Lovastatin Concentration in Pleurotus ostreatus as Affected by Acid and Blanching Treatments Combined to Drying and Canning Processes

Aims: Lovastatin is a cholesterol-lowering drug produced by several filamentous fungi as a secondary metabolite. Its concentration in mushroom can be affected by many post-harvest processes. In this study, fruiting bodies of Pleurotus ostreatus grown on corn cobs were used to evaluate the effect of conservation techniques on their lovastatin concentration. Methodology: acid and blanching treatments combined to different processes of fruiting bodies conservation like sun drying, oven drying and canning by autoclave cooking were tested to evaluate their effect on lovastatin concentration. Results: Sun drying, oven drying at 60°C/70°C and canning using autoclave cooking at 100°C did not significantly affect lovastatin concentration. On the contrary, oven drying at 80°C caused the reduction of this compound up to 45.4% with respect to fresh product irrespective of the precedent use of citric acid or blanching treatments. Also, during canning, the use of autoclave heat treatments at temperatures 110 and 121°C for 15 minute caused a significant reduction of lovastatin concentration of about 52.2% and 48.9% respectively compared to the control. In this regards, it can be concluded that processes that use dry thermal treatments higher than 80°C and autoclave heat treatments higher than 100°C will contribute to the reduction of lovastatin, the cholesterol-lowering compound in Pleurotus ostreatus.

Design and Evaluation of Lovastatin Solid Dispersions Incorporated Trilayer Matrix Tablets

The current work is aimed to design, prepare and evaluate the trilayer matrix tablets incorporated with lovastatin solid dispersion (SD) for extend drug release. The lovastatin SD prepared by using solvent evaporation technique with varying amounts of polymers (GMS II, Soluplus, Kolliphor ELP, PEG 2000 and Urea) for enhancing the drug solubility. All the formulations examined for physicochemical parameters are within the permissible limits. The optimized SD formulation was incorporated into trilayer matrix tablets which were prepared using different polymers (HPMC 15M & K100M, Chitosan, xanthan gum) by direct compression method for sustaining the drug release. The drug dissolution of optimized lovastatin SD formulation SD15 (drug, soluplus and SLN) was 99.88±5.32% within 60 min which is higher than pure drug 47.33±2.25% and other formulations. The FT-IR, XRD and SEM data assure the compatibility of drug and excipients and amorphous nature of lovastatin. The solid dispersions were further incorporated in to trilayer matrix tablets with active layer and barrier layers. Eight formulations of lovastatin trilayer matrix tablets (AF9-HF9) designed and checked for pre compression parameters. Formulation GF9 demonstrated highest drug release of 99.41±5.28% for 24 hours sustainably over an extended period of time and excellent flow properties. The release order kinetics data indicate the zero order release with highest R2 of 0.9957 for GF9, superior than market extended release formulation (R2=0.9934). All the formulations showed best fit to Higuchi model and Korsmeyer-Peppa’s model indicating diffusion and non-Fickian diffusion process of drug release. GF90 was found to be stable for 180 days at accelerated conditions. Hence the solubility, dissolution rate of lovastatin was enhanced by SD technique further incorporated in to trilayer matrix tablets for sustainable extended drug release upto 24 h.

Lovastatin combined with insulin effects on fracture healing in rat models of bilateral ovariectomized type 2 diabetic mellitus / 中国组织工程研究

