Hypolipidemic effect of triphala in experimentally induced hypercholesteremic rats

Hypercholesteremia is one of the risk factors for coronary artery disease. The present study highlights the efficacy of Ayurvedic herbal formulation Triphala (Terminalia chebula, Terminalia belerica, and Emblica officinalis) on total cholesterol, Low density lipoprotein (LDL), Very low density lipoprotein (VLDL), High density lipoprotein (HDL) and free fatty acid in experimentally induced hypercholesteremic rats. Four groups of rats were employed namely control, Triphala treated, hypercholesterolemia rats (4% Cholesterol + 1% cholic acid + egg yolk) and Triphala pre-treatment in hypercholesteremic rats. Results showed significant increase in the total cholesterol, LDL, VLDL, and free fatty acid in hypercholesteremic rats were significantly reduced in Triphala treated hypercholesteremic rats. The data demonstrated that Triphala formulation was associated with hypolipidemic effects on the experimentally induced hypercholesteremic rats.     

富含生育三烯酚的棕榈油对动脉粥样硬化小鼠糖代谢的影响

目的探讨富含生育三烯酚的棕榈油(TRF)对动脉粥样硬化小鼠糖代谢的影响及其可能的作用机制。方法载脂蛋白E基因缺陷(ApoE-/-)小鼠分为模型对照组、TRF0.05%和0.2%(W/W)组。TRF均匀混于饲料中,各组饲料中添加10%(W/W)的脂肪和0.2%(W/W)的胆固醇诱导动脉粥样硬化的形成。小鼠经TRF处理12和14周后分别进行口服葡萄糖耐量实验(OGTT)和胰岛素耐量实验(ITT);用相应试剂盒检测血清中总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)和胰岛素的含量;实时荧光定量PCR分析白色脂肪组织(WAT)中过氧化物酶体增殖物激活受体γ(PPARγ)、脂联素和葡萄糖转运体4(Glut4)的mRNA水平;利用荧光素酶报告系统检测TRF对PPRAγ的激活作用。结果OGTT和ITT实验显示,在非禁食和禁食的情况下,TRF均能够降低ApoE-/-小鼠的血糖,改善胰岛素的敏感性;TRF组小鼠血清中TG和FFA的水平均低于模型对照组;在WAT中,与模型对照组相比,TRF0.2%组上调脂联素mRNA水平(1.73±0.32)倍,TRF0.05%和0.2%组分别增加Glut4mRNA水平(1.89±0.24)和(2.01±0.61)倍,PPARγmRNA水平没有改变。荧光素酶报告系统检测结果显示,TRF对PPARγ-配体结合结构域、PPARγ1和PPARγ2的激活作用分别是溶剂对照组的(2.7±0.2),(6.1±0.6)和(5.3±0.1)倍。结论TRF能够很好地改善动脉粥样硬化小鼠的糖代谢,TRF发挥这些作用的部分原因是通过激活PPARγ来实现的。     

In vivo antioxidant potential of rice bran oil (RBO) in albino rats

Rice Bran Oil (RBO) has got many health benefits. RBO has been analyzed for physico-chemical characteristics and compared with those of groundnut oil (GNO). The two oils were similar in various physicochemical characteristics. The major difference in the two oils lay in the amount of unsaponifiable matter, which was higher in the case of RBO. To find the in vivo antioxygenic potential of RBO, particularly its ability to protect against oxidative stress, rats were divided into two groups of 10 animals, each and were maintained on diets containing RBO or GNO for a period of 4 weeks. After which stress was induced to half the animals of each group by administering intraperitoneally N-nitrosodiethylamine (NDEA) (100 mg/kg) body weight and remaining half served as respective controls. Animals were sacrified 1 week after stress induction. Intraperitoneal administration of NDEA resulted in a significant reduction in body weight and feed intake, the effect being appreciably less in RBO fed group. NDEA toxicity was mainly reflected in liver as supported by increased activities of enzymes of liver function test (AST, ALT, ALP) on stress induction but the effect was appreciably of lesser degree in the group fed on RBO. The urea levels were also less in the group fed on RBO, The lipid peroxidation (LPO) increased on stress induction in erythrocytes and in all the tissues, the increase being less in RBO fed group except in kidneys. Stress induction resulted in decreased catalase (CAT) activity, the decrease being less in RBO fed group. The increase in peroxidase (Px) activity on stress induction was more in RBO fed group. Stress induction had no significant effect on superoxide-dismutase (SOD) activity except in liver and heart where it increased on stress induction. Thus, it appears that inclusion of RBO in the diet improves the antioxygenic potential and protect against oxidative stress.     

