Chinese Medicine
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2020
·Vol. 15
·期 1
·1-18
·
IF 2.96
Qin Zifei,Jia Mengmeng,Yang Jing,Xing Han,Yin Zhao,Yao Zhihong,Zhang Xiaojian,Yao Xinsheng
Background Kang-Ai injection is widely used as an adjuvant therapy drug for many cancers, leukopenia, and chronic hepatitis B. Circulating alkaloids and saponins are believed to be responsible for therapeutic effects. However, their pharmacokinetics (PK) and excretion in vivo and the risk of drug–drug interactions (DDI) through inhibiting human cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes remain unclear.Methods PK and excretion of circulating compounds were investigated in rats using a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC–MS) method. Further, the inhibitory effects of nine major compounds against eleven CYP and UGT isozymes were assayed using well-accepted specific substrate for each enzyme.Results After dosing, 9 alkaloids were found with Cmax and t1/2 values of 0.17–422.70 μmol/L and 1.78–4.33 h, respectively. Additionally, 28 saponins exhibited considerable systemic exposure with t1/2 values of 0.63–7.22 h, whereas other trace saponins could be negligible or undetected. Besides, over 90% of alkaloids were excreted through hepatobiliary and renal excretion. Likewise, astragalosides and protopanaxatriol (PPT) type ginsenosides also involved in hepatobiliary and/or renal excretion. Protopanaxadiol (PPD) type ginsenosides were mainly excreted to urine. Furthermore, PPD-type ginsenosides were extensively bound (fu-plasma approximately 1%), whereas astragalosides and PPT-type ginsenosides displayed fu-plasma values of 12.35% and 60.23–87.36%, respectively. Moreover, matrine, oxymatrine, astragaloside IV, ginsenoside Rg1, ginsenoside Re, ginsenoside Rd, ginsenoside Rc, and ginsenoside Rb1 exhibited no inhibition or weak inhibition against several common CYP and UGT enzymes IC50 values between 8.81 and 92.21 μM. Through kinetic modeling, their inhibition mechanisms towards those CYP and UGT isozymes were explored with obtained Ki values. In vitro-in vivo extrapolation showed the inhibition of systemic clearance for CYP or UGT substrates seemed impossible due to [I]/Ki no more than 0.1.Conclusion sWe summarized the PK behaviors, excretion characteristics and protein binding rates of circulating alkaloids, astragalosides and ginsenosides after intravenous Kang-Ai injection. Furthermore, weak inhibition or no inhibition towards these CYP and UGT activities could not trigger harmful DDI when Kang-Ai injection is co-administered with clinical drugs primarily cleared by these CYP or UGT isozymes.
研究领域:
药理学
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药剂学
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药物代谢
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毒理学
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DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2021
·Vol. 413
·期 17
·4459-4469
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IF 4.157
Yang Huiyi,He Qiyi,Eremin Sergei A.,Pan Junkang,Zou Yikui,Cui Xiping,Zhao Suqing
In this paper, five fluorescein-labeled dehydroepiandrosterone (DHEA) derivatives (tracers) with different chain lengths between the fluorescein and hapten were synthesized and featured so as to establish a fluorescence polarization immunoassay (FPIA) for DHEA detection in human urine samples with previously prepared polyclonal antibody against DHEA. The outcomes of the structure of tracer on FPIA sensitivity were investigated. Under the optimal condition, the fluorescence polarization value (FP) decreases linearly in DHEA concentration, ranging from 1.6 to 243.3 ng mL −1 , with the limit of detection of 1.1 ng mL −1 and IC 50 value of 25.1 ng mL −1 . Moreover, the developed FPIA was time-saving as it could complete the detection within 3 min. FPIA and commercial enzyme-linked immunosorbent assay kit were both applied to analyze the spiked human urine samples with DHEA. Excellent recoveries (92.1–108.0%) and satisfactory correlation coefficient ( R 2 = 0.98) were acquired with the two methods, indicating that the developed FPIA was a fast and efficient screening immunoassay with accuracy and sensitivity for DHEA detection in human urine samples.
