Liver Of Hyperlipidemic Rats Research Articles

The pharmacokinetics of dabigatran in a rat model of hyperlipidaemia induced by poloxamer 407

Various pharmacokinetic changes have been reported in experimental hyperlipidemic (HL) animal models. To evaluate whether P-glycoprotein (P-gp) activity was affected in HL rats, we assessed the pharmacokinetics of dabigatran after oral administration of dabigatran etexilate (DABE); this is a dabigatran prodrug and a well-known P-gp substrate. HL and control rats exhibited similar area under the plasma concentration-time curve (AUC), total body clearance (CL), and steady state volume of distribution (Vss) values following intravenous administration of dabigatran (1 mg/kg). This suggested that the distribution and elimination of dabigatran were similar in control and HL rats. The hepatic and intestinal P-gp protein levels did not differ significantly between control and HL rats. The dabigatran AUC and extent of absolute oral bioavailability (F) values were similar in control and HL rats following oral administration of DABE (10 mg/kg as dabigatran). Therefore, there was no apparent change in intestinal P-gp activity in HL rats compared to control rats. This study revealed no significant change in P-gp expression or activity in the intestine or liver of HL rats, and similar pharmacokinetics of dabigatran. Hyperlipidaemia may not directly affect the oral absorption of P-gp substrate drugs.

Lactiplantibacillus plantarum N4 ameliorates lipid metabolism and gut microbiota structure in high fat diet-fed rats.

Lowing blood lipid levels with probiotics has good application prospects. This study aimed to isolate probiotics with hypolipidemic efficacy from homemade na dish and investigate their mechanism of action. In vitro experiments were conducted to determine the cholesterol-lowering ability of five isolates, with results showing that Lactiplantibacillus plantarum N4 exhibited a high cholesterol-lowering rate of 50.27% and significant resistance to acid (87%), bile salt (51.97%), and pepsin (88.28%) in simulated gastrointestinal fluids, indicating promising application prospects for the use of probiotics in lowering blood lipids. The findings from the in vivo experiment demonstrated that the administration of N4 effectively attenuated lipid droplet accumulation and inflammatory cell infiltration in the body weight and liver of hyperlipidemic rats, leading to restoration of liver tissue morphology and structure, as well as improvement in lipid and liver biochemical parameters. 16S analysis indicated that the oral administration of N4 led to significant alterations in the relative abundance of various genera, including Sutterella, Bacteroides, Clostridium, and Ruminococcus, in the gut microbiota of hyperlipidemia rats. Additionally, fecal metabolomic analysis identified a total of 78 metabolites following N4 intervention, with carboxylic acids and their derivatives being the predominant compounds detected. The transcriptomic analysis revealed 156 genes with differential expression following N4 intervention, leading to the identification of 171 metabolic pathways through Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Notably, the glutathione metabolism pathway, PPAR signaling pathway, and bile secretion pathway emerged as the primary enrichment pathways. The findings from a comprehensive multi-omics analysis indicate that N4 influences lipid metabolism and diminishes lipid levels in hyperlipidemic rats through modulation of fumaric acid and γ-aminobutyric acid concentrations, as well as glutathione and other metabolic pathways in the intestinal tract, derived from both the gut microbiota and the host liver. This research offers valuable insights into the therapeutic potential of probiotics for managing lipid metabolism disorders and their utilization in the development of functional foods.

Qinlian hongqu decoction ameliorates hyperlipidemia via the IRE1-α/IKKB-β/NF-κb signaling pathway: Network pharmacology and experimental validation

