Cholesterol-lowering Effect Research Articles

Acute Cholesterol-Lowering Effect of Exendin-4 in Ldlr-/- and C57BL/6J Mice.

We previously reported that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduced serum low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus receiving statins, which increased LDL receptor (LDLR) expression. Nevertheless, it remains unclear how much LDLR expression contributes to the LDL-C-lowering effect of GLP-1RAs. We examined the effect of a GLP-1RA, namely, exendin-4, on serum LDL-C levels and its mechanism in Ldlr-/- and C57BL/6J mice. Ten-week-old Ldlr-/- and C57BL/6J mice received exendin-4 or saline for 5 days, and serum lipid profiles and hepatic lipid levels were examined. Cholesterol metabolism-related gene expression and protein levels in the liver and ileum and the fecal bile acid (BA) composition were also examined. Exendin-4 treatment significantly decreased serum very-low-density lipoprotein cholesterol (VLDL-C) and LDL-C levels and mature hepatic SREBP2 levels and increased hepatic Insig1/2 mRNA expression in both mouse strains. In Ldlr-/- mice, exendin-4 treatment also significantly decreased hepatic cholesterol levels and fecal BA excretion, decreased hepatic Cyp7a1 mRNA expression, and increased small intestinal Fgf15 mRNA expression. In C57BL/6J mice, exendin-4 treatment significantly decreased small intestinal NPC1L1 levels. Our findings demonstrate that exendin-4 treatment decreased serum VLDL-C and LDL-C levels in a manner that was independent of LDLR. Exendin-4 treatment might decrease serum cholesterol levels by lowering hepatic SREBP2 levels and cholesterol absorption in Ldlr-/- and C57BL/6J mice. Exendin-4 treatment might decrease cholesterol absorption by different mechanisms in Ldlr-/- and C57BL/6J mice.

The Mechanism of Probiotics in Preventing the Risk of Hypercholesterolemia

Probiotics are beneficial live microorganisms because they provide health benefits to the host after being consumed in sufficient amounts, primarily by increasing the proliferation of native digestive microflora. Hypercholesterolemia is a condition in which cholesterol serum concentration is elevated significantly (exceeds 200 mg/dL). Hypercholesterolemia is characterized by high plasma levels of low-density lipoprotein (LDL) and low plasma concentration of high-density lipoprotein (HDL). This review aims to examine the mechanism of action of probiotics in preventing the risk of hypercholesterolemia and reducing LDL cholesterol levels in the human body. The mechanism of cholesterol-lowering effect of probiotic bacteria can be classified into four basic principles such as 1) the conversion of cholesterol to coprostanol, 2) the deconjugation of cholesterol by probiotics’ bile salt hydrolase enzyme, 3) the alteration of protein expression related to cholesterol synthesis, and 4) the production of Short Chain Fatty Acids (SCFA) by probiotics. Cholesterol converted to coprostanol is not absorbed by the small intestine and is directly excreted with the feces. The deconjugated cholesterol is easily precipitated and thus not absorbed by the small intestine. It also induces the assimilation of cholesterol into the probiotic membrane. Finally, the SCFAs, produced by probiotics fermentation within host digestive tract, can upregulate the synthesis of HDL apolipoprotein.

Hypolipidemic effect of Ashwagandha (Withania somnifera) and Arjuna (Terminalia arjuna): An in vitro study

Background: High cholesterol is the sixth-highest risk factor for death in the globe. Herbal medications regularly complement modern medical care, especially by providing safe, well-tolerated therapies for chronic conditions. Aims and Objectives: The present study was undertaken to evaluate and compare the cholesterol-lowering effects of Terminalia arjuna bark and Bacopa monnieri leaves (Brahmi) extract in human blood samples diagnosed with hyperlipidemia. Materials and Methods: Herbal extract of arjuna (T. arjuna) and Ashwagandha (Withania somnifera [WS]) in distilled water (d/w) and cow’s urine (c/u) [A1, A2, D1, and D2] was taken and added to the pooled serum samples collected aseptically and a kinetic study was performed with it. Cholesterol standard was obtained from Erba Chem Transasia kit (Trinder’s method, endpoint) with a standard cutoff value of 200 mg/dL. Results: Baseline reading of total cholesterol in all samples was 189 mg/dL. After 2 h, the total cholesterol reading in A1 was 159 mg/dL, 157, 162, and 160 mg/dL in A2, D1, and D2, respectively. After 4 h, the total cholesterol reading in A1 was 149 mg/dL, 148, 151, and 149 mg/dL in A2, D1, and D2, respectively. After 6 h, the total cholesterol reading in A1 was 109 mg/dL, 104, 112, and 110 mg/dL in A2, D1, and D2, respectively. Conclusion: From the findings of the present study, it was found that aqueous extract of Ashwagandha (WS) and Arjuna (T. arjuna) was effective in reducing total cholesterol levels. It can be considered a potential therapeutic alternative in patients with hyperlipidemia but warrants further clinical studies.

