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1.
Gut Microbes ; 14(1): 2003176, 2022.
Article in English | MEDLINE | ID: mdl-34923903

ABSTRACT

Non-fasting lipidemia (nFL), mainly contributed by postprandial lipidemia (PL), has recently been recognized as an important cardiovascular disease (CVD) risk as fasting lipidemia (FL). PL serves as a common feature of dyslipidemia in Type 2 Diabetes (T2D), albeit effective therapies targeting on PL were limited. In this study, we aimed to evaluate whether the therapy combining probiotics (Prob) and berberine (BBR), a proven antidiabetic and hypolipidemic regimen via altering gut microbiome, could effectively reduce PL in T2D and to explore the underlying mechanism. Blood PL (120 min after taking 100 g standard carbohydrate meal) was examined in 365 participants with T2D from the Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes (PREMOTE study), a random, placebo-controlled, and multicenter clinical trial. Prob+BBR was superior to BBR or Prob alone in improving postprandial total cholesterol (pTC) and low-density lipoprotein cholesterol (pLDLc) levels with decrement of multiple species of postprandial lipidomic metabolites after 3 months follow-up. This effect was linked to the changes of fecal Bifidobacterium breve level responding to BBR alone or Prob+BBR treatment. Four fadD genes encoding long-chain acyl-CoA synthetase were identified in the genome of this B. breve strain, and transcriptionally activated by BBR. In vitro BBR treatment further decreased the concentration of FFA in the culture medium of B. breve compared to vehicle. Thus, the activation of fadD by BBR could enhance FFA import and mobilization in B. breve and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL. Our study confirmed that BBR and Prob (B. breve) could exert a synergistic hypolipidemic effect on PL, acting as a gut lipid sink to achieve better lipidemia and CVD risk control in T2D.


Subject(s)
Berberine/administration & dosage , Diabetes Mellitus, Type 2/drug therapy , Hyperlipidemias/drug therapy , Probiotics/administration & dosage , Adult , Animals , Cholesterol/blood , Cholesterol, LDL/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/microbiology , Double-Blind Method , Drug Therapy, Combination , Feces/microbiology , Female , Gastrointestinal Microbiome/drug effects , Humans , Hyperlipidemias/blood , Hyperlipidemias/microbiology , Male , Middle Aged , Postprandial Period/drug effects
2.
Medicine (Baltimore) ; 100(49): e28172, 2021 Dec 10.
Article in English | MEDLINE | ID: mdl-34889292

ABSTRACT

BACKGROUND: Dyslipidemia is an important risk factor for atherosclerotic cardiovascular disease. Lycium barbarum L. are widely used as medicinal and functional food and may be particularly beneficial for patients with dyslipidemia. This systematic review protocol is designed to be used to evaluate the effects of Lycium barbarum L. on plasma lipid concentration through systematic reviews and meta-analysis. METHODS: The Following electronic databases will be searched from inception to October 2021: the China National Knowledge Infrastructure, PubMed, Cochrane Library, Web of Science, and Wan-fang database. All randomized controlled trial designs evaluated the effects of Lycium barbarum L. on plasma concentrations of lipids will be included. Two researchers will operate literature retrieval, screening, information extraction, quality assessment, and data analysis independently. The analysis will be conducted using Rstudio software (Version 1.4.1717). RESULTS: The findings will be submitted to a peer-reviewed publication. CONCLUSION: This study will provide practical and targeted evidence in investigating the impact of Lycium barbarum L. on plasma lipid concentration in adults. REGISTRATION NUMBER: INPLASY2021110043.


Subject(s)
Hyperlipidemias/therapy , Lipid Metabolism , Lycium/chemistry , China , Dietary Supplements/analysis , Humans , Hyperlipidemias/blood , Lipids/blood , Meta-Analysis as Topic , Research Design , Systematic Reviews as Topic
3.
J Diabetes Res ; 2021: 6018835, 2021.
Article in English | MEDLINE | ID: mdl-34970629

ABSTRACT

BACKGROUND: Diabetes mellitus (DM) is a metabolic disorder characterized by high blood glucose levels that occurs either due to insufficient insulin production or mounting resistance to its action. The purpose of this study was to investigate if methanolic extracts of Lepidium sativum seeds, Ficus carica, and Punica granatum leaves had any effect on blood sugar levels in normal and streptozotocin (STZ) diabetic rats, as well as to explore the most effective extract. METHOD: Healthy male albino rats weighing 185-266 g were divided into nine groups of eight rats each: normal control, diabetic control, diabetic rats with dietary supplements of L. sativum, F. carica, and P. granatum methanolic extracts, and diabetics treated with insulin. All of the rats were fed on ordinary diet with nutritional pellets and were given water ad libitum. To induce diabetes, all animals were administered with STZ intraperitoneal injection at a dose of 60 mg/kg body weight. For five weeks, the crude plant extracts were given orally to various groups of rats at doses of one hundred and two hundred mg/kg body weight. After that, animal groups were sacrificed and blood samples were taken. RESULTS: Phytochemical analysis revealed that the highest amounts of polyphenolic compounds were present in L. sativum seeds and P. granatum leaves, while leaves of F. carica showed the highest amounts of alkaloid and flavonoid content compared to other extracts. Oral administration of F. carica and L. sativum extracts at the dosage of 100 and 200 mg/kg significantly reduced glucose, lipid profile, kidney, and liver enzyme levels. A significant increase in HbAlc levels was also observed with L. sativum extract at a dose of 200 mg/kg compared to diabetic controls. Mellitus rats supplemented with 100 and 200 mg/kg methanolic extracts of P. granatum had higher serum triglycerides and lower serum low-density lipoprotein cholesterol (LDL-C) than normal control rats. F. carica extract is more effective than L. sativum and P. granatum extracts in the prevention and control of type 2 diabetes mellitus (T2DM) and its consequences.


