TOXICOLOGY LETTERS
·
2019
·
IF 3.499
Ziyue Zhou,Yanke Lin,Lu Gao,Zemin Yang,Shuai Wang,Baojian Wu
Brucine is one of the main bioactive and toxic constituents of the herb drug Semen Strychni . Here we aimed to determine dosing time-dependent hepatotoxicity of brucine, and to investigate the role of metabolism in generation of brucine chronotoxicity. Brucine was administered to wild-type or Npas2 −/− (a clock disrupted model) mice at different circadian time points for toxicity and pharmacokinetic characterization. The hepatotoxicity was evaluated by plasma alanine aminotransferase and aspartate aminotransferase measurements and histopathological analysis. The role of Cyp3a11 in brucine metabolism was determined by chemical inhibition assays and Cyp3a11-overexpressing HEK293 cells. Hepatic circadian Cyp3a11 mRNA and protein levels were determined by qPCR and Western blotting, respectively. The toxicity of brucine was more severe in the light phase [Zeitgeber time (ZT) 2 and ZT8] than in the dark phase (ZT14 and ZT20). Chemical inhibition and substrate metabolism assays suggested Cyp3a11 as a significant contributor to brucine metabolism. The Cyp3a11 mRNA, protein and activity in the livers of wild-type mice displayed significant circadian fluctuations. Npas2 ablation markedly down-regulated Cyp3a11 mRNA, protein and activity, and abrogated their circadian rhythms. The circadian time differences in brucine pharmacokinetics and liver distribution were lost in Npas2 −/− mice, so were the time differences in brucine hepatotoxicity. In conclusion, chronotoxicity of brucine was determined by circadian variations in Cyp3a11 metabolism. The findings have implications in improving brucine (and possibly Semen Strychni ) efficacy via dosing time optimization.
研究领域:
药理学
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毒理学
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生物节律学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Ning Ma,Junyang Fang,Lingxiao He,Xinxu Zhao,Shuangyu Wei,Lingchao Cai,Can Jin,Chaoqun You,Fei Wang
Coptis herbs and Sophora moorcroftiana are primary sources of alkaloids with significant application value, including matrine (MT). Currently, in the separation and purification methods of alkaloids, while the adsorption method is straightforward and practical, most adsorption materials are non-renewable synthetic compounds, which can lead to environmental pollution. Therefore, we utilized TEMPO-modified natural biomass macromolecular cellulose nanocrystals (TOCN) and environmentally degradable dendritic mesoporous organosilica nanoparticles (DMONs) as raw materials, employing a surface assembly technique to coat negatively charged cellulose onto the surface of DMONs. This process led to the synthesis of TOCN@DMONs, an effective and eco-friendly bio-based composite material. The TOCN@DMONs were subjected to various analytical techniques, which unequivocally confirmed its successful synthesis and demonstrated its impeccable physical and chemical properties. The prepared TOCN@DMONs exhibited nanoscale dimensions, abundant pore structure, and excellent thermal stability. The adsorption process of MT on TOCN@DMONs followed the pseudo-second-order kinetics and Langmuir isotherm model. Thermodynamic parameters indicated that the adsorption process was spontaneous, endothermic, and involved weak chemical bonds. These findings indicate that TOCN@DMONs, as a green and highly efficient adsorbent, has a good application potential for the concentration of total alkaloids and the purification of MT from Coptis herbs and Sophora moorcroftiana extracts.
研究领域:
植物化学
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环境科学
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药物分离与纯化
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Xiaofang Li,Lingling Guo,Liguang Xu,Liqiang Liu,Maozhong Sun,Xinxin Xu,Hua Kuang,Chuanlai Xu
The European Union (EU) has detected matrine (MAT) in honey and tea exported from China, which is neurotoxic, hepatotoxic, developmentally toxic, and reproductively toxic. To develop a rapid method for the detection of MAT in honey and tea, we designed and analyzed hapten in terms of structure-function similarity, surface electrostatic potential, 3D conformation, and Mulliken atomic charges, prepared a monoclonal antibody (mAb) with high sensitivity (IC 50 = 0.59 μg/L) and specificity to recognize MAT, and developed an immunosensor based on gold nanoparticles (GNP-based immunosensor) for the rapid qualitative detection of MAT in honey and tea samples with visual limit of detection (vLOD) of 2 and 5 μg/kg, respectively. The accuracy of the GNP-based immunosensor was verified by spiking recovery experiments. The GNP-based immunosensor is instrument-free and can be completed within 8 min with the advantages of convenience, rapidity and high sensitivity, which provides a tool for MAT monitoring of honey and tea in China.
研究领域:
食品科学
·
分析化学
·
毒理学
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DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 8
·1845
·
IF 4.2
Sitong Lai,Bing Wang,Kunhui Sun,Fan Li,Qian Liu,Xie-An Yu,Lihe Jiang,Lisheng Wang
The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors.
