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Molecular hybridization method was applied to design and synthesize a series of target compounds paeonol-based fibrate derivatives. The target compound was screened using a Triton WR-1339 induced hyperlipidemia mouse model, and compound T9 was found to have good lipid-lowering activity. The dose-dependent study of its lipid-lowering activity was also conducted. To further evaluate the lipid-lowering activity of compound T9, a hyperlipidemic mouse model induced by high fat emulsion can be used. The findings of the research illustrate that T9 is capable of significantly decreasing blood lipid levels, including TG, TC, LDL-C, and increasing HDL-C. The results of liver tissue oil red O staining and HE staining demonstrated that T9 improved the hepatic lipid accumulation, thus decreasing AST and ALT levels and protecting against hyperlipidemic liver injury. Studies into the lipid-lowering effect of T9 have indicated that it can upregulate PPAR-α protein expression in liver tissue, while simultaneously decreasing the expression of HMG-CoA protein. T9 was further demonstrated to possess antioxidant properties, as evidenced by an increase in SOD and a decrease in MDA, as well as anti-inflammatory effects, demonstrated by a decrease in TNF-α, IL-1β, and IL-6, thus confirming its potential as a hypolipidemia and hepatoprotective agent. [ABSTRACT FROM AUTHOR]

Obesity is a condition where excessive fat is accumulated, which poses a health risk. Several treatments for obesity have been carried out, ranging from lifestyle adjustments to medication to surgery. Corrosolic Acid (CA) is a natural compound that has the potential to act as an obesity agent through many mechanisms, including through reactive oxygen species (ROS). This study aims to prove that CA can reduce MDA levels and HMG-CoA reductase levels and increase leptin levels and GLP-1 levels in male Wistar rats with obesity. Wistar obese rats were orally treated with CA compound induction at a dose of 10 mg/Kg BW. MDA, HMG-CoA reductase, leptin and GLP-1 levels were examined using serum and plasma from mice in both groups of mice before and after treatment, using the ELISA method. CA to the treatment group can reduce the body weight of rat MDA levels significantly at p<0.0001, HMG-CoA reductase levels significantly at p<0.0001 and increase leptin and GLP-1 levels significantly at p<0.0001. CA's mechanism for treating obesity is through the ROS mechanism because CA has antioxidant levels that can capture free radicals in the body.CA has been proven to be an alternative drug in treating obesity by reducing body weight, MDA, and HMGCoA levels and increasing leptin and GLP-1 levels in obese Wistar rats. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). Recent Findings: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = − 0.06, 95% CI = − 0.19; 0.06 and SMD = 0.26, 95% CI = − 0.66; 1.19), but significantly different (p-value = 0.04). Meta-regression and subgroup analyses did not show any significant differences in pooled estimates across covariates. Summary: The effect of statins on CAC differs across study designs. OSs demonstrate associations between statin use and higher CAC scores and presence while being prone to confounding by indication. Effects from RCTs do not reach statistical significance and vary depending on the quantification method, hampering drawing conclusions. Further investigations are required to address the limitations inherent in each approach. [ABSTRACT FROM AUTHOR]

