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AAPS PharmSciTech Mar 2007The purpose of this research was to study whether the bioavailability of lovastatin could be improved by administering lovastatin solid lipid nanoparticles (SLN)...
The purpose of this research was to study whether the bioavailability of lovastatin could be improved by administering lovastatin solid lipid nanoparticles (SLN) duodenally to rats. Lovastatin SLN were developed using triglycerides by hot homogenization followed by ultrasonication. Particle size and zeta potential were measured by photon correlation spectroscopy. The solid state of the drug in the SLN and lipid modification were characterized. Bioavailability studies were conducted in male Wistar rats after intraduodenal administration of lovastatin suspension and SLN. Stable lovastatin SLN having a mean size range of 60 to 119 nm and a zeta potential range of -16 to -21 mV were developed. More than 99% of the lovastatin was entrapped in the SLN. Lovastatin was dispersed in an amorphous state, and triglycerides were in beta(1) form in the SLN. In vitro stability studies showed the slow release and stability of lovastatin SLN. The relative bioavailabilities of lovastatin and lovastatin hydroxy acid of SLN were increased by ~173% and 324%, respectively, compared with the reference lovastatin suspension.
Topics: Animals; Anticholesteremic Agents; Capsules; Delayed-Action Preparations; Diffusion; Drug Carriers; Drug Compounding; Drug Evaluation, Preclinical; Lipids; Liposomes; Lovastatin; Male; Materials Testing; Nanoparticles; Particle Size; Powders; Rats; Rats, Wistar
PubMed: 17408223
DOI: 10.1208/pt0801024 -
Postgraduate Medical Journal Nov 1996
Topics: Anticholesteremic Agents; Dermatomyositis; Female; Humans; Lovastatin; Middle Aged
PubMed: 8944218
DOI: 10.1136/pgmj.72.853.694 -
Molecules (Basel, Switzerland) May 2023Using the internal transcribed spacer (ITS) region for identification, three strains of were identified and designated AUMC 15760, AUMC 15762, and AUMC 15763 for the...
Exploitation of Sugarcane Bagasse and Environmentally Sustainable Production, Purification, Characterization, and Application of Lovastatin by AUMC 15760 under Solid-State Conditions.
Using the internal transcribed spacer (ITS) region for identification, three strains of were identified and designated AUMC 15760, AUMC 15762, and AUMC 15763 for the Assiut University Mycological Centre culture collection. The ability of the three strains to manufacture lovastatin in solid-state fermentation (SSF) using wheat bran was assessed using gas chromatography-mass spectroscopy (GC-MS). The most potent strain was strain AUMC 15760, which was chosen to ferment nine types of lignocellulosic waste (barley bran, bean hay, date palm leaves, flax seeds, orange peels, rice straw, soy bean, sugarcane bagasse, and wheat bran), with sugarcane bagasse turning out to be the best substrate. After 10 days at pH 6.0 at 25 °C using sodium nitrate as the nitrogen source and a moisture content of 70%, the lovastatin output reached its maximum quantity (18.2 mg/g substrate). The medication was produced in lactone form as a white powder in its purest form using column chromatography. In-depth spectroscopy examination, including H, C-NMR, HR-ESI-MS, optical density, and LC-MS/MS analysis, as well as a comparison of the physical and spectroscopic data with published data, were used to identify the medication. At an IC of 69.536 ± 5.73 µM, the purified lovastatin displayed DPPH activity. and had MICs of 1.25 mg/mL, whereas and had MICs of 2.5 mg/mL and 5.0 mg/mL, respectively, against pure lovastatin. As a component of sustainable development, this study offers a green (environmentally friendly) method for using sugarcane bagasse waste to produce valuable chemicals and value-added commodities.
Topics: Humans; Lovastatin; Cellulose; Chromatography, Liquid; Saccharum; Tandem Mass Spectrometry; Fermentation; Dietary Fiber
PubMed: 37241788
DOI: 10.3390/molecules28104048 -
Molecules (Basel, Switzerland) May 2019Red yeast rice (RYR) is made by fermenting the rice with . It is commonly used in food colorants, dyeing, and wine making in China and its neighboring countries.... (Review)
Review
Red yeast rice (RYR) is made by fermenting the rice with . It is commonly used in food colorants, dyeing, and wine making in China and its neighboring countries. Nowadays RYR has two forms on the market: common RYR is used for food products, the other form is functional RYR for medicine. However, some researchers reported that commercial lovastatin (structure is consistent with monacolin K) is illegally added to common RYR to meet drug quality standards, so as to imitate functional RYR and sell the imitation at a higher price. Based on current detection methods, it is impossible to accurately distinguish whether functional RYR is adulterated. Therefore, it is especially important to find a way to authenticate functional RYR. In the current review, the advances in history, applications, components (especially monacolins, monacolins detection methods), quality standards, authentication methods and perspectives for the future study of RYR are systematically reviewed.