Hypolipidemic effect of fucoidan from Laminaria japonica in hyperlipidemic rats

In this study, we investigated the effect of fucoidan polysaccharide sulfuric acid ester (FPS) from Laminaria japonica Aresch (Laminariaceae) on hyperlipidemic rats. FPS notably reduced the concentration of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) of hyperlipidemic rats and increased the concentration of high-density lipoprotein cholesterol (HDL-C) and the activities of lipoprotein lipase (LPL), hepatic lipoprotein (HL), and lecithin cholesterol acyltransferase (LCAT).     

Effectiveness of Amygdalus mongolica oil in hyperlipidemic rats and underlying antioxidant processes

The seeds of Amygdalus mongolica contain various constituents including flavonoids and vitamin E, which are known to exert antioxidant effects. However, the safety of the oil extract of this compound is not fully known. The aim of this study was to determine the physicochemical properties of A. mongolica oil, identify the constituents and subsequently assess the effectiveness of utilizing this seed extract in hyperlipidemia as an antioxidant agent. In particular, the toxicity and safety of A. mongolica oil were examined with emphasis on effects on blood lipids level and serum lipid peroxidation using a hyperlipidemia rat model. Treatment with 20 ml/kg A. mongolica oil produced no apparent adverse effects after 14 days in normal female and male rats. A dose of 2.5–10 ml/kg A. mongolica oil administered to hyperlipidemic male rats significantly decreased serum total cholesterol (TC), low-density lipoprotein-C (LDL-C), malondialdehyde (MDA), total cholesterol high-density lipoprotein-C (TC/HDL-C), LDL-C/HDL-C, and atherosclerosis index(AI). In contrast, glutathione (GSH) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased. Data demonstrated that A. mongolica oil may be utilized in conditions of hyperlipidemia due to its antioxidant effects.     

Metabolism of troglitazone in hepatocytes isolated from experimentally induced diabetic rats

Troglitazone (TGZ), the prototype 2,4-thiazolidinedione antidiabetic agent, is associated with hepatotoxicity in patients with Type 2 diabetes. Although the mechanism of toxicity has not been established, alterations in the clearance of TGZ from in-vitro hepatocyte cultures through metabolic conjugation reactions are believed to modulate the toxicity of the compound. In this study, the metabolism of TGZ in freshly isolated hepatocytes from the fat-fed streptozotocin-treated rat model of Type 2 diabetes is described. Biochemical parameters such as cellular reduced glutathione content, content of cytochromes P450 and b5, and the expression of glutathione-S-transferase alpha (subunits Ya and Yc2) were not affected by the induced diabetes. TGZ was metabolized primarily to a sulfonate, a quinone and a glucuronide in both control and experimentally diabetic animals. However, metabolism after induction of diabetes was characterized by a moderate increase in sulfation, a decrease in the elimination half-life of TGZ and the absence of the minor metabolites of TGZ, notably the glutathione adduct of the putative reactive intermediate (m/z = 747 (M + H)+; m/z = 745 (M - H)-).     

The triterpenoid fraction from Trichosanthes dioica root suppresses experimentally induced inflammatory ascites in rats

Abstract

Context. Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in English, is a dioecious climber found wild throughout the plains of the Indian subcontinent and traditionally used in India for several medicinal purposes.

Objective: The present study evaluated the protective effect of the triterpenoid enriched fraction from T. dioica root (CETD) against experimentally induced acute inflammatory ascites in Wistar albino rats.

Materials and methods: The CETD was administered orally at the different doses (25, 50 and 100?mg/kg body weight) to overnight fasted rats, and then ascites was induced by intraperitoneal administration of formalin solution. After 7?h, the rats were sacrificed and the volume of ascitic fluid was measured.

Results: The CETD demonstrated significant (p?<?0.01) reduction of ascitic fluid formation in a dose-dependent manner as compared with control.

Conclusion: The CETD produced significant and dose-dependent inhibition of experimentally induced inflammatory ascites in Wistar albino rats.     

Hypolipidemic and antioxidant effects of ethanol extract of Cassia fistula fruit in hyperlipidemic mice

Context: The plant Cassia fistula L. (Caesalpiniaceae) fruit was widely used by traditional practitioners to treat cardiovascular diseases (CVDs) in India. Hyperlipidemia is a lipid metabolism disorder and the major risk factor for the development of CVDs. Although most of the current hypolipidemic drugs are expensive and have potential side effects, the research focusing on natural alternative medicines is relevant.

Objective: To investigate the hypolipidemic and antioxidant effects of ethanol extract of C. fistula fruit (CFE) in high-fat diet (HFD) induced hyperlipidemia in mice.

Materials and methods: Oral administration of CFE at 100, 300 and 500?mg/kg body weight on HFD induced hyperlipidemia mice for 30 days. The standard drug atorvastatin (20?mg/kg) was used to compare the efficacy of CFE. Hypolipidemic effect was evidenced by the measurement of serum lipid profile and further confirmed by Oil Red O staining of adipose tissue. The hepatic and cardiac melondialdehyde (MDA) level and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase were determined.