BACKGROUND: Osteoporotic fracture combined with type 2 diabetic mellitus in female patients is often accompanied by dyslipidemia and hyperglycemia. In addition to insulin treatment, statins are often prescribed for combination therapy, but the combined effect of these two drugs on fracture healing has not been reported in such patients. OBJECTIVE; To investigate the effect of lovastatin combined with insulin on the fracture healing of bilateral ovariectomized rats suffering from type 2 diabetic mellitus. METHODS: The study was approved by the Ethical Committee of North China University of Science and Technology. Thirty-two female Sprague-Dawley rats were divided into control, diabetic ovariectomized, insulin and combined groups. A model of type 2 diabetes and osteoporosis fracture was established in all rats except for the control group. At 7 days after the type 2 diabetic model was successfully established by injection of streptozotocin, the rats in the insulin and combined groups received the subcutaneous injection of insulin (2-4 U in the morning, and 4-6 U in the evening) until the end of the experiment. The rats in the combined group were given 20 mg/kg lovastatin via gavage daily, and those in the other two groups were not treated. All rats were sacrificed at 3 weeks after fracture. Radiographic, clinical and histomorphometric detections of the callus were performed. The expression levels of bone morphogenetic protein 2, vascular endothelial growth factor and collagen type II were detected. All above results were used to analyze the fracture healing in each group. RESULTS AND CONCLUSION: (1)The radiographic score, micro-CT index, histologic score and the expression levels of vascular endothelial growth factor and collagen type II in the diabetic ovariectomized group were significantly poorer than those in the control group (P < 0.05). (2) All above indexes in the insulin group were significantly improved compared with the diabetic ovariectomized group (P < 0.05), which promoted the fracture healing of model rats. (3) After combined with lovastatin, although the expression levels of vascular endothelial growth factor and bone morphogenetic protein 2 in the callus were significantly increased (P < 0.05), there was no significant improvement in the radiographic appearance and microstructure of the callus.

Optimization of lovastatin production by Fusarium nectrioides (MH173849) using response surface methodology and fuzzy logic system

Aim: To enhance the productivity of lovastatin from Fusarium nectrioides isolate with liquid cheese whey as a major carbon source and to optimize the media components using Response Surface Methodology (RSM) and Fuzzy Logic System (FLS). Methodology: Euphorbia hirta was collected, surface sterilized and incubated on potato dextrose agar medium amended with ampicillin and streptomycin sulphate. F. nectrioides was isolated from E. hirta and identified using morphological and molecular methods. Primarily, media components were screened by Plackett Burman design (PBD). Further, the effect of significant nutrients was predicted using RSM and FLS and compared with experimental yield. Results: Molecular identification by gene sequencing confirmed the isolate to be F. nectrioides, given an accession number (MH173849) the sequence was submitted in the gene bank. PBD revealed that peptonized milk (which is an enzymic digest of high grade skimmed milk powder), corn steep liquor, liquid cheese whey and histidine were significant variables. The optimum levels of these significant variables in different combinations were studied by RSM in which the predicted yield of lovastatin was 1.2 gl-1. Further, it was analyzed by FLS with 14 set of fuzzy rules and the maximum production obtained was 1.8 g100 ml-1 which was closer to the experimental yield of 1.75 g100 ml-1. Therefore, compared to RSM, FLS was more suitable technique to determine the optimum levels of significant nutrients for enhanced lovastatin production. Interpretation: This study suggests that F. nectrioides (MH173849) can be used as a potent producer of lovastatin and the production highly influenced by glucose, corn steep liquor, liquid cheese whey and histidine.

Effect Of Lovastatin Nano Drug Delivery System On Bone Mineral Density (BMD) And Biomechanical Properties Of Tibia Bones Of Wistar Rats

Objective: In the present study, transdermal nanoemulsion (NE) gel of lovastatin was investigated for its anti-osteoporosis effect on the long bones of rat i.e. tibia. Methods: Male wistar rats (n=30, weighing 180-200g) were taken for this study and grouped as: 1) control (normal saline daily), 2) Dex (dexamethasone sodium; 25 mg/kg subcutaneously twice a week), 3) Dex+LNG5 (lovastatin nanoemulsion gel; 5 mg/kg/d transdermally daily), 4) Dex+LNG10 (lovastatin nanoemulsion gel; 10 mg/kg/d transdermally daily), and 5) Dex+ALN (alendronate sodium; 0.03 mg/kg/d orally daily). All the treatments were carried out for 60 d. At the end of the experiment, all animals were anesthetized using diethyl ether and collected blood samples from retro-orbital venous plexus of rats in dry eppendorf tubes followed by the sacrifice of animals by cervical dislocation method and collected tibia bones of both the legs for analysis. Results: Bone formation biomarkers (OC: osteocalcin, b-ALP: bone-specific alkaline phosphatase, PINP: N-terminal propeptides of type I procollagen) were significantly improved and resorption biomarkers (CTx: C-terminal cross-linking telopeptides of type-I collagen, TRAcP5b: isoform 5b of tartarate resistant acid phosphatase) were significantly reduced in the LNG5 (p<0.05) and LNG10 (p<0.05) treatment groups when compared to Dex. In vivo anti-osteoporotic results demonstrated the formation of new bone in osteoporotic rat tibias. Biomechanical strength testing demonstrated increased load-bearing capacity of rat tibias in the treated animals in comparison with the osteoporotic group (p<0.05 for LNG5 and p<0.01 for LNG10). Conclusion: Thus, the transdermal NE gel formulation of lovastatin demonstrated the greater potential for the treatment of osteoporosis.