Introduction- Chronic Kidney Failure (CKF) causes various problems over a period of time which includes cardiovascular diseases. Cardiovascular complications are major cause of deaths inpatients of CKF than various other cause. In this complication’s dyslipidemia is commonly observed features of CKF. Since various study shows that there is relation between CRF and cardiovascular disease and dyslipidemia is constant feature we decided to study to understand the risk involved in cardiovascular morbidity in patients of CRF by studying lipid profile Aim and Objective-To assess cardiovascular risk in cases of chronic renal failure by studying Lipid profile Material and Methodology: This study was done in Medical College, Hospital and research Centre Study population: Total 100 subjects participated in this study 50 Chronic kidney failure (CRF) cases and 50 Controls. Collection of blood samples: 8-10 ml of blood samples after fasting was collected before and after hemodialysis in a plain bulb taking all aseptic precautions. Serum was used after centrifugation. Parameters Lipid profile which includes 1. Serum Total Cholesterol-Dynamic extended stability CHOD-PAP Method (With LCF-Lipid Clearing Factor), End Point by Roeshlaus 2. Serum HDL-Cholesterol-Liquid stable reagent by Trinder reaction. 3.Serum LDL- Cholesterol-Liquid stable reagent by Trinder reaction. 4.Serum Triglyceride-Dynamic extended stability (With LCF)GPO-Trinder Method End Point Observations and Results In our study Low Density Lipoprotein-Cholesterol, Total Cholesterol and Triglyceride levels increased in cases of chronic kidney failure patients in comparison with control whereas HDL-Cholesterol decreased in cases of chronic kidney failure patients in comparison with control. Conclusion: In our study there is altered lipid profile found in our study in CRF there is increased cardio-vascular risk patients. Alteration in concentration of lipoproteins which causes acceleration of process of atherosclerosis in cases of CRF patients. These complications can be prevented by lipid lowering diet and drugs such as the HMG-CoA reductase inhibitors (statins). So, to prevent these cardiovascular complication proper diet advice and drug treatment should be given to the CRF patients. [ABSTRACT FROM AUTHOR]

Among the many types of central nervous system (CNS) disorders, seizures and epilepsy severely affect the quality of life and routine daily activity of the sufferers. We aimed to review research studies that investigated the effect of statins on the prevention and treatment of seizures and epilepsy. Both animal models and human studies were included in this review. This article starts with a brief introduction about seizure, its prevalence, treatment, and various animal models of seizures and epilepsy. Next, we discuss statin’s mechanism of action, side effects, and effects on neurological disorders with a specific focus on seizures. Finally, the effects of different types of statins on seizures are compared. The present review gives a better understanding of the therapeutic effects of statins on neurological disorders in animal models and human studies. This permits researchers to set up study designs to resolve current ambiguities and contradictions on the beneficial effects of statins on neurological disorders.

The aim of this study was the modification of lovastatin by microbes to improve its potential. Actinobacteria exhibit staggering diversity in terms of their biosynthetic capability for specialized metabolites which has been traced back to the presence of specialized gene clusters. The objective of the study is to exploit the potential of Actinobacteria strain(s), which can biotransform lovastatin to simvastatin, which might be a more potent therapeutic agent than lovastatin. We have screened 40 Actinobacteria strains and assessed their biotransformation potential primarily through thin layer chromatography (TLC) analysis, followed by high performance thin layer chromatography and high performance liquid chromatography analysis. One strain C7 (CTL S12) has been identified as a potential Actinobacteria that favored the simvastatin biotransformation. The morphological and biochemical analysis together with 16S rRNA sequencing coupled with phylogenetic analysis confirmed the ideal strain (C7) as Streptomyces carpaticus. Successively, the purified simvastatin from S. carpaticus was characterized by liquid chromatography–mass spectrometry (LC–MS), infrared spectrometry, nuclear magnetic resonance, and HMG‐CoA assay. In the LC–MS analysis, a peak at 419.24 m/z confirmed the elemental composition of simvastatin (C25H39O5). In HMG‐CoA assay, the IC50 of simvastatin was 50 μg/ml, and the inhibitory potential was 1.36 times higher compared to that of lovastatin. Thus, the biotransformation of simvastatin from lovastatin by S. carpaticus is reported for the first time. [ABSTRACT FROM AUTHOR]

Among the many types of central nervous system (CNS) disorders, seizures and epilepsy severely affect the quality of life and routine daily activity of the sufferers. We aimed to review research studies that investigated the effect of statins on the prevention and treatment of seizures and epilepsy. Both animal models and human studies were included in this review. This article starts with a brief introduction about seizure, its prevalence, treatment, and various animal models of seizures and epilepsy. Next, we discuss statin's mechanism of action, side effects, and effects on neurological disorders with a specific focus on seizures. Finally, the effects of different types of statins on seizures are compared. The present review gives a better understanding of the therapeutic effects of statins on neurological disorders in animal models and human studies. This permits researchers to set up study designs to resolve current ambiguities and contradictions on the beneficial effects of statins on neurological disorders. [ABSTRACT FROM AUTHOR]

