Hyperlipidemic Rat Model Research Articles

A comparative study of hypolipidemic effect of atorvastatin and Coriandrum sativum in triton-induced hyperlipidemic albino rat model

Background: Hyperlipidemia is the main factor responsible for coronary artery disease. Atorvastatin commonly used, as a competitive inhibitor of HMG-Co-A reductase, is known to reduce LDL and triglyceride levels and increase HDL levels. Coriandrum sativum (Coriander) belongs to the Apiaceae family and has hypolipidemic, antidiabetic, and antioxidant properties. Triton WR1339 has been used by several studies to induce hypercholesterolemia in animals which acts on both the synthesis and excretory phase. This study aimed to compare the hypolipidemic effect of Coriandrum sativum and atorvastatin in triton-induced hyperlipidemic rats. Methods: Following approval from the Institutional Animal Ethics committee, 36 Wistar albino rats were divided into 6 groups of 6 animals each. Triton 200mg IP was administered to all the groups except Group 1 (control). Groups 3 and 4 received Coriander extract 300mg/kg and Atorvastatin 80mg/kg orally with Triton. Groups 5 and 6 received Coriander extract and Atorvastatin respectively 22 hours later. Lipid profile was estimated 24 hours before, 24 and 48 hours after administering Triton. Results: In the synthesis phase, there is a statistically significant increase in the lipid levels in Groups 2, 5, and 6 compared to Groups 3 and, 4 indicating hypolipidemic effects of both Coriander extract and Atorvastatin. In the excretory phase, all groups have shown a decrease in lipid levels but a decrease in total cholesterol level in Group 5 compared to Group 3 was significant. Conclusions: Atorvastatin and Coriander extract both affect the lipid levels in the synthesis and excretory phase. Even though coriander cannot replace atorvastatin in the management of hyperlipidemia, it can be used as an adjuvant to atorvastatin to reduce the cost effects and adverse reactions caused by allopathic medicines.

Anti-Hyperlipidemic Effect of Ruta chalepensis Ethanolic Extract in Triton WR-1339-Induced Hyperlipidemia in Rats

High levels of fats like triglycerides and cholesterol in the blood can cause cardiovascular diseases, prompting the search for safer, natural treatments. This study investigates the efficacy of Ruta chalepensis ethanol extract in lowering cholesterol levels using a rat model of hyperlipidemia induced by Triton WR-1339. Leaves and flowers of R. chalepensis were extracted with ethanol, and LC-MS analysis revealed high levels of quercetin (9.5%), 2,2-Dimethyl-3-methylidenebicyclo [2.2.1] heptane (8.1%), and other compounds, with monoterpenes being the most common class. Male Wistar rats received doses of the extract at 20 and 40 mg/kg, while fenofibrate (100 mg/kg) was the positive control. After 20 h, plasma lipid levels were significantly affected, showing a 72.1% reduction in total cholesterol for the 40 mg/kg group (p < 0.01) and a 67.6% reduction for the 20 mg/kg group (p < 0.01). High-density lipoprotein cholesterol levels decreased by 68.8% in the 40 mg/kg group (p < 0.01) and 58.6% in the 20 mg/kg group (p < 0.01). Low-density lipoprotein cholesterol saw reductions of 67.3% (p < 0.001) in the 40 mg/kg group and 60.4% (p < 0.01) in the 20 mg/kg group. Triglycerides dropped by 90.6% in the 40 mg/kg group (p < 0.001) and 86.7% in the 20 mg/kg group (p < 0.001). Overall, the results highlighted a stronger anti-hyperlipidemic effect in the 40 mg/kg group across all lipid parameters measured. The extract outperformed fenofibrate, particularly at the higher dose. These results imply that R. chalepensis extract is a promising natural alternative for managing hyperlipidemia.

Correction: Substituted furan-carboxamide and Schiff base derivatives as potential hypolipidemic compounds: evaluation in Triton WR-1339 hyperlipidemic rat model

Correction: Substituted furan-carboxamide and Schiff base derivatives as potential hypolipidemic compounds: evaluation in Triton WR-1339 hyperlipidemic rat model

Substituted furan-carboxamide and Schiff base derivatives as potential hypolipidemic compounds: evaluation in Triton WR-1339 hyperlipidemic rat model

Substituted furan-carboxamide and Schiff base derivatives as potential hypolipidemic compounds: evaluation in Triton WR-1339 hyperlipidemic rat model

Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy.