Subject(s)
Blood Glucose/drug effects , Diabetes Mellitus, Experimental/drug therapy , Ficus , Hyperlipidemias/drug therapy , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/pharmacology , Lepidium sativum , Lipids/blood , Plant Extracts/pharmacology , Pomegranate , Animals , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Ficus/chemistry , Glycated Hemoglobin/metabolism , Hyperlipidemias/blood , Hyperlipidemias/chemically induced , Hypoglycemic Agents/isolation & purification , Hypolipidemic Agents/isolation & purification , Lepidium sativum/chemistry , Male , Plant Extracts/isolation & purification , Pomegranate/chemistry , Rats , Streptozocin
4.
Nutrients ; 13(10)2021 Oct 12.
Article in English | MEDLINE | ID: mdl-34684574

ABSTRACT

An herbal mixture composed of lemon, apple cider, garlic, ginger and honey as a polyphenol-rich mixture (PRM) has been reported to contain hypolipidemic activity on human subjects and hyperlipidemic rats. However, the therapeutic effects of PRM on metabolites are not clearly understood. Therefore, this study aimed to provide new information on the causal impact of PRM on the endogenous metabolites, pathways and serum biochemistry. Serum samples of hyperlipidemic rats treated with PRM were subjected to biochemistry (lipid and liver profile) and hydroxymethylglutaryl-CoA enzyme reductase (HMG-CoA reductase) analyses. In contrast, the urine samples were subjected to urine metabolomics using 1H NMR. The serum biochemistry revealed that PRM at 500 mg/kg (PRM-H) managed to lower the total cholesterol level and low-density lipoprotein (LDL-C) (p < 0.05) and reduce the HMG-CoA reductase activity. The pathway analysis from urine metabolomics reveals that PRM-H altered 17 pathways, with the TCA cycle having the highest impact (0.26). Results also showed the relationship between the serum biochemistry of LDL-C and HMG-CoA reductase and urine metabolites (trimethylamine-N-oxide, dimethylglycine, allantoin and succinate). The study's findings demonstrated the potential of PRM at 500 mg/kg as an anti-hyperlipidemic by altering the TCA cycle, inhibiting HMG-CoA reductase and lowering the LDL-C in high cholesterol rats.


Subject(s)
Citrus/chemistry , Garlic/chemistry , Honey , Hyperlipidemias/metabolism , Hyperlipidemias/therapy , Malus/chemistry , Metabolome , Plant Preparations/therapeutic use , Zingiber officinale/chemistry , Animals , Hydroxymethylglutaryl CoA Reductases/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hyperlipidemias/blood , Hyperlipidemias/urine , Least-Squares Analysis , Lipoproteins, LDL/metabolism , Metabolic Networks and Pathways/drug effects , Polyphenols/pharmacology , Principal Component Analysis , Proton Magnetic Resonance Spectroscopy , Rats, Wistar
5.
Food Funct ; 12(21): 10484-10499, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34555841

ABSTRACT

Hyperlipidemia is manifested by abnormal levels of circulating lipids and may lead to various cardiovascular diseases. Studies have demonstrated that turmeric supplemented in food can effectively prevent hyperlipidemia. The aim of this study is to elucidate the underlying mechanism. 27 male C57BL/6J mice were randomly divided into three groups, which were fed with a standard diet, a high-fat diet and a high-fat diet supplemented with turmeric powder (2.0% w/w), respectively. After eight weeks of feeding, turmeric intervention significantly reduced the plasma TC, TG, and LDL-C levels and the LDL-C/HDL-C ratio of mice compared with high-fat diet fed mice. TMT-based proteomic analysis showed that the expression of 24 proteins in mouse plasma and 76 proteins in mouse liver was significantly altered by turmeric, respectively. Bioinformatics analysis showed that differential proteins in the plasma were mainly involved in complement and coagulation cascades and the cholesterol metabolism pathway. The differential proteins in the liver were mainly involved in arachidonic acid metabolism, steroid hormone biosynthesis and the PPAR signaling pathway. Key differential proteins were successfully validated by western blot analysis. This study is the first to reveal the preventive mechanism of turmeric on hyperlipidemia from proteomics. The results showed that dietary turmeric could prevent hyperlipidemia through regulating the expression of proteins in metabolism pathways.


Subject(s)
Curcuma/metabolism , Hyperlipidemias/prevention & control , Lipids/blood , Liver/drug effects , Liver/metabolism , Proteomics/methods , Animals , Diet, High-Fat , Disease Models, Animal , Evaluation Studies as Topic , Hyperlipidemias/blood , Hyperlipidemias/metabolism , Lipid Metabolism/drug effects , Male , Mice, Inbred C57BL
6.
J Pharm Pharmacol ; 73(10): 1377-1386, 2021 Sep 07.
Article in English | MEDLINE | ID: mdl-34343336

ABSTRACT

OBJECTIVES: Inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate rate-determining enzyme for the biogenesis of cholesterol is known to show antineoplastic effects. Therefore, this study investigates the in-silico HMG-CoA reductase (HMGCR)-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin. METHODS: Carotenoids from S. mombin leaves were characterized with the aid of liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The characterized phytochemicals were obtained from PubChem. They were docked into the orthosteric site of human HMGCR (Protein Data Bank code 1HW8) using AutoDock 4.0 suites. DMBA (7,12-dimethylbenz[a]anthracene) model of breast cancer was treated with the carotenoids extract from S. mombin (100 mg/kg and 200 mg/kg doses) to assess its anti-lipidaemic cum anticancer effects. KEY FINDINGS: Carotenoids from S. mombin; beta-carotene-15,15'-epoxide, astaxanthin and 7,7',8,8'-tetrahydro-ß-ß-carotene demonstrate HMGCR inhibition. They form hydrophobic interactions with key residues within the catalytic domain of HMGCR. The carotenoids extract exhibits anti-lipidaemic/anticancer effects, lowering serum triglyceride, LDL and cholesterol concentration. It increases HDL concentration and downregulates the expression of HMGR, AFP, CEACAM-3, BRCA-1 and HIF-1 mRNAs. CONCLUSION: Carotenoids from S. mombin demonstrate HMG-CoA reductase (HMGCR) inhibition, anti-lipidaemic, and anticancer effects. The inhibition of HMGCR by the carotenoids extract further poses it as a potential anti-hypercholesterolaemia compounds.


