Processes
·
2024
·Vol. 12
·期 9
·2006
·
IF 2.8
Wei He,Benshun Chen,Bin Yin,Jianren Ye,Yucai He
Simvastatin is a widely used statin medication that is commonly prescribed to lower cholesterol levels and reduce the risk of cardiovascular events. It is marketed under the brand name Zocor and is known for its effectiveness in treating high cholesterol and managing cardiovascular disease. Monacolin J is an important precursor used to synthesize simvastatin and is mainly produced by chemical methods in industry. Here, monacolin J was synthesized through an enzymatic method under optimized reaction conditions. One recombinantEscherichia coliBL21 (DE3) strain containing lovastatin hydrolase (encoded by CDV55_102090) fromAspergillus turcosuswas constructed, which effectively transformed 100 g/L of lovastatin to monacolin J within 3.5 h at pH 8.0 and 30 °C, with a conversion rate of >99.8%. Furthermore, the T5010, the temperature at which the residual activity was half of the initial enzymatic activity after 10 min of heat treatment, was >50 °C, indicating the tremendous potential of this bioprocess for synthesizing monacolin J at an industrial scale.
研究领域:
生物化学
·
制药工程
·
工业微生物学
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产品关联
DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2021
·Vol. 35
·期 7
·e5093
·
IF 1.902
Wei Wu,Rui Cheng,Zhenzhou Jiang,Luyong Zhang,Xin Huang
A rapid and specific UPLC–MS/MS method with a total run time of 3.5 min was developed for the determination of pravastatin, fexofenadine, rosuvastatin, and methotrexate in rat primary hepatocytes. After protein precipitation with 70% acetonitrile (containing 30% H 2 O), these four analytes were separated under gradient conditions with a mobile phase consisting of 0.03% acetic acid (v/v) and methanol at a flow rate of 0.50 mL/min. The linearity, recovery, matrix effect, accuracy, precision, and stability of the method were well validated. We evaluated drug–drug interactions based on these four compounds in freshly suspended hepatocytes. The hepatic uptake of pravastatin, fexofenadine, rosuvastatin, and methotrexate at 4°C was significantly lower than that at 37°C, and the hepatocytes were saturable with increased substrate concentration and culture time, suggesting that the rat primary hepatocyte model was successfully established. Triptolide showed a significant inhibitory effect on the hepatic uptake of these four compounds. In conclusion, this method was successfully employed for the quantification of pravastatin, fexofenadine, rosuvastatin, and methotrexate and was used to verify the rat primary hepatocyte model for Oatp1, Oatp2, Oatp4, and Oat2 transporter studies. Then, we applied this model to explore the effect of triptolide on these four transporters.
研究领域:
药理学
·
分析化学
·
肝脏病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 7
·3051-3066
·
IF 6.1
Qingqing Wang,Zihou Liu,Rui Wang,Run Li,Xiaoru Lian,Yanquan Yang,Jiao Yan,Zhiqi Yin,Guangji Wang,Jianguo Sun,Ying Peng
Ginkgo biloba extract (GBE) is a common dietary supplement used by people with dyslipidaemia worldwide to reduce the risk of cardiovascular disease. Many studies have found that GBE itself has a variety of pharmacological activities. However, the role of GBE as an adjunct to conventional therapy with chemical drugs remains controversial. Therefore, this study explored the additional benefits of GBE in the treatment of hyperlipidaemia with statins in terms of both pharmacodynamics and pharmacokinetics. A hyperlipidaemia model was established by feeding rats a high-fat diet for a long time. The animals were treated with atorvastatin only, GBE only, or a combination of atorvastatin and GBE. The results showed that statins combined with GBE could significantly improve the blood lipid parameters, reduce the liver fat content, and reduce the size of adipocytes in abdominal fat. The effect was superior to statin therapy alone. In addition, the combination has shown additional liver protection against possible pathological liver injury or statin-induced liver injury. A lipidomic study showed that GBE could regulate the abnormal lipid metabolism of the liver in hyperlipemia. When statins are combined with GBE, this callback effect introduced by GBE on endogenous metabolism has important implications for resistance to disease progression and statin resistance. Finally, in the presence of GBE, there was a significant increase in plasma statin exposure. These results all confirmed that GBE has incremental benefits as a dietary supplement of statin therapy for dyslipidaemia.