Graphical abstract
研究领域:
分析化学
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免疫学
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生物化学
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医学诊断
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2017
·
IF 2.536
Qiaoqiao Shi,Jie Huang,Yaning Sun,Mengqi Yin,Mei Hu,Xiaofei Hu,Zhijun Zhang,Gaiping Zhang
An ultrasensitive method for the detection of antibiotics in milk is developed based on inexpensive, simple, rapid and portable lateral flow immunoassay (LFI) strip, in combination with high sensitivity surface-enhanced Raman spectroscopy (SERS). In our strategy, an immunoprobe was prepared from colloidal gold (AuNPs) conjugated with both a monoclonal antibody against neomycin (NEO-mAb) and a Raman probe molecule 4-aminothiophenol (PATP). The competitive interaction with immunoprobe between free NEO and the coated antigen (NEO-OVA) resulted in the change of the amount of the immobilized immunoprobe on the paper substrate. The LFI procedure was completed within 15 min. The Raman intensity of PATP on the test line of the LFI strip was measured for the quantitative determination of NEO. The IC 50 and the limit of detection (LOD) of this assay are 0.04 ng/mL and 0.216 pg/mL of NEO, respectively. There is no cross-reactivity (CR) of the assay with other compounds, showing high specificity of the assay. The recoveries for milk samples with added NEO are in the range of 89.7%–105.6% with the relative standard deviations (RSD) of 2.4%–5.3% ( n = 3). The result reveals that this method possesses high specificity, sensitivity, reproducibility and stability, and can be used to detect a variety of antibiotic residues in milk samples.
研究领域:
分析化学
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食品安全
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生物技术
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DOI
PubMed
高影响因子
EUROPEAN FOOD RESEARCH AND TECHNOLOGY
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2020
·Vol. 246
·期 9
·1857-1865
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IF 2.366
Yang Fanfan,Xu Long,Liu Xiang,Chen Chen,Dias Alberto C. P.,Zhang Xiaoying
Abstract Bisphenol S (BPS) is a major alternative to Bisphenol A (BPA) newly applied in food packing material and disrupts reproductive and developmental endpoints through endocrine pathways. This study aimed to develop a rapid, sensitive, and accurate chemiluminescence immunoassay (CLIA) for the detection of BPS in canned beverage. Anti-BPS monoclonal antibody (mAb) was generated by immunizing Balb/c mice with immunogen (BPS–BSA conjugation). CLIA assay conditions, including 3-[9-(((3-( N -succinimidyloxycarboxypropyl) [4-methxylphenyl] sulfonyl) amine) carboxyl]-10-acridiniumyl)-1-propanesulfonate inner salt (NSP-SA-NHS) labeling ratio (1:40), antigen concentration (1 μg mL −1 ) and antibody titer (1:8000; 125 ng mL −1 in PBS (0.01 M, pH 7.4)) were determined, respectively. The half inhibition concentration (IC 50 ), detection limit (IC 10 ), and working range of the CLIA in canned beverage were 0.04, 1.48, and 0.32–5 ng mL −1 , respectively. Cross-reactivity with other bisphenols (4,4′-thiodiphenol, Bisphenol F, 4,4′- dihydroxy benzophenone, Bisphenol A and Bisphenol B) was less than 0.56%, and the recovery rates of BPS in canned beverage ranged from 80 to 109.2% (intra-assay) and from 82 to 108.4% (inter-assay). The results of CLIA were compared with high-performance liquid chromatography–UV (HPLC–UV) analysis, showing a good correlation of 0.956. After proper sample pre-treatment, this method allows relatively large amounts of sample analysis in a limited time period (30 min). Thus, it was deemed suitable and efficient for routine screening of BPS in canned beverage. Graphic abstract
研究领域:
分析化学
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环境科学
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食品安全
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免疫学
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毒理学
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DOI
高影响因子
MOLECULAR PHARMACEUTICS
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2014
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IF 4.787
Yuling Bao,Yuanyuan Guo,Xiangting Zhuang,Dan Li,Bolin Cheng,Songwei Tan,Zhiping Zhang