Topics: Biological Products; Biosynthetic Pathways; Lovastatin; Quality Control
PubMed: 31137594
DOI: 10.3390/molecules24101944 -
Brazilian Journal of Medical and... Feb 2011Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering...
Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37% inhibition, respectively). Inhibitions of 20, 45 and 80% were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70%, respectively) and second phase (73, 57, and 66% inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86%, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.
Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Lovastatin; Male; Mice; Pain; Pain Measurement; Rats; Rats, Wistar
PubMed: 21243316
DOI: 10.1590/s0100-879x2011007500001 -
International Journal of Nanomedicine 2016Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate...
Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy.
Topics: Alkaline Phosphatase; Animals; Anti-Bacterial Agents; Bacteria; Bone Regeneration; Chitosan; Delayed-Action Preparations; Dogs; Drug Carriers; Lactic Acid; Lovastatin; Male; Microscopy, Electron, Transmission; Nanoparticles; Osteoblasts; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Tetracycline
PubMed: 26848264
DOI: 10.2147/IJN.S94270 -
Microbial Cell Factories Feb 2022Lovastatin is one of the first statins to be extensively used for its cholesterol-lowering ability. It is commercially produced by fermentation. Species belonging to the...
BACKGROUND
Lovastatin is one of the first statins to be extensively used for its cholesterol-lowering ability. It is commercially produced by fermentation. Species belonging to the genus Aspergillus are well-studied fungi that have been widely used for lovastatin production. In the present study, we produced lovastatin from sago processing wastewater (SWW) under submerged fermentation using oleaginous fungal strains, A. terreus KPR12 and A. caespitosus ASEF14.
RESULTS
The intra- and extracellular concentrations of lovastatin produced by A. terreus KPR12 and A. caespitosus ASEF14 were lactonized. Because A. caespitosus ASEF14 produced a negligible amount of lovastatin, further kinetics of lovastatin production in SWW was studied using the KPR12 strain for 9 days. Lovastatin concentrations in the intra- and extracellular fractions of the A. terreus KPR12 cultured in a synthetic medium (SM) were 117.93 and 883.28 mg L, respectively. However, these concentrations in SWW were 142.23 and 429.98 mg L, respectively. The yeast growth inhibition bioassay confirmed the antifungal property of fungal extracts. A. terreus KPR12 showed a higher inhibition zone of 14 mm than the ASEF14 strain. The two-way analysis of variance (ANOVA; p < 0.01) showed significant differences in the localization pattern, fungal strains, growth medium, and their respective interactions. The lovastatin yield coefficient values were 0.153 g g on biomass (Y) and 0.043 g g on the substrate, starch (Y). The pollutant level of treated SWW exhibited a reduction in total solids (TS, 59%), total dissolved solids (TDS, 68%), biological oxygen demand (BOD, 79.5%), chemical oxygen demand (COD, 57.1%), phosphate (88%), cyanide (65.4%), and void of nutrients such as nitrate (100%), and ammonia (100%).
CONCLUSION
The starch-rich wastewater serves as a suitable medium for A. terreus KPR12 for the production of lovastatin. It simultaneously decontaminates the sago processing wastewater, enabling its reuse for irrigation/recreation.
Topics: Aspergillus; Biomass; Culture Media; Fermentation; Kinetics; Lovastatin; Manihot; Spectroscopy, Fourier Transform Infrared; Starch; Wastewater
PubMed: 35164756
DOI: 10.1186/s12934-022-01751-2 -
Circulation. Cardiovascular Genetics Dec 2017
Topics: Hydroxymethylglutaryl-CoA Reductase Inhibitors; Metabolome; Pravastatin; Simvastatin
PubMed: 29237684
DOI: 10.1161/CIRCGENETICS.117.002014 -
PloS One 2017Glioblastoma is a common malignant brain tumor and it is refractory to therapy because it usually contains a mixture of cell types. The tumor necrosis factor-related...
Inhibition of NF-κB Pathway and Modulation of MAPK Signaling Pathways in Glioblastoma and Implications for Lovastatin and Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) Combination Therapy.
