Hypocholesterolemic Activity Research Articles

Bempedoic Acid, the First-in-Class Oral ATP Citrate Lyase Inhibitor with Hypocholesterolemic Activity: Clinical Pharmacology and Drug–Drug Interactions

Bempedoic acid is a new drug that improves the control of cholesterol levels, either as monotherapy or in combination with existing lipid-lowering therapies, and shows clinical efficacy in cardiovascular disease patients. Thus, patients with comorbidities and under multiple therapies may be eligible for bempedoic acid, thus facing the potential problem of drug–drug interactions (DDIs). Bempedoic acid is a prodrug administered orally at a fixed daily dose of 180 mg. The dicarboxylic acid is enzymatically activated by conjugation with coenzyme A (CoA) to form the pharmacologically active thioester (bempedoic acid–CoA). This process is catalyzed by very-long-chain acyl-CoA synthetase 1 (ACSVL1), expressed almost exclusively at the hepatic level. Bempedoic acid–CoA is a potent and selective inhibitor of ATP citrate lyase (ACL), a key enzyme in the biosynthetic pathway of cholesterol and fatty acids. The drug reduces low-density lipoprotein–cholesterol (LDL-C) (20–25%), non-high-density lipoprotein–cholesterol (HDL-C) (19%), apolipoprotein B (apoB) (15%), and total cholesterol (16%) in patients with hypercholesterolemia or mixed dyslipidemia. The drug has a favorable pharmacokinetics profile. Bempedoic acid and its metabolites are not substrates or inhibitors/inducers of cytochrome P450 (CYP450) involved in drug metabolism. On the other hand, bempedoic acid–glucuronide is a substrate for organic anion transporter 3 (OAT3). Bempedoic acid and its glucuronide are weak inhibitors of the OAT2, OAT3, and organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3). Thus, bempedoic acid could inhibit (perpetrator) the hepatic uptake of OATP1B1/3 substrate drugs and the renal elimination of OAT2 and OAT3 substrates and could suffer (victim) the effect of OAT3 transporter inhibitors, reducing its renal elimination. Based on these pharmacological characteristics, here, we describe the potential DDIs of bempedoic acid with concomitant medications and the possible clinical implications.

A Systematic Review of Barley (Hordeum vulgare Linn.) in Unani Medicine with Recent Advances

Objective: The present review article focuses on exploring the wide dimensions of barley including botanical description, nutritional composition, phytochemistry, experimental pharmacology, and clinical studies along with its traditional uses in Unani medicine. Background: Barley (Hordeum vulgare L.) which is referred to as ‘Jao’ in the Unani system of medicine has a long history of utilization as a food and medicine. It belongs to family Poaceae and is considered as one of the founder crops of old-world agriculture. Methodology: A manual literature survey of classical Unani texts was conducted to collect the information available on ‘Jao’. Besides, a comprehensive search of electronic databases like PubMed, Google Scholar, and Science Direct, was carried out to collect all the available information regarding its phytochemical, pharmacological and clinical studies. Result: In Unani medicine, barley is an important drug commonly used in many disorders of the respiratory system, gastrointestinal system, musculoskeletal system, skin, etc. It is used to treat obesity, diabetes, headache, pain and inflammation of the throat, acute swelling of joints and gout, chronic swellings, diarrhoea, fever, skin eruptions, hyperpigmentation of the skin, etc. Recent studies revealed that barley constitutes beta-glucan and a myriad of bioactive compounds that play numerous biological activities such as hypoglycemic, hypocholesterolemic, anti-inflammatory, antioxidant, anti-obesity, anticancer, and wound healing activities. Conclusion: Barley is a potent drug that exhibits a wide range of health benefits, most of which have been confirmed via preclinical and clinical studies. This review may thus be helpful for the research community as well as common people to avail the benefits of this drug. Keywords: Barley, Beta-glucan, Hordeum vulgare, Jao, Unani medicine

In Vitro Antioxidant and Hypocholesterolemic Potency of Melon (Cucumis melo L.) Seed Protein Hydrolysate