To overcome the multidrug resistance (MDR) of P-glycoprotein (P-gp) substrate anticancer drugs, such as paclitaxel (PTX), a novel dual-functional prodrug, D-α-tocopherol polyethylene glycol succinate (TPGS) based PTX prodrug (TPGS-S-S-PTX), was synthesized here to fulfill the synergistic effect of P-gp inhibiting and intracellular redox-sensitive release. The prodrug could self-assemble into stable micelles in physiological environment with a diameter of ∼140 nm, while it disassociated in reductive condition and released PTX and TPGS active derivatives rapidly. High cell cytotoxicity in PTX-resistant human ovarian cell line A2780/T was observed with enhanced PTX accumulation due to the P-gp inhibition by the TPGS moiety. The IC50 of TPGS-S-S-PTX was 55% and 91% more effective than that of Taxol (clinical formulation of PTX) and uncleavable TPGS-C-C-PTX prodrug, respectively. This was found to be related with the increased apoptosis/necrosis and cell arrest in G2/M phase. In vivo evaluation of the TPGS-S-S-PTX prodrug exhibited an extended half-life, increased AUC (area under the concentration–time curve), enhanced tumor distribution and significant tumor growth inhibition with reduced side effects as compared to Taxol and TPGS-C-C-PTX. This prodrug has great potential in improving efficiency in the treatment of MDR tumors.
研究领域:
药学
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肿瘤学
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药物递送系统
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
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2021
·
IF 6.165
Sha Li,Xing Hu,Junhui Pan,Deming Gong,Guowen Zhang
The inhibition of pancreatic lipase by apigenin, a natural dietary flavonoid, was investigated by various spectroscopic techniques and computational simulation. The results showed that apigenin reversibly inhibited pancreatic lipase activity in a competitive manner with an IC 50 value of 0.45 ± 0.03 mM, and its combination with orlistat showed a synergistic effect. Formation of a complex between apigenin and pancreatic lipase driven by hydrogen bonds resulted in the fluorescence quenching of the enzyme through a static manner. The binding constant of apigenin with the enzyme was (5.47 ± 0.01) × 10 4 L mol −1 at 298 K, and the kinetic process of their interaction was characterized by the resolved concentration profiles and pure spectra of different components from the multivariate curve resolution-alternating least squares algorithm. The inhibition of pancreatic lipase by apigenin was mainly attributed to the tighter structure of the enzyme and the interaction between apigenin and the amino acid residues in the active center of the enzyme to prevent the substrate from being oxidized, as demonstrated by the analysis of circular dichroism spectra and molecular docking. Molecular dynamics simulation further characterized the binding conformation and property of apigenin-pancreatic lipase complex. This study provides novel insights into the mechanism of apigenin as pancreatic lipase inhibitor and the development of apigenin as an anti-obesity nutrient.
研究领域:
药理学
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生物化学
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分子生物学
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营养学
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产品关联
DOI
高影响因子
PHYTOCHEMISTRY
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2017
·
IF 3.205
Miao Wang,Dongyu Gu,Haoquan Li,Qi Wang,Jie Kang,Tingting Chu,Hong Guo,Yi Yang,Jing Tian
A facile method based on gas chromatography–mass spectrometry (GC–MS) and molecular docking was established to analyze, identify, and predict lipase inhibitors in volatile oil from Pinus massoniana L. needles (PMLN). The volatile oil, with an IC 50 value of 15.25 ± 0.06 μg/mL, exhibited potential inhibitory activity against lipase in vitro. In total, 33 compounds were identified from the volatile oil through GC–MS analysis. The major compounds in the volatile oil were β-pinene (39.24%), α-pinene (14.68%), germacrene D (9.08%), caryophyllene (6.94%), α-terpineol (5.39%), β-phellandrene (4.82%), and D-limonene (3.93%). The identified compounds were individually docked with lipase as the target through molecular docking. Among the compounds, longifolene characterized by preferable binding energy and the good inhibition constant exhibited potential lipase inhibitory activity. The IC 50 value of longifolene was 25.10 ± 0.49 μM, indicating that this compound is the active ingredient responsible for the lipase inhibitory activity of PMLN volatile oil.