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.

Lipidomics study of Liujunzi decoction in hyperlipidemia rats with spleen deficiency based on UPLC-Q-TOF/MS

Hyperlipidemia refers to the abnormal levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) in peripheral blood circulation. It is a predominant risk factor underlying cardiovascular and cerebrovascular diseases, including coronary heart disease and atherosclerosis. Furthermore, it is also one of the most prevalent chronic diseases globally. Liujunzi Decoction is the basic prescription for the treatment of spleen and stomach diseases. It can tonify the spleen and qi, remove dampness, and reduce turbidity. Moreover, it is also clinically used for the treatment of spleen deficiency hyperlipidemia. However, its metabolites and therapeutic effect on spleen deficiency hyperlipidemia have not been comprehensively determined in vitro and in vivo. This study established a rat model of spleen deficiency hyperlipidemia by inducing starvation and satiety disorders, exhaustion swimming, and intragastric administration of the fat emulsion. To identify related metabolite changes and serum lipid composition, UPLC-Q-TOF-MS, PCA, and OPLS-DA lipidological methods were performed. The results demonstrated significant changes in rat's signs during the modeling process, which were consistent with the criteria for the syndrome differentiation of spleen deficiency in traditional Chinese medicine. Furthermore, this study identified 100 potential biomarkers in rat serum, of which 52 were associated with lipid synthesis, such as LPC, PC, PI, PE, PA, Cer, SM, etc. The pathways involved were glycerol phospholipid, sphingomyelin, and glycerol ester metabolisms. After the Liujunzi decoction intervention, 56 potential biomarkers were observed in the high-dose group, alleviating the metabolic spectrum imbalance by reducing metabolite levels. In addition, metabolic pathway disturbances were markedly improved. This study provides references for future studies on Liujunzi decoction and furnishes essential data for assessing the relationships between chemical constituents and pharmacological activities of Liujunzi decoction.

Purple Sweet Potato Extract and Aerobic Exercise Reduce Lipid Profiles in Hyperlipidemic Rats Model

Obesity and dyslipidemia are the major risk factors for cardiovascular disease. It has been shown that dietary supplementation combined with exercise at appropriate intensity improves lipid profile and reduces the risk of cardiovascular disease. This study investigates the effect of purple sweet potato extract and swimming training on the lipid profile of a hyperlipidemic rat model. Twenty-five male Wistar rats were grouped into standard diet and high-fat diet and given their respective diet for two weeks. Afterward, they were randomly divided into five weight-matched groups; normal control (C; n=5), high-fat diet (HF; n=5), exercise (E; n=5), purple sweet potato extract (PSP; n=5), and exercise combined with purple sweet potato extract (EPSP; n=5). Purple sweet potato extract was given 100 mg/day through oral gavage for three weeks. Swimming exercise was performed for 30 minutes/day, five days a week, for three weeks at an intensity of 6% of body weight. At the end of the experimental period, intracardiac blood samples were drawn to measure lipid profiles. Data analysis technique using a one-way ANOVA test with a significant level of 5%. The findings revealed that the concentration of TC and LDL was highest in HF. The combination of exercise and purple sweet potato extract significantly reduced LDL and increased HDL levels compared to exercise or PSP alone (p ≤ 0.05). It indicates that purple sweet potato extract combined with swimming exercise is shown to be effective in improving lipid profiles in hyperlipidemic rat models. Keyword: Aerobic exercise, hyperlipidemia, lipid profile, purple sweet potato.

An Evaluation of Anti-hyperlipidemic Activity of Ethanolic Extract of Moringa oleifera on High Fat Induced Hyperlipidemic Rat Model

