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nifedipine induced autophagy through Beclinl and mTOR pathway in endometrial carcinoma cells

Chinese Medical Journal 2012年第17期125卷 3120-3126页

作者： BAO Xiao-xia XIE Bu-shan LI Qi LI Xiao-ping WEI Li-hui WANG Jian-liu Department of Obstetrics and Gynecology Peking University People's Hospital Beijing 100044 China Department of Gastroenterology First Affiliated Hospital of Nanchang University Nanchang Jiangxi 330006 China

Background Endometrial carcinoma is one of the most common female tract genital malignant tumors. nifedipine, an L-type calcium channel antagonist can inhibit cell proliferation of carcinomas. Recent studies indicated that a rise in the free cytosolic calcium （[Ca2±]c） was a potent inducer of autophagy. Here, we investigated the relationship between nifedipine and autophagy in Hec-IA cells. Methods Cells were cultured with nifedipine （10 μmol/L） and harvested at different times for counting cell number. MTT assay was applied to evaluate the cell viability and transwell assay to reveal cell migration. Apoptotic cells were detected with annexin V/PI assay. Then cells were treated with 3-methyladenine （3-MA）（2.5 mmol/L） for 0, 5, 15, 30, 60, and 120 minutes and the expression of the L-type calcium channel alphalD （Cavl.3） protein was detected. At last, cells were cultured and assigned to four groups with different treatment： untreated （control group）, 10 μmol/L nifedipine （N group）, 2.5 mmol/L 3-MA （3-MA group）, and 10 μmol/L nifedipine plus 2.5 mmol/L 3-MA （N±3MA group）. Autophagy was detected with GFP-LC3 modulation by fluorescent microscopy, and expression of the autophagy-associated proteins （LC3, Beclinl and P70s6K） by Western blotting and monodansylcadaverine （MDC） labeled visualization. Results Proliferation of Hec-lA cells was obviously suppressed by nifedipine compared with that of the untreated cells for 24, 48, and 96 hours （P=0.000 for each day）. The suppression of migration ability of the nifedipine-treated cells （94.0±8.2） was significantly different from that of the untreated cells （160.00±9.50, P=0.021 ）. The level of early period cell apoptosis induced by nifedipine was （2.21_±0.19）%, which was （2.90±0.13）% in control group （P=-0.052）, whereas the late period apoptosis level reached （10.38_±0.96）% and （4.40_±0.60）% （P=0.020）, respectively. The 3-MA group induced a slight increase in the Cavl.3 levels within 15 minutes, but significantly attenuated the Cavl.3 levels after 30 minutes. There were more

关键词： nifedipine L-type autophagy endometrial carcinoma

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Role of kaempferol to increase bioavailability and pharmacokinetics of nifedipine in rats

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Chinese Journal of Natural Medicines 2019年第9期17卷 690-697页

作者： PARK Ji-Won CHOI Jin-Seok Hazardous Substances Analysis Division Gwangju Regional Office of Food and Drug SafetyGwangju 61012Republic of Korea Department of Medical Management Chodang UniversityJeollanam-do 58530Republic of Korea

Herein,the purpose of this study is to evaluate the effects of kaempferol on bioavailability and pharmacokinetics of nifedipine and its metabolite dehydronifedipine in rats.The experimental design is based on with or without kaempferol in the oral and intravenous administration of nifedipine in rats.Moreover,the pharmacokinetic parameters including nifedipine and dehydronifedipine were evaluated in rats.The in vitro studies of kaempferol were investigated on P-glycoprotein(P-gp)and cytochrome P450(CYP)3A4 activity.Kaempferol reduced a 50%inhibitory concentration(IC50)of 8.6μmol·L-1 on CYP3A4 enzyme activity.Moreover,kaempferol clearly improved the cell internalization of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp.Depending on increased concentrations of kaempferol,the areas under the plasma concentration–time curve(AUC0-∞)and the peak concentration(Cmax)of nifedipine were increased after oral and intravenous administration.Moreover,the absolute bioavailability(AB)and relative bioavailability(RB)of nifedipine in the presence of kaempferol was significantly higher than those of the control group after oral and intravenous administration.Improvement of bioavailability of nifedipine by kaempferol may be mainly because of the inhibition of the P-gp-mediated efflux transporter in the small intestine and CYP3A4-mediated metabolism in the small intestine or liver,or both.

