Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica

ContextThe petroleum ether extract (PET) of Amygdalus mongolica (Maxim.) Ricker (Rosaceae) has an ameliorative effect on renal fibrosis (RF).ObjectiveTo evaluate the antifibrotic effects of A. mongolica seeds PET on RF by serum metabolomics, biochemical and histopathological analyses.Materials and methodsSixty male Sprague-Dawley rats were randomly divided into the sham-operated, RF model, benazepril hydrochloride-treated model (1.5 mg/kg) and PET-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. Biochemical indicators including BUN, Scr, HYP, SOD, and MDA were measured. Haematoxylin and eosin and Masson staining were used for histological examination. The serum metabolomic profiles were determined by UPLC-Q-TOF/MS and metabolism network analysis. Acute toxicity test was performed to validate biosafety.ResultsThe PET LD₅₀ was >23.9 g/kg in rats. PET significantly alleviated fibrosis by reducing the levels of Scr (from 34.02 to 32.02), HYP (from 403.67 to 303.17) and MDA (from 1.84 to 1.73), and increasing that of SOD (from 256.42 to 271.85). Metabolomic profiling identified 10 potential biomarkers, of which three key markers were significantly associated with RF-related pathways including phenylalanine, tyrosine and tryptophan biosynthesis, amino sugar and nucleotide sugar metabolism and tyrosine metabolism. In addition, three key biomarkers were restored to baseline levels following PET treatment, with the medium dose showing optimal effect.ConclusionsThese findings revealed the mechanism of A. mongolica PET antifibrotic effects for RF rats on metabolic activity and provided the experimental basis for the clinical application.     

Hypolipidemic and antioxidant properties of tocotrienol rich fraction isolated from rice bran oil in experimentally induced hyperlipidemic rats.

We investigated a dose-dependent hypolipidemic and antioxidant effect of tocotrienol rich fraction (TRF) isolated from rice bran oil on experimentally induced hyperlipidemic rats. Feeding of atherogenic diet (5% hydrogenated fat, 0.5% cholic acid and 1% cholesterol) for three weeks resulted in a significant increase in plasma triglyceride (3.3-fold) and total cholesterol (2.4-fold) levels. There was a 5-fold increase in the level of LDL cholesterol with only a small increase in HDL cholesterol. On the other hand, HMG-CoA reductase activity was significantly reduced in these animals. The formation of TBARS, thiobarbituric acid reactive substances, (86%) and conjugated dienes (78%) were also significantly higher in these rats compared to normals. After the induction of hyperlipidemia for three weeks, rats were supplemented with different doses of TRF for one week. TRF supplementation decreased the lipid parameters in a dose-dependent manner with an optimum effect at a dose of 8 mg TRF/kg/day. HMG-CoA reductase activity, which was increased after the withdrawal of atherogenic diet, remained significantly decreased during the TRF treatment. Feeding of TRF also decreased TBARS and conjugated dienes significantly. These results suggest that TRF supplementation has significant health benefits through the modulation of physiological functions that include various atherogenic lipid profiles and antioxidants in hypercholesterolemia.     

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.     

蒙古扁桃石油醚提取物对肝纤维化大鼠肝脏的作用观察

目的：研究蒙古扁桃石油醚提取物对肝纤维化大鼠肝脏的影响。方法：SD大鼠按体重随机分为对照组、模型组、阳性药水飞蓟素组和蒙古扁桃石油醚提取物高、中、低剂量组。除对照组外,其余各组大鼠按四氯化碳（CCl4）造模法造模,造模同时各给药组灌胃给药。8周后取大鼠肝脏、脾脏进行称重,计算脏器指数;测定肝组织中超氧化物歧化酶（SOD）、丙二醛（MDA）含量,测定羟脯氨酸（HYP）水平。结果：大鼠肝纤维化损伤时,模型组SOD明显降低,MDA明显升高,HYP明显升高,与对照组比较差异显著（P<0.05）;与模型组比较,蒙古扁桃石油醚提取物可提高血清SOD含量,降低MDA含量,降低肝组织HYP水平,差异显著（P<0.05）。结论：蒙古扁桃石油醚提取物对四氯化碳所致的大鼠肝纤维化具有良好的保护作用。     