Background: The art or practice of herbal remedies refers to the use of herbs and herbal treatments for the purpose of maintaining health and preventing, treating, or curing sickness. In some areas, herbal treatments can also be referred to as herbal medicine.
 Aim: The present study was designed to investigate the antihyperlipidemic and antiatherogenic potentiality of ethanolic extract of Moringa oleifera extract in high fat diet-induced hyperlipidemic rats.
 Materials and Methods: Moringa oleifera ethanolic extract was prepared using Soxhlet apparatus. Male rats were made hyperlipidemic by giving high fat diet. M. oleifera was administered in a dose of 250, 500 and 750 mg/kg.b.w./day for 30 days in high fat diet-induced hyperlipidemic rats. The SGPT, SGOT, total cholesterol,triglyceride, LDL,HDL , Urea and creatinine levels were measured after the treatment.
 Results: For both the SGPT and the SGOT, it was seen that groups 5 and 6 exhibited statistically significant (p< 0.05) outcomes in the case of the SGPT. When conducting the renal function test, it was observed that the levels of creatinine and urea were statistically significant (p< 0.05) in the cases of groups 4, 5, and 6. In the case of high-density lipoprotein (HDL) and low-density lipoprotein (LDL), groups 4, 5, and 6 showed statistically significant findings (p< 0.05) in HDL levels, while groups 5 and 6 showed statistically significant LDL levels. The triglyceride levels in the group were found to be statistically significant (p< 0.05), while the findings obtained from groups 5 and 6 were also found to be statistically significant.
 Conclusion: The study revealed that M. oleifera has anti hyperlipidemic activity.

Exploring the Anti-hyperlipidemic Potential of Rivea hypocrateriformis (Desr) Leaf Extracts: A Study on Triton-induced Hyperlipidemia Rat Model and Oxidative Stress

Exploring the Anti-hyperlipidemic Potential of Rivea hypocrateriformis (Desr) Leaf Extracts: A Study on Triton-induced Hyperlipidemia Rat Model and Oxidative Stress

Hypolipidemic effect and gut microbiota regulation of Gypenoside aglycones in rats fed a high-fat diet

Ethnopharmacological relevanceGynostemma pentaphyllum (Thunb.) Makino has traditional applications in Chinese medicine to treat lipid abnormalities. Gypenosides (GPs), the main bioactive components of Gynostemma pentaphyllum, have been reported to exert hypolipidemic effects through multiple mechanisms. The lipid-lowering effects of GPs may be attributed to the aglycone portion resulting from hydrolysis of GPs by the gut microbiota. However, to date, there have been no reports on whether gypenoside aglycones (Agl), the primary bioactive constituents, can ameliorate hyperlipidemia by modulating the gut microbiota. Aim of the studyThis study explored the potential therapeutic effects of gypenoside aglycone (Agl) in a rat model of high-fat diet (HFD)-induced hyperlipidemia. MethodsA hyperlipidemic rat model was established by feeding rats with a high-fat diet. Agl was administered orally, and serum lipid levels were analyzed. Molecular techniques, including RT-polymerase chain reaction (PCR) and fecal microbiota sequencing, were used to investigate the effects of Agl on lipid metabolism and gut microbiota composition. ResultsAgl administration significantly reduced serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and mitigated hepatic damage induced by HFD. Molecular investigations have revealed the modulation of key lipid metabolism genes and proteins by Agl. Notably, Agl treatment enriched the gut microbiota with beneficial genera, including Lactobacillus, Akkermansia, and Blautia and promoted specific shifts in Lactobacillus murinus, Firmicutes bacterium CAG:424, and Allobaculum stercoricanis. ConclusionThis comprehensive study established Agl as a promising candidate for the treatment of hyperlipidemia. It also exhibits remarkable hypolipidemic and hepatoprotective properties. The modulation of lipid metabolism-related genes, along with the restoration of gut microbiota balance, provides mechanistic insights. Thus, Agl has great potential for clinical applications in hyperlipidemia management.

Phytochemical study and biological activities of Teucrium mideltense (Batt.) Humbert.

Teucrium mideltense (Batt.) Humbert (T. mideltense) is an endemic Moroccan species that grows exclusively in the Oriental High Atlas Mountains of Morocco. In this work, we aim at determining the chemical profile and biological properties of the traditionally used aqueous extract of this plant. HPLC analysis, estimation of the amounts of total phenolic compounds including flavonoids, and in vitro antioxidant activity was evaluated according to the literature procedures (DPPH, ABTS, and FRAP). Additionally, safety assessment was carried out according to the organization for economic cooperation and development guidelines and the anti-hyperlipidemic activity was evaluated in triton-induced hyperlipidemic rat model. Our findings revealed that the aqueous extract of this plant contains significant amounts of phenolic compounds (91.94 mg GAE/gE) including flavonoids (27.41 mg RE/gE). HPLC analysis revealed the presence of vanillic acid, hesperidin, and rutin. Moreover, a considerable in vitro antioxidant effect was evaluated (DPPH IC50 = 36.10± 0.02 μg/mL; ABTS IC50 = 34.98± 1.31 μg/mL; FRAP EC50 = 129.74±2.18 μg/mL). Furthermore, T. mideltense (Batt.) Maire extract exerted significant lipid-lowering effects by reducing the levels of total cholesterol (-88.78%), triglycerides (-62.12%), and non-HDL cholesterol (-68.37%). We conclude that the supplementation with the aqueous extract of T. mideltense would be effective in lowering lipids under hyperlipidemic conditions.