Ethnopharmacological relevanceQinlian Hongqu decoction (QLHQD) is a traditional Chinese medicine (TCM) formula. It has previously been found to mitigate hyperlipidemia, although its mechanism requires further clarification. Aim of the studyThis study explored QLHQD's mechanism in treating hyperlipidemia based on network pharmacology and experimental validation. Materials and methodsThe components of QLHQD were analyzed by means of ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UHPLC-Q-Orbitrap-HRMS) and the targets of hyperlipidemia were predicted using the Swiss ADME, GeneCards, OMIM, DrugBank, TTD, and PharmGKB databases. A drug-component-target-disease network was constructed using Cytoscape v3.7.1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed using the Bioinformatics platform. Based on the KEGG results, the non-alcoholic fatty liver disease signaling pathways were selected for experimental validation in an animal model. ResultsWe identified 34 components of QLHQD, 94 targets of hyperlipidemia, and 18 lipid metabolism-related pathways from the KEGG analysis. The results of the animal experiment revealed that QLHQD alleviated lipid metabolism disorders, obesity, insulin resistance, and inflammation in rats with hyperlipidemia induced by high-fat diets. Additionally, it reduced the expression of IRE1-α, TRAF2, IKKB-β, and NF-κB proteins in the liver of hyperlipidemic rats. ConclusionQLHQD is able to significantly mitigate hyperlipidemia induced via high-fat diets in rats. The mechanism of action in this regard might involve regulating the IRE1-α/IKKB-β/NF-κB signaling pathway in the liver, thereby attenuating inflammatory responses and insulin resistance.

Mechanism of Danzhi Jiangtang Capsules on improving liver injury in hyperlipidemia rats based on MAPK pathway

This study aimed to investigate the protective effect and preliminary mechanism of Danzhi Jiangtang Capsules( DJC) on liver of hyperlipidemic rats. The hyperlipidemia models were successfully made by high-fat diet for 12 weeks in male SD rats,and then divided into model control group and DJC treatment groups( 500 and 1 000 mg·kg~(-1)·d-1) via gavage administration for additional 8 weeks.The levels of serum lipid and liver metabolism indices were detected; HE and oil red O staining were used to observe the pathological changes of liver. Expression levels of extracellular regulated protein kinase 1/2( ERK1/2),c-Jun N-terminal kinase( JNK),and p38 mitogen-activated protein kinase( p38 MAPK) were detected by real-time polymerase chain reaction( RT-PCR). Expression of MCP-1,phosphorylated ERK( p-ERK),phosphorylated JNK( p-JNK),and phosphorylated p38 MAPK( p-p38) were analyzed by immunohistochemistry and Western blot. The results showed that DJC decreased body weight and serum levels of total cholesterol( TC),triglyceride( TG),alanine aminotransferase( ALT),aspartate aminotransferase( AST),increased serum high-density lipoprotein cholesterol( HDL-C) level,ameliorate injury and lipid deposition in the liver induced by the high-fat diet,decreased mRNA expression of ERK1/2,JNK and p-38 MAPK as well as protein expression of p-ERK,p-JNK,p-p38,and MCP-1,somewhat showing a dose-dependent effect. Therefore,DJC has an obvious protective effect on liver of hyperlipidemic rats with certain dose-dependent effect,and the mechanism may be related with inhibiting MAPK pathways and inflammation.

Correlation between ratio of Nrf2/Keap1 and catalase gene expression in liver of hyperlipidemic rats after administration of 7-hydroxy-2-(4-hydroxy- 3-methoxyphenyl)-chromen-4-one

Hyperlipidemia results in excessive superoxide anion radicals that are the cause ofoxidative stress. Phytochemical compounds can reduce oxidative stress. The aim of thisstudy was to investigate the correlations between ratio of Nrf2/Keap1 and catalase geneexpression in livers of hyperlipidemic rats after administration of 7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-chromen-4-one. Twenty-four Rattus norvegicus rats, aged 8 weeks andweighing an average of 200 g were randomly divided into 6 groups i.e. Group 1 wasnormal group (N), Group 2 was hyperlipidemic rats (HL), Group 3 was hyperlipidemicrats with simvastatin (HL+SV), and Groups 4-6 were hyperlipidemic rats with 7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-chromen-4-one doses 10 mg (HL+10), 30 mg (HL+30) or 90 mg/200 g BW (HL+90), respectively, administered orally by gavages. At the end ofthe study, the rats were euthanized and the livers were used to analyze the ratio of Nrf2/Keap 1 and catalase gene expression. Nrf2/Keap1 ratio and catalase gene expressionbetween groups were analyzed by Kruskal Wallis test. Spearman’s correlation test wasused to analyze the correlations between Nrf2/Keap1 ratio and catalase gene expression.The administration of 3 different doses of 7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-chromen-4-one on hyperlipidemic rats increased catalase gene expression. There wasno correlation between ratio Nrf2/Keap1 and catalase gene expression. In conclusion,administration of 7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-chromen-4-one can improvecatalase gene expression in hyperlipidemic rats. However, there is no correlation betweenthe ratio of Nrf2/Keap1 gene expression and the catalase gene expression.