Effect of multigrain porridge on postprandial glucose level in diabetic individuals

A metabolic disorder called diabetes mellitus is brought on by issues with insulin production, action, or both. Chronic hyperglycemia is caused by insulin deficiency with aberrant carbohydrate, lipid and protein metabolism. Postprandial glucose level is the glucose level after a meal. This test is done to observe how the body responds to sugar and carbohydrates after eating. To lower postprandial glucose level in diabetic individuals, multigrain porridge has been regarded as the most effective mean. Multigrain porridges were prepared with millet, barley, sorghum and whole wheat. All these grains are loaded with soluble and insoluble fiber, antioxidant, phytochemicals, proteins, essential vitamins and minerals. Barley, sorghum and millet have low glycemic index because of a high proportion of fiber, which helps to keep blood sugar level stable after eating. The current study was planned to evaluate the postprandial glucose and cholesterol lowering effect of multigrain porridges in diabetic individuals. Multigrain porridges were prepared by grinding all grains into raw porridge form then boiling in water and adding half to one cup of milk. The raw materials were subjected to proximate analysis, mineral analysis, antioxidant assay, dietary fiber analysis, sensory analysis and efficacy study.

Chitosan Oligosaccharides as a Nanomaterial Platform: Biological Properties and Applications in the Biomedical and Pharmaceutical Fields

Chitosan oligosaccharides (COS) have been introduced as marine-derived biomaterials with potential health benefits and good water solubility properties. This study presents an overview of the promising nanomaterial platform for biomedical and pharmaceutical applications of COS. The health benefits of COS, primarily their antioxidant and protective effects, anti-inflammatory activity, antidiabetic properties, and cholesterol-lowering effects are discussed. Furthermore, the promising recent articles on specific topics such as drug delivery systems and nanobiomaterials, are highlighted

Familial Hypercholesterolemia Patients with COVID-19-Effective Cholesterol-Lowering Therapy is Urgent both during and after Infection.

Heterozygous familial hypercholesterolemia (HeFH) patients are the prime example of subjects who are at high risk for both acute myocardial infarction (AMI) and ischemic stroke during, and post, SARS-CoV-2 infection. HeFH per se, if left untreated, results in premature clinical atherosclerosis often presenting in the fourth or fifth decade of life. The other concern in HeFH is endothelial dysfunction which is already evident from early childhood. In untreated HeFH patients, the severe hypercholesterolemia causes endothelial dysfunction from an early age, and as a result thereof, atherosclerotic lesions develop prematurely, particularly in the coronary arteries, and result in further endothelial dysfunction and inflammation in these critical segments of the arterial tree. As the pre-existing endothelial dysfunction in HeFH patients is most likely sensitive to further direct and indirect SARS-CoV-2 virus-dependent damage, we can infer that HeFH serves as an example of a comorbidity that predicts a poorer prognosis with COVID-19 infection. Indeed, a large US national database study showed that patients diagnosed with HeFH and SARS-CoV-2 infection had significantly increased Annualized Incidence Density Rates (AIDRs) of AMI when compared to matched HeFH controls not having been diagnosed with SARS-CoV-2 infection. Effective cholesterol lowering is essential for the prevention, or at least alleviation, of the detrimental effects of SARS-CoV-2 infection among HeFH patients. Due to the pre-existing subclinical or even clinical atherosclerotic cardiovascular disease in subjects with HeFH, cholesterol-lowering treatment needs to be continued or, better still, intensified during, and for an extended period post, SARS-CoV-2 infection.