Protective effects of silymarin-loaded chitosan nanoparticles in the diet-induced hyperlipidemia rat model.

Obesity is a metabolic syndrome that leads to many chronic diseases worldwide. In this study, we investigate the antihyperlipidemic activities of chitosan nanoparticles (CH NPs) on silymarin (SIL) as a carrier in the drug delivery system that can improve some biochemical parameters and hormones in the model of hyperlipidemic rats receiving a high-fat diet (HFD). Physicochemical characterization of silymarin-loaded chitosannanoparticles (CH-SIL NPs) was done by Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and drug loading efficiency (LE). Diet-induced hyperlipidemic rats were treated with SIL (15 mg/kg/day) and CH-SIL NPs(15 mg/kg/day) for twelve weeks orally daily. The body weight loss (BW), food consumption, serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), levels of fasting blood glucose (FBG) in serum, serum insulin, cortisol, testosterone, and brain neuropeptide Y (NPY), Y1 and Y5 receptor mRNA expression were analyzed. A significant reduction in BW and food consumption from 417 ± 16 g and 33 ± 1.03 in group HFD to 338 ± 10 g and 17.33 ± 1.02 in group CHS+HFD was observed, respectively. This data revealed that CH-SIL NPs improved hyperlipidemia, hyperinsulinemia, and hyperglycemia, reduced serum cortisol, and down-regulated NPY and Y1R with a significant increase in HDL and testosterone hormones compared to the control group. The developed Sil-loaded CH NPs were good agents for improving efficacy. It is the first report of the proposed weight loss mechanism of SIL CH NPs, thereby providing information about the anti-hyperlipidemic and antihyperglycemic effects of silymarin-loaded chitosan nanoparticles, a natural food with proper effects against metabolic disorders in case of hyperlipidemia that may lead to obesity and up-regulation of brain NPY.

Antihyperlipidemic Bioactivity Guided Isolation and Structural Elucidation of Isolated Phytoconstituents from Convolvulus pluricaulis Choisy

Background: Atherosclerosis is a crucial element in the origination of coronary heart disease (CHD). Lipid aggregation inside the coronary arteries walls lead to the occurrence of hyperlipidemia. Aim: The research was conducted for assessing the lipid lowering effect of ethanol extract and chloroform fraction from Convolvulus pluricaulis Choisy. aerial parts in Triton induced hyperlipidemic rat model. Methodology: The active fraction was obtained from antihyperlipidemic bioactivity. The phytocomponents were separated from the active fraction using flash chromatography technique resulting in the isolation of n-hexatriacontane; 9-octadecenoic acid- octyl ester; 12, 14-heptacosanedione; dodecyl-octadeca-9,12-dienoate; tetracosanyl 9-hexadecenoate; heptacosan-14-ol; stigmasta- 5, 22- dien-3 beta-ol and stigmast-5-en-3 beta-ol. The phytocomponent structures were established by spectral data analysis. Intraperitoneal (i.p.) injection of Triton WR- 1339 at a dose of 400 mg/kg body weight (b.w.) was given to the animals. The ethanol extract at a dose of 200 mg/kg b.w. and chloroform fraction at a dose of 400 mg/kg b.w. were administered orally in rats after 24 hours of the Triton administration. Results: The study resulted in dose dependent inhibition of triglycerides (p <0.01), total cholesterol (p <0.05), Low density lipoprotein level (p <0.05) while significant increased HDL (p <0.01) level. Alteration in lipid profile in Triton treated rats was restored and found more effective in the chloroform fraction probably due to the presence of phytocomponents. The study elucidated different phytocomponents isolated from the active chloroform fraction of C. pluricaulis. Conclusion: Treatment with extract and fraction manifested significant decrease in triglyceride level. HDL exerts an inhibitory action in the etiology of atherosclerosis. It is considered as a beneficial lipoprotein and its lower level leads to the greater risk of CHD. It may be concluded that the isolated components were responsible for the lipid lowering level of active fraction. GRAPHICAL ABSTRACT

Integrated metabolomics and network pharmacology to reveal the lipid-lowering mechanisms of Qizha Shuangye granules in hyperlipidemic rats.