Euphorbia lathyris L.-modulated hyperlipidemia induced by high-fat diet in an experimental animal model

Background and objectives Hyperlipidemia has been embroiled in atherosclerosis, which is the primary factor of heart disease and stroke. An important aim in the pivotal restrain of atherosclerosis awaits an affordable and safe drug that will fundamentally confirm to have a great effect where treatment is decisive. Humans have been served by a variety of drugs extracted from a natural source, and the most of these cures were provided by higher plants. Materials and methods The aim of this study is to investigate and assess the hypolipidemic effect of Euphorbia lathyris L. extracts on high-fat diet-induced hyperlipidemia in rats, and it shows a scientific proof for expansion of E. lathyris L. as a prospect naturalistic oral hypolipidemic drug. Rats were administrated orally with cholesterol in a dose of 100 mg/1 ml olive oil/1 kg five times a week for 12 consecutive weeks. This was accomplished by assessing the activities of particular biochemical parameters associated with liver functions in tissue of high-fat-diet group when compared with those of control one. Liver function tests, included aspartate aminotransferases; alanine and alkaline phosphatases; antioxidants and oxidative stress biomarkers, such as glutathione, catalase, and glutathione-S-transferase; total antioxidant capacity; nitric oxide; and lipid peroxide. In addition, lipid profile (cholesterol, total lipid, high-density lipoprotein-cholesterol, and triglyceride) were also evaluated. Moreover, histological examination of liver, heart, and kidney was done to prove the biochemical outcomes. Results and conclusion The present findings strongly clarify defects in all biochemical measurements, such as increase in the malondialdehyde level and liver function enzyme activities. However, reductions in enzymatic and nonenzymatic antioxidant in liver of hyperlipidemic rats were marked. On the contrary, treatment of hyperlipidemic rats with low and high dose of methanol and petroleum ether extract of E. lathyris natural product proved to have ameliorating effects in all biochemical parameters under investigation. The previous biochemical observations were also accompanied by histopathological examinations of the heart, liver, and kidney sections, which showed significant recovery of hepatocytes and amelioration in histological architectures of heart and kidney. It could be concluded that the two extracts of E. lathyris showed improvement in liver function enzyme activities, oxidant–antioxidant biomarkers, and lipid profile activities in liver of high-fat-diet rats.

Electroacupuncture ameliorates poloxamer 407-induced hyperlipidemia through suppressing hepatic SREBP-2 expression in rats

AimsAcupuncture, particularly electroacupuncture (EA) has been shown to have the lipid-lowering effects, but not completely investigated. The present study was aimed to examine whether EA could attenuate poloxamer-407 (P-407)-induced hyperlipidemia in the rats and to investigate its potential mechanisms. Main methodsRats received P-407 (0.4 g/kg, i.p.) to induce hyperlipidemia. EA was performed at ST36 and ST40 acupoints a total of three times with 12 h-interval starting 1 h before the P-407 injection at 0.6 mA intensity and 2 Hz frequency for 10 min. Key findingsIn P-407-induced hyperlipidemic rats, EA stimulation at ST36 and ST40 acupoints significantly lowered the serum levels of triglycerides, total cholesterol, LDL-cholesterol and atherogenic index, while markedly increasing the serum HDL-cholesterol levels. Meanwhile, hyperlipidemic rats had significantly higher expression of sterol regulatory element-binding protein (SREBP)-2, without any difference in SREBP-1 expression in the liver, as compared with normal ones. EA significantly attenuated the expression of SREBP-2 with a subsequent decrease in 3-hydroxy-3-methylglutaryl coenzyme A reductase and an increase in low-density lipoprotein receptor at both mRNA and protein levels in the liver of hyperlipidemic rats. These changes did not occur after electrical stimulation at a non-acupoint. SignificanceTaken together, our findings indicate that EA stimulation to P-407-induced hyperlipidemic rats improves the lipid abnormalities, which may be associated with regulation of the expression of key enzymes of cholesterol synthesis in the liver through modulation of SREBP-2.