Aim: To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. Materials & methods: A systematic review and metaanalysis was conducted to summarize the effect sizes in randomized controlled trials and cohort studies that compared high-intensity statins. Results: Based on 44 articles, similar effectiveness was observed across the statins in reducing LDL levels from baseline. All statins were observed to have similar adverse drug reactions (ADRs), although higher dosages were associated with more ADRs. Based on a pooled quantitative analysis of atorvastatin 80 mg versus rosuvastatin 40 mg, rosuvastatin was statistically more effective in reducing LDL. Conclusion: This review further confirms that high-intensity statins reduce LDL by ≥50%, favoring rosuvastatin over atorvastatin. Additional data are needed to confirm the clinical significance on cardiovascular outcomes using real-world studies.

In recent years, many studies have demonstrated that the system of orexin plays a pivotal role in regulating lipogenesis enzymes. However, its effect on the mammary glands is not entirely known. This study answers the question of whether intra-ductal injection of orexin antagonists (OX1RA and OX2RA) into the mammary glands can result in the expression of fatty acid synthase (Fas) and HMG-CoA reductase (Hmgcr) genes and the secretion of cholesterol in lactating female rats or not. To this end, 42 Lactating rats were randomly divided into experimental groups including a control group and groups receiving OX1RA and OX2RA intraductal (with doses of 5, 10, and 20 µg/kg, i.duc). Milk samples were collected for cholesterol testing. Using specific primers for each gene, the target genes were measured via real-time PCR. Data differences were considered significant with P <0.05. PCR exhibited that the injection of orexin antagonists significantly reduced Fas and Hmgcr gene expression. Moreover, the injection of antagonists significantly reduced milk cholesterol. Intra-mammary injection of orexin antagonists reduces milk cholesterol levels by affecting the expression of Fas and Hmgcr genes. [ABSTRACT FROM AUTHOR]

BackgroundBlepharitis is a common eye disorder that may be overlooked by patients and clinical practitioners. The symptoms of blepharitis often manifest as irritation, a burning sensation, grittiness, and itchiness and may decrease visual acuity if not treated promptly. Meibomian gland dysfunction (MGD), a common cause of blepharitis, is believed to be associated with increased inflammatory marker levels that may disrupt the composition of lipids produced by the sebaceous glands in the eyelids and ultimately cause tear film instability.MethodsThis is a retrospective, population-based study using National Health Insurance Research Database (NHIRD) data from a 14-year period (2000–2015). Pearson chi-squared and Student's t-tests were used to assess the differences in categorical and continuous variables, respectively, between statin users and non-statin users. Univariate and multivariate Cox regression analyses were performed to calculate the hazard ratios (HRs) after adjusting for confounders. Kaplan-Meier analysis was used to assess the cumulative risk of blepharitis between the two cohorts.ResultsA total of 67,014 patients who used statins were enrolled as the study cohort, and 268,056 patients who did not use statins were enrolled as the comparison cohort. The incidence of blepharitis was 3.04% with statin treatment and 3.72% without statin treatment (p < 0.001). Patients who used statins had a lower risk of developing blepharitis [adjusted hazard ratio (aHR): 0.746, p < 0.001] than those who did not. In addition, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), stroke, chalazion, rosacea, Sjogren syndrome, psoriasis and atopy were found to be possible risk factors for blepharitis.ConclusionStatin use can decrease the risk of developing blepharitis. However, further prospective studies are needed to evaluate statin treatment for various subtypes of blepharitis and to identify the associated mechanism.