Qizha Shuangye granules (QSG) comprise six traditional Chinese herbal medicines (TCHMs), which have a long history of treating hyperlipidemia (HLP) in China. This study aimed to evaluate the potential lipid-lowering effects of QSG in an HLP rat model and investigate possible mechanisms. The HLP rat model was induced by a high-fat diet. Lipid-related indicators in serum were detected. Serum and liver metabolites were investigated using a liquid chromatography-mass spectrometry-based metabolomics approach. A herb-compound-target-metabolite (H-C-T-M) network was further constructed to reveal the possible molecular mechanism of QSG to alleviate HLP. The administration of QSG inhibited the HLP-induced changes in total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and non-esterified fatty acid (NEFA) levels. Additionally, QSG significantly attenuated the liver histopathological changes induced by HLP. Metabolomic analysis showed the serum and liver metabolic disorders presented in HLP rats. QSG can reverse the abnormal metabolism caused by HLP. Through network pharmacology analysis, key proteins such as androgen receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and peroxisome proliferator-activated receptor-α were screened out, and they were speculated to be possible therapeutic targets for QSG to treat HLP. The present study integrated metabolomics and network pharmacology analysis to reveal the efficacy and possible mechanism of QSG in treating HLP, which provides a new reference for the research and development of QSG as a functional food. © 2023 Society of Chemical Industry.

Hypolipidemic Activity of a Polyherbal Formulation in Triton WR-1339 and High Fat Diet-induced Hyperlipidemic Rats

In hyperlipidemic wistar albino rat models produced by triton and diet, the efficacy of polyherbal formulations containing four different plants was assessed. Rats exposed to Triton WR 1339 had their blood cholesterol and triglyceride levels raised. However, this was reversed when the rats were given syrup or a comparable formulation. Both formulations better lipid outlines in rats with high-fat diet-induced hyperlipidemia. Effects were marginally better with the usual medication Atrovastatin. Liver sinusoidal capillary dilations, cytoplasmic fatty infiltration, and granular degeneration were considerably reduced in polyherbal formulation-treated group II animals related with other groups. As per results, polyherbal formulations in dyslipidaemic circumstances reduce lipid levels by blocking the production of cholesterol and reducing lipid utilization.

Protective effects of phosphocreatine on human vascular endothelial cells against hydrogen peroxide-induced apoptosis and in the hyperlipidemic rat model

Phosphocreatine (PCr) has been shown to have a cardio-protective effect during cardiopulmonary resuscitation (CPR). However, little is known about its impact on atherosclerosis. In this study, we first evaluated the pharmacological effects of PCr on antioxidative defenses and mitochondrial protection against hydrogen peroxide (H2O2) induced human umbilical vascular endothelial cells (HUVECs) damage. Then we investigated the hypolipidemic and antioxidative effects of PCr on hyperlipidemic rat model. Via in vitro studies, H2O2 significantly reduced cell viability and increased apoptosis rate of HUVECs, while pretreatment with PCr abolished its apoptotic effect. PCr could reduce the generation of ROS induced by H2O2. Moreover, PCr could increase the activity of SOD and the content of NO, as well as decrease the activity of LDH and the content of MDA. PCr could also antagonize H2O2-induced up-regulation of Bax, cleaved-caspase3, cleaved-caspase9, and H2O2-induced down-regulation of Bcl-2 and p-Akt/Akt ratio. In addition, PCr reduced U937 cells’ adhesion to H2O2-stimulated HUVECs. Via in vivo study, PCr could decrease MDA, TC, TG and LDL-C levels in hyperlipidemic rats. Finally, different-concentration PCr could increase the leaching of TC, HDL, and TG from fresh human atherosclerotic plaques. In conclusion, PCr could suppress H2O2-induced apoptosis in HUVECs and reduce hyperlipidemia through inhibiting ROS generation and modulating dysfunctional mitochondrial system, which might be an effective new therapeutic strategy to further prevent atherosclerosis.

N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation.

