染色观察小鼠肝脏组织形态变化和脂滴分布。结果 款冬花水提物含有黄酮类和萜类化合物；与空白组相比，模型组TG、CHO、LDL-C、GLU、GSP水平显著升高(P< 0.01或P<0.05)，HDL-C显著降低(P<0.05)，肝脏中脂滴聚集面积显著增加(P<0.01)；与模型组相比，款冬花水提组均能显著降低TG、LDL-C、CHO、GLU、GSP，升高HDL-C，减少脂滴的蓄积，给药各组血脂血糖状况均较模型组显著降低，其中款冬花水提物高剂量组效果最好。结论 款冬花水提物能够通过降低血脂、CHO，改善肝脏组织病理形态，起到改善肥胖小鼠糖脂代谢的作用。     

Toxicological evaluation of Tetracarpidium conophorum nut oil-based diet in rats

The effects of Tetracarpidium conophorum nut oil-based diet on the growth performance and some biochemical constituents of rat tissues was investigated following a feeding period of 6 weeks. The results revealed that the volume of water taken, the amount of feed consumed and the weight gained by the animals maintained on the nut oil-based diet were not significantly (P > 0.05) different from those fed on soybean oil-based diet. The reduction in the activities of ALP, GOT and GPT in the liver and heart of animals fed on the nut oil-based diet was accompanied by increase in the serum enzymes. The nut oil-based diet significantly reduced (P < 0.05) serum concentrations of total cholesterol and HDL-C whereas triglycerides and atherogenic index increased. The serum LDL-C level of the nut oil-based diet fed animals compared well with those of soybean oil-based diet. These alterations suggested that adverse effects have occurred, possibly by altered membrane permeability of the hepatocytes and cardiac cells. Similar alterations in the serum lipids of animals maintained on nut oil-based diet also portends cardiovascular risk. Although, T. conophorum nut oil did not adversely affect growth performance and the feeding appetite of the animals, it is not completely ‘safe’ for consumption.     

Supplementation of the maternal diet during pregnancy with chocolate and fructose interacts with the high‐fat diet of the young to facilitate the onset of metabolic disorders in rat offspring

相似文献   

葛根素对高脂血症大鼠血脂、血凝及血小板聚集的影响

目的研究葛根素对高脂血症大鼠血脂、血凝及血小板聚集的影响。方法建立大鼠的高脂血症模型,同时连续腹腔注射给予葛根素（50mg·kg-1）或空白溶媒（0.9％NaCI）30d,测定大鼠血浆总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL.C）、低密度脂蛋白胆固醇（LDL－C）、丙二醛（MDA）、超氧化物歧化酶（SOD）、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、ADP诱导的血小板5min最大聚集率（MAR）。结果与高脂饲料组比较,饲高脂饲料大鼠在连续腹腔注射给予葛根素（50mg·kg－1）30d后,大鼠血浆TG含量平均下降27％,Tc含量平均下降21％,LDL－C含量平均下降39％,HDL．C含量平均增加24％;MDA降低,SOD升高,血浆PT、APTT显著延长、MAR降低（尸〈0.05）。结论葛根素不但能有效降低高脂血症大鼠血脂水平,而且可能通过防止脂质过氧化而有效改善动物血凝系统。     

Effect of dietary lipid on locomotor activity and response to psychomotor stimulants

Spontaneous locomotor activity was investigated in developing rats fed diets rich in either saturated fat (coconut oil) or polyunsaturated fat (sunflower oil). The locomotor activity response to amphetamine, methylphenidate, and atropine in the dietary groups was also measured. Rats from dams fed sunflower oil had a late developing (20 days of age) increase in basal locomotor activity when compared to rats from dams fed coconut oil and the standard laboratory diet. The locomotor activity response to d-amphetamine administered IP to 30-day-old animals was potentiated in rats exposed to coconut oil compared to the other two groups. A dose-response analysis of the effect of methylphenidate revealed no differences among the dietary groups. A low dose of atropine (2 mg/kg) decreased 1 h locomotor activity 40% below basal level in rats fed sunflower oil but increased locomotor activity 90% over basal activity in rats fed coconut oil. These results indicate that dietary lipid can have a marked effect on basal locomotor activity as well as on the response to stimulant drugs.     

