1.Wuzhi Tablet protects against APAP-induced liver injury at different pretreated intervals in mice
Le-qian XU ; Yan-ying ZHOU ; Yi-ming JIANG ; Yun-hui XING ; Min HUANG ; Hui-chang BI
Acta Pharmaceutica Sinica 2021;56(4):1147-1154
Acetaminophen (APAP, also known as paracetamol)-induced liver injury is the leading cause of drug-induced liver injury in the world. Wuzhi Tablet (WZ, an ethanol extract of
2.Determination of protein binding rate of oleanolic acid in human plasma and serum albumin.
Hong ZHANG ; Hui-fen ZHANG ; Hui-chao CHANG ; Xiao HAN ; Kai-shun BI ; Xiao-hui CHEN
Acta Pharmaceutica Sinica 2011;46(2):243-246
A LC-MS method was established for the determination of the protein binding rates of oleanolic acid in human plasma and serum albumin. The equilibrium dialysis combined with LC-MS to determine the total concentration in plasma and free drug concentration of oleanolic acid was carried out. The human plasma protein binding rates of oleanolic acid at three concentrations were 79.6%, 81.9% and 63.3%, respectively. The human serum albumin protein binding rates of oleanolic acid at three concentrations were 53.5%, 56.6% and 47.7%, respectively. The method is shown to be simple, accurate, sensitive and specific for the determination of biological samples. The protein binding rates in human plasma and serum albumin were of high strength.
Chromatography, Liquid
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methods
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Dialysis
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Humans
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Mass Spectrometry
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methods
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Oleanolic Acid
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blood
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Protein Binding
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Sensitivity and Specificity
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Serum Albumin
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metabolism
3.Dynamic change of hepatocyte during PXR-induced liver enlargement
Jia-ning TIAN ; Rui-min WANG ; Xiao YANG ; Jie YANG ; Yi-fei ZHANG ; Min HUANG ; Hui-chang BI
Acta Pharmaceutica Sinica 2021;56(5):1360-1368
Pregnane X receptor (PXR), a member of nuclear receptor superfamily, plays an important role in xenobiotic and endogenous metabolism, endocrine balance, and cell proliferation,
4.Effects of posttranslational modification on the activity of cytochrome P450: current progress.
Yu-hua LI ; Hui-chang BI ; Min HUANG
Acta Pharmaceutica Sinica 2011;46(5):487-492
Regulation of the activity of CYP450 has always been research focus of drug metabolism. The effect of compounds on the mRNA and protein expression level of CYP450 is the main purpose of most of the existing reports. In recent years, the protein modification in the posttranslation level has been found to participate in maintaining the proper function of CYP450, thus effect of posttranslational modification on the enzyme activity has been paid more and more attention. Posttranslational modifications including phosphorylation, nitration, and ubiquitination have been described to regulate the activity of CYP450. In this paper, recent developments in the effects of posttranslational modifications on the activity of CYP450 have been reviewed.
Animals
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Cytochrome P-450 Enzyme System
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genetics
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metabolism
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Glycosylation
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Humans
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Nitric Oxide
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metabolism
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Oxidation-Reduction
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Phosphorylation
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Protein Processing, Post-Translational
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RNA, Messenger
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metabolism
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Ubiquitination
5.Microstructure of novel solid lipid nanoparticle loaded triptolide.
Dong-zhi HOU ; Chang-sheng XIE ; Xiang-liang YANG ; Hui-bi XU ; Qi-neng PING
Acta Pharmaceutica Sinica 2007;42(4):429-433
Novel solid lipid nanoparticle (SLN) system is prepared with Compritol ATO 888 and tricaprylic glyceride. DSC, XRD, SAXS and NMR are employed to study the novel carrier property and microstructure. When the peak melting point decreased from 70.8 degrees C to 61.4 degrees C, the enthalpy sharply decreased. It could be concluded that the regular crystal lattices in the novel carriers are broken out for the oil joined in them. Melting behavior is occurred at -17.7 degrees C while novel SLN is composed of oil and solid lipid mixture from the DSC measurement. Most alpha phase and least beta' phase are in the nano carrier system whether drug loading or not from the XRD investigation. There is only 0.1 nm change of long space among the novel SLN made of mixture and the lipid matrix and traditional SLN; therefore, it is impossible of the oil molecular insert into the solid glyceride structure. Since the different melting behavior (DSC measurements) and molecular move state (NMR investigations), two lipid matrix are still in two state of liquid and solid lipid in the novel SLN carrier. Presume the microstructure of the novel SLN prepared by our experiment would be that liquid oil has formed superfine nano accommodation encapsulated with solid lipid, but the whole particle is still in nano size range.
Calorimetry, Differential Scanning
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Caprylates
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chemistry
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Diterpenes
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administration & dosage
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chemistry
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Drug Carriers
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chemistry
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Drug Delivery Systems
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Epoxy Compounds
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administration & dosage
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chemistry
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Fatty Acids
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chemistry
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Magnetic Resonance Spectroscopy
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Nanoparticles
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Particle Size
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Phenanthrenes
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administration & dosage
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chemistry
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Triglycerides
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chemistry
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X-Ray Diffraction
6.Experimental study on the effect of ginkgo bioba extract on the expression of heme oxygenase-1 in bronchial asthma.
Jin-Rong ZENG ; Chang-Ming WANG ; Yan ZENG ; Bi-Wen MO ; Hui HUANG
Chinese Journal of Applied Physiology 2003;19(3):302-305
AIMTo explore the effect of the ginkgo bioba extract on the expression of heme oxygenase-1 (HO-1) in bronchial asthma.