Results: Treatment with CFE at different doses has significantly restored the levels of serum lipid, MDA and enzymes activities in the liver and heart of hyperlipidemia mice. Oil Red O staining of visceral adipose tissue has shown marked reduction of lipid accumulation in adipocytes; whereas, administration of CFE at 500?mg/kg showed remarkable (p?<?0.001) hypolipidemic and antioxidant effects in HFD fed mice.

Conclusion: C. fistula fruit demonstrated hypolipidemic and antioxidant properties in vivo and the results corroborate the use of this plant in traditional medicine for cardiac ailments.     

Hypolipidemic activity of Phellinus rimosus against triton WR-1339 and high cholesterol diet induced hyperlipidemic rats

Patients with the risk for atherosclerotic disease will be targeted to reduce the existing hyperlipidemia. The hypolipidemic activity of Phellinus rimosus was studied using triton WR-1339 and high cholesterol diet (HCD) induced models. The triton induced elevated lipid profile was attenuated by P. rimosus or standard drug atorvastatin. Similarly, administration of P. rimosus along with HCD significantly decline serum triglyceride, total cholesterol, low-density lipoprotein, with elevating the high-density lipoprotein. Thiobarbituric acid reacting substances in heart and liver significantly decreased; where as activity of enzymatic antioxidants and level of reduced glutathione were significantly increased. In both models, P. rimosus extract showed a significant ameliorative effect on the elevated atherogenic index as well as LDL/HDL-C ratio. The hypolipidemic activity of P. rimosus can be ascribed to its inhibitory effect on the liver HMG CoA reductase activity. The results suggest the possible therapeutic potential of this fungus as hypolipidemic agent.     

Hypolipidemic activity of Anthocephalus indicus (kadam) in hyperlipidemic rats

The hypolipidemic action of Anthocephalus indicus (family, Rubiaceae: Hindi name, Kadam) fruit extract has been studied in hyperlipidemic rats fed a triton- and cholesterol-rich high-fat diet. In triton WR-1339-induced hyperlipidemic rats, feeding with the fruit extract (500 mg/kg b.w.) exerted a lipid-lowering effect as assessed by reversal of plasma levels of total cholesterol, phospholipids, and triglyceride following reactivation of the post-heparin lipolytic activity. In another model, chronic feeding of this natural product (500 mg/kg, b.w.) to animals simultaneously fed a high-fat diet for 30 days caused lowering of lipid levels in plasma and liver accompanied with stimulation of hepatic lipolytic activity. The hypolipidemic activity of Anthocephalus indicus fruit extract iscompared with guggulipid, a known lipid-lowering drug, in both models.     

Rice bran oil prevents neuroleptic-induced extrapyramidal symptoms in rats: Possible antioxidant mechanisms

Tardive dyskinesia (TD) is one of the serious side effects of long-term antipsychotic treatment. Chronic treatment with neuroleptic leads to the development of abnormal oral movements called vacuous chewing movements (VCMs). The oxidative stress hypothesis of TD is one of the possible pathophysiologic models for TD. Preclinical and clinical studies of this hypothesis indicate that neurotoxic free radical production is likely to be a consequence of antipsychotic medication and is related to occurrence of TD. Oxidative stress is implicated in the pathophysiology of TD. Rats chronically treated with haloperidol orally at a dose of 0.2 mg/kg/day for a period of 5 weeks developed VCMs, which increased in a time-dependent manner as the treatment continued for 5 weeks. Motor coordination impairment started after the 1^st week and was maximally impaired after 3 weeks and gradually returned to the 1^st week value. Motor activity in an open field or home cage (activity box) not altered. Administration of rice bran oil (antioxidant) by oral tubes at a dose of 0.4 mL/ day prevented the induction of haloperidol-elicited VCMs as well impairment of motor coordination. The results are discussed in the context of a protective role of antioxidant of rice bran oil in the prevention of haloperidol-induced extrapyramidal symptoms.     

The impact of cyanoglycoside rich fraction isolated from Cassava (Manihot esculenta) on alcohol induced oxidative stress.

