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BIOMEDICAL CHROMATOGRAPHY · 2024 ·Vol. 39 ·期 1 ·e6055 · IF 1.8

Development of a UPLC-MS/MS Method for Bioanalysis of Ethoxysanguinarine and Its Application in Pharmacokinetic Study of Ethoxysanguinarine Nanoemulsion

Jianhui Luo,Songshen Chen,WenYang Song,Yongtong Huang,Song Gao,Jiu Wang

Ethoxysanguinarine (ETSG), a benzophenanthridine alkaloid, exhibits diverse biological activities, including antibacterial, antifungal, anti-inflammatory, antioxidant, and anti-tumor effects. Despite these properties, limited research exists on ETSG in vivo pharmacokinetics due to its poor solubility and low bioavailability. In this study, we developed a rapid and specific UPLC-MS/MS method for ETSG bioanalysis. Sample preparation involved one-step protein precipitation using methanol and phellodendrine as an internal standard (IS). The Waters HSS T3 column (2.1 * 50 mm, 1.8 μM) employed a gradient elution with mobile phases A (2 mmol/L ammonium formate aqueous solution-formic acid [99.8:0.2, v/v]) and B (methanol-formic acid [99.8:0.2, v/v]). Mass analysis via Waters Q-mass spectrometer utilized positive scan mode and multiple reaction monitoring. ETSG and IS were detected at m/z 332.0 → 274.0 and 342.0 → 177.0, respectively, within 7.0 min. The method demonstrated excellent precision, accuracy, recovery, and stability, with a linear calibration curve (1.1–560 ng/mL) and strong correlation coefficient (0.9984). Successful pharmacokinetic evaluation in Sprague–Dawley rats included intravenous ETSG administration and intragastric ETSG nanoemulsion/suspension. This method enables steroidal saponin analysis from ETSG in biological samples.

CAS / MDL: 67-68-5 25322-68-3
研究领域: 药物分析 · 生物化学 · 药理学
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TALANTA · 2015 · IF 3.545

Microchip electrophoretic separation and fluorescence detection of chelerythrine and sanguinarine in medicinal plants

Yue Sun,Yuanyuan Li,Jiajian Zeng,Qixian Lu,Paul C.H. Li

A new method has been developed for separation of chelerythrine and sanguinarine in medicinal plants used in traditional Chinese medicine (TCM). The separation is achieved by microchip electrophoresis (CE) using laser-induced fluorescence detection. The CE separation is achieved by using a hydro-organic medium as the electrolyte buffer. The experimental results are consistent with the prediction by theory in terms of resolution and migration speed because of the low Joule heat generated in microchip CE . In addition, formamide was found to have a potential for separation of molecules with similar chemical structures. Based on these findings, a run buffer containing 50% formamide was used to separate chelerythrine (CHE) and sanguinarine (SAN). The influencing factors, such as solvent of run buffer, pH of buffer, separation distance, and separation voltage, were optimized. Baseline separation of chelerythrine and sanguinarine was achieved within 120   s under an electrical voltage of 1.8   kV. Good linearity was observed in the concentration range of 0.15–550   μg   mL −1 ( r =0.9993) for CHE and in the range of 0.3–600   μg   mL −1 ( r =0.9998) for SAN. A low limit of detection (LOD) was achieved because of the high sensitivity achieved by laser-induced fluorescence detection (i.e. 5.0   ng   mL −1 and 2.0   ng   mL −1 for CHE and SAN, respectively). The contents of CHE are found to be 641.8±7.5 and 134.0±2.3   mg/kg in extracts of Macleaya cordata and Chelidonium majus , respectively, with good recovery of above 99%. The corresponding values for SAN found in these Chinese herbal extracts are 681.8±7.9   mg/kg and 890.5±8.9   mg/kg, respectively.