Randomized Trials Fit for the 21st Century: A Joint Opinion From the European Society of Cardiology, American Heart Association, American College of Cardiology, and the World Heart Federation.

Randomized Trials Fit for the 21st Century: A Joint Opinion From the European Society of Cardiology, American Heart Association, American College of Cardiology, and the World Heart Federation.

682 UNEXPECTED TRIGLYCERIDES-LOWERING EFFECT OF A NOVEL NUTRACEUTICAL COMPOUND FOR IBS

Abstract Background In the last few years the role of gut microbiome in human health has been reported. Growing evidence indicate that it is linked to intestinatal diseases, such as the irritable bowel syndrome (IBS), and atherosclerotic disorders. The effect on lipid metabolism seems to be one of the potential mechanisms by which gut microbiome might favour the atherosclerotic process. IBS is a functional bowel disorder defined by the presence of recurrent episodes of abdominal pain associated with altered bowel habits. The severity of psychological and gastrointestinal symptoms in IBS has been linked with a distinct intestinal microbiota signature. In this retrospective study the effect of a novel nutraceutical compound, namely Triobiotix, on gastrointestinal symptoms in IBS patients has been evaluated. Effects on lipid profile have bee also recorded. Methods Triobiotix is a nutraceutical consisting of: Maltodextrin; mineralized extract of Lithothamnion (Lithothamnion calcareum (Pallas) Areschoug, thallus dry extract); Bioecolians® gluco-oligosaccharides; Ferment mix (corn starch, Bifidobacterium animalis ssp. Lactis BLC1 (DSM 17741), Lactobacillus acidophilus LA3 (DSM 17742), Lactobacillus rhamnosus IMC 501 (DSM 16104), Lactobacillus paracasei Streptococc5 501 IMC102 SP4 (DSM 19385); short-chain fructo-oligosaccharides powder. The database of 40 Italian General Practitioners (GPs) were analyzed. At total of 587 patients with IBS and on Triobiotix were identified. Of these in only 535, a complete first and second control data was available. The primary endpoint of these analysis was to assess whether Triobiotix resulted in a reduction in pain and meteorism, thus resulting in a lesser intensity of the main gastrointestinal symptoms. Secondary endpoints were to look for significative changes in lab values of total cholesterol, triglycerides levels and glycaemia. Results Treatment with Triobiotix for four weeks resulted in a reduction in the frequency and intensity of bloating, abdominal pain, and tenesmus. Unexpectedly, at the T1 control, mean cholesterol values were significatively reduced compared to the T0 evaluation. Triglycerides levels were also significantly decreased (186.37±66.4 vs. 176.13±67.9; p < 0.05). Conclusions Our analysis showed an unexpected effect of this combination of micronutrients on lipid profile beyond IBS symptoms. However, further studies are needed to confirm this evidence and to evaluate the particular compound responsible of this effect. A goal of LDL-C less of 115mg/dL is desirable for patients at low to moderate CVR, a significative portion of population is far from this target. The discovery of novel micronutrients combinations with cholesterol lowering effects could be of great importance for the management of patients with low-moderate dyslipidaemia.

Mechanism Underlying Naringenin Hypocholesterolemic Effects: Involvement of Estrogen Receptor α Subtype

Naringenin (Nar) is one of major citrus flavonoids predominantly found in grapefruit and orange. In vivo studies have demonstrated Nar potential as a normolipidemic agent capable to reduce circulating cholesterol in hypercholesterolemic rabbits, rats, and patients, suggesting a new role for this molecule in cardiovascular disease prevention. Although Nar cholesterol-lowering effects are known, the underlying mechanisms have not yet been elucidated. Interestingly, Nar binds to the estrogen receptors (ERs), modulating both transcriptional and membrane-initiating signals. Although estrogen and ERs are deeply involved in lipid metabolism, no data are available regarding a putative role of these nuclear receptors as mediators of the hypocholesterolemic effect exerted by Nar. Thus, the aim of this work was to study the involvement of ERs in Nar-induced modulation of cholesterol metabolism. Results obtained in HepG2 cell line demonstrate that Nar can modulate the molecular network of cholesterol homeostasis. However, these effects were only partially dependent on the activity of estrogen receptor α. As a whole, our data highlight new molecular mechanisms by which Nar influences cholesterol metabolism, opening a new scenery about dietary impact on human health.