研究领域:
药理学
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分析化学
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植物科学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2024
·
IF 6.1
Lingfeng Wang,Ying Qian
In this paper, the heavy-atom-free BODIPY dendrimer TM4-BDP was synthesized for the near-infrared photodynamic therapy, which was composed of the triphenylamine-BODIPY dimer and four 1-(2-morpholinoethyl)-1H-indole-3-ethenyl groups. The TM4-BDP could achieve the near-infrared photodynamic therapy through two different photosensitive pathway, which include the one-photon excitation at 660 nm and two-photon excitation at 1000 nm. In the one-photon excitation pathway, the TM4-BDP could generate singlet oxygen and superoxide radical under 660 nm illumination. In addition, the one-photon PDT experiment in human nasopharyngeal carcinoma (CNE-2) cells also indicated that the TM4-BDP could specific accumulate in lysosomes and shown great cell phototoxicity with the IC50 at 22.1μM. In the two-photon excitation pathway, the two-photon absorption cross section at 1030 nm of TM4-BDP was determined as 383 GM, which make it could generate the reactive oxygen species (ROS) under 1000 nm femtosecond laser excitation. Moreover, the two-photon PDT experiment in zebrafish also indicated the TM4-BDP could be used for the two-photon fluorescence imaging and the two-photon induced ROS generation in biological environment. Besides that, in the ROS generation mechanism aspect, the TM4-BDP employ the novel spin-vibronic coupling intersystem crossing (SV-ISC) process for the mechanism of ROS generation and the femtosecond transient absorption spectra indicated that this novel SV-ISC mechanism was closely related with its’ lifetime of charge transfer state. These above experiments of TM4-BDP demonstrate that the dendrimer design was an effective strategy for constructing heavy-atom-free NIR BODIPY photosensitizers and lay the foundation for the two-photon photodynamic therapy in the future clinical trails.
研究领域:
光动力疗法
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纳米技术
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生物医学工程
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材料科学
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光学
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药物化学
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分子生物学
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细胞生物学
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斑马鱼研究
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Hong-Jiao Zhang,Li-Wei He,Ke-Min Dong,Song-Yuan Li,Can Luo,Jia-Qi Han,Rui Li
The development of simple, selective and sensitive analytical methods to effectively monitor α-glucosidase (α-Glu) and discover its new inhibitors is very critical for the diagnosis and treatment of diabetes. Herein, an autofluorescence-free sensing method based on β-cyclodextrin (β-CD) functionalized persistent luminescence nanoparticle (PLNP) is established for the detection of α-Glu activity and its inhibitor. The p-nitrophenol (PNP) produced by the hydrolysis of substrate p-nitrobenzene-α-D-glucopyranoside (PNPG) by α-Glu in the system can be selectively captured by the β-CD on the nanoprobe to form adducts through the host guest effect between them, resulting in persistent luminescence quenching due to electron transfer (ET) effect. The proposed method provides a good linear relationship within the range of 5–80 U/L and a low detection limit of 0.9 U/L, and can detect α-Glu in human serum with the recovery rate of 95.4–103.3 %. Furthermore, the detection system can measure the inhibitory ability of acarbose with an IC 50 value of 349 μM, proving its good potential for application.