Subject(s)
Anacardiaceae/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Breast Neoplasms/metabolism , Carotenoids/pharmacology , Hydroxymethylglutaryl CoA Reductases/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hypolipidemic Agents/pharmacology , Acyl Coenzyme A/metabolism , Animals , Anticholesteremic Agents/analysis , Anticholesteremic Agents/pharmacology , Antineoplastic Agents, Phytogenic/analysis , Antineoplastic Agents, Phytogenic/therapeutic use , Breast/drug effects , Breast/metabolism , Breast Neoplasms/chemically induced , Breast Neoplasms/drug therapy , Carotenoids/analysis , Down-Regulation , Female , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/drug therapy , Hypercholesterolemia/metabolism , Hyperlipidemias/blood , Hyperlipidemias/drug therapy , Hyperlipidemias/metabolism , Hypolipidemic Agents/analysis , Hypolipidemic Agents/therapeutic use , Lipids/blood , Molecular Docking Simulation , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats, Wistar , Xanthophylls/analysis , Xanthophylls/pharmacology , beta Carotene/analysis , beta Carotene/pharmacology
7.
Eur J Pharmacol ; 909: 174420, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34391767

ABSTRACT

Atherosclerosis is a widespread and progressive chronic arterial disease that remains the leading cause of mortality and morbidity worldwide. It is generally accepted that atherosclerosis is a multifactorial disease characterized by dyslipidemia and inflammation in the vessel walls. Nonpharmacological interventions to treat chronic diseases like atherosclerosis have gained considerable attention in recent years. Thymoquinone (TQ), the major bioactive constituent of Nigella sativa seeds, presents one such example of a natural therapeutic agent that has captured the attention of many researchers due to its wide array of medicinal properties, including its potent anti-atherosclerotic effects. Various in vitro and in vivo studies support the potential of TQ in ameliorating hyperlipidemia, hypercholesterolemia, oxidative stress, and inflammation, all of which are key hallmarks of atherosclerosis. However, to date, no review has been conducted to substantiate the role of TQ in preventing and/or treating atherosclerosis. This comprehensive review aims to examine recent in vitro and in vivo experimental findings reported on the potential anti-atherosclerotic effects of TQ. The roles of TQ in combatting hyperlipidemia, oxidative stress, and inflammation in atherosclerosis are highlighted. We also shed light on the role of TQ in preventing foam cell formation by decreasing low-density lipoprotein (LDL) availability and oxidation. Moreover, recent findings on the protective role of TQ on early markers of atherosclerosis, including homocysteinemia and endothelial dysfunction, are also underscored. Experimental evidence suggests that TQ can potentially be employed as a natural therapeutic agent with minimal side effects against the development and/or progression of atherosclerosis and its associated complications.


Subject(s)
Atherosclerosis/drug therapy , Benzoquinones/pharmacology , Hyperlipidemias/drug therapy , Nigella sativa/chemistry , Animals , Atherosclerosis/blood , Atherosclerosis/immunology , Benzoquinones/therapeutic use , Clinical Trials as Topic , Disease Models, Animal , Drug Evaluation, Preclinical , Humans , Hyperlipidemias/blood , Hyperlipidemias/immunology , Inflammation/blood , Inflammation/drug therapy , Inflammation/immunology , Oxidative Stress/drug effects , Seeds/chemistry , Treatment Outcome
8.
Biomed Pharmacother ; 142: 111930, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34416631

ABSTRACT

Dyslipidemia is a chronic non-transmissible condition that has increased due to an unhealthy lifestyle. Statins have been used as the standard treatment to control hyperlipidemia. However, side effects and high costs may be associated with its prolonged treatment, so plants derivatives have been an attractive therapy to overcome these problems. Among the compounds extracted from plants, the p-hydroxycinnamic diesters (HCE), present in carnauba wax (CW), have been found with good pharmacological properties. Therefore, this study aimed to evaluate the potential anti-hypercholesterolemic and possible toxicological effects of HCE in C57BL/6J mice under a high-fat (HF) diet. Male C57BL/6J mice were fed during 60 days under the HF diet and therefore were either treated with HCE (200 and 400 mg/kg) or simvastatin (20 mg/kg) or received saline (controls) by gavage for 30 days under the same diet. HCE treatment was able to reduce serum total cholesterol and LDL levels. Besides, this compound increased liver X receptor (LXR) and but not significantly affected IL-1ß and TNF-α liver mRNA transcription activity. In conclusion, HCE treatment was found safe and may attenuate the deleterious effects of dyslipidemia due to chronic feeding with western diets.