Protein hydrolysates have been reported to possess numerous bioactivities. However, research on melon (Cucumis melo L.) seed protein (MSP) hydrolysate is limited. This study aimed to analyze the antioxidant and hypocholesterolemic properties of MSP hydrolysate. Protein from melon seed was obtained by conventional alkaline extraction-isoelectric precipitation method. Enzymatic hydrolysis of MSP was carried out using three different proteases: pepsin, thermolysin, and trypsin, with the enzyme-to-substrate (E/S) ratio of 1:50 (w/w). The results showed that all hydrolysates exhibited antioxidant and hypocholesterolemic activity. The thermolysin-digested hydrolysate had significantly greater (p < 0.05) radical scavenging properties, while trypsin produced the highest (p < 0.05) metal ion chelating activity. At 2 mg/mL, thermolysin-derived MSP hydrolysate showed no significant difference (p > 0.05) in HMGR inhibition activity compared to pravastatin. Additionally, the thermolysin hydrolysate had significantly higher (p < 0.05) bile acid binding ability than other hydrolysates. Overall, the MSP hydrolysate produced by thermolysin exhibited stronger antioxidant and hypocholesterolemic activities when compared to those produced by pepsin and trypsin, suggesting its potential effectiveness in nutraceutical applications.

Nuclear receptors behind the therapeutic effects of plant sterols on metabolism: A review.

Plant sterols are known for their hypocholesterolemic action, and the molecular mechanisms behind this within the gut have been extensively discussed and demonstrated to the point that there is a degree of consensus. However, recent studies show that these molecules exert an additional umbrella of therapeutic effects in other tissues, which are related to immune function, lipid metabolism, and glucose metabolism. A strong hypothesis to explain these effects is the structural relationship between plant sterols and the ligands of a group of nuclear receptors. This review delves into the molecular aspects of therapeutic effects related with lipid and energy metabolism that have been observed and demonstrated for plant sterols, and turns the perspective to explore the involvement of nuclear receptors as part of these mechanisms.

Bioactive peptides from by-products of shrimp processing: A review

Currently, the mismanagement of marine by-products (head, skin, guts, blood, and bones) is a problem for the seafood processing industry, causing economic losses and environmental problems. Shrimp is a high-protein marine plankton species, and after processing, 45% of the total weight is discarded. Therefore, processes must be developed to recover biomolecules from this waste. Hydrolysis of shrimp by-products is an efficient way to add value to the protein for the extraction of bioactive peptides. The present review focuses on recent research on the use of marine by-products to obtain bioactive peptides, especially those from shrimp waste, and discusses their benefits for human health. Protein hydrolysates from shrimp by-products are a viable and technological strategy to obtain peptides of different sizes and improved antioxidant, anti-hypertensive, anti-inflammatory, and hypocholesterolaemic activities. Therefore, the reuse and valorisation of shrimp by-products by obtaining bioactive peptides is an active research area, with potential applications and beneficial effects for human health, the environment, and the economy. However, further studies are needed to ensure their safe use, and to understand their mechanism of action.

Відбір пробіотичних мікроорганізмів та їх композицій як основи для лінійки функціональних продуктів харчування з гіпохолестеринемічними властивостями

In modern clinical practice, the main methods for correcting elevated serum cholesterol levels are drugs that block the activity of the enzyme hydroxymethylglutaracyl-CoA-reductase (HMG-CoA-reductase) – statins or drugs that inhibit the absorption of cholesterol and sterols in the intestines ezetimibe. All hypocholesterolemic drugs are rather expensive and have side effects, the main of which is hepatotoxicity. During mono- and combined therapy with HMG-CoA reductase inhibitors and ezetimibe, cases of increased activity of alanine and asparagine transaminases (biochemical indicator of cytolytic syndrome), disorders of the digestive and respiratory systems, the central and peripheral nervous systems, and the sense organs along with weight gain, etc. have been found. Scientific literature has increasingly reported on the ability of lactic acid bacteria to lower serum cholesterol. The ability of certain strains of representatives of the normal microbiota to assimilate and precipitate deconjugated bile acids, as well as to destroy, bind, and assimilate cholesterol, is the basis of their hypocholesterolemic activity (the ability to reduce the level of serum cholesterol). A high level of cholesterol, both in the total blood serum and in low-density lipoproteins, is one of the main risk factors for coronary heart disease, atherosclerosis, cerebrovascular atherosclerosis, hypertension, tumors of the digestive tract, etc. The aim of the study was to establish the hypocholesterolemic activity in vitro and in vivo of previously selected highly effective probiotic strains of lactic- and bifidobacteria for the further creation on their basis of a line of effective functional food with hypocholesterolemic activity for the prevention and concomitant treatment of pathological conditions associated with high cholesterol levels. Methods. Bacterial hypocholesterolemic activity in vitro was determined according to Rudel L.L. and in vivo – on the mice model that was designed by us. Two schemes of the administration of probiotic strains – the prophylactic and therapeutic ones–were developed. Results showed that Lactobacillus acidophilus IMV B-7279 and Bifidobacterium animalis IMV B-7286 strains, as well as the Bifidobacterium animalis IMV B-7286: Bifidobacterium animalis IMV B-7285 (1:1) composition were the most effective probiotics used for treatment of mice with hypercholesterolemia. The cholesterol-lowering activity of all studied probiotic strains and their compositions ranged between 40–78 %. At the same time, it should be noted that the hypocholesterolemic activity of the other studied strains was not lower, and in some cases even higher than that of most of the drugs currently used for cholesterinosis. Conclusions. The obtained results allow us to assert that it is necessary to develop a series of functional foods and probiotics based on the studied strains and their compositions in an encapsulated form, for the prevention and treatment of diseases associated with the negative manifestations of high cholesterol levels.