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

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

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

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

The pharmacokinetics of dronedarone in normolipidemic and hyperlipidemic rats

The objectives of the current study were to characterize the pharmacokinetic profile of dronedarone in the rat, and to examine the effect of hyperlipidemia on its pharmacokinetics. Single doses of dronedarone were administered to rats intravenously (4 mg/kg), orally (55 mg/kg) and intraperitoneally (65 mg/kg). To induce hyperlipidemia, some of the rats were administered intraperitoneal doses of poloxamer 407 before giving an oral dose of dronedarone. After intravenous doses of 4 mg/kg dronedarone, plasma clearance and volume of distribution at steady‐state were 25.1 ± 8.09 mL/min/kg and 10.8 ± 4.77 L/kg, respectively. After oral doses the maximum plasma concentrations (Cmax) and their median time of attainment (tmax) were 1.87 ± 1.65 mg/mL and 3.5 h, respectively. Intraperitoneal administration of 65 mg/kg dronedarone base yielded plasma Cmax and median tmax of 0.816 ± 0.611 mg/mL and 3 h, respectively. Protein binding was high in NL and HL plasma. Dronedarone is extensively distributed with high volume of distribution in the rat. The drug showed poor bioavailability (<20%) after oral and intraperitoneal administration. The increased plasma concentrations after oral dosing to hyperlipidemic rats appears to be attributable to a direct effect on metabolizing enzymes or transport proteins. Copyright © 2016 John Wiley & Sons, Ltd.     

Effectiveness of Aloe vera on the antioxidant status of different tissues in irradiated rats

This study was performed to evaluate the role of Aloe vera (Aloe barbadensis Miller) on the antioxidant status in different tissues of animals whole body exposed to 7 Gy gamma radiations, delivered as a shot dose. Aloe vera (leaf juice filtrate) was supplemented daily to rats (0.25 ml/kg body weight/day), by gavage, 5 days before irradiation and 10 days after irradiation. Experimental investigations performed 3, 7 and 10 days after exposure to radiation showed that Aloe vera treatment has significantly minimized the radiation-induced increase in the amount of malondialdehyde in liver, lungs, and kidney tissues of irradiated rats. Significant amelioration in superoxide dismutase (SOD) and catalase activities was observed from the 3rd up to the 10th days for lungs, on the 7th and 10th days for kidneys and at 10 days for liver. Data obtained showed that for the different tissues, improvement in the decrease of reduced glutathione (GSH) contents was obvious on the 10th day after irradiation. Treatment with Aloe vera was also effective in minimizing the radiation-induced increase in plasma glucose levels throughout the experimental period, while it has not ameliorated the increase in plasma insulin levels. It could be concluded that the synergistic relationship between the elements found in the leaf of Aloe vera could be a useful adjunct for maintaining the integrity of the antioxidant status.     

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.     

Pharmacokinetic alterations in poloxamer 407-induced hyperlipidemic rats

1. Plasma lipid profile abnormalities in hyperlipidemia can potentially alter the pharmacokinetics of a drug in a complex manner. To evaluate these pharmacokinetic alterations in hyperlipidemia and to determine the underlying mechanism(s), poloxamer 407-induced hyperlipidemic rats (HL rats), a well-established animal model of hyperlipidemia have been used.

2. In this review, we summarize findings on the pathophysiological and gene expression changes in drug-metabolizing enzymes and transporters in HL rats. We discuss pharmacokinetic changes in drugs metabolized primarily via hepatic cytochrome P450 (CYPs) in terms of alterations in hepatic intrinsic clearance (CL^′_int), free fraction in plasma (f_u) and hepatic blood flow rate (Q_H), depending on the hepatic excretion ratio, as well as drugs eliminated primarily by mechanisms other than hepatic CYPs.

3. For lipoprotein-bound drugs, increased binding to lipoproteins resulted in lower f_u values and volumes of distribution, with some exceptions. Generally, slower non-renal clearance (or total body clearance) of drugs that are substrates of hepatic CYP3A and CYP2C is well explained by the following factors: alterations in CL^′_int (due to down-regulation of hepatic CYPs), decreased f_u and/or possible decreased Q_H.

4. These consistent findings across studies in HL rats suggest more studies are needed at the clinical level for optimal pharmacotherapies for hyperlipidemia.     

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.     

Effects of taurine on neutrophil function in hyperlipidemic rats

In dietary hyperlipidemic rats, an increase in serum lipid level may cause an increase in membrane lipid level of the neutrophils, and phagocytosis and bactericidal capacity may be thereby lowered. Treatment with taurine (470 mg/kg/day, p.o.) strengthened the bactericidal capacity of neutrophils which was decreased by cholesterol diet feeding, as the capacity was stronger on the 40th day than that in animals fed laboratory chow. The results suggest that taurine may play an important role in the mechanism of host defense through the neutrophil function.     

