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MICROCHEMICAL JOURNAL · 2023 · IF 4.8

Analytical quality by design oriented development of the UPLC method for analysing multiple pharmaceutical process intermediates: A case study of Compound Danshen Dripping Pills

Yanni Tai,Dandan Ren,Wanshun Zhao,Haibin Qu,Haoshu Xiong,Xingchu Gong

This work presented the integration of the Analytical Quality by Design concept in developing a UPLC method for the quantification of saponins and phenolic acids in two Compound Danshen Dripping Pills intermediates of a concentrated extract and a supernatant. Prior knowledge and systematic risk analysis were conducted to identify potential critical method parameters (CMPs) that affected critical quality attributes (CQAs). A definitive screening design was employed to investigate the quantitative relationship among the intermediate type, CPPs, and CQAs. Intermediate type was added in the experimental design table as a categorical variable. After the models were built, the method operable design region (MODR) was calculated with an exhaustive search-Monte Carlo method. The CPP combinations with a 95 % or higher probability of reaching the preset standard were collected in MODR. The MODR robustness test was conducted with a Plackett–Burman design. The separation of analytes was achieved with a Waters Acquity HSS T3 (100 × 2.1 mm, 1.8 µm) column at 30 °C, using 0.05 % phosphoric acid and acetonitrile as the mobile phases in gradient elution at a flow rate of 0.40 mL/min. The elution was monitored at UV detection wavelengths of 280 nm and 203 nm. The optimized method was also validated. Good robustness, accuracy, precision, stability and repeatability, and linear regression (R > 0.9997) were obtained. All recoveries of the 9 compounds ranged from 97.8 % to 101.7 %, with an RSD of less than 3.49 %. Nine batches of Danshensu, protocatechualdehyde, rosmarinic acid, salvianolic acid B, salvianolic acid A, notoginsenoside R 1 , ginsenoside Rg 1 , ginsenoside Re, and ginsenoside Rb 1 were analysed. Danshensu was found to be the compound with the highest content.

CAS / MDL: 7664-38-2
研究领域: 药物分析 · 中药学 · 分析化学
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JOURNAL OF NANOBIOTECHNOLOGY · 2025 ·Vol. 23 ·期 1 ·1-26 · IF 12.6

Microglia-targeting nanosystems that cooperatively deliver Chinese herbal ingredients alleviate behavioral and cognitive deficits in Alzheimer’s disease model mice

Zhou Peng,Chao Quan,Li Chen,Wang Ningjing,Guo Siqi,Wang Pingping,Ge Pingyuan,Li Caihong,Guo Rui,Yang Nianyun,Lu Zhangdi,Tang Zhishu,Zhang Qichun,Fu Tingming,Xiao Qingqing,Zhu Huaxu

The effective treatment of Alzheimer’s disease (AD) is challenging because of its complex and controversial pathological mechanisms. Moreover, multiple barriers, such as the blood–brain barrier (BBB), reduce drug delivery efficiency. Microglia-related neuroinflammation has recently attracted increasing attention as a possible cause of AD and has become a novel therapeutic target. Therefore, overcoming the BBB and targeted delivery of anti-inflammatory agents to microglia seem to be effective practical strategies for treating AD. A large proportion of natural active extracts possess exceptional immunomodulating capabilities. In this study, the cooperative delivery of berberine (Ber) and palmatine (Pal) by transferrin-decorated extracellular vesicles (Tf-hEVs-Ber/Pal), which can cross the BBB and precisely target microglia, was performed. This nanosystem effectively cleared amyloid β-protein (Aβ) aggregates, significantly regulated the neuroinflammatory environment both in vitro and in vivo and markedly altered the behavior and improved the cognitive and learning abilities of AD model mice. The efficacy of a microglia-targeting combined therapeutic approach for AD was demonstrated, which broadens the potential application of Chinese herbal ingredients.Graphical abstract

CAS / MDL: 3326-32-7
研究领域: 神经科学 · 药理学 · 纳米医学
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Separations · 2021 ·Vol. 8 ·期 4 ·49 · IF 2.777

Determination of the Dissociation Constants of 16 Active Ingredients in Medicinal Herbs Using a Liquid–Liquid Equilibrium Method

Wanying Wang,Baixiu Zheng,Jiahao Wu,Weisong Lv,Peiying Lin,Xingchu Gong

The dissociation constant is an important physicochemical property of drug molecules that affects the pharmacokinetic and pharmacodynamic properties of drugs. In this study, the distribution coefficients of 16 active ingredients extracted from herbal materials were determined at different pH values in liquid–liquid equilibrium systems; the active ingredients were sinomenine, aescin A, aescin B, aescin C, aescin D, chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, isochlorogenic acid C, baicalin, wogonoside, calycosin-7-glucoside, astraisoflavan-7-O-β-D-glucoside, and isomucronulatol 7-O-glucoside. The dissociation constants of these active ingredients were calibrated and compared with reported values. The dissociation constants obtained were close to those reported in other studies, which means that the results of this work are reliable.Keywords:liquid–liquid equilibrium method;dissociation constant;distribution coefficient;Caulis Sinomenii;Semen Aesculi;Flos Lonicerae;Radix Scutellariae;Radix Astragali

CAS / MDL: 107-15-3 108-10-1
研究领域: 药理学 · 中药化学 · 药物分析
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2021 ·Vol. 413 ·期 7 ·1917-1927 · IF 4.157

Construction of graphene quantum dots-decorated EGFR cell membrane chromatography for screening active components from Peucedanum praeruptorum Dunn