Pine nut skin as a source of phytosterols and alkanediols - Hypocholesterolemic potential and development of sustainable vegan emulsifiers

Pine nut skin is a byproduct arising from the pine nut industry, whose composition and bioactive potential are currently unexplored. For this purpose, its characterization is required for the development of sustainable food ingredients.Pine nut skin was separated into finer (<500 μm) and coarser (≥500 μm) fractions, composed of carbohydrates (35 g/100 g and 11 g/100 g, respectively), lignin (47 g/100 g and 72 g/100 g), lipids (8 g/100 g and 9 g/100 g), and protein (7 g/100 g and 3 g/100 g). The lipophilic extract of both fractions had similar amounts of β-sitosterol (30 mg/g), differing in the amount of long-chain aliphatic alcohols, namely nonacosan-10-ol (8 mg/g and 51 mg/g for finer and coarser fractions, respectively) and secondary/secondary alkanediols (18 mg/g and 185 mg/g), known as emulsifier compounds. The composition of pine nut skin fractions indicated their potential in affecting the cholesterol absorption in the intestinal lumen. The lipophilic extract from the finer fraction showed to decrease cholesterol micellar solubilization, and the polysaccharides and lignin had bile salt sequestration properties, rendering this byproduct an hypolipidemic potential. The coarser fraction showed potential as a substitute of egg yolk (3.4 g/100 g dry weight) in a mayonnaise formulation (49 g/100 g oil-in-water emulsion), an emulsifying capacity ascribed to the dietary fiber content and to its lipophilic fraction. From pine nut skin it is possible to obtain low-cost food ingredients with relevance as emulsifiers and potential hypocholesterolemic activity.

Anti-Obesity Potentials of Methanol Extracts of Phragmanthera Incana Leaves Hemi-Parasitic on Guava, Cashew, Kolanut and Mango Trees in High-Fat Diet-Induced Obese Rats

The anti-obesity potential of methanol extracts of Phragmanthera incana leaves hemi-parasitic on guava Psidium guajava (PIPG), cashew Anacardium occidentale (PIAO), mango Mangifera indica (PIMI) and kolanut Cola acuminata (PICA) trees were evaluated. Thirty high-fat diet-induced rats were grouped into six; four experimental, negative control and positive controls were orally administered lipid emulsion (5 mL/kg). Experimental received 400 mg/kg body weight from each of the four methanol extracts in addition to the lipid emulsion, positive control received 120 mg/kg bw Orlistat in addition to lipid emulsion while negative control received lipid emulsion alone. Blood samples were collected from ophthalmic venous plexus at 0, 90, and 180 minutes to determine plasma pancreatic lipase (PL) activity, alpha amylase activity and lipid profiles. PL inhibitory activity of the four methanol extracts showed that methanol extracts of PICA and PIAO had greater than 50% inhibition at 400 µg/mL. The α-amylase inhibitory activity of PICA was significantly higher (p &lt; 0.05) when compared with PIAO, PIPG and PIMI. A significant decrease (p &lt; 0.05) in total cholesterol, low density Lipoprotein-cholesterol levels and atherogenic index of plasma of PICA when compared with other treatment groups after 180 minutes of extracts administration was observed. Methanol extract of PICA was found to exhibit higher inhibitory pancreatic lipase and α-amylase activities and higher hypocholesterolemic activity when compared with those of guava (PIPG), cashew (PIAO) and mango (PIMI). This indicates that methanol extract of P. incana leaves could serve as a source of phyto-compounds that could be developed as antiobesity drugs.