Background: Elevated brain cholesterol increases the risk of Alzheimer's disease. Production of 24-hydroxycholesterol (24s-OHC) by neurons prevents cholesterol accumulation in the brain. In this study, we investigated the effect of 24s-OHC on the HMG-COA reductase and ABCA1 which are involved in the brain cholesterol homeostasis with or without β-amyloid in astrocytes. Methods and Materials: Astrocytes were treated with 24s-OHC with or without Aβ. Western blot and real-time polymerase chain reaction were done to detect protein and gene expression of β-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and ABCA1, respectively. Cholesterol release was determined using a quantitation kit. Results: Protein levels of HMGCR and ABCA1 were significantly increased by Aβ; however, the 24s-OHC was able to restore their levels and diminish the effect of amyloid-β. Aβ did not have a significant effect on HMGCR expression, while 24s-OHC reduced it by 68%. Aβ-induced ABCA1 expression did not increase cholesterol efflux as the lower levels of cholesterol in conditioned medium of Aβ-treated cells were found. Conclusion: Our novel findings show that Aβ affects two key elements in the brain cholesterol homeostasis, HMGCR and ABCA1, which are crucial in cholesterol synthesis and efflux. Since 24s-OHC could suppress the Aβ effects on enhancement of HMGCR and ABCA1, therefore the cytochrome P450 46A1 (Cyp46A1), which is exclusively expressed in the central nervous system and responsible for producing of 24s-OHC, could consider as a therapeutic target in the cholesterol-related neurodegenerative diseases such as Alzheimer's disease.

Functional staple food is the trend of industrialization of staple food in our country. It is an important way to make staple food with some specific functions.The physicochemical properties and HMG-CoA inhibition of extruded rice with red yeast rice flour (RYRF) addition were investigated. Results showed that RYRF addition was beneficial to produce hypolipidemic functional staple foods from extruded rice, involving in color, short-range order, HMG-CoA inhibition, porosity, crystallinity, and mass loss. These were mainly attributed to the biochemical reaction of RYRF which could inhibit the recrystallization of amylopectin and HMG-CoA reductase activity. Among the five concentrations of RYRF additives (0.5%, 1.0%, 2.0%, 3.0%, 4.0% w/w), the extruded rice with 3% RYRF addition achieved the best data in terms of porosity, crystallinity, mass loss and HMG-CoA inhibition rate. [Display omitted] • The red yeast rice flour (RYRF) improved the quality and function of extruded rice. • The RYRF inhibited recrystallization of amylopectin and HMG-Co A reductase activity. • The study provides a new idea for the application of red yeast in functional food. [ABSTRACT FROM AUTHOR]

• The designed model of lipid rafts serves as a platform hosting a transmembrane protein. • Activity of immobilized HMG-CoA reductase was confirmed by the electroreduction of NADP generated in the process. • Inhibition of HMG-CoA reductase by statin is demonstrated on the example of fluvastatin. Electrochemical methods are used to characterize transport phenomena in the presence of membrane proteins to monitor changes in their catalytic properties or activity in the presence of activators or inhibitors. Because membrane proteins are fully active in their natural environment, the lipid membrane, electrochemical investigations of enzymes should be carried out when they are present in an appropriate lipid bilayer deposited on an electrode surface. Here, HMG-CoA reductase (HMGR), the membrane protein responsible for cholesterol synthesis, and its related coenzyme (HMG-CoA) were incorporated into a lipid bilayer obtained by spreading proteoliposomes on the surface of a gold electrode modified with a thioglucose. Nicotinamide adenine dinucleotide phosphate, NADPH was oxidized to NADP+ during the enzymatic reaction when HMG-CoA was reduced to the product, mevalonate, which is further transformed into cholesterol. The reconstitution of HMG-CoA reductase and its mechanism were investigated by following the NADP+ reduction on the electrode using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The activity of HMGR was studied over time and in the presence of fluvastatin, an exemplary HMGR reductase inhibitor commonly used to treat hypercholesterolemia. The inhibitory effect of the statin was electrochemically evaluated by monitoring the decrease of NADP+ reduction current and changes in the impedance parameters of the HMGR-proteoliposome-derived bilayer. [Display omitted] [ABSTRACT FROM AUTHOR]