Zhang Liyang,Yi Xinyao,Wang Saisai,Liang Peida,Zhou Huaxin,Fu Jia,Jia Qianqian,Gao Jiapan,Lv Yanni,Han Shengli

A novel stability-enhanced graphene quantum dot (GQD)-decorated epidermal growth factor receptor (EGFR) cell membrane chromatography was constructed to study the potential application of GQDs in bioaffinity chromatography, and to screen active components acting on EGFR from traditional Chinese medicine (TCM). The carboxyl groups on the surface of GQDs reacted with the amino groups of the amino-silica gel ( SiO 2 -NH 2 ) to form a covalent bond, thereby preparing the GQD-decorated silica gel ( SiO 2 -GQDs ). The EGFR cell membrane was further immobilized on the SiO 2 -GQDs through the same covalent binding method to obtain the GQD-decorated cell membrane stationary phase ( SiO 2 -GQDs-CMSP ). In this way, the cell membrane was firmly immobilized on the decorated silica carrier. The life span and stability of the GQD-decorated cell membrane chromatographic ( SiO 2 -GQDs-CMC ) column were both enhanced, and the optimal immobilization conditions of the EGFR cell membrane were also determined. This model was then verified by establishing a SiO 2 -GQDs-CMC online liquid chromatography-ion trap-time-of-flight (LC-IT-TOF) system to screen possible active components in Peucedanum praeruptorum Dunn . As a result, praeruptorin B (Pra-B) was screened out, and its inhibitory effect against EGFR cell growth was evaluated by the cell counting kit-8 (CCK-8) assay. Molecular docking assay was also conducted to further estimate the interaction between Pra-B and EGFR. Overall, this research indicated that GQDs may be a promising nanomaterial to be used in prolonging the life span of the CMC column, and Pra-B could be a potential EGFR inhibitor so as to treat cancer. Graphical abstract

研究领域: 分析化学 · 药理学 · 纳米生物学
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TALANTA · 2022 · IF 6.556

Magnetic nanoparticles covalently immobilizing epidermal growth factor receptor by SNAP-Tag protein as a platform for drug discovery

Huaxin Zhou,Jia Fu,Qianqian Jia,Saisai Wang,Peida Liang,Yamin Wang,Yanni Lv,Shengli Han

Magnetic nanoparticles (NPs) cloaked with cell membranes expressing high levels of the epidermal growth factor receptor (EGFR) have been used to screen for EGFR-targeting active compounds in traditional Chinese medicine (TCM) formulations. However, previous strategies involved physical immobilization of the biomaterials on the surface of the nanocarrier , resulting in highly unstable platforms since the biological materials could dislodge easily. Chemical bonding of biomaterials to the nanoparticles surface can improve the stability of the biomimetic platforms. In this study, membrane fragments from cells expressing SNAP-Tag-EGFR (ST-EGFR) were immobilized on the surface of magnetic NPs. The ST-EGFR magnetic cell membrane nanoparticles (ST-EGFR/MCMNs) showed greater stability, and higher binding capacity, selectivity adsorption of gefitinib after 7 days compared to the un-immobilized magnetic cell membrane nanoparticles (EGFR/MCMNs). The ST-EGFR/MCMNs were used to screen for the EGFR-targeting active compounds of Zanthoxyli Radix (ZR), and identified toddalolactone and nitidine chloride. The latter significantly inhibited the proliferation of EGFR-overexpressing cancer cells, and was more effective compared to gefitinib. This innovative technology can be used to rapidly screen for active compounds from complex extracts, and aid in drug discovery.

研究领域: 生物医学工程 · 药理学 · 分子生物学
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Materials Today Communications · 2025 · IF 4.5

Integrating Periosteum Derived Organoids and 3D Printed Scaffolds for Enhanced Craniofacial Bone Regeneration

Yueming Tian,Zhenrui Zhang,Bingyan Wu,Zibo Liu,Ting Zhang,Yongcong Fang,Zhuo Xiong

Craniofacial bone defects, particularly those of substantial size, require a significant quantity of cells for effective regeneration. Although developmental engineering strategies using bone mesenchymal stem cells (BMSCs) aggregates have demonstrated potential, they do not fully replicate natural cellular processes. In contrast, periosteal mesenchymal stem cells (PMSCs) exhibit superior efficacy for craniofacial bone regeneration compared to BMSCs. This study aims to engineer periosteum-derived organoids (PDOs) by integrating PMSCs with osteogenic induction centers in 3D-printed polycaprolactone (PCL) scaffolds. Cell condensation was initiated with fibroblast growth factor 8b (FGF8b) and Vitamin C (Vc) to develop a high-density bioink possessing strong osteogenic differentiation capabilities, thereby mimicking osteoblast condensation integral to craniofacial bone repair. Composite scaffolds comprising PCL/β-TCP and naringin-loaded GelMA hydrogel bio-ink were fabricated, successfully forming calcification centers. Transcriptomic analysis revealed the molecular mechanisms underlying the formation and osteogenic differentiation of PDOs in vitro. This study presents a novel approach to biomimetic periosteum-based bone regeneration in vitro and highlights a promising strategy for scaffold fabrication incorporating calcified centers. These innovations contribute to the ongoing efforts to address the clinical challenge of repairing large craniofacial bone defects, offer valuable insights into the potential of 3D bioprinting for creating biomimetic bone structures, and explore the incorporation of traditional Chinese medicine compounds into bone tissue engineering.

CAS / MDL: 7758-87-4 9002-93-1
研究领域: 组织工程 · 再生医学 · 生物材料 · 颅颌面外科学 · 干细胞生物学 · 转化医学 · 药物递送系统
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