Subject(s)
Arecaceae/chemistry , Coumaric Acids/pharmacology , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Plant Extracts/pharmacology , Administration, Oral , Animals , Biomarkers/metabolism , Body Weight/drug effects , Coumaric Acids/administration & dosage , Coumaric Acids/isolation & purification , Coumaric Acids/toxicity , Diet, High-Fat/adverse effects , Disease Models, Animal , Female , Hyperlipidemias/blood , Hyperlipidemias/chemically induced , Hypolipidemic Agents/administration & dosage , Hypolipidemic Agents/toxicity , Inflammation/genetics , Interleukin-1beta/metabolism , Lipid Metabolism/genetics , Lipids/blood , Liver/drug effects , Liver/metabolism , Liver X Receptors/metabolism , Male , Mice, Inbred C57BL , Plant Extracts/administration & dosage , Plant Extracts/toxicity , Simvastatin/administration & dosage , Simvastatin/pharmacology
9.
Biosci Rep ; 41(6)2021 06 25.
Article in English | MEDLINE | ID: mdl-34036306

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Gualou Xiebai Banxia (GLXBBX) decoction is a well-known traditional Chinese herbal formula that was first discussed in the Synopsis of the Golden Chamber by Zhang Zhongjing in the Eastern Han Dynasty. In traditional Chinese medicine, GLXBBX is commonly prescribed to treat cardiovascular diseases, such as coronary heart disease and atherosclerosis. OBJECTIVE: The present study aimed to examine GLXBBX's preventative capacity and elucidate the potential molecular mechanism of Poloxamer 407 (P407)-induced hyperlipidemia in rats. MATERIALS AND METHODS: Both the control and model groups received pure water, and the test group also received a GLXBBX decoction. For each administration, 3 ml of the solution was administered orally. To establish hyperlipidemia, a solution mixed with 0.25 g/kg P407 dissolved in 0.9% normal saline was injected slowly into the abdominal cavity. At the end of the study, the rats' plasma lipid levels were calculated using an automatic biochemical analyzer to evaluate the preventative capability of the GLXBBX decoction, and the serum and liver of the rats were collected. RESULTS: The GLXBBX decoction significantly improved P407-induced hyperlipidemia, including increased plasma triglycerides (TGs), aspartate aminotransferase (AST) elevation, and lipid accumulation. Moreover, GLXBBX decoction treatment increased lipoprotein lipase (LPL) activity and mRNA expression of LPL. Furthermore, GLXBBX significantly suppressed the mRNA expression of stearoyl-CoA desaturase (SCD1). CONCLUSION: GLXBBX significantly improved P407-induced hyperlipidemia, which may have been related to enhanced LPL activity, increased LPL mRNA expression, and decreased mRNA expression of SCD1.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Hyperlipidemias/prevention & control , Hypolipidemic Agents/pharmacology , Lipids/blood , Animals , Biomarkers/blood , Disease Models, Animal , Hyperlipidemias/blood , Hyperlipidemias/chemically induced , Lipoprotein Lipase/genetics , Lipoprotein Lipase/metabolism , Male , Poloxamer , Rats, Wistar , Stearoyl-CoA Desaturase/genetics , Stearoyl-CoA Desaturase/metabolism
10.
Eur J Pharmacol ; 902: 174120, 2021 Jul 05.
Article in English | MEDLINE | ID: mdl-33905703

ABSTRACT

Atherosclerosis can cause severe cardiovascular diseases, which is the most common cause of death in the world. It's of great significance to study the prevention and treatment of atherosclerosis. Selenium nanoparticles (SeNPs) has drawn more and more attention due to high biological activity, high bioavailability, strong antioxidant capacity and low toxicity, exhibiting great potential in biomedical application. Thus, this study aimed at explore the anti-atherosclerotic effect of two kinds of SeNPs, bovine serum albumin (BSA) surface-decorated SeNPs and chitosan (CS) surface-decorated SeNPs (CS-SeNPs), in apolipoprotein E deficient (ApoE-/-) mice fed with a high-cholesterol and high-fat diet, and the possible mechanisms. The results demonstrated that both BSA-SeNPs (25, 50 and 100 µg Se/kg body weight/day) and CS-SeNPs (50 µg Se/kg body weight/day) could reduce atherosclerotic lesions in ApoE-/- mice after oral administration for 12 weeks. And these effects might mainly attributed to the ability of BSA-SeNPs and CS-SeNPs to inhibit hyperlipidemia by suppressing hepatic cholesterol and fatty acid metabolism, and alleviate oxidative stress by enhancing antioxidant activity. Moreover, the benefits of BSA-SeNPs were dose-dependent and the medium dose of BSA-SeNPs (50 µg Se/kg body weight/day) was optimal. Generally, BSA-SeNPs with mean size 38.5 nm and negative surface charge showed better anti-atherosclerotic effect than CS-SeNPs with mean size 65.8 nm and positive surface charge. These results suggested that SeNPs could significantly alleviate the formation of atherosclerosis in ApoE-/- mice, possibly by inhibiting hyperlipidemia and oxidative stress, exhibiting a potential to serve as an anti-atherosclerotic agent.


Subject(s)
Atherosclerosis/prevention & control , Hyperlipidemias/prevention & control , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Nanoparticles/chemistry , Selenium/chemistry , Selenium/pharmacology , Administration, Oral , Alanine Transaminase/blood , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/pathology , Apolipoproteins E/deficiency , Atherosclerosis/chemically induced , Atherosclerosis/genetics , Atherosclerosis/pathology , Body Weight/drug effects , Chitosan/administration & dosage , Chitosan/chemistry , Cholesterol/genetics , Cholesterol/metabolism , Cholesterol/toxicity , Diet, High-Fat/adverse effects , Disease Models, Animal , Fatty Acids/genetics , Fatty Acids/metabolism , Hyperlipidemias/blood , Hyperlipidemias/chemically induced , Hyperlipidemias/genetics , Hypolipidemic Agents/administration & dosage , Male , Mice, Inbred C57BL , Mice, Knockout , Nanoparticles/administration & dosage , Nitric Oxide/blood , Oxidative Stress/drug effects , Selenium/administration & dosage , Selenium/metabolism , Serum Albumin, Bovine/administration & dosage , Serum Albumin, Bovine/chemistry , Sodium Selenite/administration & dosage , Sodium Selenite/chemistry , Sodium Selenite/pharmacology , Tumor Necrosis Factor-alpha/blood
11.
Food Funct ; 12(5): 2044-2057, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33532813