Удосконалення технології виробництва функціональних плодово-ягідних напівфабрикатів

The object of this study is a functional fruit-and-berry paste with healthy properties with the selection of components (apples, Ziziphus jujuba, blueberries), which are sources of dietary fiber, vitamin C, low molecular weight polyphenolic compounds and phytosterols, which are used as an immunostimulant to create products with cholesterol-lowering effect. The task to increase the content of these substances is solved by concentrating in a rotary film evaporator (RFE) under mild regime pa¬rameters (60...65 °C) to a dry matter (DM) content of 30...32% for 45...50 s and by the pasteurization of concentrated paste in a scraper heat exchanger (SHE) at a temperature of 95...98 °C followed by packing. The effective viscosity (Pa·s) of the mixtures of the original purees (DM 16...17%) and resulting pastes (30...32%) was determined and its increase 1.65...1.85 times was established in the pastes compared to puree. The obtained data indicate a strengthening of the structure of the resulting functional paste, which, compared to control sample, has 3.6 times more effective viscosity. A significant advantage has a paste containing 45% of apple; 35% of Ziziphus jujuba; 20% of blueberries. It is characterized by 3.8 timesenhanced content of dietary fiber; 2.25 times more content of vitamin C; low-molecular polyphenolic compounds and tannins, phytosterols. Therefore, it can be used as an immunostimulant to manufacture products with cholesterol-lowering effect. It was established that in order to effectively conduct the process of concentration in RFE and subsequent pasteurization in SHE, it is rational to grind puree to a particle size within 0.1...0.5 mm. The heat transfer coefficient when concentrating samples with a particle size of 0.5 mm has a higher rate, by 6%, compared to the sample with a particle size of 1.5 mm. The technology could be introduced at the enterprises of the canning and confectionery industries.

Distribution, cholesterol-lowering and immunomodulation effects of lactic acid bacteria from fermented mussel (Hoi-dong)

Forty-eight lactic acid bacteria (LAB) isolated from fermented mussels in Thailand were evaluated for their probiotic properties, bile salt hydrolase (BSH), cholesterol assimilation and immunomodulatory effects. They were identified as Companilactobacillus formosensis (Group I, 10 isolates), Lentilactobacillus buchneri (Group II, 8 isolates), Lactiplantibacillus plantarum subsp. plantarum (Group III, 16 isolates), Lacticaseibacillus rhamnosus (Group IV, 1 isolate), Pediococcus pentosaceus (Group V, 5 isolates) and P. acidilactici (Group V, 1 isolate), Enterococcus thailandicus (Group VI, 2 isolates), En. hirae (Group VII, 1 isolate), En. durans (Group VI, 1 isolate), Lactococcus lactis subsp. lactis (Group VII, 1 isolate), Lc. lactis subsp. hordinae (Group VII, 1 isolate), and Leuconostoc lactis (Group VIII, 1 isolate), based on their phenotypic and genetic characteristics. Seven isolates, L. plantarum subsp. plantarum LM6-1, LM6-2, LM7-2-2B, LM12-1, LM14-1, LM15-1P and LM15-2 expressed bile salt hydrolase activity. All isolates assimilated cholesterol ranging from 20.73 to 79.40%. BSH-producing isolates were tolerant to acidic and bile conditions and showed the adhesion ability to Caco-2 cells. The BSH-producing and selected isolates showed the immunomodulatory effects to stimulate interleukin-12 (IL-12), interferon-gamma (IFN-γ), human beta defensin-2 (hBD-2) and nitric oxide (NO) production at various levels. Therefore, these results indicated that the isolates meet the standard probiotic criteria and beneficial effects.