Olive (Olea europaea L.) Seed as New Source of Cholesterol-Lowering Bioactive Peptides: Elucidation of Their Mechanism of Action in HepG2 Cells and Their Trans-Epithelial Transport in Differentiated Caco-2 Cells.

The production of olive oil has important economic repercussions in Mediterranean countries but also a considerable impact on the environment. This production generates enormous quantities of waste and by-products, which can be exploited as new raw materials to obtain innovative ingredients and therefore make the olive production more sustainable. In a previous study, we decided to foster olive seeds by generating two protein hydrolysates using food-grade enzymes, alcalase (AH) and papain (PH). These hydrolysates have shown, both in vitro and at the cellular level, antioxidant and antidiabetic activities, being able to inhibit the activity of the DPP-IV enzyme and modulate the secretion of GLP-1. Given the multifunctional behavior of peptides, both hydrolysates displayed dual hypocholesterolemic activity, inhibiting the activity of HMGCoAR and impairing the PPI of PCSK9/LDLR, with an IC50 equal to 0.61 mg/mL and 0.31 mg/mL for AH and PH, respectively. Furthermore, both samples restored LDLR protein levels on the membrane of human hepatic HepG2 cells, increasing the uptake of LDL from the extracellular environment. Since intestinal bioavailability is a key component of bioactive peptides, the second objective of this work is to evaluate the capacity of AH and PH peptides to be transported by differentiated human intestinal Caco-2 cells. The peptides transported by intestinal cells have been analyzed using mass spectrometry analysis, identifying a mixture of stable peptides that may represent new ingredients with multifunctional qualities for the development of nutraceuticals and functional foods to delay the onset of metabolic syndrome, promoting the principles of environmental sustainability.

Fermented Beverages Revisited: From Terroir to Customized Functional Products

Fermented beverages have been a constant companion of humans throughout their history. A wide range of products have been developed with time, depending on the availability of raw materials and ambient conditions. Their differentiation was based on the specific characteristics of each product, resulting from the cultivation of different varieties and the variability of environmental conditions and agricultural practices, collectively described by the term ‘terroir’ that was developed in winemaking. The health benefits that have been associated with their consumption, which include the control of blood pressure and glycemic control, along with immunomodulatory, hypocholesterolemic, hepatoprotective, and antiproliferative activities, directed their re-discovery that occurred over the last few decades. Thus, the dynamics of the microbial communities of fermented beverages during fermentation and storage have been thoroughly assessed. The functional potential of fermented beverages has been attributed to the chemical composition of the raw materials and the bioconversions that take place during fermentation and storage, due to the metabolic capacity of the driving microbiota. Thus, the proper combination of raw materials with certain microorganisms may allow for the modulation of the organoleptic properties, as well as enrichment with specific functional ingredients, enabling targeted nutritional interventions. This plasticity of fermented beverages is their great advantage that offers limitless capabilities. The present article aims to critically summarize and present the current knowledge on the microbiota and functional potential of fermented beverages and highlight the great potential of these products.

Hexagonal plate ultrasound pretreatment on the correlation between soy protein isolate structure and cholesterol-lowering activity of peptides, and protein's enzymolysis kinetics, thermodynamics

In this study, a hexagonal plate ultrasound (HPU) pretreatment technology was employed to modify soy protein isolate (SPI) and enhance the hypocholesterolemic activity of enzymatic digests from SPI. Results demonstrated that under the condition of ultrasound power density of 40 W/L, the hypocholesterolemic activity of enzymatic digests from HPU-pretreated SPI (HPU-SPI) increased by 88.40 % compared to control group after gastrointestinal digestion. The sulfhydryl content of HPU-SPI increased by a maximum of 45.32 % compared to control group. Fourier transform infrared and scanning electron microscopy revealed that HPU pretreatment partially unfolded the SPI conformation, reduced the intermolecular interactions, and exposed the internal hydrophobic regions. Pearson correlation analysis showed that sulfhydryl groups (r = 0.860), disulfide bonds (r = −0.875) and random coil (r = 0.917) were strongly correlated with the cholesterol-lowering activity of soy protein hydrolysate (SPH), following a simulated gastrointestinal digestion. Finally, the effects of HPU pretreatment on enzymolysis kinetics and thermodynamics of the SPI enzymatic process showed that HPU pretreatment significantly reduced the Mie's constant, activation energy, activation enthalpy, activation entropy and Gibbs free energy. Overall, the study outcome suggested that HPU pretreatment could positively influence the hypocholesterolemic peptide activity, and thus, may be beneficial to the pharmaceutical/food industry.