CHILD syndrome: successful treatment of skin lesions with topical lovastatin and cholesterol lotion

Abstract: CHILD syndrome (Congenital Hemidysplasia, Ichthyosiform erythroderma, Limb Defects) is a rare X-linked dominant disease. The authors report a 2-month-old patient presenting with typical features of CHILD syndrome that was treated with a topical solution containing cholesterol and lovastatin, with complete clearance of her CHILD nevus. The changes in skin lipid metabolism that explain the CHILD ichthyosiform nevus and their correction through topical application of cholesterol and lovastatin are discussed.

Evaluation and comparison of the hepatoprotective effects of trimetazidine and lovastatin against doxorubicin-induced hepatotoxicity

Background: The dosage of highly efficacious anti-cancer drug doxorubicin (DOX) is often constrained as limited data exists on its hepatotoxic potential. The present study not only evaluated the extent of its hepatotoxicity but also aimed at curtailing it, by administration of two drugs i.e. trimetazidine and lovastatin, both of which are otherwise known for their cardioprotective benefits.Methods: The study was a lab-based randomized controlled study on mice. Acute toxicity was introduced with DOX injected intraperitoneally at a dose of 10 mg/kg and it was protected by oral administration of trimetazidine and lovastatin, both in a dose of 10 mg/kg. The protective drugs were both given for five and ten consecutive days in short and long term study designs whereby DOX was administered on the third and eighth days of the respective studies.Results: Doxorubicin administration caused significant hepatotoxicity reflected by markedly raised biomarkers (serum alanine aminotransferase and aspartate aminotransferase) and mild inflammation of liver parenchyma with a score of 4 as per Ishak grading scale. The changes were significantly attenuated by both the protective drugs in the ten days study design. However, in the five days study, lovastatin exhibited more significant hepatoprotection than trimetazidine.Conclusions: Pretreatment with two commonly available, cost effective and safe drugs can effectively prevent a potentially life-threatening adverse effect of DOX. This approach might prove very convenient for the health care providers as well as for the patients without burdening the economics.

Comparison of Transforming Growth Factor-Beta1 and Lovastatin on Differentiating Mesenchymal Stem Cells toward Nucleus Pulposus-like Phenotype: An In Vitro Cell Culture Study

STUDY DESIGN: In Vitro cell culture study. PURPOSE: This study aims to investigate the impact of transforming growth factor-beta1 (TGF-β1) and lovastatin on differentiating human mesenchymal stem cells (MSCs) toward nucleus pulposus (NP)-like phenotype. OVERVIEW OF LITERATURE: MSCs offer a cell source to the cell-based therapy for intervertebral disc degeneration. TGF-β1 is used to induce MSCs to differentiate into NP-like cells; however, an undesired expression of collagen type I has been reported. Statins reportedly stimulate expression of bone morphogenetic protein-2 (BMP-2) and promote the chondrogenic phenotype to NP cells. However, the effects of statins with or without TGF-β1 on the differentiation of MSCs into NP-like cells remain unclear. METHODS: Human MSCs were treated with TGF-β1 alone, lovastatin alone, and simultaneous or sequential treatment with TGF-β1 and lovastatin. After the proposed stimulation, the total RNA was extracted to assess the expression profile of NP cells-specific genes. Hematoxylin–eosin staining was used for examining the microscopic morphology. Furthermore, we detected the syntheses of S-100 protein, aggrecan, and collagen type II in the extracellular matrix using immunohistochemical staining. RESULTS: Simultaneous or sequential treatment of TGF-β1 and lovastatin could further augment the BMP-2 overexpression compared with lovastatin-alone treatment. However, the mRNA expression of aggrecan and collagen type II was not compatible with the expression level of BMP-2. Immunohistochemical studies revealed compatible production of aggrecan, collagen type II, and S-100 protein in all three groups treated with lovastatin. Cells in groups treated with lovastatin were less populated than that in the group treated with TGF-β1 alone. CONCLUSIONS: This study demonstrates a promising role of lovastatin in inducing human MSCs into NP-like cells. However, further optimization of cell density before lovastatin treatment, treatment duration, and combination with TGF-β1 are warranted to attain better stimulatory effects.