研究领域:
药理学
·
药代动力学
·
代谢
·
心血管疾病
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Wen-Juan Tang,Di Xu,Ming-Xing Liang,Guan-Qun Wo,Wen-Quan Chen,Jin-Hai Tang,Wei Zhang
Triple-negative breast cancer (TNBC) is more prone to recurrence and metastasis relative to other subtypes of breast cancer, leading to an extremely poor prognosis. The increasing potential chemoresistance of TNBC patients is mainly due to that tumor cells escape from apoptosis. In recent years, statins have demonstrated extensive anti-tumor effects. It is worth noting that statins have more effective anti-tumor effects on TNBC cells and drug-resistant breast cancer cells. Therefore, this study examines the superior cytotoxic effects of statins on TNBC cell lines and further explores their potential therapeutic mechanisms. We detected different cell phenotypes and found that statins significantly reduced the cell viability of TNBC cells. Specifically, pitavastatin showed an obvious induction in cell death, cell cycle arrest and oxidative stress in TNBC MDA-MB-231 cells. The reversal effect of iron chelator desferrioxamine (DFO) on the morphological and molecular biological changes induced by pitavastatin has revealed a new mode of cell death induced by pitavastatin: ferroptosis. This ferroptotic effect was strengthened by the decreased expression of glutathione peroxidase 4 (GPx4) as well as newly discovered ferroptosis suppressor protein 1 (FSP1). The data showed that ferroptotic death of MDA-MB-231 cells is autophagy-dependent and mediated by the mevalonate pathway. Finally, we found that therapeutic oral doses of statins can inhibit the growth of transplanted tumors, which establishes statins as a potential treatment for TNBC patients. In conclusion, we found pitavastatin could induce autophagy-dependent ferroptosis in TNBC cells via the mevalonate pathway which may become a potential adjuvant treatment option for TNBC patients.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
癌症研究
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DOI
PubMed
高影响因子
Vietnam Journal of Chemistry
·
2022
·
IF 0
Ha Manh Hung,Vu Quoc Manh,Vu Thi Thu Thao,Dao Thi Phuong Thuy,Pham Tien Dung,Nguyen Thi Bich Viet,Duong Khanh Linh,Nguyen Ngoc Linh,Doan Thi Yen Oanh,Nguyen Thuy Chinh,Thai Hoang,Vu Quoc Trung
The chitosan/carrageenan/lovastatin biomaterials were prepared using a solution technique with 5 % lovastatin and a variable chitosan/carrageenan mass ratio. Fourier transform infrared spectroscopy (FT-IR) and field emission scanning electron microscopy (FESEM) images revealed that the complex's components were well dispersed into each other without changing the chemical structure, forming dipole interactions and hydrogen bonds among them. The abilities to release Lovastatin (Lov) in pH 2 and pH 7.4 solutions, corresponding to the environments in stomach and intestinal fluids, respectively, are both affected by the ratio of polymer components. The best results were obtained with the chitosan/carrageenan/lovastatin (w/w/%w = 10/90/5%) (CsCL195) biomaterial sample in which the particles are evenly dispersed. While the drug release process was poor in the pH 2 solution (gastric juice), a good release observed in the pH 7.4 solution (intestinal fluid) allows facilitating drug absorption through the intestinal mucosa cells into the blood, from which the effects of hypercholesterolemia treatment can be obtained.
研究领域:
生物材料学
·
药剂学
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产品关联
DOI
BIOCHEMICAL PHARMACOLOGY
·
2018
·
IF 4.235
Binbin Sun,Zeyu Zhong,Fan Wang,Jiong Xu,Feng Xu,Weimin Kong,Zhaoli Ling,Nan Shu,Ying Li,Tong Wu,Mian Zhang,Liang Zhu,Xiaodong Liu,Li Liu
Skeletal muscle accounts for approximately 75% of glucose disposal in body and statins impair glucose metabolism. We aimed to investigate the effect of atorvastatin on glucose metabolism in C2C12 cells. Glucose metabolism and expression of glucose transporter 4 (GLUT4) and hexokinase II (HXKII) were measured following incubation with atorvastatin or pravastatin . Roles of cholesterol in atorvastatin-induced glucose metabolism impairment were investigated via adding cholesterol or mevalonic acid and confirmed by cholesterol depletion with methyl-β-cyclodextrin. Hypercholesterolemia mice induced by high fat diet (HFD) feeding, orally received atorvastatin (6 and 12 mg/kg) or pravastatin (12 mg/kg) for 22 days. Results showed that atorvastatin not pravastatin concentration-dependently impaired glucose consumption, glucose uptake and GLUT4 membrane translocation in C2C12 cells without affecting expression of HXKII or total GLUT4 protein. The atorvastatin-induced alterations were reversed by cholesterol or mevalonic acid. Cholesterol depletion exerted similar impact to atorvastatin, which could be alleviated by cholesterol supplement. Glucose consumption or GLUT4 translocation was positively associated with cellular cholesterol levels. In HFD mice, atorvastatin not pravastatin significantly increased blood glucose levels following glucose or insulin dose and decreased expression of membrane not total GLUT4 protein in muscle. Glucose exposure following glucose or insulin dose was negatively correlated to muscular free cholesterol concentration. Expression of membrane GLUT4 protein was positively related to free cholesterol in muscle. In conclusion, atorvastatin impaired glucose utilization in muscle cells partly via inhibiting GLUT4 membrane translocation due to inhibition of cholesterol synthesis by atorvastatin, at least, partly contributing to glucose intolerance in HFD mice.