Pharmacist intervention in cardiovascular disease prevention: lipid modifying treatment optimisation in type 2 diabetes within hastings primary care network

Abstract Introduction Cardiovascular disease (CVD) leads to 1 in 4 premature deaths with higher likelihood in the most deprived population1. Consistent data demonstrated efficacy of statins in CVD prevention and mortality reduction through modifying lipid profile1,2. NICE:CG181 recommends high-intensity statin, namely atorvastatin 20mg daily in type 2 diabetes (T2DM) with high risk of developing CVD1, whilst the European Society of Cardiology suggests LDL-C target below 1.4mmol/L, the lower the better 2. In contrast, 30% of patients in Hastings Primary Care Network (PCN) are prescribed sub-optimal statin therapy3 with scope to promote medicine optimisation through modification of CVD risk factor in one of the England’s most deprived areas. Aim Lowering patient’s CVD risk through optimising statin therapy and improving practice’s compliance with NICE:CG181. Methods NHS Health Research Authority Decision tool was followed, ethics approval was not required. Statin prescribing data were obtained through OpenPrescribing database. This pilot study focused on the prescribing of simvastatin at one surgery within the PCN where patients were identified using the surgery medical information system with the inclusion clinical codes of: “T2DM”, “QRISK2>10%”, “latest LDL-C>1.4mmol/L” and “current simvastatin 10/20/40mg prescription”. Systematic review of patient medical records was followed, including medical history, latest lipid profile and liver function, allergies, history of statin intolerance, previous lipid therapy and frailty status determined using the electronic frailty index, Rockwood score and medical notes. Patients with heterozygous familial hypercholesterolaemia diagnosis, confirmed statin intolerance and moderately-to-severely frail were excluded. Patients were contacted to exercise shared decision-making. Once intervention agreed, prescription was initiated for prescriber authorisation. Blood test 3 months post-intervention monitored for liver function and lipid profile. Results Search in February 2022 identified 44 patients with 39 suitable for intervention after exclusion. Thirty-six contactable patients were all switched to high-intensity statin. Thirty-four were switched to atorvastatin 20 mg whilst two with prior atorvastatin intolerance were switched to rosuvastatin 10 mg. At baseline, 32 patients (88%) had cholesterol profile done within a year as per NICE:CG181. Three-month post-intervention blood tests were completed for 21, with 15 pending; 33% (7/21) had a reduction of LDL-C. In February 2022, 28.9% of the practice’s statin prescriptions were of low and medium intensity and was reduced to 25.6% post intervention. Discussion/Conclusion All contactable patients had statin therapy optimised after exercising shared decision-making with improvement of prescribing compliance to NICE:CG181 demonstrated in this practice. Findings were inconclusive whether the intensification of statin therapy demonstrated cholesterol lowering effect in this cohort. Study limitations due to small sample size, currency of baseline profile at time of intervention and patient compliance not measured. Raised LDL-C observed could have been influenced by lifestyle changes such as poor diet and lack of exercise1. The limitations of this study will be reviewed for future roll out across Hastings PCN. Further exploration of therapy compliance, lifestyle education and the barriers to regular blood test would facilitate such medicine optimisation intervention. In conclusion, patients prescribed with sub-optimal lipid therapy should be reviewed and managed through healthy lifestyle recommendations and aggressive pharmacological intervention.

Lactobacillus gasseri RW2014 Ameliorates Hyperlipidemia by Modulating Bile Acid Metabolism and Gut Microbiota Composition in Rats