Statins are HMG-CoA reductase inhibitors and decrease plasma low-density lipoprotein cholesterol (LDL-C) levels. They are well tolerated, and because of their LDL-C-lowering effect, they are utilized to decrease the risk of atherosclerosis and cardiovascular disease. However, statins have pleiotropic effects, including immunomodulatory, anti-inflammatory, antioxidant, and anticancer. Currently, oral administration is the only Food and Drug Administration (FDA)-approved route of administration for statins. However, other administration routes have demonstrated promising results in different pre-clinical and clinical studies. For instance, statins also seem beneficial in dermatitis, psoriasis, vitiligo, hirsutism, uremic pruritus, and graft-versus-host disease. Topically applied statins have been studied to treat seborrhea, acne, rhinophyma, and rosacea. They also have beneficial effects in contact dermatitis and wound healing in animal studies, (HIV) infection, osseointegration, porokeratosis, and some ophthalmologic diseases. Topical and transdermal application of statins is a non-invasive drug administration method that has shown significant results in bypassing the first-pass metabolism in the liver, thereby reducing possible adverse effects. This study reviews the multifaceted molecular and cellular impacts of statins, their topical and transdermal application, novel delivery systems, such as nanosystems for topical and transdermal administration and the challenges concerning this approach., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Atorvastatin, a lipid-lowering drug that is widely used in the treatment of cardiovascular diseases, has significant clinical significance. This article focuses on the synthetic procedures of atorvastatin, including Paal-Knorr synthesis and several new synthetic strategies. It also outlines chemical and chemo-enzymatic methods for synthesizing optically active side chain of atorvastatin. In addition, a comprehensive overview of the analytical monitoring techniques for atorvastatin and its metabolites and impurities is reported, alongside a discussion of their strengths and limitations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to increase ketone bodies in patients with type 2 diabetes; however, the underlying mechanisms have not been fully elucidated. Here we examined the effect of the SGLT2 inhibitor dapagliflozin (1 mg/kg/day, formulated in a water, PEG400, ethanol, propylene glycol solution, 4 weeks) on lipid metabolism in obese Zucker rats. Fasting FFA metabolism was assessed in the anesthetized state using a [9,10- 3 H(N)]-palmitic acid tracer by estimating rates of plasma FFA appearance (R a ), whole-body FFA oxidation (R ox ), and nonoxidative disposal (R st ). In the liver, clearance (K β-ox ) and flux (R β-ox ) of FFA into β-oxidation were estimated using [9,10- 3 H]-(R)-bromopalmitate/[U- 14 C]palmitate tracers. As expected, dapagliflozin induced glycosuria and a robust antidiabetic effect; treatment reduced fasting plasma glucose and insulin, lowered glycated hemoglobin, and increased pancreatic insulin content compared with vehicle controls. Dapagliflozin also increased plasma FFA, R a , R ox , and R st with enhanced channeling toward oxidation versus storage. In the liver, there was also enhanced channeling of FFA to β-oxidation, with increased K β-ox , R β-ox and tissue acetyl-CoA, compared with controls. Finally, dapagliflozin increased hepatic HMG-CoA and plasma β-hydroxybutyrate, consistent with a specific enhancement of ketogenesis. Since ketogenesis has not been directly measured, we cannot exclude an additional contribution of impaired ketone body clearance to the ketosis. In conclusion, this study provides evidence that the dapagliflozin-induced increase in plasma ketone bodies is driven by the combined action of FFA mobilization from adipose tissue and diversion of hepatic FFA toward β-oxidation., Competing Interests: Conflict of interest All authors are or were employed by AstraZeneca and have shares in the company., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)