Effect of Moringa Oleifera on Lipid Profile in Rats

Background: Coronary heart disease, stroke, atherosclerosis and hyperlipidemia are primary causes of death worldwide. Moringa Oleifera tree was used as a health supplement introduced to Africa from India. Its leaves have various biological activities, including hypolipidemic effect. Objective(s): The aim of present study was to assess the effect of Moringa Oleifera consumption on lipid profile and histopathology of the liver in hyperlipidemic rats. Methods: A total of 50 male albino rats were divided into five equal groups. Group I was left as control and fed on standard diet only. Group II was fed on standard diet and orally injected with 400 mg/kg of rat body weight extract of Moringa Oleifera. Hyperlipidemia was induced in the remaining 30 rats by feeding an atherogenic diet for four weeks. Group III was fed on atherogenic diet only. Group IV was fed on atherogenic diet and orally injected with 400 mg/kg of rat body weight extract of Moringa Oleifera. Group V was fed on atherogenic diet with 2mg/kg of rat body weight Atorvastatin drug. Lipid profile of rat blood was measured including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), and very low density lipoprotein (VLDL). Liver tissue was evaluated by carrying out histopathological examination. Results: The rats fed on Moringa Oleifera showed a significant decrease in total cholesterol and LDL by 26.8% and 40.6% respectively compared to baseline values after 4 weeks. Although VLDL and TG showed slight increase by 5.6% and 5.1% respectively, they were still within the normal range. Otherwise, there was a significant increase in LDL, VLDL, TC, and total TG levels in rats fed on atherogenic diet only by 17.13%, 195.4%, 29.2%, and 193% respectively compared to baseline values after 4 weeks. Atorvastatin drug affected the HDL level, as it increased by 16.4% % 28% from baseline after two and four weeks respectively. Atorvastatin and Moringa Oleifera decreased VLDL level by 53.9% & 36.5% respectively when compared to rats fed on atherogenic diet. Conclusion: Moringa Oleifera was comparable to hypolipidemic medication (Atorvastatin) in improving the lipid profile of rats fed on atherogenic diet. Moringa Oleifera intake is more effective in prevention than in treatment of hyperlipidemia. Keywords: lipid profile, atherosclerosis, Moringa Oleifera, atherogenic diet, atorvastatin.

The beneficial effects of almond (Prunus amygdalus Batsch) hull on serum lipid profile and antioxidant capacity in male rats.

Almond hull is produced in high amounts and mostly used as livestock feed. This study was designed to examine the impact of almond hull powder (AHP) administration on lipid profile and antioxidant activities in plasma and liver in hyperlipidemic rats. As the first step, the antioxidant capacity and radical scavenging activity of AHP were determined using calorimetric methods. Then 36 adult male Wistar rats were randomly divided into 6 groups: group 1 with oral administration of 10% AHP, group 2 with oral administration of 20% AHP, group 3 with oral administration of 30% AHP, group 4 as a positive control with a high cholesterol diet, group 5 as a negative control with a normal diet, and group 6 as a sham group with a normal diet and 20% AHP. The rats were fed a hypercholesterolemic diet to create a hyperlipidemia rat model and then they received AHP for 30 days. Antioxidant and radical scavenging activity of the AHP extract showed a high content of antioxidants that exert potent radical scavenging activity. According to the results obtained, upon the administration of AHP the levels of cholesterol and triglycerides significantly decreased, while the antioxidant capacity of plasma increased. AHP with bioactive compounds and fiber can reduce total cholesterol and triglycerides and improve serum antioxidant capacity.