CAS / MDL: 2447-54-3
研究领域: 分析化学 · 药学
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Journal of Biomaterials and Tissue Engineering · 2022 ·Vol. 12 ·期 9 ·1699-1707 · IF 0.144

Application of Central Composite Design-Based Response Surface Methodology in Optimization of the Preparation Process of Sanguinarine Chitosan Microspheres

Li Chunmei,Ji Yubin,Li Wenlan

We designed the present experiment to prepare the sanguinarine chitosan microspheres. First, using the chitosan as a carrier, we prepared sanguinarine microspheres by emulsion cross-linking method, and determined the drug loading and encapsulation efficiency of sanguinarine microspheres by high performance liquid chromatography (HPLC). Then, taking the particle size as the evaluation indicator, we optimized the preparation process by the central composite design-based response surface methodology (CCD-based RSM). Finally, we performed in vitro release test to examine the cumulative release of sanguinarine microspheres. As a result, the optimal process conditions: 0.06 g for sanguinarine dosage, 0.07 g for chitosan dosage, 2% for acetic acid concentration, 3:10 for volume ratio of oil to water, 40 °C for emulsion cross-linking temperature, 500 r/min for rotation speed, and 5% for emulsifier dosage. Under such conditions, the sanguinarine microspheres had round shape, the average particle size was (8.14±0.13) μm, the particle size distribution was 2–20 μm, the drug loading was (4.58±0.93)%, and the encapsulation efficiency was (54.64±0.39)%, the cumulative release within 24 h was (78.34±1.08)%. In conclusion, we successfully prepared the sanguinarine chitosan microspheres, and they have excellent morphology, suitable particle size, and good sustained-release effect.

研究领域: 药剂学 · 生物医学工程
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JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY · 2018 · IF 4.841

Synthesis and characterization of magnetic molecularly imprinted polymers for enrichment of sanguinarine from the extraction wastewater of M. cordata

Ming Zhong,Yan-Hong Wang,Lu Wang,Rui-Qing Long,Chun-Lin Chen

A novel and efficient pretreatment method is proposed for the enrichment of sanguinarine (SA) from the extraction wastewater of Macleaya cordata (Willd) R. Br. using magnetic molecularly imprinted polymers (MMIPs) as solid phase adsorbent. The obtained MMIPs were synthesized by molecular imprinted technology and were well characterized with TEM, FT-IR, XRD, TGA, and VSM. The adsorption capacity and selectivity of MMIPs were also investigated. The results showed that the obtained MMIPs were core–shell spherical morphologies with an average diameter of 300   nm. The adsorption experiments showed that the MMIPs exhibited an almost three times higher adsorption capacity towards SA ( Q max   =   12.24   mg/g) than magnetic molecularly non-imprinted polymers (MNIPs) ( Q max   =   4.15   mg/g). The calculated parameters of adsorption isotherms and kinetics suggested that the adsorption process matched the Langmuir adsorption isotherm and pseudo-second-order kinetics model. The thermodynamic parameters were calculated, indicating that the adsorption process was spontaneous (ΔG 298K   =   −3.24   kJ/mol). The selectivity experiment showed that the MMIPs displayed higher selective adsorption capacity for SA compared to its reference compounds. Moreover, the MMIPs were applied to enrich SA from the extraction wastewater of M. cordata . The proposed method could provide an effective, simple and environmentally friendly way to identify and enrich SA from the extraction wastewater of M. cordata .

研究领域: 分析化学 · 环境科学 · 药学
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TALANTA · 2020 · IF 5.339

Fishing antitumor ingredients by G-quadruplex affinity from herbal extract on a three-phase-laminar-flow microfluidic chip

Qidan Cai,Jiang Meng,Yuewei Ge,Yan Gao,Yu Zeng,Haifang Li,Yue Sun

A new method for fishing antitumor ingredients by G-quadruplex recognition from Macleaya cordata seeds extracts was established using a three-phase-laminar-flow-chip (TPL chip). The TPL chip integrated the separation of drugs from the complex ingredients and organic solvent extraction, simplifying pretreatment processes and reducing reagents and time. In addition, the chip method showed a lower false negative result, owing to the gentle membrane-free filtration process based on diffusion separation in microchannel. Four ligands with high content in alkaloids of Macleaya cordata seeds were selected, those are chelerythrine (CHE), sanguinarine (SAN), protopine (PRO), and allocryptopine (ALL), which demonstrated affinity with G-quadruplex and were potential for antitumor.