A combination of Chinese herbs, Astragalus membranaceus var. mongholicus and Angelica sinensis, improved renal microvascular insufficiency in 5/6 nephrectomized rats

Chronic renal ischemia and hypoxia in the tubulointerstitium are involved in the mechanisms of progressive chronic kidney disease. Previous studies showed that the decoction of a combination of two Chinese herbs, Astragalus membranaceus var. mongholicus and Angelica sinensis (A & A) has antifibrotic effects through multiple pathways in different animal models. In this study, remnant kidney model was employed to investigate whether A & A affect the expression of VEGF, the density of the renal microvasculature and thus alleviate the renal injury. Rats were divided randomly into four groups: sham group (N = 31), 5/6 Nx group (5/6 nephrectomy, N = 43), A & A treated group (A & A group, N = 40, A & A 12 g/kg/d po), enalapril treated group (Ena group, N = 56, enalapril 4 mg/kg/d po). Rats from each group were sacrificed at the 2th, 4th, 8th and 12th weeks respectively after surgery and treatment. The 24 h urinary protein excretion, serum creatinine (Scr) and urea were measured. The collagen IV (COL-IV), fibronectin (FN), aminopeptidase P (APP) and VEGF were stained using immunohistochemistry. The COL-IV, FN and APP were semi-quantitatively analyzed. Peritubular capillary density in the cortical interstitial area was quantified. The level of VEGF was assayed by ELISA. The results revealed that Scr, urea and urinary protein excretion remained constant at each time point in sham group. Compared to sham group, 5/6 Nx group was shown severe glomerulosclerosis, tubulointerstitial lesions and vascular damage, as well as higher level of Scr from the 2nd week (72.3 ± 5.2 vs. 48.6 ± 2.6 μmol/L, P < 0.05) to the 12th week (71.9 ± 8.0 vs. 55.7 ± 4.5 μmol/L, P < 0.05). Although there was no significant difference in Scr level after treatment of enalapril or A & A (P > 0.05), kidney damage was alleviated at the 8th and the 12th week in the two treatment groups (P < 0.05, vs. 5/6 Nx group). The urinary protein excretion of 5/6 Nx group was significantly increased from the 4th week, it was 1.5, 2.4 and 3.8 fold of that of sham group at the 4th, 8th and 12th week, respectively. Compared to 5/6 Nx group, proteinuria was decreased by enalapril to 59%, 33% at 8th and 12th week. After A & A administration, urinary protein excretion decreased to 66%, 56%, 75%, 55% of 5/6 Nx group at the 2nd, 4th, 8th and 12th, respectively (P < 0.05). Compared with sham group, there was increased expression of FN and COL-IV in rats with 5/6 Nx. After A & A or enalapril administration, the expression of FN and COL-IV was significantly decreased compared with that in the 5/6 Nx group at 8th and 12th week (P < 0.05). On the other hand, the capillary density was decreased at the 8th and 12th week in 5/6 Nx rats (P < 0.01). In A & A-treated group, similarly with enalapril group, the amount of APP-positive glomerular capillary increased by 36% (P < 0.01), and the peritubular capillary density was increased 94% at 8th week and 52% at 12th week compared with 5/6 Nx group (P < 0.05). The renal level of VEGF was decreased in 5/6 Nx rats, but increased at the 8th and 12th week in A & A group (P < 0.05, vs. 5/6 Nx group). In conclusion, A & A has renoprotective effects by suppression of extra cellular matrix deposition in 5/6 Nx rat. The renoprotective effects may be associated with reduction of proteinuria, up-regulation of VEGF which may reduce the loss of capillaries and improve microstructure dysfunction.