ABSTRACT

This study aimed to investigate the effects and mechanism of selenium-enriched kiwifruit (Se-Kiwi) on lipid-lowering and liver protection in hyperlipidaemic mice induced by consuming a long-term high-fat diet. Selenium-enriched cultivation can significantly improve the contents of vitamins and functional elements in kiwifruits, especially vitamin C, selenium, and manganese, thus enhancing the activity of antioxidant enzymes in Se-Kiwi. Se-Kiwi can significantly improve the activity of antioxidant enzymes in the liver of hyperlipidaemic mice, restore the liver morphology of mice close to normal, reduce the fat content in the liver, and inhibit the accumulation of abdominal fat cells. Meanwhile, the expression levels of inflammation-related factors (TNF-α and NF-κB) and lipid synthesis related genes (SREBP-1c and FAS) are inhibited at the gene transcription and protein expression levels, and the expression levels of energy expenditure related genes (PPAR-α and CPT1) are increased, resulting in lipid reductions and liver protection. In conclusion, our results indicate that the protective mechanism of Se-Kiwi on high-fat diet mice is associated with enhancing the activity of antioxidant enzymes, reducing the degree of the inflammatory reaction, inhibiting the fat synthesis, and accelerating body energy consumption.


Subject(s)
Actinidia/chemistry , Adipose Tissue/drug effects , Hyperlipidemias , Liver/drug effects , Selenium/pharmacology , Animals , Cell Line , Diet, High-Fat , Fruit/chemistry , Hyperlipidemias/blood , Hyperlipidemias/metabolism , Mice , Protective Agents/pharmacology
12.
J Ethnopharmacol ; 272: 113926, 2021 May 23.
Article in English | MEDLINE | ID: mdl-33596472

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Jiang-Zhi-Ning (JZN) is a traditional Chinese medicine formula, which has the effect of lowering blood lipid level and softening blood vessels. It is clinically used in the treatment of hyperlipidemia with significant curative effect. AIM OF THE STUDY: This study aims to screen the active components of JZN that are responsible for its blood lipids lowering effect and lay the foundation for elucidating pharmacodynamic material basis of the hypolipidemic effect of the formula. MATERIALS AND METHODS: The hyperlipidemia model was used to evaluate the efficacy of the JZN effective extraction with the TC and TG of rat plasma as evaluation index. Then the established ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MSn) method was utilized to analyze the components of JZN effective extraction and the absorbed components in rat plasma, the potential active components were screened by using the combined analysis results of in vivo and in vitro component identification. Then an established ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QqQ-MSn) method was used to determine the content of potential active components and its natural ratio in JZN effective extraction, and a potential active components combination (PACC) was formed accordingly. Then a HepG2 cell hyperlipidemia model induced by sodium oleate was used to study the hypolipidemic activity of PACC by detecting the content of TG level in the model. Meanwhile, the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to conduct preliminary research on its hypolipidemic mechanism. Then combined with the concept of "combination index" in the "median-effect principle", to calculate the half inhibitory concentration (IC50) values of PACC and each monomer component on inhibiting the TG level in the cell model. Subsequently, the "activity contribution study" was carried out, and the components with the sum of the "activity contribution value" of 85% were finally selected as the hypolipidemic active components of JZN. RESULTS: The pharmacodynamics results showed that JZN effective extraction has displayed a good hypolipidemic effect. 45 components were identified in vitro, 108 components were identified from rat plasma, and 17 potential active components were screened out. The content determination result showed that the ratio of each potential active components in PACC as following: cassiaside C: rubrofusarin-6-O-gentiobioside: aurantio-obtusin-6-O-glucoside: hyperoside: isoquercitrin: quercetin-3-O-glucuronide: (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside: rutin: emodin-8-O-glucoside: astragalin: armepavine: N-nornuciferine: coclaurine: O-nornuciferine: nuciferine: N-norarmepavine: higenamine = 3.30: 16.06: 9.15: 23.94: 98.40: 417.45: 189.68: 8.62: 1.28: 5: 3.51: 14.57: 1.06: 1.35: 1: 5.64: 6.06, and the activity study results showed that it has displayed a good hypolipidemic activity. Finally, the hypolipidemic active components screened out by the "activity contribution study" were: quercetin-3-O-glucuronide, (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside, isoquercitrin, O-nornuciferine, hyperoside and rubrofusarin-6-O-gentiobioside. CONCLUSIONS: A scientific and rational approach of screening the hypolipidemic active ingredients of JZN has been developed in the current study. In addition, the research revealed the blood lipid lowering mechanism of those ingredients, which provide a solid basis for further elucidating the hypolipidemic pharmacodynamic material basis and action mechanism of JZN.