Effects of Licorice on Pharmacokinetics of Lovastatin in Hyperlipidemic Rats / 中国医科大学学报

Objective To study the effect of licorice on the pharmacokinetics of lovastatin in hyperlipidemic rat model.Methods Eighteen rats were randomly divided into control group (n =6) and test group (n =12).Rats in the test group were administered high fat diet to construct hyperlipidemic rat model.The 12 hyperlipidemic rats were then randomly divided into two groups:lovastatin group (n =6) and lovastatin combined with hcorice group (n =6).The rats in both groups were administered lovastatin capsule (20 mg/kg,0.5％ CMC-Na solution) after receiving licorice (for lovastatin combined with licorice group) or saline (for lovastatin group) for 7 days.Blood samples were collected at different time points before and after the administration of lovastatin capsule.The plasma concentrations of lovastatin and lovastatin acid (an active metabolite of lovastatin) were determined by LC-MS/MS method.Pharmacokinetics parameters were calculated using DAS 2.0 software,and the two groups were compared using SPSS 18.0 software.Results Long-term administration of licorice resulted in a significant increase in the plasma level of lovastatin acid in the hyperlipidemic rat,and the corresponding mean Cmax was approximately 80％ higher than that of the lovastatin group (P ＜ 0.05),while AUC0-t and AUC0-t increased by 115％ and 109％,respectively (P =0.005 and P =0.027).Cmax and AUC of lovastatin also increased,but there was no statistical significance (P ＞ 0.05).Conclusion Licorice can inhibit the metabolism of lovastatin in hyperhpidemic rats and increase its exposure in vivo.

Association of lovastatin overcoming gefitinib resistance with integrin β1 and survivin / 第二军医大学学报

Objective To investigate the association of lovastatin overcoming gefitinib resistance with the levels of integrin β1 and Survivin in human non-small cell lung cancer (NSCLC) cell line PC9 in vitro, and to explore the possible mechanism. Methods The NSCLC cell line PC9 with acq uired gefitini-resistance were divided into 4 groups; control group (RPM1 1640), gefitinib group (1 /μmol/L gefitinib), lovastatin group (5 μmol/L lovastatin), and gefitinib combined with lovastatin group (1 μmol/L gefitinib+5 /μmol L lovastatin). After treatment with different drugs in each group, the inhibition of cell proliferation was detected by cell counting kit-8 (CCK-8) test, the levels of integrin ft 1 and Survivin mRNA were detected by PCR, and the expressions of integrin (31 and Survivin protein were detected by Western blotting analysis. Results Compared with the control group, lovastatin group and gefitinib group, lovastatin combined with gefitinib treatment had significantly inhibited proliferation of PC9 cells with acquired gefitinib-resistance (P<0. 01), and the expressions of integrin)31. Survivin protein and mRNA in PC9 cells were significantly decreased in the three groups (P<0. 05, P<0. 01). Conclusion Mechanisms of lovastatin combined with gefitinib in overcoming gefitinib resistance may be through blocking integrin β1-p-Akt-Survivin signaling pathway, indicating that the combination treatment might be an effective strategy for gefitinib resistance.