研究领域:
药理学
·
细胞生物学
·
代谢
·
内分泌学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 11
·2534
·
IF 6.525
Bo Wei,Yuanfang Li,Meiying Ao,Wenxiang Shao,Kun Wang,Tong Rong,Yun Zhou,Yong Chen
Previously, we found that exogenous ganglioside GM3 had an antiatherosclerotic efficacy and that its antiatherosclerotic efficacy could be enhanced by reconstituted high-density lipoprotein (rHDL). In this study, we hypothesized that GM3-functionalized rHDL (i.e., GM3-rHDL) as a nanocarrier can promote the efficacy of traditional antiatherosclerotic drugs (e.g., statins). To test this hypothesis, lovastatin (LT) was used as a representative of statins, and LT-loaded GM3-rHDL nanoparticle (LT-GM3-rHDL or[email protected]; a mean size of ~142 nm) and multiple controls (e.g., GM3-rHDL without LT, LT-loaded rHDL or LT-rHDL, and other nanoparticles) were prepared. By using two different microsphere-based methods, the presences of apolipoprotein A-I (apoA-I) and/or GM3 in nanoparticles and the apoA-I-mediated macrophage-targeting ability of apoA-I/rHDL-containing nanoparticles were verified in vitro. Moreover, LT-GM3-rHDL nanoparticle had a slowly sustained LT release in vitro and the strongest inhibitory effect on the foam cell formation of macrophages (a key event of atherogenesis). After single administration of rHDL-based nanoparticles, a higher LT concentration was detected shortly in the atherosclerotic plaques of apoE−/−mice than non-rHDL-based nanoparticles, suggesting the in vivo plaque-targeting ability of apoA-I/rHDL-containing nanoparticles. Finally, among all nanoparticles LT-GM3-rHDL induced the largest decreases in the contents of blood lipids and in the areas of atherosclerotic plaques at various aortic locations in apoE−/−mice fed a high-fat diet for 12 weeks, supporting that LT-GM3-rHDL has the best in vivo antiatherosclerotic efficacy among the tested nanoparticles. Our data imply that GM3-functionalized rHDL (i.e., GM3-rHDL) can be utilized as a novel nanocarrier to enhance the efficacy of traditional antiatherosclerotic drugs (e.g., statins).Keywords:ganglioside GM3;atherosclerosis;reconstituted high-density lipoprotein (rHDL);lovastatin (LT);drug delivery system;statins;ApoA-I
研究领域:
药理学
·
心血管疾病
·
纳米技术
·
药物递送
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产品关联
DOI
PubMed
高影响因子
APPLIED SPECTROSCOPY
·
2023
·
IF 3.5
Xinyuan Chen,Xiuzhi Chen,Hongyan Sun,Xiumin Li,Shizhao Ren,Can Jin,Hongjun Jin,Fenghua Chen,Rongrong Xue
Amorphous simvastatin (amorphous SIM) and Form I of SIM were prepared separately from SIM acetone (AC)/ethyl acetate (ETAC)/ethanol (ET) solutions by simply controlling the solvent evaporation rate, and the kinetic formation of amorphous SIM from SIM AC/ETAC/ET solutions was explained using mid-frequency Raman difference spectra analysis. The mid-frequency Raman difference spectra analysis results indicate that the amorphous phase has close connections with solutions and might be the bridge, playing an important role in the intermediate phase, between solutions and their outcome polymorphs.