CAS / MDL: 75-78-5 75-09-2 111-27-3
研究领域: 药理学 · 分子生物学 · 药物化学
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TOXICOLOGY MECHANISMS AND METHODS · 2024 · IF 2.8

Studies on pharmacokinetic properties and intestinal absorption mechanism of sanguinarine chloride: in vivo and in situ

Wenqing Sun,Yufeng Xu,Zhiqin Liu,Wei Liu,Hongting Wang,Guanyu Chang,Zihui Yang,Zhen Dong,Jianguo Zeng

Sanguinarine (SAN) is an alkaloid with multiple biological activities, mainly extracted from Sanguinaria canadensis or Macleaya cordata. The low bioavailability of SAN limits its utilization. At present, the nature and mechanism of SAN intestinal absorption are still unclear. The pharmacokinetics, single-pass intestinal perfusion test (SPIP), and equilibrium solubility test of SAN in rats were studied. The absorption of SAN at 20, 40, and 80 mg/L in different intestinal segments was investigated, and verapamil hydrochloride (P-gp inhibitor), celecoxib (MPR2 inhibitor), and ko143 (BCRP inhibitor) were further used to determine the effect of efflux transporter proteins on SAN absorption. The equilibrium solubility of SAN in three buffer solutions (pH 1.2, 4.5 and 6.8) was investigated. The oral pharmacokinetic results in rats showed that SAN was rapidly absorbed (Tmax=0.5 h), widely distributed (Vz/F = 134 L/kg), rapidly metabolized (CL = 30 L/h/kg), and had bimodal phenomena. SPIP experiments showed that P-gp protein could significantly affect the effective permeability coefficient (Peff) and apparent absorption rate constant (Ka) of SAN. Equilibrium solubility test results show that SAN has the best solubility at pH 4.5. In conclusion, SAN is a substrate of P-gp, and its transport modes include efflux protein transport, passive transport and active transport.

研究领域: 药理学 · 药剂学 · 药物递送
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Virulence · 2025 · IF 5.4

EefR mutations drive sanguinarine resistance by activating cryptic multidrug efflux pumps in AcrB-Null Escherichia coli

Hao-Jie Shen,Jun-Feng Wang,Zheng-Jie Xue,Jia-Qi Shi,Bing Chen,Dong-Min Chen,Ni-Pi Chen,Yu-Dong Li,Chao-Dong Qian

Antimicrobial resistance is one of the greatest threats to global health. A thorough comprehension of the underlying processes through which bacteria evolve the ability to withstand diverse stressors is vital for the development of efficacious strategies to address this challenge. This study aimed to elucidate the mechanisms underlying the adaptation of an acrB-deficient strain of Escherichia coli ATCC 35218 (35218m) to sanguinarine (SAN), the main component of phytobiotic derived from Macleaya cordata. Analysis of the in vitro-selected SAN-resistant clones of strain 35218m led to the identification of a functionally uncharacterized TetR regulator, EefR. The regulator represses its own expression and that of four neighboring genes forming the eefRABCD operon, encoding components of a tripartite RND-efflux pump (EefABC) and a putative MFS-type exporter (EefD). Overexpression of these pumps reduces the susceptibility of acrB-deficient E. coli to SAN and structurally diverse antibiotics. The eefR-eefABC-eefD cluster, widely distributed across Enterobacteriaceae genomes, is also found on plasmids in several E. coli isolates, indicating a significant risk for the rapid spread of this multidrug resistance mechanism.