Metabolic profiling analysis of fatty acids from hyperlipidemic rats treated with Gynostemma pentaphyllum and atorvastatin based on GC/MS

Gynostemma pentaphyllum (GP) is widely used for the treatment of diseases such as hyperlipidemia, fatty liver and obesity in China, and atorvastatin is a popular anti-hyperlipidemia drug. Based on GC/MS and metabonomic methods, this study focuses on the comparative metabolic profiling analysis of fatty acids in the plasma and liver of hyperlipidemic rats before and after treatment, in order to identify the treatment mechanism of the two drugs. Results obtained show that GP and atorvastatin can effectively improve the levels of saturated fatty acids, although atorvastatin has only a relatively weak regulatory effect on unsaturated fatty acids, whereas the traditional Chinese medicine (TCM) GP can significantly improve the levels of arachidonic acid and docosahexaenoic acid (DHA).

The Regulation of Alfalfa Saponin Extract on Key Genes Involved in Hepatic Cholesterol Metabolism in Hyperlipidemic Rats

To investigate the cholesterol-lowering effects of alfalfa saponin extract (ASE) and its regulation mechanism on some key genes involved in cholesterol metabolism, 40 healthy 7 weeks old male Sprague Dawley (SD) rats were randomly divided into four groups with 10 rats in each group: control group, hyperlipidemic group, ASE treatment group, ASE prevention group. The body weight gain, relative liver weight and serum lipid 1evels of rats were determined. Total cholesterol (TC) and total bile acids (TBA) levels in liver and feces were also measured. Furthermore, the activity and mRNA expressions of Hmgcr, Acat2, Cyp7a1 and Ldlr were investigated. The results showed the following: (1) The abnormal serum lipid levels in hyperlipidemic rats were ameliorated by ASE administration (both ASE prevention group and treatment group) (P<0.05). (2) Both ASE administration to hyperlipidemic rats significantly reduced liver TC and increased liver TBA level (P<0.05). TC and TBA levels in feces of hyperlipidemic rats were remarkably elevated by both ASE administration (P<0.05). (3) mRNA expressions of Hmgcr and Acat2 in the liver of hyperlipidemic rats were remarkably down-regulated (P<0.05), as well as mRNA expressions of Cyp7a1 and Ldlr were dramatically up-regulated by both ASE administration (P<0.05). The activities of these enzymes also paralleled the observed changes in mRNA levels. (4) There was no significant difference between ASE treatment and ASE prevention group for most parameters evaluated. Our present study indicated that ASE had cholesterol-lowering effects. The possible mechanism could be attributed to (1) the down-regulation of Hmgcr and Acat2, as well as up-regulation of Cyp7a1 and Ldlr in the liver of hyperlipidemic rats, which was involved in cholesterol biosynthesis, uptake, and efflux pathway; (2) the increase in excretion of cholesterol. The findings in our study suggested ASE had great potential usefulness as a natural agent for treating hyperlipidemia.

Effects of serum lipoproteins on cyclosporine A cellular uptake and renal toxicity in vitro

In-vitro studies were performed to shed light on previous findings that showed increased uptake of cyclosporine A in the kidneys and liver of hyperlipidemic rats, and increased signs of kidney toxicity. Hepatocytes were obtained from rats, cultured, and exposed to a diluted serum from hyperlipidemic rats. Some cells were also exposed to lipid-lowering drugs. After washing out the rat serum or lipid-lowering drugs, cells were exposed to cyclosporine A embedded in serum lipoproteins. Pretreatment with hyperlipidemic serum and lipid-lowering drugs was associated with an increased uptake of cyclosporine A. As expected, atorvastatin caused an increase in low density lipoprotein receptor and a decrease in MDR1A mRNA in the hepatocytes. A decrease in NRK-52E rat renal tubular cellular viability caused by cyclosporine A was noted when cells were preincubated with diluted hyperlipidemic serum. This was matched with evidence of hyperlipidemic-serum-associated increases in the NRK-52E cellular uptake of cyclosporine A and rhodamine-123. The findings of these experiments suggested that in hyperlipidemia the expression and (or) the functional activity of P-glycoprotein was diminished, leading to greater hepatic and renal uptake of cyclosporine A, and renal cellular toxicity.