Glioblastoma is a common malignant brain tumor and it is refractory to therapy because it usually contains a mixture of cell types. The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has been shown to induce apoptosis in a range of tumor cell types. Previously, we found that two human glioblastoma cell lines are resistant to TRAIL, while lovastatin sensitizes these glioblastoma cells to TRAIL-induced cell death. In this study, we investigated the mechanisms underlying the TRAIL-induced apoptosis in human glioblastoma cell lines by lovastatin. Furthermore, we have confirmed the anti-tumor effect of combination therapy with lovastatin and TRAIL in the subcutaneous brain tumor model. We showed that lovastatin significantly up-regulated the expression of death receptor 5 (DR5) in glioblastoma cell lines as well as in tumor-bearing mice with peri-tumoral administration of lovastatin. Further study in glioblastoma cell lines suggested that lovastatin treatment could inhibit NF-κB and Erk/MAPK pathways but activates JNK pathway. These results suggest that lovastatin sensitizes TRAIL-induced apoptosis by up-regulation of DR5 level via NF-κB inactivation, but also directly induces apoptosis by dysregulation of MAPK pathway. Our in vivo study showed that local peri-tumoral co-injection of lovastatin and TRAIL substantially reduced tumor growth compared with single injection of lovastatin or TRAIL in subcutaneous nude mice model. This study suggests that combined treatment of lovastatin and TRAIL is a promising therapeutic strategy to TRAIL-resistant glioblastoma.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Glioblastoma; HEK293 Cells; Humans; Lovastatin; MAP Kinase Signaling System; Mice, Inbred BALB C; Mice, Nude; Models, Biological; NF-kappa B; Receptors, TNF-Related Apoptosis-Inducing Ligand; Subcutaneous Tissue; TNF-Related Apoptosis-Inducing Ligand; Up-Regulation
PubMed: 28135339
DOI: 10.1371/journal.pone.0171157 -
Se Pu = Chinese Journal of... Dec 2021In capillary electrophoresis, determination of the basic physical and chemical properties of compounds, such as absolute mobility () and dissociation constant (p), is of...
In capillary electrophoresis, determination of the basic physical and chemical properties of compounds, such as absolute mobility () and dissociation constant (p), is of great practical significance. This is because the aforementioned properties are often used for the qualitative or quantitative analyses of the relevant compounds toward their application as potential drugs. Lovastatin is a potential drug candidate that can reduce the levels of cholesterol and low-density lipoprotein cholesterol in the blood, as well as prevent atherosclerosis and coronary heart disease. For a more convenient and rapid investigation of the properties and applications of lovastatin, it is necessary to determine its and p values. However, existing research on capillary electrophoresis for lovastatin and other related drugs focus on their quantitative determination, and their action mechanism and functions. Unfortunately, there are very few studies aimed at the determination of the and p values of lovastatin. Based on related studies, this paper herein proposed a novel method to determine and p of lovastatin. The present study mainly included a calculation method and experimental verification. The calculation method was based on capillary zone electrophoresis (CZE) and the empirical formula of ion mobility. First, on the basis of the empirical formula, the calculation formula for was derived from the relationship between the actual mobility (), effective mobility () and . Second, for a monovalent acid (HA), according to the calculation formula for part, considering the hydrogen ion concentration as the independent variable and the reciprocal of as the dependent variable, a straight line was obtained on the coordinate axis. From the slope of this straight line, the dissociation equilibrium constant was obtained directly, and p was calculated easily. After the derivation of and p in the theoretical part, the feasibility and reliability of this method were verified by using it to determine the and p values of several organic acids and bases (barbituric acid, benzoic acid, benzylamine, phenol, and -cresol) in the experimental part. Note that for the buffer system with pH<6.0, reverse capillary electrophoresis was used for the determination of p, because this technique helped shorten the migration time and facilitates the detection of analytes that could not reach the cathode. After obtaining and p, the theoretical reference values for these parameters were obtained by PeakMaster 5.1. The experimental data were well consistent with the theoretical and p values. The standard deviation (SDs) of and p were less than 6.0% and 6.2%, respectively. From the correlation coefficient () of the linear regression equation, it was found that the linear regression lines of p fit well, indicating the excellent reliability of this method. Finally, with this simple and reliable method, dimethyl sulfoxide (DMSO) was used as a marker for electroosmotic flow to determine the and p values of lovastatin (-1.70×10 m/(V·s) and 9.00, respectively). This method is suitable for the determination of and p of acidic and basic analytes. The method has high accuracy and is expected to play an indispensable role in drug analysis.
Topics: Acids; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Lovastatin; Reproducibility of Results
PubMed: 34812009
DOI: 10.3724/SP.J.1123.2021.01014