关键词： nifedipine Kaempferol CYP3A4 P-gp Pharmacokinetics Bioavailability

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Development and characterization of ethylcellulose based microsphere for sustained release of nifedipine

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Journal of Pharmaceutical Analysis 2016年第5期6卷 341-344页

作者： Patitapabana Parida Subash Chandra Mishra Subhashree Sahoo Ajit Behera Bibhukalyan Prasad Nayak Department of Biotechnology and Medical Engineering NIT Rourkela Odisha 769008 India Department of Metallurgical and Materials Engineering NIT Rourkela Odisha 769008 India Department of Pharmaceutics Kanakmanjari Institute of Pharmaceutical Sciences Rourkela Odisha 769015 India Department of Metallurgical and Materials Engineering IIT Kharagpur West Bengal 721302 India

This article introduced the work of ethylcellulose based polymeric microsphere loaded with nifedipine for reduction in frequency of administration with low solubility in aqueous medium and high rate of absorption in the stomach. The non-aqueous polymeric suspension was put dropwise into an aqueous medium containing polyvinyl alcohol as a surfactant for the synthesis of microsphere by solvent evaporation. The microspheres were characterized by different techniques, namely, XRD, SEM, and NMR. The formation of microspheres was confirmed by SEM. XRD analysis revealed the semi-crystallinity nature of microspheres. The NMR study indicated the presence of hetero-aromatic nucleus in the microsphere.

关键词： nifedipine Microsphere Solvent evaporation Sustained release

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Development and characterization of nifedipine-amino methacrylate copolymer solid dispersion powders with various adsorbents

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Asian Journal of Pharmaceutical Sciences 2017年第4期12卷 335-343页

作者： Yotsanan Weerapol Sontaya Limmatvapirat Jurairat Nunthanid Srisuda Konthong Supakij Suttiruengwong Pornsak Sriamornsak Pharmaceutical Biopolymer Group(PBiG) Faculty of PharmacySilpakorn UniversityNakhon Pathom 73000Thailand Faculty of Pharmaceutical Sciences Burapha UniversityChonburi 20131Thailand Department of Pharmaceutical Technology Faculty of PharmacySilpakorn UniversityNakhon Pathom 73000Thailand Department of Materials Science and Engineering Faculty of Engineering and Industrial TechnologySilpakorn

Solid dispersions of nifedipine(NDP), a poorly water-soluble drug, and amino methacrylate copolymer(AMCP) with aid of adsorbent, that is, fumed silica, talcum, calcium carbonate,titanium dioxide, and mesoporous silica from rice husks(SRH), were prepared by solvent method. The physicochemical properties of solid dispersions, compared to their physical mixtures, were determined using powder X-ray diffractometry(PXRD) and differential scanning calorimetry(DSC). The surface morphology of the prepared solid dispersions was examined by scanning electron microscopy(SEM). The dissolution of NDP from solid dispersions was compared to NDP powders. The effect of adsorbent type on NDP dissolution was also examined. The dissolution of NDP increased with the ratio of NDP:AMCP:adsorbent of 1:4:1 when compared to the other formulations. As indicated from PXRD patterns, DSC thermograms and SEM images, NDP was molecularly dispersed within polymer carrier or in an amorphous form, which confirmed the better dissolution of solid dispersions. Solid dispersions containing SRH provided the highest NDP dissolution, due to a porous nature of SRH, allowing dissolved drug to fill in the pores and consequently dissolve in the medium.The results suggested that solid dispersions containing adsorbents(SRH in particular) demonstrated improved dissolution of poorly water-soluble drug when compared to NDP powder.