安络化纤丸对大鼠高脂性脂肪肝的治疗作用

目的探讨安络化纤丸对大鼠高脂性脂肪肝的治疗作用。方法以连续饲以高脂饲料(基础饲料加10%猪油、2%胆固醇、0.5%胆酸钠、5%蛋黄)1个月的方法建立高脂性大鼠脂肪肝模型,造模成功后给予安络化纤丸治疗4周,观察一般情况及测定血清丙氨酸氨基转换酶(ALT)、天门冬氨酸氨基转换酶(AST)、总胆固醇(TC)和甘油三酯(TG)水平,测定肝匀浆TG、丙二醛(MDA)及肝组织超氧化物歧化酶(SOD)水平,并对大鼠肝脏行病理学检查。结果安络化纤丸可明显降低高脂性脂肪肝大鼠血清ALT、AST、TC和TG水平,降低肝组织TG含量,提高肝组织SOD活性,并降低肝组织MDA水平。安络化纤丸可显著改善高脂性脂肪肝大鼠肝组织的病理损害。结论安络化纤丸对大鼠高脂性脂肪肝有明显的治疗作用,其作用可能与其抗氧化作用有关。     

玉郎伞提取物对高脂血症大鼠血液流变学的影响

目的 研究玉郎伞(YLS)块根提取物(总黄酮、多糖及其水提物)对食饵性高脂血症大鼠脂质代谢及血液流变学指标的影响.方法 建立食饵性高脂血症大鼠模型,将YLS提取物给予高脂血症大鼠,连续灌胃14 d后,检测各组大鼠脂质水平及全血黏度(WBV)、血浆黏度(PV)、全血还原黏度(RV)、红细胞压积(HCT)等8项血流变学指标.结果 与高脂模型组比较,各用药组TC、TG、LDL-C、apoB、AI水平降低;apoA1、HDL-C、apoA1/apoB水平显著性升高(P＜0.01或P＜0.05);各给药组8项血液流变学指标显著降低(P＜0.01或P＜0.05),YLS总黄酮高、低剂量组效果最明显.结论 YLS提取物对高脂血症大鼠的脂质代谢紊乱有显著的调节作用,对防治高脂血症和改善血液流变学有积极的意义.     

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.     

油酰乙醇胺对高脂血症大鼠降血脂及肝脏的保护作用

目的观察油酰乙醇胺(OEA)对高脂血症模型大鼠降血脂及肝脏保护作用。方法高脂饮食建立高脂血症大鼠模型,分别观察OEA(10,203,0 mg/kg)对高脂血症大鼠的血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、谷丙转氨酶(ALT)、肝重和肝脏系数、肝脏丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的影响。制作冰冻切片观察大鼠肝脏脂质变性程度。结果与模型组相比,OEA(20,30mg/kg)具有降血脂作用,同时降低血清ALT、肝脏脂质、肝重和肝脏系数、肝脏MDA水平,升高肝脏GSH-Px活力。结论 OEA能降低高脂血症大鼠血脂、抑制肝脏脂肪沉积,并减轻脂质过氧化物对肝脏的损伤。     

The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats

The effect of thymoquinone (TQ), the main constituent of the volatile oil of Nigella sativa seeds, on the nephropathy and oxidative stress induced by doxorubicin (DOX) in rats was investigated. A single intravenous injection of DOX (6 mg/kg) induced a severe nephrotic syndrome (after 5 weeks) associated with hypoalbuminemia, hypoproteinemia, elevated serum urea, hyperlipidemia, and a high urinary excretion of protein, albumin and N-acetyl-beta-D-glucosaminidase (NAG). In the kidney, DOX induced a significant increase in total triglycerides (TG), total cholesterol (TC), and lipid peroxides and a significant decrease in non-protein sulfhydryl (NPSH) content and catalase (CAT) activity. Treatment of rats with TQ (10 mg/kg per day) supplemented with the drinking water for 5 days before DOX, and daily thereafter, significantly lowered serum urea, TG, and TC. Similarly, TG, TC and lipid peroxides in the kidneys of TQ-treated rats were decreased significantly compared with DOX alone. Moreover, NPSH content and CAT activity in the kidneys of TQ-treated DOX group were significantly elevated compared with DOX alone. Treatment with TQ significantly suppressed DOX-induced proteinuria, albuminuria, and urinary excretion of NAG. The results confirm the involvement of free radicals in the pathogenesis of nephropathy induced by DOX. Likewise, the study demonstrates the high antioxidant potential of TQ and its marked effect on the suppression of DOX-induced nephropathy. The data suggest that TQ might be applicable as a protective agent for proteinuria and hyperlipidemia associated with nephrotic syndrome.