Hyperlipidemia is a leading risk of cardiovascular and cerebrovascular disease. Dietary supplementation with probiotics has been suggested as an alternative intervention to lower cholesterol. In the current study, we isolated a strain of Lactobacillus gasseri RW2014 (LGA) from the feces of a healthy infant fed with breast milk, and it displayed bile salt hydrolase (BSH) activity. Using this strain we determined its cholesterol-lowering and fatty liver-improving functions. SD rats were randomly divided into four groups. The control rats were fed a commercial chow diet and the other three groups were fed a high-fat diet (HFD) for a 7-week experiment period. After two weeks of feeding, the rats in PBS, simvastin, and LGA group were daily administered through oral gavage with 2 mL PBS, simvastin (1 mg/mL), and 2 × 109 CFU/mouse live LGA in PBS, respectively. After five weeks of such treatment, the rats were euthanized and tissue samples were collected. Blood lipid and inflammatory factors were measured by ELISA, gut microbiota was determined by 16S rRNA sequencing, and bile acids profiles were detected by metabolomics. We found that LGA group had lower levels of blood cholesterol and liver steatosis compared to the simvastin group. LGA also significantly reducedthe levels of inflammatory factors in the serum, including TNFα, IL-1β, MCP-1, IL-6, and exotoxin (ET), and increased the levels of short-chain fatty acids in feces, including isobutyric acid, butyric acid, isovaleric acid, valeric acid, and hexanoic acid. In addition, LGA altered the compositions of gut microbiota as manifested by the increased ratio of Firmicutes/Bacteroides and the relative abundance of Blautia genus. Targeted metabolomics results showed that bile acids, especially free bile acids and secondary bile acids in feces, were increased in LGA rats compared with the control rats. Accordingly, the rats administrated with LGA also had a higher abundance of serum bile acids, including 23-norcholic acid, 7-ketolithocholic acid, β-muricholic acid, cholic acid, and deoxycholic acid. Together, this study suggests that LGA may exert a cholesterol-lowering effect by modulating the metabolism of bile acids and the composition of gut microbiota.

Temporal Association of Total Serum Cholesterol and Pancreatic Cancer Incidence.

Previous studies have suggested a "cholesterol-lowering effect" of preclinical pancreatic cancer, suggesting lower total cholesterol as a potential diagnostic marker. Leveraging repeated measurements of total cholesterol, this study aims to examine the temporal association of total cholesterol and pancreatic cancer incidence. We conducted a nested case-control study based on a Korean National Health Insurance Service-Health Screening Cohort, including 215 pancreatic cancer cases and 645 controls matched on age and sex. Conditional logistic regression was applied to estimate the odds ratio (OR) and 95% confidence interval (CI) for the associations of pancreatic cancer incidence with total cholesterol levels across different time windows over 11 years before pancreatic cancer diagnosis (recent, mid, distant). We found that, compared to participants with total cholesterol < 200 mg/dL in the recent 3 years prior to diagnosis, those having total cholesterol ≥ 240 mg/dL showed a significantly lower pancreatic cancer incidence (OR = 0.50 (0.27-0.93)). No significant association was found in relation to total cholesterol measured in the mid and distant past. When changes in total cholesterol over the three time periods were analyzed, compared with those with total cholesterol levels consistently below 240 mg/dL over the entire period, the OR of pancreatic cancer was 0.45 (0.20-1.03) for participants with recent-onset hypercholesterolemia, 1.89 (0.95-3.75) for recent-resolved hypercholesterolemia, and 0.71 (0.30-1.66) for consistent hypercholesterolemia. In conclusion, while high total cholesterol in the recent past may indicate a lower pancreatic cancer incidence, a recent decrease in total cholesterol may suggest an elevated incidence of pancreatic cancer.

Understanding hypocholesterolemic activity of soy isoflavones: Completing the puzzle through computational simulations

The hypocholesterolemic activity of soy isoflavones has been studied, but the exact mechanism underlying the activity remains unclear. This study reveals the proposed mechanism of the cholesterol-lowering effect of soy isoflavones by computational simulations. Daidzin, Glycitin, Genistin, Daidzein, Glycitein, Genistein, Glyceollin I, Glyceollin II, and Glyceollin III were selected to be analyzed their interaction with 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase (HMGCR) and Sterol Regulatory Element-Binding Protein 2 (SREBP2) as key factors in cholesterol biosynthesis as well as Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) as a common target for hypercholesterolemia. Protein-isoflavones interaction was analyzed using AutoDock. According to binding energy calculations, a total of five out of those nine isoflavones, including Glycitin, Genistin, Genistein, Glyceollin II, and Glyceollin III, were favored to be a HMGCR inhibitor but not with SREBP2 and PCSK9. Those isoflavones were then compared with Simvastatin as known inhibitor of HMGCR. Isoflavone with binding energy lower than Simvastatin then directed to molecular dynamics using YASARA and headed into toxicity estimations. Almost all of those isoflavones could bind with HMGCR with better stability than Simvastatin according to molecular dynamics simulations. Toxicity prediction filtered two out of the five isoflavones mentioned earlier as the proper candidate to be an HMGCR inhibitor. Those isoflavones were Genistin and Genistein. In summary, the hypocholesterolemic activity of soy isoflavones may occur by blocking the cholesterol biosynthesis pathway. Communicated by Ramaswamy H. Sarma

Research progress on Walnut oil: Bioactive compounds, health benefits, extraction methods, and medicinal uses.