STUDY OF THE COMPOSITION OF BIOLOGICALLY ACTIVE FORMS OF SEA BUCKTHORN (HIPPOPHAE RHAMNOIDES L.) LEAVES BY GC-MS

Hippophae rhamnoides L. is a perennial shrub of the Elaegnaceae family, which has a significant distribution area (both in cultivation and in the wild) and an annually renewable raw material base (fruits and leaves). The leaves of sea buckthorn are characterized by a high accumulation of various groups of biologically active substances. However, the fraction of lipophilic biologically active substances of this type of medicinal plant material remains poorly understood in terms of composition and pharmacological properties. The aim of the work was to study the phytochemical composition of the lipophilic fractions of sea buckthorn leaves by GC/MS with a predictive in silico assessment of promising types of pharmacological activity of the identified compounds for the subsequent targeted development of medicinal herbal preparations based on this medicinal plant material with a certain spectrum of action. The object of the study was the leaves of three phenological phases of plant life collected in the territory of the Voronezh region and dried by the air-shadow method to a residual moisture content of not more than 10% in 2022. On the chromatograms in the leaves harvested in different phenophases of development, the presence of peaks of about 40 compounds is observed – 20 each in the preparations removed from the leaves of phases I and III; 16 – phases II of blanks, of which 14 compounds were identified – 7, 8, and 10 in phenophases I, II, and III, respectively.The greatest number of compounds of the group of sugars, sterols, aliphatic and alicyclic alcohols was typical for the leaves of the phenological phase III – the phase of technical maturity of the fruit, which is due to the accumulation of these biologically active substances in the process of life. However, leaves already in the first phase of harvesting can be considered as a potential source of vitamins and sterols due to their significant accumulation. The results of the in silico study position phytosterols (betulin and γ-sitosterol) as the target group of biologically active substances in the lipophilic fraction of the leaves of the third phase of the harvest due to the large accumulation and the presence of a high probability of hypolipidemic, hypocholesterolemic and hepatoprotective activities. At the same time, the maximum accumulation of this fraction in the leaves during the harvesting period of fruits, the main pharmacopoeial valuable raw material of this plant, contributes to the possibility of waste-free rational use of plant resources.

The use of statin drugs in medical practice. Literature review

Relevance. Simvastatin is a statin drug used for the clinical control of hypercholesterolemia. Over the past decades, there has been a steady increase in the number of studies on the possibilities of simvastatin, in many respects superior to the effect of lowering blood cholesterol levels. The use of simvastatin in the field of bone tissue regeneration, as well as its ability to reduce the inflammatory response, is being actively investigated.The purpose of the review: to consider modern ideas about simvastatin and to study its pleiotropic effects.Materials and methods. The analysis of scientific publications in the electronic databases eLIBRARY, PubMed and Google Scholar (articles, meta-analyses, systematic reviews) for the time interval from 2015 to 2022 was carried out. Materials containing information on the hypocholes-terolemic activity of simvastatin and its mechanism of action, the use of simvastatin in periodontal practice, as well as the osteoinductive effect of simvastatin and its use in bone engineering are included.Results. The review reviewed 83 articles, from which 53 articles were selected after reviewing the literature.Conclusion. Based on the analyzed data, it can be concluded that the effects of simvastatin are multifaceted. Its anti-inflammatory activity has been proven by inhibiting interleukins and inflammatory mediators, participation in bone tissue regeneration by gene expression and stimulation of osteoblast cell differentiation.

Schisandrin A in Schisandra chinensis Upregulates the LDL Receptor by Inhibiting PCSK9 Protein Stabilization in Steatotic Model.