研究领域: 微生物学 · 分子生物学 · 耐药机制 · 细菌遗传学 · 抗生素耐药性
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY · 2014 · IF 2.291

Competitive binding assay for G-quadruplex DNA and sanguinarine based on room temperature phosphorescence of Mn-doped ZnS quantum dots

Li-Na Wen,Meng-Xia Xie

s G-quadruplex DNA is an effective target for anticancer drug, and investigation of the G-quadruplex DNA with natural compounds plays a key role in the development of anticancer drugs. In this article, room temperature phosphorescence sensing system based on l -cysteine-capped Mn-doped ZnS QDs has been established. Sanguinarine can adsorb on the surface of Mn-doped QDs and quenched the phosphorescence emission of the sensor. When the G-quadruplex sequences combined with the sanguinarine of the QDs-sanguinarine system, the phosphorescence intensities of the QDs sensors would be restored, and the binding abilities of the G-quadruplex DNA with the sanguinarine can be evaluated by the phosphorescence recoveries of the sensor system. Based on the developed approach, the interaction of sanguinarine and six G-quadruplex DNA with various sequences (tel24-1, tel24-2, tel22, k-ras, HIF-1α and c-kit1) has been investigated. The results showed that the binding abilities of the G-quadruplex DNA with sanguinarine were related to their number of bases and conformations. The conformational changes of the six G-quadruplex DNA, after binding with sanguinarine, have also been probed by circular dichroism. Combining the changes of the phosphorescence lifetime, the binding mechanism of the G-quadruplex DNA and sanguinarine has been discussed. The developed method was simple, rapid and specific, and can avoid fluorescence interferences of the system, and it would be prospective to evaluate the interaction of the drug with different G-quadruplexes.

研究领域: 生物化学 · 分析化学 · 分子生物学 · 癌症研究
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JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH · 2025 · IF 1.3

Activity of 6-methoxydihydrosanguinarine from Hylomecon japonica against wild-type and fluconazole-resistant Candida albicans biofilms

Ying Liu,Miao Wang,Guang-Xiong Zhou

The threat posed by microorganisms to food safety in development necessitates the discovery of new antimicrobial agents. Here, we unravel the antifungal activity of 6-methoxydihydrosanguinarine (6-ME) derived from Hylomecon japonica. 6-ME disrupted the biofilm formation of Candida albicans (C. albicans). 6-ME could cause the blockage of filamentation and classical cyclic adenosine monophosphate (cAMP) signaling pathway is involved in this process. 6-ME downregulated the expression of EFG1, CDC35, RAS1, and TPK2, all of which are critical components of the cAMP pathway. Furthermore, 6-ME changed the membrane permeability of C. albicans and caused reactive oxygen species accumulation, leading to cell death.

CAS / MDL: 1132-61-2
研究领域: 微生物学 · 药理学 · 真菌学 · 生物化学 · 食品安全
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2016 · IF 2.653

Spectroscopic investigation of the interaction between G-quadruplex of KRAS promoter sequence and three isoquinoline alkaloids

Li-Na Wen,Meng-Xia Xie

KRAS promoter can form G-quadruplex structure and regulate gene transcription. The drugs which can bind with G-quadruplex of KRAS promoter may be potential remedy for treatment of cancers associated with KRAS mutation. The interaction mechanism between the G-quadruplex of KRAS promoter and three isoquinoline alkaloids (jatrorrhizine, berberine and sanguinarine) has been investigated by UV-visible, fluorescence and circular dichroism spectroscopic methods. The results showed that the three alkaloids can form complexes with G-quadruplex KRAS promoter with the molecular ratio of 1:1, and the binding constants were (0.90   ±   0.16)   ×   10 6   L   mol −   1 , (0.93   ±   0.21)   ×   10 6   L   mol −   1 and (1.16   ±   0.45)   ×   10 6   L   mol −   1 for jatrorrhizine , berberine and sanguinarine . The absorption spectra, KI quenching and fluorescence anisotropy and polarization studies suggested jatrorrhizine and berberine interacted with G-quadruplex by not only end-stacking binding mode but also grooves or loops binding mode, while sanguinarine by end-stacking binding mode. Sanguinarine was more beneficial to maintain the stability and parallel conformation of KRAS promoter G-quadruplex. MTT assay was performed to evaluate antiproliferation effects of the three isoquinoline alkaloids on SW620 cells, and the antiproliferation effects of the three alkaloids were sanguinarine > berberine > jatrorrhizine. All the three alkaloids can bind with KRAS promoter G-quadruplex, and sanguinarine had the better binding property and antiproliferation effects on SW620 cells. The results obtained are meaningful to explore potential reagents targeting the parallel G-quadruplex structure of KRAS promoter for gene theraphy of colorectal carcinomas.