Lipid regulating effect of mixture fermentation products of Crataegi Fructus, Alismatis Rhizoma, and Cassiae Semen with Monascus purpureus on hyperlipidemic rats / 中草药

Objective: To explore the lipid regulating effect of fermentation product of Crataegi Fructus, Alismatis Rhizoma, and Cassiae Semen on hyperlipidemic rats. Methods: SD rats were fed with high fat diet and established as hyperlipidemia animal model, the subjects were divided into six groups: control group, model group, positive control group, fermentation product prevention group, red yeast rice group, and fermentation product treatment group. After four weeks continuous oral administration, the effect of different medicine samples on serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) of hyperlipidemic rats were observed to assess the regulation effect. Results: Four weeks' continuous oral administration could regulate the TC, TG, LDL-C levels significantly lower (P < 0.001) and HDL-C level significantly increased (P < 0.05) in the prevention group compared with the model group. After modeling, continuous administration for four weeks, compared with the levels before giving medicines, TC, TG, LDL-C levels of positive control group and fermentation product treatment group were significantly regulated lower (P < 0.05, 0.01) and HDL-C level significantly increased (P < 0.05, 0.01). while the only TC and LDL-C levels in red yeast rice group showed significant effect. Conclusion: Product of lipid-lowering traditional Chinese medicines (TCMs) treated by solid-state fermentation with Monascus purpureus could effectively inhibit the formation of foodborne hyperlipidemia, as well as control and regulate hyperlipidemia, and synergistic effect also appeared between ingredients from TCMs and lovastatin.

Antagonism of lovastatin on oxidative stress and apoptosis in primary rat hippocampal neurons induced by β-amyloid peptide / 中华病理学杂志

Objective@#To investigate the effect of lovastatin on oxidative stress and apoptosis in neurons induced by β-amyloid peptide (Aβ).@*Methods@#Primary culture of rat hippocampal neuron was treated with Aβ oligomers alone or combined with lovastatin. The levels of OH-, H2O2, O2·-, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were measured by biochemical methods and protein expression of caspase-3 and bcl-2 was detected by Western blot.@*Results@#As compared with the control group, treatment of 0.5 μmol/L Aβ oligomers for 48 h led to significant increase of OH-, H2O2, O2·- and malondialdehyde content, inhibition of SOD and GSH-PX activities, enhanced caspase-3 expression and decreased bcl-2 expression. Interestingly, these neurotoxic modifications on the levels of OH-, H2O2, O2·- and malondialdehyde content, SOD and GSH-PX activities, and the protein expression of cleaved caspase-3 and bcl-2 were significantly attenuated when the cells were pretreated with 0.1 μmol/L lovastatin for 24 h before exposure of Aβ oligomers.@*Conclusion@#Lovastatin may play an important role in antagonizing the neurotoxicity of Aβ through a mechanism likely related to the inhibition of oxidative stress.

Genome Shuffling of Mangrove Endophytic Aspergillus luchuensis MERV10 for Improving the Cholesterol-Lowering Agent Lovastatin under Solid State Fermentation

In the screening of marine mangrove derived fungi for lovastatin productivity, endophytic Aspergillus luchuensis MERV10 exhibited the highest lovastatin productivity (9.5 mg/gds) in solid state fermentation (SSF) using rice bran. Aspergillus luchuensis MERV10 was used as the parental strain in which to induce genetic variabilities after application of different mixtures as well as doses of mutagens followed by three successive rounds of genome shuffling. Four potent mutants, UN6, UN28, NE11, and NE23, with lovastatin productivity equal to 2.0-, 2.11-, 1.95-, and 2.11-fold higher than the parental strain, respectively, were applied for three rounds of genome shuffling as the initial mutants. Four hereditarily stable recombinants (F3/3, F3/7, F3/9, and F3/13) were obtained with lovastatin productivity equal to 50.8, 57.0, 49.7, and 51.0 mg/gds, respectively. Recombinant strain F3/7 yielded 57.0 mg/gds of lovastatin, which is 6-fold and 2.85-fold higher, respectively, than the initial parental strain and the highest mutants UN28 and NE23. It was therefore selected for the optimization of lovastatin production through improvement of SSF parameters. Lovastatin productivity was increased 32-fold through strain improvement methods, including mutations and three successive rounds of genome shuffling followed by optimizing SSF factors.