Schisandra chinensis extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks. WD increased final body weight and blood LDL cholesterol levels as well as alanine transaminase and aspartate aminotransferase expression. However, SCE supplementation significantly attenuated the increase in blood markers caused by WD. SCE also attenuated WD-mediated increases in hepatic LDLR protein expression in the obese mice. In addition, SCE increased LDLR protein expression and attenuated cellular PCSK9 levels in HepG2 cells supplemented with delipidated serum (DLPS). Non-toxic concentrations of schisandrin A (SA), one of the active components of SCE, significantly increased LDLR expression and tended to decrease PCSK9 protein levels in DLPS-treated HepG2 cells. High levels of SA-mediated PCSK9 attenuation was not attributable to reduced PCSK9 gene expression, but was associated with free PCSK9 protein degradation in this cell model. Our findings show that PCSK9 secretion can be significantly reduced by SA treatment, contributing to reductions in free cholesterol levels.

Analysis of the safety and probiotic properties of Bifidobacterium longum B2-01 by complete genome sequencing combined with corresponding phenotypes

Bifidobacterium longum is an important probiotic in the human and animal intestine, wherein both infant and long subspecies are edible strains with numerous uses in food and medicine. Here, we aimed to explore some significant phenotypes and potential genes involved in the safety and probiotic functions of Bifidobacterium longum subsp. infantis B2-01 isolated as well identified from the feces of 3-month-old infants in Guangzhou. The complete genome sequence showed that B. infantis B2-01 contained a 2,615,705 bp circular chromosome with a 59.22% G + C content, lacking plasmids. It featured 2149 coding genes in total. The detection of harmful metabolites, hemolysis test, antibiotic resistance test, and acute oral toxicity test in mice, combined with the analysis of genes involved in antibiotic resistance, virulence factors, and harmful metabolite production, we tentatively proved B. infantis B2-01 to be a safe strain. In vitro tolerance tests and genes involved in adaptive responses confirmed that B. infantis B2-01 has excellent gastrointestinal fluid tolerance, hydrophobicity capability, auto aggregation capability, adhesion capacity, antioxidant activity, and hypocholesterolemic activity, indicating that B. infantis B2-01 may be able to be a probiotic with high application value.

The association of rs1799983 eNOS gene polymorphism with dyslipidemia and efficacy of atorvastatin in correction of lipid exchange disorders in patients with diabetic nephropathy and essential hypertension

Objective — to search an association of rs1799983 endothelial nitric oxide synthase (eNOS) gene polymorphism with dyslipidemia (DLP) and the efficacy of atorvastatin used in correction of lipid exchange disorders in patients with diabetic nephropathy (DN) and essential hypertension (EH).&#x0D; Materials and methods. The study had been conducted in the clinical Department of Arterial Hypertension and Kidney Disease at L. T. Mala National Therapy Institute of NAMS of Ukraine (Kharkiv). Clinical examinations involved 89 patients (pts) (43(48.3%) females and 46(51.7%) males) with DN of II—IV stages and EH of II—III stages aged 34 to 78 years old (an average age is 57.11±1.89 years old). They were also genotyped for rs1799983 eNOS gene polymorphism (G894T) with a use of polymerase chain reaction. GG genotype was revealed in 29(32.6%) of pts, GT genotype was found in 33(37.1%) of cases and 27(30.3%) participants of the study had TT genotype. With the use of immune enzyme method, serum levels of total cholesterol (TC), high‑density lipoprotein cholesterol (HDL‑C) and triglycerides (TG) were measured in all included pts. Very low density lipoprotein cholesterol (VLDL‑C), low‑density lipoprotein cholesterol (LDL‑C), non‑HDL‑C and coefficient of atherogenicity were calculated by known formulas. Atorvastatin was prescribed to all the pts included in study for correction of lipid exchange disorders in daily doses of 10—20 mg (an average daily dose was 16.7±0.91 mg) for 24 weeks.&#x0D; Results. Rs1799983 eNOS gene polymorphism in pts with DN and EH was found to be associated with lipid parameters characterized a phenotype of diabetic DLP with its peculiar disorders in the systems of reverse cholesterol transport and lipoprotein lipolysis of TG‑containing VLDL. In this case a dominant G allele was associated with less significant lipid disorders than a recessive T allele. A homozygous state with allele G (genotype GG) in pts with DN and EH was associated with abnormalities in the system of TG‑containing VLDL lipolysis and an appearance of T allele in genotype (genotypes GT and TT) made an additional negative contribution to the state of lipid exchange and transport. In pts with genotype GT abnormalities in reverse cholesterol transport added to disorders in the system of TG‑containing VLDL lipolysis and in pts with genotype TT there was a combination of disorders in the systems of direct, reverse cholesterol transport and lipoprotein lipolysis. The study of hypolipidemic effects of atorvastatin depended on genotype of rs1799983 eNOS gene polymorphism showed that in GG genotype atorvastatin demonstrated mainly a hypocholesterolemic action while in genotypes contained T allele (GT and TT) we observed a reduction of hypocholesterolemic effect against the background of significant hypotriglyceridemic action and elevation of HDL‑C.&#x0D; Conclusions. In pts with DN and EH rs1799983 eNOS gene polymorphism was associated with diabetic DLP. A recessive allele T was associated with significant lipid disorders compared with a dominant G allele. A significant hypocholesterolemic effect of atorvastatin was observed in case of a presence of G allele in pts genotype while a presence of T allele in pts genotype (GT and TT) was associated with a reduction of atorvastatin cholesterol lowering action.&#x0D;