研究领域:
分析化学
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纳米技术
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生物医学工程
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糖尿病研究
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产品关联
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Ruimin Lu,Yan Zhang,Daoping Zeng,Qihua Xu,Dan Wang,Peng Dai,Weijie Deng,Lin Kang,Xiaoxiao Ke,Luying Duan,Yanping Hong,Wuying Yang
An ultrasensitive indirect competitive chemiluminescence immunoassay (icCLEIA) based on monoclonal antibodies (mAb) for the effective detection of nitrofurantoin metabolite 1-aminohydantoin was developed under optimal conditions in our study. 1-aminohydantoin (AHD) was derivatized with m-formylphenoxyacetic acid (MCEP) to obtain a hapten MCEPAHD. The developed icCLEIA based on anti-MCEPAHD mAb showed high sensitivity to competing drugs 2-nitrophenyl derivative of AHD (2NPAHD) with a limit of detection (LOD) 0.04 ng/mL and a 50 % inhibitory concentration (IC 50 ) 0.27 ng/mL, and the icCLEIA had an ultra-high specificity for 2NPAHD, with little cross-reactivity with structural analogues other than parent drug nitrofurantoin. The mean recovery of AHD in fish samples was found to be 97.0 % to 118.5 %, with a coefficient of variation of less than 7.0 %. A comparison of the results of ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with those of icCLEIA demonstrated good linearity. These assay results indicated that the prepared mAb against MCEPAHD and the developed icCLEIA in our research can be used for simple, fast and sensitive detection of AHD residues in animal tissues.
研究领域:
分析化学
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免疫学
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兽医学
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食品安全
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产品关联
DOI
高影响因子
FOOD CHEMISTRY
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2024
·
IF 8.5
Haotong Zhang,Li Liang,Baoguo Sun,Rui Yang,Zunying Liu,Xiangzhao Mao,Yuyu Zhang
Angiotensin-I-converting enzyme (ACE) inhibitory activity and saltiness-enhancing properties of chicken-derived umami peptides were investigated. DGGRYY and NEFGYSNR were screened and the IC 50 values were 28.71 μM and 283.24 μM, indicating their potential as novel ACE inhibitors. DGGRYY and NEFGYSNR have good pH and thermal stability. After gastrointestinal digestion, the ACE-inhibitory activity of DGGRYY retained about 53 %, whereas NEFGYSNR retained about 57 %. The inhibition pattern of both peptides was determined to be uncompetitive, consisting with the result of multiple ligand docking that the binding sites were outside the ACE active pocket. Trp59, Tyr62, Asp121, Arg124, and Ser516 were the key binding sites that contributed to the total binding energy. In addition, saltiness and palatability models were established according to sensory analysis and central composite design. In 0.1 % ∼ 0.3 % NaCl solutions, the addition of DGGRYY and NEFGYSNR could enhance the salty intensity and compensate for the palatability loss caused by salt reduction.
研究领域:
食品科学
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生物化学
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营养学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2020
·
IF 4.192
Shuangshuang Zhao,Cheng Xiao,Jiajie Wang,Kailin Tian,Wenxia Ji,Tingting Yang,Babar Khan,Guoliang Qian,Wei Yan,Yonghao Ye
β-Ketoacyl-acyl carrier protein synthase III (KAS III, FabH) is essential for bacterial fatty acid biosynthesis. Recent studies indicate that FabH can be a potential target for bactericide development. In the present study, an immobilized FabH column was developed and used to screen FabH inhibitors from complex natural product extracts. Combined with HPLC, four secondary metabolites, alternariol (1), altenuisol (2), alterlactone (3), and dehydroaltenusin (4), were site-directed, isolated, and identified from the crude extract of Alternaria alternata ZHJG5. These compounds showed inhibitory activities on FabH of Xanthomonas oryzae pv. oryzae (Xoo) with IC50 values from 29.5 to 74.1 μM and also displayed a varying degree of antibacterial activities against Xoo with minimal inhibitory concentration values from 4 to 64 μg/mL. Molecular modeling was then used to picture how the compounds interact with XooFabH. Two inhibitors, compounds 1 and 3, exhibited significant bactericidal activity against rice bacterial leaf blight with a protective efficiency of 66.2 and 82.5% at the concentration of 200 μg/mL, respectively, suggesting that they could be lead candidates to develop novel bactericides.
研究领域:
微生物学
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药理学
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植物病理学
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生物化学
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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）