Hyperlipidemia is a major risk factor for erectile dysfunction (ED). Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) are the key pathological factors of ED. N-acetylcysteine (NAC) can inhibit oxidative stress; however, whether NAC can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear. A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley (SD) rats fed a high-fat and high-cholesterol diet (hyperlipidemic rats, HR). In addition, 9 male SD rats were fed a normal diet to serve as controls (NC). HR rats were divided into three groups: HR, HR+normal saline (NS), and HR+NAC (n = 9 for each group; NS or NAC intraperitoneal injections were administered daily for 16 weeks). Subsequently, the lipid profiles, erectile function, oxidative stress, phenotypic modulation markers of CCSMCs, and tissue histology were analyzed. The experimental results revealed that erectile function was significantly impaired in the HR and HR + NS groups, but enhanced in the HR + NAC group. Abnormal lipid levels, over-activated oxidative stress, and multi-organ lesions observed in the HR and HR + NS groups were improved in the HR + NAC group. Moreover, the HR group showed significant phenotypic modulation of CCSMCs, which was also inhibited by NAC treatment. This report focuses on the therapeutic effect of NAC in restoring erectile function using a hyperlipidemic rat model by preventing CCSMC phenotypic modulation and attenuating oxidative stress.

Hesperidin Supplementation Improves Altered PON -1, LDL Oxidation, Inflammatory Response and Hepatic Function in an Experimental Rat Model of Hyperlipidemia.

In this study, we have examined the effect of hesperidin on rats fed on an experimental high-fat diet. Male Wistar rats were given a high-fat diet orally for one month for developing an HFD (High fat- diet) model. Rats were also supplemented with hesperidin (100mg/kg body weight) for one month. We determined serum LDL (Low-density lipoprotein) oxidation, Paraoxonase-1 (PON-1) activity, and histopathological profile of the liver. Inflammatory cytokines levels were also measured in serum. HFD induced significant changes in LDL oxidation and PON-1 activity. Liver tissue histopathology and gene expression of inflammatory markers (Il-6(Interleukin-6), TNF- alpha (Tumor necrosis factor alpha), NF-KB (Nuclear factor kappa B) show that significant changes occur in the hyperlipidemic model of rats. We also show that hesperidin can effectively improve plasma antioxidant, LDL oxidation, and inflammatory cytokine expression in rats already subjected to hyperlipidemic stress. We conclude that hesperidin may protect the liver from oxidative stress by improving hepatic function.

Moxibustion of 45 ℃ at "Zusanli" (ST36) improves vascular endothelial oxidative stress in hyperlipidemia rats

To explore the antioxidant effect of moxibustion on vascular endothelial function and the under-lying mechanism. Forty male SD rats were randomly divided into blank, model, moxibustion and endothelial nitric oxide synthase (eNOS) inhibitor groups, with 10 rats in each group. Hyperlipidemia rat model was established by high fat diet for 8 weeks. Rats in the moxibustion group received 45 ℃ moxibustion at "Zusanli" (ST36) for 10 min once daily for consecutive 4 weeks. Rats in the eNOS inhibitor group received intraperitoneal injection of eNOS inhibitor L-NAME (1 mg/100 g) at the same time of moxibustion intervention. The morphology of abdominal aorta endothelium was observed by HE staining. Lipid deposition in abdominal aorta was observed by oil red O staining. The contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) in serum and reactive oxygen species (ROS), nitric oxide (NO), superoxide dismutase (SOD), oxidized LDL lipoprotein (ox-LDL), endothelin-1 (ET-1), eNOS, malondialdehyde (MDA) in serum and abdominal aorta were determined by ELISA. The expression of eNOS in abdominal aorta was detected by immunofluorescence. HE staining of the abdominal aorta showed no significant pathological abnormality in the blank group; the endovascular cortex was rough, and the inner, media and outer membrane were rough in the model group; the nucleus and surrounding tissue structure were clear and the vascular wall was smooth in the moxibustion group; abdominal aorta texture was rough in the eNOS inhibitor group. Compared with the blank group, the area of oil red O staining in abdominal aorta increased (P<0.05); the contents of serum TC, TG and LDL-C increased (P<0.01, P<0.05) while HDL-C decreased (P<0.05); the contents of ET-1 in serum and abdominal aorta were increased (P<0.01, P<0.05) while the contents of NO and eNOS were decreased (P<0.05, P<0.001); the contents of ROS, ox-LDL and MDA in serum and abdominal aorta were increased (P<0.001, P<0.01, P<0.000 1) while the content of SOD in abdominal aorta was decreased (P<0.000 1); the expression level of eNOS in abdominal aorta was decreased (P<0.05) in the model group. Compared with the model group, the area of oil red O staining in abdominal aorta decreased (P<0.05); the contents of TC, TG and LDL-C in serum decreased (P<0.05) while HDL-C increased (P<0.05); the contents of ET-1 in serum and abdominal aorta were decreased (P<0.01, P<0.05) while the contents of NO and eNOS in abdominal aorta were increased (P<0.001, P<0.01); the contents of ROS and MDA in serum and abdominal aorta were decreased (P<0.001, P<0.01, P<0.05), the content of ox-LDL was decreased (P<0.01) and the content of SOD was increased (P<0.000 1) in abdominal aorta; the expression level of eNOS in abdominal aorta was increased (P<0.05) in the moxibustion group. Compared with the moxibustion group, the contents of serum TC, LDL-C and MDA in the eNOS inhibitor group were increased (P<0.05); the contents of ET-1, ROS, ox-LDL and MDA in abdominal aorta were increased (P<0.05), the contents of NO, eNOS and SOD were decreased (P<0.05); the expression level of eNOS in abdominal aorta was decreased (P<0.05). 45 ℃ moxibustion at ST36 can protect and repair vascular endothelial injury in abdominal aorta of hyperlipidemia rats and improve the oxidative stress of vascular endothelium.