Formulation and Evaluation of Antibacterial and Anti-Inflammatory Capsules Containing Phyllanthus emblica L. Fruit Nanoparticles

Phyllanthus emblica fruit has diuretic, antibacterial, hepatoprotective, antitumor, hypocholesterolemic, antioxidant, and antiulcerogenic activities making it possible as a traditional medicine in capsule form. Capsule preparations have the advantage of covering the unpleasant taste and smell of medicinal ingredients, easy to swallow, so they are practical to use. This study aimed to formulate Phyllanthus emblica fruit nanoparticles in capsules and to test the antibacterial activity against Streptococcus mutans and Pseudomonas aeruginosa and anti-inflammatory activity by observing denaturation inhibition in vitro. The method used to manufacture Phyllanthus emblica fruit simplicia nanoparticles was used using a High Energy Ball mill grinding machine. Capsule formulation was carried out with various doses of nanoparticles (100, 150, and 200 mg). Evaluation includes weight uniformity and disintegration time. Test of its antibacterial activity against Streptococcus mutans and Pseudomonas aeruginosa and its anti inflammatory activity in vitro. The study found that all formulas could be made into capsules that met the evaluation test requirements. The results of the evaluation of disintegration time ranged from 6.17-11.33 minutes. For the evaluation results of weight uniformity, it was found that weight deviations in columns A1 and A2 were in the range between 0.9% to 2.8% and 0.9 to 1.3%. The study reports on the antibacterial activity of Phyllanthus emblica fruit nanoparticle capsules (PFNP) against Streptococcus mutans and Pseudomonas aeruginosa. The results indicate that PFNP exhibits a dose-dependent antibacterial effect, with inhibition zone diameters of 10.83 mm, 11.6 mm, and 12.63 mm observed at 100 mg, 150 mg, and 200 mg, respectively, against Streptococcus mutans. Similarly, PFNP demonstrated a dose-dependent antibacterial effect against Pseudomonas aeruginosa, with inhibition zone diameters of 10.7 mm, 11.4 mm, and 12.1 mm observed at doses of 100 mg, 150 mg, and 200 mg, respectively. PFNP capsules showed inhibition results with a value of 5.63%, 6.13%, and 6.80%. It was concluded that Phyllanthus emblica fruit nanoparticles (Phyllanthus emblica L.) could be formulated in capsule dosage forms with doses of 100 mg, 150 mg, and 200 mg; has antibacterial activity against Streptococcus mutans and Pseudomonas aeruginosa, and has no anti-inflammatory activity.