Walnut oil is extracted from walnut kernels (Juglans regia Linne) or iron walnut kernels (Juhlans sigillata Dode). The percentage of oil in walnuts is 52%-70%. The main constituents in oil are fatty acids, phenols, sterols, squalene, melatonin, vitamins, and minerals. Many extraction methods such as supercritical carbon dioxide extraction, maceration, modified "bligh and dyer extraction," aqueous enzymatic extraction, ultrasonic extraction, soxhlet extraction, and cold-press extraction methods are reported in the literature. Walnut oil showed anti-inflammatory, antitumor, antioxidant, immunomodulatory, neuroprotective, cardioprotective, antidiabetic, and antihyperlipidemic activities. The reported data in the literature suggest that walnut oil has many health benefits. This review summarizes the extraction methods, bioactive constituents, health benefits, and pharmacological actions of walnut oil. PRACTICAL APPLICATIONS: Walnut oil is a natural vegetable oil of significant importance due to their nutritional, and intelligence-boosting benefits. Several factors, including the processing parameters and the phytochemical profile, affect walnut oil products' flavor and color. In addition, storage environment of walnut oil can also affect walnut oil quality. Apart from the predominant ingredient fatty acids, the chemical composition of walnut oil comprises phenols, sterols, squalene, melatonin, vitamins, and minerals. These bioactive compounds are of potential value owing to their health-promoting benefits, including antioxidant, antitumor, and cholesterol-lowering effects. Many chemical constituents were isolated from walnut oil; however, all the compounds are not explored for their possible medicinal value. Thus, clinical studies, exploration of the therapeutic potential and the molecular mechanisms of all the compounds, and development of convenient dosage forms either for therapeutic or functional food purposes are warranted.

Enterococcus faecium GEFA01 alleviates hypercholesterolemia by promoting reverse cholesterol transportation via modulating the gut microbiota-SCFA axis.

This study aimed to identify cholesterol-lowering commensal strains from healthy lean individuals and to evaluate the cholesterol-lowering capacity of Enterococcus faecium GEFA01 in mice fed a high-cholesterol and high-fat diet. E. faecium GEFA01 was isolated from the feces of a healthy lean individual in a selective basal salt medium supplemented with cholesterol. E. faecium GEFA01 exhibited a cholesterol removal rate (CRR) of 46.13% by coprecipitation, assimilation, and degradation of cholesterol. Moreover, E. faecium GEFA01 significantly decreased the body weight of mice and the levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), hepatic TC, triglycerides (TG), and LDL-C, and increased serum high-density lipoprotein cholesterol (HDL-C) levels in mice fed a high-cholesterol diet compared with the HCD group. We also observed that E. faecium GEFA01 significantly downregulated the gene expression of HMG-CoA reductase (Hmgcr), Srebp-1c, Fxr, Shp, and Fgf 15, upregulated the gene expression of low-density lipoprotein receptor (Ldlr), Abcg5/8, Abca1, cholesterol 7 alpha-hydroxylase (Cyp7a1), and Lxr in the liver of mice in relative to the HCD group, markedly increased the relative abundance of Lactobacillus, Akkermansia, Bifidobacterium, and Roseburia, and decreased the abundance of Helicobacter in the feces. Collectively, we confirmed that E. faecium GEFA01 exhibited cholesterol-lowering effects in mice fed a high-cholesterol diet, which was achieved through assimilation, coprecipitation, and degradation of cholesterol, and through modulation of the gut microbiota short-chain fatty acid (SCFA) axis that promoted reverse cholesterol transport and bile acid excretion. Our study demonstrated that E. faecium GEFA01 may be used as a probiotic candidate to lower cholesterol levels in the future.

Inhibitory Effect of Isoliquiritigenin in Niemann-Pick C1-Like 1-Mediated Cholesterol Uptake.