Determination of Related Substances in Lovastatin Tablet by HPLC / 中国药房

OBJECTIVE:To establish a method for the determination of related substances in Lovastatin tablet. METHODS:HPLC was performed on the column of Waters XTerra? MS C18 with mobile phase A of 0.01%Phosphoric acid solution and B of acetonitrile(gradient elution)at a flow rate 1.0 ml/min,column temperature was 40 ℃,the detection wavelength was 238 nm,and the injection volume was 10 μl. RESULTS:The impurity components were well separated in principal components;the linear range of lovastatin was 17.5-700 μg/ml(r=0.9999);RSDs of precision,stability and reproducibility tests were lower than 1%;recov-ery was 99.30%-100.67%(RSD=0.4%,n=9). CONCLUSIONS:The method is reproducible with good durability and high preci-sion,and can be used for the quality control of Lovastatin tablet.

One-step fermentation for producing simvastatin via RNAi silencing of lovF gene in Aspergillus terreus / 生物工程学报

Simvastatin is one of the important prescription drugs for hypercholesterolemia. Monacolin J is a key intermediate during simvastatin synthesis, and also an intermediate of lovastatin biosynthesis. In this work, we construct a monacolin J producing strain via RNA interference to achieve one-step fermentation to obtain simvastatin. The lovF gene silencing plasmid pMHJ137 was constructed and transformed into Aspergillus terreus by Agrobacterium tumefaciens mediated transformation method. Precursor DMB-S-MMP was supplied during the fermentation to screen positive strains of transformants; which also further confirmed the simvastatin producing capability of MJ1-24 by one-step fermentation. Strain MJ1-24 produced monacolin J rather than lovastatin, and the feeding of DMB-S-MMP resulted in the generation of simvastatin. This study suggested that RNAi can efficiently silence the lovF gene of A. terreus and promote the simvastatin production by one-step fermentation.

Association between HMG CoA reductase inhibitors and anxiety: an experimental study using elevated plus maze and light dark arena behavioural models.

Background: Aims: To investigate the effect of HMG CoA reductase inhibitors on behavioural models of anxiety in male swiss mice using Elevated plus maze test and light-dark arena test. Methods: It was an experimental study, carried out in department of Pharmacology, J. N. Medical College, KLE University, Belgaum. The in vivo behavioural activity of simvastatin, lovastatin, atorvastatin was studied using EPM and light-dark arena test. The mice received the drugs as per their weight and subjected for experimentation. Group mean time spent and number of entries into open arm in EPM test and group mean number of entries and time spent in the light area was calculated in treated and control groups for comparison. Statistical analysis was done using ANOVA followed by Bonferroni’s multiple comparison test (P<0.05). Results: Going through the results of this study an evidence for the association between lowered serum cholesterol and symptoms of anxiety can be seen as statins used in the present study failed to show significant anxiolytic effect when compared to standard but in turn showed even more less activity when compared to control, indicating anxiogenic behavior. Conclusions: Our findings support the evidence of the negative effects of statins on psychological outcomes. It's generally understood that having low cholesterol is a good health sign, combined with other factors; it could actually put a person at risk by causing anxiety and stress. Further research comprising a greater number of studies is required to confirm the effects of this agent on psychological outcomes.

Effect of lovastatin on shedding of heparan sulfate proteoglycan and syndecan-1 in lung tissues of rats with sepsis-induced acute lung injury / 中华麻醉学杂志