Antihyperlipidemic effect of Vaccinium dunalianum buds based on biological activity screening and LC-MS.

The buds of Vaccinium dunalianum Wight are used as folk medicine in the Yi settlement of the Yunnan Province, China. It has long been used as herbal tea in the local area owing to its effects of lowering blood lipids and body weight. However, there are only a few studies on its antihyperlipidemic effects, effective substances and mechanisms, especially its effectiveness in diet-induced hyperlipidemia. This study aimed to elucidate the therapeutic effects, pharmacodynamic material bases, and mechanisms of V. dunalianum buds on diet-induced hyperlipidemia. A high-fat diet-induced hyperlipidemic Sprague-Dawley (SD) rat model was established. Rats were gavaged with different doses of aqueous extract of V. dunalianum(VDW) for 8 weeks and their sera and organ samples were collected. The antihyperlipidemic effect of VDW on SD rats was evaluated based on the biochemical indices and histopathological outcomes. Liquid chromatography-mass spectrometry(LC-MS) was used to determine the main components in VDW, which were separated and purified using sequential chromatographic methods. Their chemical structures were determined using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. 6'-O-caffeoyl-arbutin, as the principal component of VDW, was also evaluated for its antihyperlipidemic activity using an approach similar to that used for VDW. Lastly, the potential targets of VDW and 6'-O-caffeoyl-arbutin in lowering blood lipids were screened out using network pharmacology, and the selected targets were docked with arbutin derivatives. The expression of target proteins was determined using western blotting to illustrate the antihyperlipidemic mechanisms of VDW and 6'-O-caffeoyl-arbutin. VDW reduced triglyceride, total cholesterol, low-density lipoprotein, alanine transaminase, and aspartate transaminase levels in the serum of modeled rats, and increased high-density lipoprotein levels. There was an improvement in steatoses, and lipid droplet accumulation decreased in vivo after VDW intervention. LC-MS revealed that VDW mainly contained arbutin and chlorogenic acid derivatives. Sixteen compounds were isolated and identified. 6'-O-caffeoyl-arbutin was the main compound of VDW (>21.67%) that showed obvious antihyperlipidemic effect with low hepatic damage at different doses. PTGS2, ADH1C, and MAOB were screened out using network pharmacology and they showed strong correlations with arbutin derivative through molecular docking. Results from WB showed that VDW and 6'-O-caffeoyl-arbutin could reduce blood lipid levels by reducing the protein expression of PTGS2, ADH1C, and MAOB. 6'-O-caffeoyl-arbutin was the main component of V. dunalianum buds. VDW and 6'-O-caffeoyl-arbutin could regulate blood lipid levels in the high-fat diet-induced rat model of hyperlipidemia without damaging their vital organs. Furthermore, they could regulate the expression of PTGS2, ADH1C, and MAOB proteins and play a role in lowering blood lipids. The findings of this study lay a foundation for the further development of V. dunalianum and 6'-O-caffeoyl-arbutin as health supplements or drugs for the management of hyperlipidemia.