Isoliquiritigenin (ISL) is a flavonoid with a chalcone structure extracted from the natural herb Glycyrrhiza glabra. Its anti-inflammatory, antibacterial, antioxidant, and anticancer activities have been extensively studied. Moreover, ISL also possess hypolipidemic and atherosclerosis-reducing effects. However, its cholesterol-lowering mechanisms have not been reported yet. Niemann Pick C1 Like 1 (NPC1L1) is a specific transporter of cholesterol uptake. In this study, we found for the first time that ISL downregulates NPC1L1 expression and competitively inhibits cellular cholesterol uptake by binding to NPC1L1 in a concentration-dependent manner in vitro. This study provides a theoretical basis for further investigation of the molecular mechanisms of its cholesterol-lowering effect in vivo and inspired emerging drug research for cholesterol-lowering purposes through NPC1L1 inhibition.

Antihyperglycemic, Antihyperlipidemic and Antioxidant Effects of Eclipta prostrata L. Aqueous Extract in Streptozotocin-Induced Diabetic Rats

With the rising prevalence of diabetes mellitus around the world, researchers have been searching for a new treatment option that is both more effective and safer than chemotherapy. This study evaluated the antidiabetic activities of aqueous extracts of Eclipta prostrataL. in streptozotocin (STZ)-induced diabetic rats. The rats were randomized into six groups: Normal control, STZ-induced diabetic rats (50 mg/kg), STZ + EPE (100 mg/kg), STZ + EPE (200 mg/kg), STZ+glibenclamide (600 µg/kg) and EPE alone (200 mg/kg). The STZ-induced diabetic rats showed significantly (p<0.05) elevated glucose, HbA1c, lipid profile, hepatic, and kidney markers, while significantly (p<0.05) decreased insulin levels. The changes in activities of carbohydrate metabolizing enzymes such as glucose-6-phosphatase, fructose-1,6–bisphosphatase were significantly (p<0.05) increased in diabetic rats, while the activity of glucokinase and glucose-6-phosphate dehydrogenase were significantly (p<0.05) reduced. Oral treatment of STZ-induced diabetic rats with E. prostrata(100 and 200 mg/kg) and glibenclamide (600 µg/kg) prevented the alteration as mentioned earlier and brought back them to near normalcy. The current findings in experimental diabetic rats suggest that oral treatment with E. prostrate ameliorated carbohydrate metabolizing enzymes, showed total cholesterol-lowering effects, improved serum high-density lipoprotein (HDL) cholesterol levels and exhibited intriguing antioxidant activities.

A novel polyphyllin I-based liposome delivery system sensitizes hepatic carcinoma to doxorubicin via cholesterol modulation

Cholesterol and its metabolites act as important signaling molecules that promote tumor development. In recent years, increasing evidence has indicated that targeting cholesterol biosynthesis, metabolism, and membrane distribution could potentially sensitize cancer cells to chemotherapy. However, because of the lack of selectivity and the large differences in half-life, metabolism, and clearance between drugs, combining cholesterol inhibitors with chemotherapy agents can produce toxic side effects and contradictory results, making this kind of treatment highly controversial. Here, we developed a PPI-based multifunctional liposome system to effectively cope with the above challenges. As a steroidal saponin, PPI acts as a membrane stabilizer to replace the cholesterol needed to form liposomes, avoiding the shortcomings caused by extra cholesterol intake. Moreover, as a chemotherapy adjuvant, PPI has great potential to interfere with cancer-derived cholesterol disorders, exerting a cholesterol-lowering effect as strong as lovastatin. The expression of important cholesterol synthesis-related proteins, SOAT1, HMGCR, and SREBP2, were only 1/3-1/2 of lovastatin. In addition, by forming complexes with membrane cholesterol, PPI not only improves plasma membrane fluidity and permeability but also disrupt the distribution of lipid rafts, which decreased the expression of ABC transporters to 0.6–1.0-fold, allowing more chemotherapy agents to reach the intracellular targets. Finally, PPI-DOX co-loaded liposomes (DLPs) exhibited stronger tumor inhibition effect in in vivo animal studies, which was 1.3-fold that of Chol-DOX-LP. Therefore, PPI-based liposomes offer a new strategy and opportunity for cancer treatment by combining cancer-derived cholesterol modulation with other anti-cancer therapies.