研究领域: 分子生物学 · 癌症研究 · 药理学 · 生物化学
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ANALYST · 2021 ·Vol. 146 ·期 15 ·4934-4944 · IF 4.616

Screening of high-efficiency and low-toxicity antitumor active components in Macleaya cordata seeds based on the competitive effect of drugs on double targets by a new laminar flow chip

Yan Gao,Huaidong Peng,Lisi Li,Feng Wang,Jiang Meng,Hongling Huang,Shumei Wang,Paul C. H. Li,Yue Sun

It is urgent to obtain targeted drugs that selectively bind to pathological targets rather than physiological targets in the early stage of drug screening. G-Quadruplex has become one of the important targets in the development of anti-tumor drugs. However, drugs that target quadruplexes may also bind to dsDNA, which may lead to adverse reactions. In this study, a new three-phase laminar flow chip was constructed to enable the multi-components of a traditional Chinese medicine extract to dynamically and competitively bind with G-quadruplex DNA (on target) and double-stranded DNA (off target), so as to select high-efficiency and low-toxicity anti-tumor drugs. The results showed that there were five compounds in the extracts of Macleaya cordata seeds that exhibited obvious differences in binding to the two targets. Furthermore, the binding constants and modes of four identified alkaloids as they bound to two DNA targets were verified by fluorescence spectra and molecular docking methods. The toxicity to HepG2 and LO2 cells from the four alkaloids was also compared. The results showed that sanguinarine and chelerythrine could be used as candidate drugs with stronger binding to HT24 than DNA26. The chip can also be used for other types of double-target screening of other traditional Chinese medicine extracts or compound libraries.

研究领域: 药理学 · 生物技术 · 癌症研究 · 分子生物学
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JOURNAL OF MATERIALS RESEARCH · 2020 ·Vol. 35 ·期 18 ·2427-2440 · IF 2.502

Biomimetic synthesis of vaterite CaCO3 microspheres under threonine for preparation of pH-responsive antibacterial biofilm

Tingyu Yang,Yu Wu,Xiaoqing Yue,Cuiyan Wang,Jianbin Zhang

The synthesis of antibacterial biomaterial with specific functions responsive to specific bacterial growth environments is of significant importance to achieve effective sterilization and reduce the resistant bacteria. Herein, inspired by biomineralization, we develop a one-pot, threonine (Thr)-mediated biomineralization method using a CO2 bubbling procedure to green, simply and quickly prepare vaterite CaCO3 microspheres as a platform for antibacterial Sanguinarine (SAN) delivery. The loading capacity of vaterite CaCO3 microspheres for SAN drugs reached 159.8 mg/g, corresponding to the loading efficiency of 83.7%. And for the first time, a novel Sanguinarine@calcium carbonate (SAN@CaCO3) organic–inorganic hybrid antibacterial biofilm was constructed by using vaterite CaCO3 microspheres with pH-responsive and high SAN drug-loading. Importantly, the film showed bacteria-triggered, pH-responsive SAN release properties and strong bactericidal ability (96.19%) for Staphylococcus aureus (S. aureus). Meanwhile, it also had antibacterial capabilities in real environments. In 7 days, it can significantly inhibit the adhesion and growth of bacteria in the air. The biomineralized synthetic vaterite CaCO3 microspheres and the application in the construction of pH-responsive antibacterial biofilm have bright future in resisting bacterial infections and reducing the production of resistant bacteria.

CAS / MDL: 72-19-5
研究领域: 材料科学 · 生物技术 · 药学 · 生物医学工程
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