Subject(s)
Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Hyperlipidemias/drug therapy , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Phytochemicals/chemistry , Phytochemicals/pharmacology , Administration, Oral , Animals , Chromatography, High Pressure Liquid , Disease Models, Animal , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/analysis , Hep G2 Cells , Humans , Hyperlipidemias/blood , Hypolipidemic Agents/administration & dosage , Hypolipidemic Agents/analysis , Lipids/blood , Oleic Acid/toxicity , Phytochemicals/administration & dosage , Phytochemicals/analysis , Rats, Wistar , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry , Therapeutic Equivalency
13.
Pak J Pharm Sci ; 34(6): 2205-2211, 2021 Nov.
Article in English | MEDLINE | ID: mdl-35034882

ABSTRACT

Plant components have been extensively evaluated for their pharmacological activities. This study provides scientific rationale towards the therapeutic effect of Eucalyptus camaldulensis aqueous bark extract against induced atherosclerosis and hyperlipidemia in pigeons. Phytochemical components of Eucalyptus bark extract possess a great antioxidant activity that potentially reduced the risk of heart diseases. A total of 42 Pigeons of both sexes were distributed into negative control (fed normal grain diet), hyperlipidemic control (fed HFD 1% animal fat oil and 0.1% cholesterol for 3 months), test groups of variable doses (0.05, 0.1, 0.2 to 0.4 gms/kg BW for 21 days) and the group received atorvastatin daily after induction used. At the end of the experiment biochemical and histological evaluation has been performed. After HFD induction the serum levels of liver enzyme AST, glucose, urea, cholesterol, LDL, VLDL, and TG were significantly increased with the reduction in HDL levels. The atherogenic index was also found significantly raised. Microscopic examination of the liver and aorta showed the appearance of lipid-filled foam cells all over the liver parenchyma and intima after the HFD induction. Thus it was concluded that Eucalyptus aqueous bark extract can be effective against atherosclerosis and hyperlipidemia.


Subject(s)
Aortic Diseases/prevention & control , Atherosclerosis/prevention & control , Eucalyptus , Hyperlipidemias/prevention & control , Hypolipidemic Agents/pharmacology , Plant Extracts/pharmacology , Animal Feed , Animals , Aorta/drug effects , Aorta/metabolism , Aorta/pathology , Aortic Diseases/blood , Aortic Diseases/etiology , Aortic Diseases/pathology , Atherosclerosis/blood , Atherosclerosis/etiology , Atherosclerosis/pathology , Biomarkers/blood , Columbidae , Diet, High-Fat , Disease Models, Animal , Eucalyptus/chemistry , Female , Hyperlipidemias/blood , Hyperlipidemias/etiology , Hypolipidemic Agents/isolation & purification , Lipids/blood , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Plant Bark , Plant Extracts/isolation & purification , Plaque, Atherosclerotic
14.
Biomed Pharmacother ; 133: 111014, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33246225

ABSTRACT

BACKGROUND: Intestinal microbiota is a novel drug target of metabolic diseases, especially for those with poor oral bioavailability. Nuciferine, with poor bioavailability, has an anti-hyperlipidemic effect at low dosages. PURPOSE: In the present study, we aimed to explore the role of intestinal microbiota in the anti-hyperlipidemic function of nuciferine and identify the key bacterial targets that might confer the therapeutic actions. METHODS: The contribution of gut microbes in the anti-hyperlipidemic effect of nuciferine was evaluated by conventional and antibiotic-established pseudo-sterile mice. Whole-metagenome shotgun sequencing was used to characterize the changes in microbial communities by various agents. RESULTS: Nuciferine exhibited potent anti-hyperlipidemic and liver steatosis-alleviating effects at the doses of 7.5-30 mg/kg. The beneficial effects of nuciferine were substantially abolished when combined with antibiotics. Metagenomic analysis showed that nuciferine significantly shifted the microbial structure, and the enrichment of Akkermansia muciniphila was closely related to the therapeutic effect of nuciferine. CONCLUSIONS: Our results revealed that gut microbiota played an essential role in the anti-hyperlipidemic effect of nuciferine, and enrichment of Akkermansia muciniphila represented a key mechanism through which nuciferine exerted its therapeutic effects.


Subject(s)
Aporphines/pharmacology , Gastrointestinal Microbiome/drug effects , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Intestines/microbiology , Lipids/blood , Akkermansia/drug effects , Akkermansia/genetics , Akkermansia/growth & development , Animals , Anti-Bacterial Agents/pharmacology , Bacteroides/drug effects , Bacteroides/genetics , Bacteroides/growth & development , Biomarkers/blood , Diet, High-Fat , Disease Models, Animal , Hyperlipidemias/blood , Hyperlipidemias/microbiology , Male , Metagenome , Metagenomics , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/microbiology , Non-alcoholic Fatty Liver Disease/prevention & control , Obesity/blood , Obesity/microbiology , Obesity/prevention & control , RNA-Seq
15.
Pak J Pharm Sci ; 33(3): 929-935, 2020 May.
Article in English | MEDLINE | ID: mdl-33191215

ABSTRACT

Dendrobium officinale is a traditional Chinese herbal medicine exhibiting multiple bioactivities, showing antitumor and immune-enhancing effects. The purpose of the study is to explore the effect of aqueous extract from Dendrobium officinale on blood lipids and lipid peroxidation in hyperlipidemic rats. Hyperlipidemic rats were prepared and daily given an intragastric administration of Dendrobium officinale at doses of 0.25g/kg, 0.5g/kg, or 1g/kg, or an intragastric administration of 8mg/kg simvastatin. We determined increased serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate transaminase (AST), reduced serum levels of HDL-C, elevated MDA levels, decreased activity of GSH-Px, SOD and CAT in liver tissues of hyperlipidemic rats. Intragastric administration of Dendrobium officinale reduced serum levels of TC, TG, LDL-C, ALT, AST, increased serum levels of HDL-C, reduced MDA levels, and enhanced activity of GSH-Px, SOD and CAT in liver tissues of hyperlipidemic rats in a dose-dependent manner. Taken together, aqueous extract from Dendrobium officinale plays an inhibitory role in the formation of high blood lipid and strengthens the antioxidant capacity in hyperlipidemic rats.