Objective To evaluate the effect of lovastatin on shedding of heparan sulfate proteoglycan (HSPG) and syndecan-1 (SDC-1) in the lung tissues of rats with sepsis-induced acute lung injury.Methods One-hundred and twenty male Wistar rats aged 8-12 weeks,weighing 325-425 g,were randomly divided into 3 groups (n =40 each) using a random number table:sham operation group (group S),cecal ligation and puncture (CLP) group and lovastatin group (group L).Lovastatin 4 mg/kg was injected once a day for 5 consecutive days in S and L groups,while the equal volume of 0.5％ CMC (the solvent) was given in CLP group.Sepsis was produced by CLP on 5th day of administration in CLP and L groups.The left lung was lavaged at 24 h after operation.The broncho-alveolar lavage fluid (BALF) was collected for determination of protein concentrations,white blood cell (WBC) count and percentage of neutrophils.Blood samples were collected for determination of the concentrations of HSPG and SDC-1 in serum (by ELISA).Evans blue was injected at 24 h after operation in the remaining 20 rats of each group.The lungs were removed for examination of the pathological changes and for measurement of HSPG and SDC-1 mRNA and protein expression (using Western blot and PCR),and Evans blue content (reflecting pulmonary capillary permeability) in the lung tissue.Results Compared with group S,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly increased,and HSPG and SDC-1 mRNA and protein expression was down-regulated in CLP and L groups.Compared with group CLP,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly decreased,and HSPG and SDC-1 mRNA and protein expression was up-regulated in group L.The pathological changes of lungs were significantly attenuated in group L as compared with group CLP.Conclusion The mechanism by which lovastatin attenuates acute lung injury induced by sepsis may be related to reduced shedding of HSPG and SDC-1 in lung tissues and improved function of pulmonary vascular endothelium in rats.

Endophytic Fungi: A Poor Candidate for the Production of Lovastatin.

Aim: The aim of the present study was to screen soil and endophytic fungi for production of lovastatin. Methodology: Soil fungi were isolated by dilution plating technique and endophytic fungi from selected medicinal plants by using standard procedures. All isolates were tested for lovastatin production by Solid State Fermentation (SSF) using wheat bran as substrate. Results: The soil isolate, Aspergillus terreus NCBI (KM017963) showed positive for lovastatin (1.0 mg/G DWS) whereas none of the endophytic fungi tested showed positivefor lovastatin production.

The Effect of Lovastatin Combined with Calcitonin on Fracture Repair in Osteoporotic Rats / 天津医药

Objective To investigate the effects of lovastatin alone or combined with calcitonin on fracture repair in osteoporotic rats. Methods Forty 4-month-old female SD rats were randomized into 5 groups(8 rats in each group):normal fractured group (A), osteoporotic fractured group (B), lovastatin treatment group(C), calcitonin treatment group (D) and lovastatin combined with calcitonin treatment group. All rats except group A received bilateral ovariectomy. The midshaft femur fracture model was established in all rats 8 weeks after operation. The serum level of procollagen amino-terminal propeptide (PINP) was assessed by ELISA. X-ray and bone mineral density detection was used to observe the fracture healing process. The maximal loading of femoral fractures was analyzed by biomechanical method. Results (1) The serum level of PINP was significantly lower in group A than that of other groups. There was a significantly higher level of PINP in group C and group E than that of group B, and the level of PINP was significantly lower in group D than that of group C. (2) The X-ray showed more progressed fracture healing in group A and group E. The accordingly score indicated that there was a markedly higher score in groups A and group E compared to that of other three groups. (3) There was a highest bone mineral density in the full-length and in the middle of femur bone in group A, followed by group E, group D and group C. The lowest bone mineral density was found in group B. (4) The biomechanical test showed that the maximal loading in femur fracture side was significantly higher in group A than that of other four groups, in which it was higher in group E than that of group B. Conclusion The osteoporosis decreased bone mass and delayed fracture healing process in rat model. The treatment of lovastatin combined with calcitonin showed more positive effect on preventing bone loss and promoting fracture repair than lovastatin alone.