KAJIANPUSTAKA: HIPERKOLESTEROLEMIADAN PENANGGULANGANNYA DENGAN MENGGUNAKANBERBAGAI SENYAWA BIOAKTIF

Hypercholesterolemia is characterized by levels of total cholesterol and low-density lipoprotein (LDL) above normal. Hypercholesterolemia is a major risk factor for cardiovascular disease. This study was aimed to explore and analyze various bioactive compounds to manage hypercholesterolemia. Efforts to overcome the condition of hypercholesterolemia are to reduce the consumption of a diet rich in cholesterol and calories, and consuming contemporary hypercholesterolemic drugs such as statins, as well as by regulating the body’s cholesterol metabolism with various antihypercholesterolemic bioactive compounds. Various findings of antihypercholesterolemic bioactive compounds have various sources and effects on cholesterol profiles. Bioactive compounds can be classified according to their mechanism of hypocholesterolemic action, which are inhibition of cholesterol absorption, inhibition of cholesterol biosynthesis, increased cholesterol excretion, increased cholesterol reverse transport, and increased cholesterol catabolism. Several bioactive compounds are involved in a dual mechanism. The development of these various bioactive compounds can be used as an alternative treatment for hypercholesterolemia since contemporary medicines have proven to have many side effects.

Multi-Faceted Bioactivity Assessment of an Exopolysaccharide from Limosilactobacillus fermentum NCDC400: Antioxidant, Antibacterial, and Immunomodulatory Proficiencies.

Exopolysaccharides (EPS) are acknowledged for their diverse functional and technological properties. This study presents the characterization of EPS400, an acidic exopolysaccharide sourced from the native probiotic Limosilactobacillus fermentum NCDC400. Notably, this strain has demonstrated previous capabilities in enhancing dairy food texture and displaying in vivo hypocholesterolemic activity. Our investigation aimed to unveil EPS400's potential biological roles, encompassing antioxidant, antibacterial, and immunomodulatory activities. The results underscore EPS400's prowess in scavenging radicals, including the 2,2-diphenyl-1-picrylhydrazyl radical, 2,2'-azino-di-(3-ethylbenzthiazoline sulfonic acid) radical, superoxide radical, hydroxyl radical, and chelating activity targeting the ferrous ion. Furthermore, EPS400 displayed substantial antibacterial effectiveness against prevalent food spoilage bacteria such as Pseudomonas aeruginosa NCDC105 and Micrococcus luteus. Remarkably, EPS400 exhibited the ability to modulate cytokine production, downregulating pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and nitric oxide, while concurrently promoting the release of anti-inflammatory cytokine IL-10 within lipopolysaccharide-activated murine primary macrophages. Additionally, EPS400 significantly (p ≤ 0.05) enhanced the phagocytic potential of macrophages. Collectively, our findings spotlight EPS400 as a promising contender endowed with significant antioxidant, antibacterial, and immunomodulatory attributes. These characteristics propose EPS400 as a potential pharmaceutical or bioactive component, with potential applications in the realm of functional food development.

Wild Mushrooms: A Hidden Treasure of Novel Bioactive Compounds.

Secondary metabolites are hidden gems in mushrooms. Understanding these secondary metabolites' biological and pharmacological effects can be aided by identifying them. The purpose of this work was to profile the mycochemical components of the extracts of Auricularia auricula judae, Microporus xanthopus, Termitomyces umkowaani, Trametes elegans, and Trametes versicolor to comprehend their biological and pharmacological capabilities. Mushroom samples were collected from Kenya's Arabuko-Sokoke and Kakamega National Reserved Forests and identified using morphological and molecular techniques. Chloroform, 70% ethanol, and hot water solvents were used to extract the mycochemical components. Gas chromatography mass spectrometry (GC-MS) was used to analyze the chloroform, 70% ethanol, and hot water extracts of all the species examined. A total of 51 compounds were isolated from all extracts and classified as carboxylic acids, esters, phenols, fatty acids, alcohol, epoxides, aldehydes, fatty aldehydes, isoprenoid lipids, and steroids. Tetracosamethyl-cyclododecasiloxane (18.90%), oleic acid (72.90%), phenol, 2, 6-bis (1, 1-dimethylethyl)-4-methyl-, and methylcarbamate (26.56%) were all found in high concentrations in A. auricular judae, M. xanthopus, T. umkowaani, T. elegans, and T. versicolor, respectively. Fatty acids make up the majority of the compounds isolated from the T. elegans chloroform extract and the T. umkowaani 70% ethanol extract, respectively. Particularly, these fatty acids play crucial roles in the anti-inflammatory, hypocholesterolemic, anticancer, and antibiofilm formation activities. These bioactive elements indicate that the extracts of five wild mushrooms may be reliable sources of secondary metabolites for therapeutic development. Therefore, additional research is required to comprehend the usefulness of these chemicals in many functional areas and to improve the present understanding of macrofungi.