The effects of feeding a cassava (Manihot esculenta) rich diet on alcohol induced peroxidative damages were investigated in male albino rats. Rats were divided into four groups and maintained for 60 days as follows. (1) Control group: cassava free diet, (2) alcohol group: cassava free diet+ethanol (4 g/kg body wt/day), (3) cassava group: cassava diet and (4) alcohol+cassava group: cassava diet+ethanol (4 g/kg body wt/day). Results revealed that alcohol induced significant lipid peroxidation, since the lipid peroxidation products malondialdehyde (MDA), hydroperoxides and conjugated dienes were elevated in the liver. The activities of free radical scavenging enzymes such as superoxide dismutase (SOD), catalase and glutathione reductase were reduced and glutathione content was decreased in the liver. But the co-administration of a cassava rich diet increased the activity of free radical scavenging enzymes and glutathione content. The level of lipid peroxides in the liver was also decreased on co-administration of cassava. But the oxidative damage caused by cassava was potentiated by alcohol administration. These studies suggested that consumption of alcohol along with cassava offered some protection against the alcohol induced oxidative stress. So we isolated the cyanoglycoside rich fraction from cassava and its impact on rats administered alcohol was also investigated. The results revealed that alcohol induced oxidative stress was potentiated by the co-administration of cyanoglycoside rich fraction. These studies suggested that the fiber and antioxidant vitamins present in the cassava may be playing a protective role against the alcohol induced oxidative stress.     

An evaluation of crude palm oil (CPO) and tocotrienol rich fraction (TRF) of palm oil as percutaneous permeation enhancers using full-thickness human skin

The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol-rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright ‘Franz-type’ diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log p values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6?µg/cm² h and 23.0?µg/cm² h respectively, compared to the control with a flux of 16.2?µg/cm² h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil.     

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.     

Lipid lowering and antioxidant activity of flavones in triton treated hyperlipidemic rats

Flavones are plant derived polyphenolic compounds which are consumed by our diet. Epidemiological studies indicating that high dietary intake of flavones reduces the risk of mortality due to coronary heart disease. The lipid lowering action of flavones—myricetin, rutin, naringenin-7-rhamnoglucosides and naringenin hydrates has been studied in triton treated hyperlipidemic rats (in vivo) and antioxidant activity (in vitro). Among these myricetin and naringenin hydrate showed potent antidyslipidemic and antioxidant activities. The antidyslipidemic and antioxidant activities of these flavones may help in prevention of hyperlipidemia and related cardiovascular diseases.     

In-vivo antioxidant and immunomodulatory activity of mesuol isolated from Mesua ferrea L. seed oil

Mesua ferrea L. (Nagkesar) is traditionally being used for antiseptic, anti-inflammatory, antiasthmatic and antiallergic activities. It is an ingredient of ayurvedic formulations like Brahma Rasayana and Chyavanprash which are being used to improve immunity. The present study was performed to evaluate immunomodulatory activity of mesuol isolated from M. ferrea seed oil in experimental animals. In humoral immune response model, mesuol evoked a significant dose dependent increase in antibody titer values in cyclophosphamide (50 mg/kg, i.p., 9th and 16th day) induced immunosuppression which was sensitized with sheep red blood cells (SRBC) on the 7th and 14th day of experiment. In cellular immune response model, an increase in paw volume was recorded on the 23rd day in cyclophosphamide-induced immunosuppressed rats treated with SRBC (0.03 ml 2% v/v, s.c.) on the 21st day. Mesuol restored the hematological profile in cyclophosphamide induced myelosuppression model. Mesuol potentiated percentage neutrophil adhesion in neutrophil adhesion test in rats and phagocytosis in carbon clearance assay. The study indicated immunomodulatory activity of mesuol.     

Oral toxicity of a tocotrienol preparation in rats.

Tocotrienols are added as antioxidants to food. As there have been no reports of toxicological evaluation, a 13-week oral toxicity study was performed in Fischer 344 rats of both sexes at dose levels of 0 (group 1), 0.19 (group 2), 0.75 (group 3) and 3% (group 4) of a preparation in powdered diet. Suppression of body weight gain was observed in group 4 males. On hematological examination, significant decrease in mean corpuscular volume (MCV) was observed in all treated males. Platelets were significantly reduced in group 3 and 4 males. Hemoglobin concentration, MCV, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were significantly decreased in group 3 and 4 females and hematocrit in group 4 females. On serum biochemical examination, increase in the albumin/globulin ratio (A/G) and alkaline phosphatase in all treated males, elevated alanine transaminase in group 4 of both sexes and increases in asparagine transaminase and gamma-glutamyl transaminase in group 4 females were observed. With regard to relative organ weights, liver weights in group 4 of both sexes and adrenal weights in all treated males demonstrated an increase, and ovary and uterus weights in group 4 females were reduced. Histopathologically, slight hepatocellular hypertrophy in group 3 and 4 males, and reduction of cytoplasmic vacuolation in the adrenal cortical region in group 4 males were observed. Because of pathological changes in male liver and hematological changes in females, the no-observed-adverse-effect level (NOAEL) was concluded to be 0.19% in the diet (120 mg/kg body weight/day for male rats and 130 mg/kg body weight/day for female rats). As a decrease in MCV, an increase in the A/G, elevation of alkaline phosphatase and increase in adrenal weight were observed in all treated males, a no-observed-effect level (NOEL) could not be determined in this examination.