Subject(s)
Antioxidants/pharmacology , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Lipid Peroxidation/drug effects , Lipids/blood , Orchidaceae , Plant Extracts/pharmacology , Animals , Antioxidants/isolation & purification , Biomarkers/blood , Disease Models, Animal , Dose-Response Relationship, Drug , Hyperlipidemias/blood , Hypolipidemic Agents/isolation & purification , Orchidaceae/chemistry , Plant Extracts/isolation & purification , Rats, Sprague-Dawley , Solvents/chemistry , Water/chemistry
16.
Biomed Res Int ; 2020: 2043785, 2020.
Article in English | MEDLINE | ID: mdl-33145340

ABSTRACT

Three novel low molecular weight polysaccharides (RLP-1a, RLP-2a, and RLP-3a) with 9004, 8761, and 7571 Da were first obtained by purifying the crude polysaccharides from the fruits of a traditional Chinese medicinal herb Rosae Laevigatae. The conditions for polysaccharides from the R. Laevigatae fruit (RLP) extraction were optimized by the response surface methodology, and the optimal conditions were as follows: extraction temperature, 93°C; extraction time, 2.8 h; water to raw material ratio, 22; extraction frequency, 3. Structural characterization showed that RLP-1a consisted of rhamnose, arabinose, xylose, glucose, and galactose with the ratio of 3.14 : 8.21 : 1 : 1.37 : 4.90, whereas RLP-2a was composed of rhamnose, mannose, glucose, and galactose with the ratio of 1.70 : 1 : 93.59 : 2.73, and RLP-3a was composed of rhamnose, arabinose, xylose, mannose, glucose, and galactose with the ratio of 6.04 : 26.51 : 2.05 : 1 : 3.17 : 31.77. The NMR analyses revealed that RLP-1a, RLP-2a, and RLP-3a contained 6, 4, and 6 types of glycosidic linkages, respectively. RLP-1a and RLP-3a exhibited distinct antioxidant abilities on the superoxide anions, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and hydroxyl radicals in vitro. RLPs could decrease the serum lipid levels, elevate the serum high-density lipoprotein cholesterol levels, enhance the antioxidant enzymes levels, and upregulate of FADS2, ACOX3, and SCD-1 which involved in the lipid metabolic processes and oxidative stress in the high-fat diet-induced rats. These results suggested that RLPs ameliorated the high-fat diet- (HFD-) induced lipid metabolism disturbance in the rat liver through the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Low molecular weight polysaccharides of RLP could be served as a novel potential functional food for improving hyperlipidemia and liver oxidative stress responses.


Subject(s)
Antioxidants/pharmacology , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Polysaccharides/pharmacology , Rosa/chemistry , Animals , Antioxidants/chemistry , Antioxidants/isolation & purification , Biphenyl Compounds/antagonists & inhibitors , Catalase/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Diet, High-Fat/adverse effects , Factor Analysis, Statistical , Fruit/chemistry , Glutathione Reductase/blood , Hyperlipidemias/blood , Hyperlipidemias/etiology , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/isolation & purification , Liquid-Liquid Extraction/methods , Male , Molecular Weight , Picrates/antagonists & inhibitors , Plant Extracts/chemistry , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Rats , Superoxide Dismutase/blood , Superoxides/antagonists & inhibitors , Triglycerides/blood
17.
Int J Biol Macromol ; 165(Pt B): 1694-1705, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-33058986

ABSTRACT

Polysaccharides are important active constituents of Radix Puerariae lobatae (RPL). In this study, a novel homogeneous polysaccharide from RPL was successfully obtained by HP-20 macroporous resin and purified by Sepharose G-100 column chromatography. Nuclear magnetic resonance (NMR) analysis showed that the main glycosidic bonds were composed of α-1,3-linked and α-1,4-linked glucose. The molecular weight of PL-S2 was 18.73 kDa. The hypolipidemic effect of PL-S2 on hyperlipidemic rats was evaluated in histopathology and metabolomics analyses. PL-S2 significantly reduced plasma lipid levels and inhibited bile acid metabolism. We also demonstrated that treatment with PL-S2 activated FXR, CYP7A1, BESP, and MRP2 in rat liver. Our findings first indicate that PL-S2 decreases plasma lipid levels in hyperlipidemic rats by activating the FXR signaling pathway and promoting bile acid excretion. Therefore, PL-S2 derived from RPL is implicated as a functional food factor with lipid-regulating activity, and highlighted as a potential food supplement for the treatment of hyperlipidemia.


Subject(s)
Bile Acids and Salts/metabolism , Drugs, Chinese Herbal/therapeutic use , Hyperlipidemias/drug therapy , Polysaccharides/therapeutic use , Receptors, Cytoplasmic and Nuclear/metabolism , Animals , Biomarkers/metabolism , Carbon-13 Magnetic Resonance Spectroscopy , Chromatography, Gel , Drugs, Chinese Herbal/pharmacology , Hyperlipidemias/blood , Lipids/blood , Liver/drug effects , Liver/injuries , Liver/pathology , Male , Metabolic Networks and Pathways/drug effects , Metabolome , Metabolomics , Methylation , Microscopy, Atomic Force , Molecular Weight , Monosaccharides/analysis , Polysaccharides/blood , Polysaccharides/pharmacology , Proton Magnetic Resonance Spectroscopy , Pueraria , Rats, Wistar , Reference Standards , Signal Transduction/drug effects , Spectrophotometry, Infrared
18.
Article in English | MEDLINE | ID: mdl-33115396