关键词： Solid dispersion Poorly water-soluble drug nifedipine Amino methacrylate copolymer Adsorbent Mesoporous silica from rice husks

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Effects　of　Isoprenaline，Phenylephrine　on　Heart　and　Influence　of　nifedipine　on　These　Effects

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1994年第4期14卷 216-219页

作者：马业新余枢赵华月 Department of Internal Medicine Tongji Hospital Tongji Medical University Wuhan

In a perfused isovolumetrically contracting rat heart model, the effects of isoprenaline(IPN) and phenylephrine (PE) on myocardial contraction and relaxation were investigated,and the influence of nifedipine on these effects was studied. Both IPN and PE increased the myocardial contraction and improved its relaxation, but some differences existed.nifedipine (10 nmol/L)substantially inhibited the PE-mediated inotropic effect, but in case of IPN-mediated inotropic ones, it did not.It was assumed that there may be various types of slow channels, one was activated by IPN,and the other, by PE.

关键词： isoprenaline phenylephrine nifedipine myocardial contraction myocardial relaxation slow channel

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Panax Notoginseng Saponins Increases the Blood Concentration of nifedipine by Inhibiting CYP3A4 Enzyme through PXR-and CAR-Mediated Pathway

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World Journal of Traditional Chinese Medicine 2021年第3期7卷 332-338页

作者： Qiu-Hong Li Jiao Zhao Ai-Xia Ju Yong Hu Qing-Song Qie Hong-Bin Xiao Guang Xu Xi-Jun Wang Clinical Pharmacy Laboratory Department of PharmaceuticsSchool of PharmacyHeilongjiang University of Chinese MedicineHarbinChina 9601 Medical Center Drive RockvilleMDUSA

Objective:To explore the mechanism underlying the effect of Panax notoginseng saponins(PNS)on the pharmacokinetics of nifedipine(NF)in rats.Materials and Methods:Twenty-four rats were randomly divided into blank(BL)group,PNS group,NF group,and PNS+NF group,with six rats in each group.Noncompartmental analysis and t-test were carried out to determine the difference between the pharmacokinetic parameters of NF in different groups.CYP3 A4 enzyme activity was calculated using the probe drug method.The mRNA and protein contents of CYP3 A4,nuclear receptor CAR,and PXR in rat liver were quantitatively analyzed by qRT-PCR and Western blot.Results:After the rats were treated with the combination of PNS and NF,the plasma concentration,half-life,peak time,and area under the concentration-time curve of NF increased,whereas the clearance rate decreased.The inhibitory effect on CYP3 A4 enzyme activity was in the following order:PNS+NF group(strongest)>PNS group>NF group,and BL group(weakest).Similar changes were observed for the inhibitory effect on CYP3 A4,CAR,and PXR mRNA and protein content,and the order was as follows:PNS+NF group(weakest)

关键词： CAR CYP3A4 nifedipine Panax notoginseng saponins pharmacokinetics PXR

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STUDY ON PHOTOCHEMICAL DEGRADATION OF nifedipine ANALOGS AND NEW PHOTODEGRADATION-ASSAY METHOD UNDER FLUORESCENT LAMP

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Chinese Science Bulletin 1992年第18期37卷 1565-1570页

作者：梁颖彬武国杰马小亚王莉芳 Institute of Clinical Pharmacology Xi'an Medical University Xi'an 710004 PRC

Dihydropyridine is one of the most potent calcium channel blockers at present, in which nifedipine (nif) has been widely used for the treatment of cardiovascular diseases. It has been recorded in the Chinese Pharmacopeia (1990) and many other countries’ pharmacopeias. In recent years, the Chinese scholars have found out that mnifedipine has a stronger and more lasting effect on the cardiovascular than nifedipine, but its inhibitory effect on myocardium is weaker. For further study on nifedipine, we intend to search for a highly selective and simple analytical method. The analysis

关键词： nifedipine fluorescent lamp with daylight color photodegradative kinetics photodegradatlon-assay method UV lamp.