研究领域:
药学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-10
·
IF 3.998
He Huiqing,Qin Xiangjing,Dong Fangyun,Ye Jingmin,Xu Chunbao,Zhang Hanhui,Liu Zhanmei,Lv Xiaojing,Wu Yuehua,Jiang Xuhong,Cheng Xingan
The invasion of Spodoptera frugiperda has imposed a serious impact on global food security. Matrine is a botanical pesticide with a broad spectrum of insecticidal activity which was recommended for controlling Spodoptera frugiperda . In order to discover effective insecticide for Spodoptera frugiperda , two matrine derivatives modified with carbon disulfide and nitrogen-containing groups were systhesized. And their inhibition activities on Sf9 cell were evaluated. The structural configuration of compounds were characterized by IR, HPLC, MS, NMR and XRD, with yields of 52% and 65%, respectively. The IC 50 of the two newly synthesized compounds on Sf9 cell reduced to 0.648 mmol/L and 1.13 mmol/L, respectively, compared with that of matrine (5.330 mmol/L). In addition, microscopic observation of Sf9 cell treated with the compounds showed that the number of adherent cells decreased, the cells shrunk, vacuolated and apoptotic bodies appeared. The two newly synthesized compounds exhibited better inhibitory effect on Sf9 cell than that of the parent matrine, suggesting that the positive effect of the introduction of 1-pyrrolidinecarbodithioate and diethylcarbamodithioate groups to matrine. The morphological observation of Sf9 cell induced by derivatives indicated that apoptosis induction may be a mechanism that inhibits insect cell proliferation and exerts insecticidal effect.
研究领域:
植物化学
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昆虫学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
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2024
·
IF 2.3
Qingxia Guan,Yumeng Liu,Zhaorui Xia,Yue Zhang,Liping Wang,Yanhong Wang,Shujun Zou,Shaowa Lv,Xiaoying Zhou
Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3’-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.
研究领域:
药理学
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纳米医学
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病毒学
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DOI
PubMed
高影响因子
MOLECULES
·
2017
·Vol. 22
·期 4
·575
·
IF 2.861
Junping Zhang,Yanchun Wang,Wei Zheng
A simple and sensitive electrochemical sensor fabricated with graphene nanosheets (GNs) and a hydroxyapatite (HA) nanocomposite–modified glassy carbon electrode (GCE) was developed for the determination of matrine (MT). The as-prepared electrode (GNs/HA/GCE) was verified to outperform bare a GCE and GNs-modified electrode with increased oxidation peak currents and the decreased over-potential in the redox process of MT, indicating the great enhancement of electrocatalytic activity toward the oxidation of MT by the composite of GNs and HA. Under the optimized conditions, the oxidation peak currents were related linearly with the concentration of MT, ranging from 2 μM to 3 mM, and the detection limit (S/N = 3) was 1.2 μM. In addition, the proposed electrochemical sensor can be successfully applied in the quantitative determination of MT inSophora flavescensextract.Keywords:matrine;voltammetric sensors;Sophora flavescens;electrochemistry;hydroxyapatite
研究领域:
分析化学
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药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHYSICAL CHEMISTRY B
·
2025
·
IF 2.9
Zhuoni Liu,Xianshuo Zhang,Xiaoyong Wang,Tianxiang Yin
Eutectic solvents (ESs) have shown great efficiency on increasing the solubility, stability, and bioactivity of active pharmaceutical ingredients (APIs) in recent research studies. Curcumin is an important API driven from natural plants, which displayed a series of biofunctions like antibacterials, anti-inflammatory, and anticancer activities etc. However, its poor water solubility and stability hindered its further clinic application. Herein, a series of novel ESs based on matrine and fatty acids (i.e., octanoic acid, decanoic acid, and lauric acid) were developed. The phase behavior and cytotoxicity of these ESs were investigated. Moreover, the prepared ESs displayed excellent ability on enhancing the solubility of curcumin with the highest solubility being 28 mg/mL at 298 K, which was nearly 50000-fold than that in water. The curcumin showed high stability in ESs, where only 10% of curcumin decomposed under light irradiation for 6 h. Furthermore, biofilms based on these ES solutions of curcumin have been prepared and displayed high antioxidant and antibacterial activities. To summarize, the prepared eutectic systems provide a new strategy for further application of curcumin.