Hypolipidemic effects of a new piperine derivative GB-N from Piper longum in high-fat diet-fed rats

Context: Long pepper, Piper longum Linn. (Piperaceae), is widely used in traditional Mongolian medicine for treating hyperlipidemia and coronary heart disease.Objective: To investigate the hypolipidemic effects of a new piperine derivative GB-N isolated from long pepper in high-fat diet-fed rats.Methods: The levels of serum total cholesterol, triacylglycerols (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by enzymatic colorimetric method. The levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), CYP7A1, lecithin cholesterol acyltransferase (LCAT) and LDL receptor (LDLR) mRNA and protein expression were detected by real-time polymerase chain reaction and western blot analysis.Results and discussion: Compared with model rats, oral administration of GB-N at doses of 2.5–10 mg/kg to hyperlipidemic rats could significantly decrease the levels of serum TG from 1.54 mmol/L in hyperlipidemic rats to 0.94–1.02 mmol/L, with an increase in serum HDL-C levels from 0.40 mmol/L in hyperlipidemic rats to 1.21–2.26 mmol/L. Treatment with GB-N (10 mg/kg) could also significantly upregulate levels of hepatic HMG-CoA reductase, CYP7A1, LCAT and LDLR mRNA and protein expression.Conclusion: GB-N had hypolipidemic activity via regulating lipid metabolism pathways in liver of hyperlipidemic rats and could be explored as a potential agent for the prevention of hyperlipidemia diseases.

Mangiferin Decreases Plasma Free Fatty Acids through Promoting Its Catabolism in Liver by Activation of AMPK

Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism.

The antioxidative effects of probiotic Lactobacillus casei Zhang on the hyperlipidemic rats

To evaluate the antioxidant potential of Lactobacillus casei Zhang (L. casei Zhang), we use hyperlipidemic rat as a model induced by high-fat diet. And then, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels of the plasma, and SOD, MDA, GSH-Px, total antioxidant capability (T-AOC), glutamic-pyruvic transaminase (GPT) and glutamic oxalacetic transaminase (GOT) of the 10% liver homogenate were determined. Except normal and hyperlipidemic control, normal prevention group (2 × 109 CFU/d of L. casei Zhang for oral administration) and three different doses of therapeutic groups (2.0 × 108, 2.0 × 109 and 2.0 × 1010 CFU/d of L. casei Zhang, respectively) were involved. Results analysis revealed that normal prevention group showed a non-significant effect on various antioxidant indexes. For therapeutic groups, supplementation of L. casei Zhang significantly decreased MDA levels (P < 0.01), whereas SOD (P < 0.05) and GSH-Px (P < 0.01) significantly increased both in serum and liver of hyperlipidemic rats. Hepatic activities of GPT and GOT were obviously reduced (P < 0.01), while T-AOC (P < 0.01) was obviously promoted by L. casei Zhang. Especially, some antioxidant indexes could recover to normal level. Antioxidative effect of L. casei Zhang was more effective for hyperlipidemic rat than normal rat. In addition, application of different therapeutic doses had variant effects on hyperlipidemic rats, and most indexes were slight except liver GSH-Px activities. It is suggested that L. casei Zhang might help to alleviate oxidative stress, as they appeared to reduce lipid peroxidation and improved lipid metabolism both in blood and liver with hyperlipidemic in vivo.