研究领域:
药学
·
材料科学
·
光谱学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Dongmei Guo,Yue Huang,Kun Wang,Chenguang Yang,Lili Ma,Yu Zhang,Haiyang Yu,Manhua Cui,Zhaohui Tang
Purpose Cervical cancer (CC) is a highly vascularized tumor with abundant abnormal blood vessel, which could be targeted by therapeutic strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential as nano vascular disrupting agents (VDAs) in the realm of synergistic cancer therapy.Methods In this study, we investigated the nanocharacteristics of CB-NPs, focusing on active pharmaceutical ingredients (API), as well as lyophilized samples combining API with protective agents (PAs). The in vivo efficacy of final sample (API + PAs) was evaluated.Results The assembled sphere of API with complex core and thin-shell structure was confirmed. PAs were found to significantly influence in vivo efficacy. Collaborative efforts between API and PAs, namely mannitol and lactose, resulted in the most promising lyophilized sample, ie, the final sample (FS2) for CC therapy. Impressively, FS2 demonstrated an exceptional 100% cure rate on the CC U14-bearing mice model.Conclusion FS2 has provided significant insights for cervical cancer therapy. It is also crucial to develop a comprehensive evaluation strategy for the formulation of nanomedicine, which has the potential to serve as a guideline for future clinical trials.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2011
·
IF 2.13
Zhangliang Gui,Jinwen Qian,Qiang Zhao,Yanli Ji,Yanxing Liu,Tao Liu,Quanfu An
A layer-by-layer (LbL) self-assembly technique was used to construct temperature-responsive multilayer films of polybetaine poly-3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (PDMAPS) and poly(acrylic acid) (PAA). The assembly and disintegration behaviors of PDMAPS/PAA multilayer films were investigated by quartz crystal microbalance (QCM) and atomic force microscopy (AFM). The results indicated that the assembly behaviors of PDMAPS/PAA multilayer films could be well regulated by the pH and temperature of dipping solutions. The disintegration of PDMAPS/PAA multilayer films could be well controlled by varying the disintegration temperature ( T d ) and the pH of buffer solution. The critical disintegration temperature ( T cd ) decreased with increasing pH of buffer solution used. The ionization of carboxylic acid groups (COOH) of PAA and the breakage of intra-chain associations of PDMAPS in multilayer films are two main reasons for the film disintegration. Based on the controllable disintegration of the PDMAPS/PAA multilayer, free-standing multilayer films were successfully prepared by LbL self-assembly of poly(4-vinylpyridiniomethanecarboxylate) (PVPMC) and PAA using PDMAPS/PAA as a sacrificial sublayer.
研究领域:
材料科学
·
生物医学工程
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产品关联
DOI
高影响因子
PHARMAZIE
·
2016
·Vol. 71
·期 5
·269-273
·
IF 1.264
Zhu Chaoran,Zhai Xuejia,Chen Fen,Wang Nanxi,Zhang Xinlin,Lu Yongning
Capsaicin (CAP, trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent substance in hot pepper. However, little is known about the interactions between CAP and clinically used drugs. This study investigated the effect of acute and chronic ingestion of CAP on pharmacokinetics of
simvastatin (SV) and the mechanism of this CAP–drug intercation. CAP was orally administered at doses of 3 and 8 mg·kg-1 for seven consecutive days once daily and on the 1st day and the 7th day, SV (8 mg·kg-1) was injected intravenously. Plasma concentrations
of SV were determined using LC/MS/MS and expression of Ugt1a1 was analyzed by RT-qPCR and Western Blotting. We found that there were 78.0 % (P< 0.05) and 81.2% (P< 0.05) reduction in the AUC(0-∞) of SV, respectively, following pretreatment with two doses
of CAP. The AUC(0-∞) of SV in the two dose group pretreated with CAP for 7 days were decreased significantly, compared to the group for 1 day. Both the RT-qPCR and Western Blotting data indicated that 7 days pretreatment with CAP increased the expression level of Ugt1a1 in
liver. In conclusion, chronic ingestion of CAP enhanced the expression level of Ugt1a1 in liver, causing the food -drug interaction and decrease in SV exposure in rats to a significant extent.
研究领域:
药理学
·
分子生物学
·
毒理学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Xuejing Yang,Wenyu Cao,Xun Gu,Lijie Zheng,Qiuyue Wang,Yingying Li,Fang Wei,Tao Ma,Lu Zhang,Qingqing Wang
Currently, one of the main problems encountered in wound healing therapy is related to inefficient drug delivery. However, dissolving microneedles (DMNs) can be administered percutaneously to effectively deliver a drug to a deep wound area. Simvastatin (SIM) can promote wound healing, albeit its insolubility in water limits its application. Here, we designed a DMNs (SIM-NC@DMNs) drug delivery system loaded with SIM nanocrystals (SIM-NC) and evaluated its efficacy in wound healing. Based on our observations, the dissolution performance of insoluble SIM is significantly improved after the preparation of SIM-NC. For example, the saturation solubility of SIM-NC in deionized water and PBS increased by 150.57 times and 320.14 times, respectively. After the SIM-NC@DMNs are deeply inserted into the wound, the needle portion, which is composed of hyaluronic acid (HA), dissolves rapidly, and the SIM-NC loaded on the needle portion is efficiently released into the deep wound area for optimal therapeutic efficacy. The combination of NC and DMNs makes this system further effective for wound healing. Our cumulative work suggests that the newly developed SIM-NC@DMNs possess great potential in accelerating wound healing. By day 12 after treatment, the residual wound area in the Control group was 21.34 %, while the residual wound area in the SIM-NC@DMNs group was only 2.36 %. This result as well as provides certain evidence of its efficacy for wound healing therapy. The SIM-NC@DMNs drug delivery system may become an efficient treatment modality that promotes wound healing, with a promising potential in the field of wound healing research.
研究领域:
药剂学
·
生物医学工程
·
伤口护理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）