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Formulation, optimization & evaluation of mouth dissolving film of nifedipine by using design of experiment

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Asian Journal of Pharmaceutical Sciences 2016年第1期11卷 74-76页

作者： Anil M. Pethe Riddhi B. Desai Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management SVKM’S NMIMS University

The oral mucosa is vascularized,drugs can be absorbed directly and can enter the systemic circulation without firstpass metabolism[1].This advantage can be used in preparing products with increased oral bioavailability of molecules that undergo first pass metabolism.Thus oral mucosa is an attractive site for drug delivery[2,3].The objective of this research work is to formulate mouth dissolving film of nifedipine for enhanced bioavailability.nifedipine is used to treat hypertension and angina pectoris.

关键词： nifedipine Mouth dissolving films DOE

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Dissolution improvement by solid dispersions composed of nifedipine, Eudragit?E and silica from rice husk

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Asian Journal of Pharmaceutical Sciences 2016年第1期11卷 195-196页

作者： Pornsak Sriamornsak Srisuda Konthong Sontaya Limmatvapirat Supakij Suttiruengwong Department of Pharmaceutical Technology Faculty of PharmacySilpakorn UniversityNakhon Pathom 73000Thailand Pharmaceutical Biopolymer Group(PBiG) Faculty of PharmacySilpakorn UniversityNakhon Pathom 73000Thailand Department of Materials Science and Engineering Faculty of Engineering and Industrial TechnologySilpakorn UniversityNakhon Pathom 73000Thailand

nifedipine is a practically water-insoluble drug used therapeutically as a calcium-channel blocker for systemic and coronary vasodilation.Poorly soluble drugs that undergo dissolution rate-limited gastrointestinal absorption generally show increased bioavailability when dissolution is improved by formulation techniques[1].In solid dispersion system,a drug may exist as an amorphous form in polymeric carriers,and this may result in improved solubility and dissolution rate as compared with crystalline drug.Solid dispersion can be prepared by either fusion or solvent method[2].

关键词： nifedipine Solid dispersion Silica Eudragit^(■)E Solvent method

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nifedipine对烟草花粉萌发、花粉管生长及生殖核分裂的影响

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Acta Botanica Sinica 1996年第9期38卷 686-691页

作者：范六民杨弘远周嫦武汉大学生命科学学院植物生殖生物学研究室武汉430072

用细胞学和统计学方法研究了Ｃａ２＋通道专一性阻滞剂ｎｉｆｅｄｉｐｉｎｅ（Ｎｉｆ）对烟草（ＮｉｃｏｔｉａｎａｔａｂａｃｕｍＬ．）离体花粉萌发、花粉管生长及生殖核分裂的影响。１０－４ｍｏｌ／ＬＮｉｆ可抑制花粉萌发。... 详细信息

用细胞学和统计学方法研究了Ｃａ２＋通道专一性阻滞剂ｎｉｆｅｄｉｐｉｎｅ（Ｎｉｆ）对烟草（ＮｉｃｏｔｉａｎａｔａｂａｃｕｍＬ．）离体花粉萌发、花粉管生长及生殖核分裂的影响。１０－４ｍｏｌ／ＬＮｉｆ可抑制花粉萌发。Ｎｉｆ对花粉管生长的影响与其浓度和处理持续时间有关，１０－４ｍｏｌ／ＬＮｉｆ始终抑制花粉管生长；而１０－７～１０－５ｍｏｌ／ＬＮｉｆ在较短时间内起不同程度的促进作用，之后逐渐过渡为抑制花粉管生长。较高浓度处理可使花粉管形态趋向异常，细胞质流动趋于停滞。Ｎｉｆ抑制生殖核的有丝分裂，相对推迟分裂高峰。Ｎｉｆ使花粉管中的金霉素（ＣＴＣ）荧光趋于减弱，表明Ｎｉｆ通过抑制Ｃａ２＋通道活性产生生理效应。

关键词：烟草 nifedipine 花粉管生殖核花粉萌发

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