Protective effects of lovastatin on lung injury and adiponectin expression in septic rats / 中国基层医药

Objective To observe the protective effects of lovastatin against lung injury and the expression changes of adiponectin in the septic rats.Methods Fifty four male Wistar rats weighting 250-300g were randomly divided into the three groups:sham operation group ( group Sham) ,sepsis group ( group CLP) and lovastatin interven tion group (group LOV).Rats were injected with lovastatin (4mg/kg) or 0.5%CMC (vehicle) for five days and then subjected to CLP.At 4h,12h and 24h after operation.BALF was collected to determine the levels of TNF-αand IL-6,lung tissue was obtained to observe histopathological changes,and to detect the content of MPO and MDA,the blood sample was obtained to detect the level of adiponectin.Results In the group Sham,at 4h,12h and 24h time points,the levels of TNF-αwere (1.80 ±0.13)pg/mL,(2.04 ±0.15)pg/mL and (1.930.19)pg/mL;the levels of IL-6 were (20.56 ±0.23)pg/mL,(18.35 ±0.15) pg/mL and (21.23 ±0.20) pg/mL;the contents of MPO were (2.82 ±0.14) U/g tissue,(2.88 ±0.07) U/g tissue and (2.76 ±0.18) U/g tissue;and the levels of MDA were (3.32 ±0.12)nmol/mg,(3.09 ±0.11)nmol/mg and (3.21 ±0.08)nmol/mg;the concentrations of adiponectin were (2.68 ±0.14)μg/mL,(2.80 ±0.07)μg/mL and (2.86 ±0.18)μg/mL.Compared with group Sham,both LOV group and CLP group had increased pulmonary damage:(1)the levels of TNF-α[4h,12h and 24h were (4.23 ± 0.18)pg/mL,(5.62 ±0.24)pg/mL and (5.14 ±0.10)pg/mL,t=28.41,30.98 and 36.62]and IL-6[4h,12h and 24h were (39.12 ±0.17) pg/mL,(47.25 ±0.21) pg/mL and (44.690.27) pg/mL,t =158.90,273.40 and 127.28] of the CLP group in BALF were both increased,and MPO[4h,12h and 24h were (4.85 ±0.13) U/g tissue, (6.17 ±0.08)U/g tissue and (7.84 ±0.10)U/g tissue,t=26.39,79.40 and 60.43]and MDA[4h,12h and 24h were (6.24 ±0.06)nmol/mg,(7.56 ±0.15)nmol/mg and (8.43 ±0.10)nmol/mg,t=53.31,58.86 and 90.06] concentrations in lung homogenate were raised with the decreased expression of serum adiponectin[4h,12h and 24h were (1.35 ±0.10)μg/mL,(1.17 ±0.07)μg/mL and (1.24 ±0.11)μg/mL,t=19.86,12.75 and 18.81](all P<0.05);(2) meanwhile the levels of TNF-α[4h,12h and 24h were (2.85 ±0.17) pg/mL,(3.720.13) pg/mL and (3.240.09)pg/mL,t=12.02、20.73 and 16.68]and IL-6[4h,12h and 24h were (30.75 ±0.22)pg/mL, (37.52 ±0.29)pg/mL and (32.43 ±0.26)pg/mL,t=78.42,68.29 and 83.67]in BALF of the LOV group were all increased,the contents of MPO[4h,12h and 24h were(3.59 ±0.05)U/g tissue,(4.67 ±0.11)U/g tissue and (5.33 ± 0.05)U/g tissue,t=12.03,33.63 and 33.70]and MDA[4h,12h and 24h were (4.45 ±0.10)nmol/mg,(5.01 ± 0.11)nmol/mg and (5.83 ±0.04) nmol/mg,t =17.72,30.23 and 71.75] were also increased with the serum adiponectin concentrations[4h,12h and 24h were (2.09 ±0.08)μg/mL,(2.07 ±0.05)μg/mL and (2.03 ± 0.10)μg/mL,t=8.96,20.79 and 6.30]dicreased(all P<0.05).There were less histopathological changes in the LOV group,and the levels of TNF-α(t=13.46,17.05 and 15.43),IL-6(t=73.70,64.10 and 80.12),MPO(t=22.16,27.01and 32.86) and MDA(t=37.59,42.72 and 59.13) were lower than those in CLP group,also the level of adiponectin(t=14.15,8.10 and 3.19) increased siginificantly(all P<0.05).Conclusion Administration of lovastatin could attenuate lung injury of the sepsis by down-regulate the level of TNF-αand IL-6,with reduced inflam-matory response and oxidative stress,and could upregulate the level of adiponectin in serums of rats with sepsis.