ABSTRACT

AIMS: To study the toxicological profile and anti-hyperlipidemic effects of Spondias mombin leaves methanolic extract in experimental rats. BACKGROUND: Preventing high levels of lipids or its recurrence is currently one of the key aims of clinical and experimental studies. OBJECTIVE: This study was carried out to investigate the toxicological profile and anti-hyperlipidemic effects of methanolic extract of leaves of Spondias mombin. METHODS: The acute toxicity study was carried out where the limited dose of 2000 mg/kg body weight was administered to five rats at 48 h intervals. The interpretation was prepared and recorded for 24 h. In the sub-acute toxicity study, rats were treated with 250, 500, and 1000 mg/kg doses of the extract every 24 h for 28 days. The hematological, biochemical, and histopathological tests of treated animals were carried out at the end of the test. The anti-hyperlipidemic activity of plant extract (100, 200 mg/kg) was studied on Triton-X-100 induced hyperlipidemia in rats. Histopathological changes in the liver of rats were examined. RESULTS: For acute and subacute treatment, the extract did not reveal any signs of toxicity or mortality, or any significant effects on hematological, biochemical parameters, and histopathology of organs. The extract demonstrated an important anti-hyperlipidemic result by decreasing the serum levels of cholesterol, TGs, LDL, VLDL, and enhancing HDL. CONCLUSION: Taking up the evidence of the experimental study, we can conclude that the methanolic extract of Spondias mombin leaves helps in declining hyperlipidemia in rats and it can be safely used for a period of 28 days to treat hyperlipidemia.


Subject(s)
Anacardiaceae , Hypolipidemic Agents/pharmacology , Plant Extracts/pharmacology , Anacardiaceae/chemistry , Animals , Cholesterol/blood , Female , Hyperlipidemias/blood , Hyperlipidemias/drug therapy , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/toxicity , Male , Plant Extracts/chemistry , Plant Extracts/toxicity , Plant Leaves/chemistry , Rats , Triglycerides/blood
19.
Acta Sci Pol Technol Aliment ; 19(3): 271-278, 2020.
Article in English | MEDLINE | ID: mdl-32978910

ABSTRACT

BACKGROUND: Diabetes is a serious public health problem which poses serious socio-economic burden at the national and global level. Most synthetic agents for treating diabetes are expensive and not devoid of adverse effect hence, the need for continuous effort in the search for affordable and natural effective treatment of diabetes. This study investigated the anti-diabetic, anti-hyperlipidemic, and hepatoprotective effects of Citrus maxima peel extract on alloxan-induced diabetic rats. METHODS: Twenty-eight adult male Wistar rats were categorized into four groups of seven rats with similar body weights. Diabetes was induced using alloxan and baseline data obtained. Rats in groups A, B, and C were administered with 200 mg, 400 mg, and 600 mg of Citrus maxima peel extract per kg body weight/day, respectively for 14 days. Group D (control) received 200 mg of plain water per kg body weight/day. Biochemical analyses of blood glucose, lipid profile, and liver enzyme activities were performed afterthe feeding trial. Data were analyzed using SPSS, version 21. RESULTS: Citrus maxima peel extract significantly decreased (p < 0.05) the blood glucose level by 70.17%. The extract (600 mg) resulted in a percentage increase in high-density lipoprotein cholesterol (4.43%) and decrease in total cholesterol (30.86%), triglyceride (10.58%) and low-density lipoprotein cholesterol (10.20%). Liver enzyme activities of the control groups significantly increased while the treated groups showed no significant change. CONCLUSIONS: Citrus maxima peel extract has proven to be effective in diabetes management. However, use of standardized extract and proper laboratory tests are necessary.


Subject(s)
Citrus , Diabetes Mellitus, Experimental/blood , Fruit , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/pharmacology , Liver/drug effects , Plant Extracts/pharmacology , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Hyperlipidemias/blood , Hyperlipidemias/etiology , Hyperlipidemias/prevention & control , Lipids/blood , Liver/enzymology , Male , Phytotherapy , Plant Epidermis , Plant Extracts/therapeutic use , Protective Agents , Rats, Wistar
20.
J Pharm Pharmacol ; 72(12): 1798-1811, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32812253

ABSTRACT

OBJECTIVES: The management of diabetes is considered a global problem, and a cure is yet to be discovered. This study investigated the modulatory effect of Kigelia africana fruit on oxidative stress and hyperlipidaemic biomarkers in STZ-induced diabetic rats, profiled phytoconstituents using GC-TOF-MS and evaluated antidiabetic effects on 3T3 L1 adipocytes. METHODS: Thirty male Wistar rats (120-150 g) were divided into six groups (n = 5). Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) and treated with 100, 200 and 400 of hexane fraction of KA for 28 days. Immunohistochemical evaluation was carried out using avidin-biotin immunoperoxidase (ABI) method. Catalase and SOD activities as well as the levels of total protein, albumin, bilirubin, triglyceride, cholesterol, and high-density lipoprotein were measured. KEY FINDINGS: The expressions of oxidative stress and hyperlipidaemic biomarkers alongside fasting blood glucose concentrations were remarkedly decreased in KA-treated diabetic rats. Moreover, there was a significant increase in endocrine cell distribution, area covered with increase in ß-cell mass, composition and morphology of KA-treated animals. Additionally, there was constant up-regulation in 3T3 L1 adipocytes due to the presence of phytoconstituents. CONCLUSION: Kigelia africana fruit can act as a modulatory agent due to its ameliorative effects against oxidative stress.


Subject(s)
Adipocytes/drug effects , Antioxidants/pharmacology , Bignoniaceae , Blood Glucose/drug effects , Diabetes Mellitus, Experimental/drug therapy , Hyperlipidemias/drug therapy , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/pharmacology , Lipids/blood , Oxidative Stress/drug effects , Plant Extracts/pharmacology , 3T3-L1 Cells , Adipocytes/metabolism , Animals , Antioxidants/isolation & purification , Bignoniaceae/chemistry , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Fruit , Hyperlipidemias/blood , Hyperlipidemias/chemically induced , Hypoglycemic Agents/isolation & purification , Hypolipidemic Agents/isolation & purification , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Male , Mice , Plant Extracts/isolation & purification , Rats, Wistar , Streptozocin
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