METHODS30 guinea pigs were randomly divided into 3 groups (n = 10): (1) Normal control group; (2) Asthmatic group; (3) Therapeutic group. Blood carbon monoxide Hb (COHb) percent value, Airway resistance and eosinophilic inflammation of airway wall were observed, the expression of HO-1 in lung tissue were observed by immunohistochemical staining.
RESULTSThe expression of HO-1 was mainly located in airway epithelium in these 3 groups, the optical densities were 0.170 +/- 0.020, 0.707 +/- 0.058, 0.397 +/- 0.034, respectively. The asthmatic group showed higher optical densities than that of the normal control group (P < 0.01), and the therapeutic group showed lower optical density than asthmatic group (P < 0.01).
CONCLUSIONThe expression of HO-1 is inhibited significantly by the treatment of the ginkgo bioba extract, which may be one of the mechanism for treating asthma by ginkgo bioba extract.
Animals ; Asthma ; drug therapy ; metabolism ; Ginkgo biloba ; Guinea Pigs ; Heme Oxygenase-1 ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology
7.Construction and function identification of luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR.
Shuo YANG ; Jia-li LI ; Hui-chang BI ; Shou-ning ZHOU ; Xiao-man LIU ; Hang ZENG ; Bing-fang HU ; Min HUANG
Acta Pharmaceutica Sinica 2016;51(1):80-85
This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3-vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P < 0.001). For rs696G > A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P < 0.05) and 56.1% (P < 0.001) lower than those containing G allele (pGL3-rs8904C/rs696G and pGL3-rs8904T/rs696G), respectively. For rs8904C > T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity.
3' Untranslated Regions
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Genes, Reporter
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Genetic Vectors
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Humans
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I-kappa B Proteins
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genetics
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Luciferases
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NF-KappaB Inhibitor alpha
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Plasmids
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Polymorphism, Single Nucleotide
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Promoter Regions, Genetic
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Transfection
8.Inhibition of human cytochrome P-450 CYP1A2 by flavonoids: a quantitative structure-activity relationship study .
Jian-Kang LI ; Fan HE ; Hui-Chang BI ; Zhong ZUO ; Bai-dong LIU ; Hai-bin LUO ; Min HUANG
Acta Pharmaceutica Sinica 2008;43(12):1198-1204
The inhibition activity of 36 flavonoids against CYP1A2 was determined by our previously developed in vitro method. The Comparative Molecular Similarity Indexes Analysis (CoMSJA) approach was used to probe the quantitative relationships between the flavonoids' molecular structural descriptors and their inhibitory activities. A reliable CoMSIA model with the combined electrostatic and hydrophobic fields was derived with the regression coefficient R2 of 0.948 and the cross-validation regression coefficient q2 of 0.630, separately, which is capable of elucidating the quantitative relationship between the 3D structural descriptors of the flavones and their bioactivities. Comparing with flavone, the larger pi-pi conjugated system of alpha-naphthoflavone significantly improved the biologically inhibitory ability. Based on the core structure of the latter, either electropositive substituents or hydrophobic groups at the 6, 3', and 4' ring positions or electronegative counterparts at the 5 ring position, can enhance the inhibitory potency against CYP1 A2 according to the CoMSIA contour maps.
Cytochrome P-450 CYP1A2
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metabolism
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Cytochrome P-450 CYP1A2 Inhibitors
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Flavonoids
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chemistry
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pharmacology
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Humans
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Microsomes, Liver
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metabolism
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Models, Molecular
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Molecular Structure
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Quantitative Structure-Activity Relationship
9.Advances in the research of pregnane X receptor and constitutive androstane receptor.
Bing-fang HU ; Hui-chang BI ; Min HUANG
Acta Pharmaceutica Sinica 2011;46(10):1173-1177
Nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are originally characterized as transcription factors regulating many target genes. Recent works have revealed that these nuclear receptors play critical roles in regulating genes that encode drug metabolism enzymes and modulating hepatic energy metabolism, such as down-regulating gluconeogenesis, fatty acid oxidation, and ketogenesis, as well as up-regulating lipogenesis. Studies on PXR and CAR have important implication on drug-drug interaction (DDI) and potential disease treatment targets.
Animals
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Drug Interactions
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Energy Metabolism
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Glucose
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metabolism
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Glucose-6-Phosphate
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metabolism
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Humans
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Inflammation
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metabolism
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Lipid Metabolism
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Liver
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metabolism
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NF-kappa B
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metabolism
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Receptors, Cytoplasmic and Nuclear
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physiology
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Receptors, Steroid
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physiology
10.A review on regulation of drug transporters during inflammation.
Hang ZENG ; Hui-Chang BI ; Min HUANG
Acta Pharmaceutica Sinica 2011;46(7):773-779
Drug metabolism will change significantly during inflammation, including the reduction of expression and activity of many drug metabolizing enzymes and transporters. Body would release a series of inflammatory cytokines which can regulate drug metabolizing enzymes. Recent studies have revealed that drug transporters are also regulated by the cytokines with obvious species difference. Mechanism studies show that several transcription factors play important roles during the signal pathways of regulation. This review focuses on the progress in the regulation of drug transporters during inflammation.
ATP Binding Cassette Subfamily B Member 11
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ATP Binding Cassette Transporter, Sub-Family B
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metabolism
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ATP Binding Cassette Transporter, Sub-Family G, Member 2
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ATP-Binding Cassette Transporters
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metabolism
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Animals
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Biological Transport
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Humans
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Inflammation
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metabolism
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Membrane Transport Proteins
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metabolism
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Multidrug Resistance-Associated Proteins
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metabolism
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Neoplasm Proteins
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metabolism
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Organic Anion Transporters
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metabolism
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Organic Cation Transport Proteins
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metabolism
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Signal Transduction