研究领域:
药学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Lingxiao He,Ning Ma,Zhengyun Liang,Sidan Zhao,Jiaming Yan,Hanchen Lin,Chaoqun You,Lingchao Cai,Fei Wang
Matrine is a type of alkaloid found in plants, exhibiting a wide range of biological and pharmacological activities. The process of separating and purifying matrine poses challenges due to its low concentration and frequent presence in mixtures during raw extraction. This work aims at synthesizing suitable adsorbents for efficient separation and purification of matrine from plant materials. The sulfonated cellulose nanocrystals/sodium alginate beads (SCNCs/SA) were synthesized by the ionic gelation method, characterized and investigated for the adsorption of matrine from water. The equilibrium adsorption capacity of SCNCs/SA beads for matrine at 298 K was approximately 55.66 mg/g. The adsorption enthalpy, entropy, and free energy of matrine on the SCNCs/SA beads were evaluated, indicating that the adsorption process was spontaneous, exothermic, and primarily driven by physisorption. 95 % of the adsorption equilibrium could be achieved within 60 min, and approximately 20 bed volumes of an 80 % (v/v) ethanol aqueous solution for effective recovery. The adsorption isotherms are analyzed using both Langmuir and Freundlich models, the kinetic of adsorption using the pseudo-first-order and pseudo-second-order models, and the breakthrough curves using four breakthrough models. These results suggested that the rapid adsorption and effortless regeneration render SCNCs/SA beads as promising adsorbents for the efficient adsorption and separation of matrine from plants.
研究领域:
材料科学
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药学
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植物化学
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产品关联
DOI
高影响因子
ELECTROANALYSIS
·
2012
·Vol. 24
·期 3
·691-698
·
IF 2.872
Fangyuan Zhao,Le Wang,Yanling Liu,Ge Song,Fei Wang,Baoxian Ye
A new voltammetric sensor for matrine was fabricated via the polymerization of L -cysteine on graphene oxide, which served as templates. The fabricated electrode can improve the oxidation of matrine intensively, and enable the determination of matrine in the range from 4×10 −6 to 1×10 −4 mol L −1 , with a detection limit of 2×10 −6 mol L −1 . The oxidation process of matrine was studied and some dynamic parameters were calculated using various electrochemical techniques. This present sensor displayed good stability, reproducibility and sensitivity for matrine. It was successfully applied to the quantitative determination of matrine in matrine injection with satisfactory results.
研究领域:
分析化学
·
药物分析
·
电化学
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产品关联
DOI
高影响因子
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
·
2025
·
IF 1.7
Xiaoyan Ding,Jinxi Wang,Xiangning Huang,Juan Huang
Diabetic cardiomyopathy (DCM), a life-threatening cardiovascular complication of diabetes, manifested as progressive cardiac dysfunction mediated through oxidative stress, inflammation, and apoptosis. Loganic acid (LA), a natural iridoid compound with anti-inflammatory and antioxidant properties, has demonstrated therapeutic potential in various inflammatory disorders, but its role in DCM remains unexplored. Here, we systematically investigated LA’s cardioprotective potential and its mechanisms. Utilizing a high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mouse model, LA (30 mg/kg, oral gavage) was administered for 8 weeks post-diabetes confirmation. Echocardiographic assay indicated that LA improved cardiac function. Histopathologic evaluation displayed that LA attenuated myocardial structural disorders, reduced collagen deposition, and suppressed cardiomyocyte apoptosis. Furthermore, LA treatment normalized redox imbalance (decreased MDA and increased GSH) and reduced inflammatory cytokine levels. In vitro , a diabetic cell model was established with AC16 cardiomyocytes exposed to high glucose (HG; 30 mM). The findings demonstrated that LA (25 or 50 μM) dose-dependently ameliorated HG-induced cardiomyocyte damage, oxidative stress, and inflammatory cytokine release. Mechanistically, LA treatment suppressed HG-induced activation of TLR4 signaling and phosphorylation of p38 MAPK. Collectively, these findings highlight LA as a novel therapeutic candidate in DCM, targeting the TLR4/p38 MAPK axis to attenuate diabetes-induced cardiac damage.
研究领域:
心血管病学
·
糖尿病学
·
分子药理学
·
氧化应激
·
炎症生物学
·
信号转导
✓ 已验证
DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2018
·Vol. 34
·期 1
·173-181
·
IF 2.441
Sun Kaiyue,Bai Yuting,Zhao Rong,Guo Zijiao,Su Xiang,Li Peiqi,Yang Pengyu
The present study was designed to evaluate the effects of matrine (MAT) on scopolamine (SCOP)-induced learning and memory impairment. After successive oral administration of MAT to mice for three days at doses of 0.4, 2, and 10 mg/kg, we assessed improvements in learning and memory and investigated the mechanism of action of SCOP-induced amnesia. Donepezil at a dose of 3 mg/kg was used as a standard memory enhancer. MAT significantly improved SCOP-induced learning and memory impairment in novel object recognition and Y-maze tests at doses of 0.4, 2, and 10 mg/kg. Furthermore, MAT inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and decreased oxidative stress in the brain, as evidenced by increased total antioxidant capacity, total superoxide dismutase levels, and catalase activities as well as decreased malondialdehyde levels. Additionally, there was a significant negative correlation between the percentage of spontaneous alternation in the Y maze and AChE activity in the cortex and hippocampus. MAT ameliorated SCOP-induced amnesia by the inhibition of both AChE/BuChE activities and oxidative stress. This study provides further evidence to encourage the development of MAT as a drug for the prevention or treatment of Alzheimer’s disease.
研究领域:
神经科学
·
药理学
·
阿尔茨海默病研究
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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）