Hypolipidemic Effects of Citrus bergamia Risso et Poiteau Juice in Rats Fed a Hypercholesterolemic Diet

Citrus bergamia Risso et Poiteau fruits have been traditionally utilized, in Calabria (Italy), as a popular remedy for their hypolipidemic properties. C. bergamia juice total phenol content (2474.35+/-38 microg/mL) was evaluated by the Folin-Ciocalteu method; moreover, HPLC analysis led to the identification of naringin (520 ppm), neoeriocitrin (370 ppm), and neohesperidin (310 ppm). The present study was designed to investigate the hypolipidemic effects of C. bergamia juice and its protective effect on liver of hyperlipidemic rats. Chronic administration of C. bergamia (1 mL/rat/day) provoked a significant reduction in serum cholesterol, triglycerides, and low-density lipoprotein (LDL) levels and an increase in high-density lipoprotein (HDL) levels; moreover, histopathological observations showed, in rats submitted to C. bergamia treatment, a protection of hepatic parenchyma. In addition, fecal neutral sterols and fecal bile acid excretion was found to be increased after C. bergamia treatment. These results suggest that the hypocholesterolemic effect of C. bergamia may be mediated by the increase in fecal neutral sterols and total bile acids excretion. In addition to the hypolipidemic effect, the juice shows radical scavenging activity in the diphenylpicrylhydrazyl (DPPH) test; probably the two effects are related. These observations suggest that the positive intake of C. bergamia may reduce the risk of some cardiovascular diseases through its radical scavenging function and hypocholesterolemic action.

Protective role of Melissa officinalis L. extract on liver of hyperlipidemic rats: A morphological and biochemical study

In this study, the effects of Melissa officinalis L. extract on hyperlipidemic rats were investigated, morphologically and biochemically. The animals were fed a lipogenic diet consisting of 2% cholesterol, 20% sunflower oil and 0.5% cholic acid added to normal chow and were given 3% ethanol for 42 days. The plant extract was given by gavage technique to rats to a dose of 2 g/kg every day for 28, 14 days after experimental animals done hyperlipidemia. The degenerative changes were observed in hyperlipidemic rats, light and electron microscopically. There was a significant increase in the levels of serum cholesterol, total lipid, alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), a significant decrease in the levels of liver tissue glutathione (GSH), a significant increase in the levels of tissue lipid peroxidation (LPO) in this group. On the other hand, the administration of Melissa officinalis L. extract reduced total cholesterol, total lipid, ALT, AST and ALP levels in serum, and LPO levels in liver tissue, moreover increased glutathione levels in the tissue. As a result, it was suggested that Melissa officinalis L. extract exerted an hypolipidemic effect and showed a protective effect on the liver of hyperlipidemic rats.

Metabolic alterations of toxic and nonessential elements by the treatment of Sempervivum tectorum extract in a hyperlipidemic rat model.

A hyperlipidemic rat model was used to examine the therapeutic effect of Sempervivum tectorum plant extract on the metabolic alterations of Al, As, B, Ba, Cd, Hg, Ni, Pb, and Ti in the liver and bile. Hyperlipidemia was produced by lipogenic diet and alcohol and verified by morphological investigation of the liver with the aid of light and an electron microscope. Element concentration in the liver and bile were determined by inductively coupled plasma optical emission spectrometry (ICP-OES). The concentration values in the liver higher than the detection limit (Al, Ba, Ni, Ti) were unambiguous. Significant differences were found for the four groups at p < 0.05 level (ANOVA). A significant difference was observed between Al and B concentration in the bile fluids of the 4 groups (p < 0.05). The excretion of Al and Ti into the bile fluid increased significantly (p < 0.05). Following the administration of S. tectorum extract to rats with hyperlipidemia, the excretion of Al, B and Ba increased, whereas the excretion of Ti decreased significantly (p < 0.05). The favorable action of the extract (protecting the liver in hyperlipidemic rats) was verified by morphological studies, and its detoxicating property was shown by the elimination of Al, Ba, Ni, and Ti from the liver.