SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2016
·
IF 2.653
Yong Hu,Hai-Long Wu,Xiao-Li Yin,Hui-Wen Gu,Rong Xiao,Li Wang,Huan Fang,Ru-Qin Yu
A rapid interference-free spectrofluorometric method combined with the excitation-emission matrix fluorescence and the second-order calibration methods based on the alternating penalty trilinear decomposition (APTLD) and the self-weighted alternating trilinear decomposition (SWATLD) algorithms, was proposed for the simultaneous determination of nephrotoxic aristolochic acid I (AA-I) and aristololactam I (AL-I) in five Chinese herbal medicines. The method was based on a chemical derivatization that converts the non-fluorescent AA-I to high-fluorescent AL-I, achieving a high sensitive and simultaneous quantification of the analytes. The variables of the derivatization reaction that conducted by using zinc powder in acetose methanol aqueous solution, were studied and optimized for best quantification results of AA-I and AL-I. The satisfactory results of AA-I and AL-I for the spiked recovery assay were achieved with average recoveries in the range of 100.4–103.8% and RMSEPs < 0.78 ng mL − 1 , which validate the accuracy and reliability of the proposed method. The contents of AA-I and AL-I in five herbal medicines obtained from the proposed method were also in good accordance with those of the validated LC-MS/MS method. In light of high sensitive fluorescence detection, the limits of detection (LODs) of AA-I and AL-I for the proposed method compare favorably with that of the LC-MS/MS method, with the LODs < 0.35 and 0.29 ng mL − 1 , respectively. The proposed strategy based on the APTLD and SWATLD algorithms by virtue of the “second-order advantage”, can be considered as an attractive and green alternative for the quantification of AA-I and AL-I in complex herbal medicine matrices without any prior separations and clear-up processes.
研究领域:
中药学
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分析化学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 23
·8271
·
IF 4.927
Jinghe Zhang,Yinan Wang,Changhong Wang,Kan Li,Weifang Tang,Jing Sun,Xikui Wang
When Aristolochia plants wilt and decay, aristolochic acids (AAs) are released into the soil, causing soil contamination. It has been demonstrated that aristolochic acid can be accumulated and enriched in crops through plant uptake. However, there is a lack of systematic studies on the migration and accumulation of AAs in a realistic simulated soil environment. In this study, Aristolochia herbal extracts were mixed with soil for growing three typical vegetables: lettuce, celery, and tomato. The contents of AAs in the above-mentioned plants were determined by an established highly sensitive LC-MS/MS method to study the migration and accumulation of AAs. We found that AAs in the soil can be transferred and accumulated in plants. AAs first entered the roots, which were more likely to accumulate AAs, and partially entered the above-ground parts. This further confirms that AAs can enter the food chain through plants and can have serious effects on human health. It was also shown that plants with vigorous growth and a large size absorbed AAs from the soil at a faster rate. The more AAs present in the soil, the more they accumulated in the plant.Keywords:aristolochic acid;vegetables;uptake;translocation;fate
研究领域:
环境科学
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农业
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Dihao Xie,Simin Zhong,Meixue Luo,Jiahao Xu,Ruoyan Zheng,Jiading Luo,Yiting Wang,Yongxing Guo,Lianxia Guo,Baojian Wu,Danyi Lu
Background Aristolochic acid I (AAI), an emerging biogenic contaminant widely present in Aristolochic plants, has been implicated in the progression of tubulointerstitial disease, known as aristolochic acid nephropathy (AAN). The circadian clock, a vital regulator of organ homeostasis, is susceptible to external chemical cues, including toxins. However, the reciprocal interactions between AAI and the circadian clock remain unexplored. Methods We initially assessed sex- and time-dependent nephropathy and behavioral responses in C57BL/6J mice exposed to AAI. Subsequently, we evaluated changes in the expression of circadian clock genes following treatment with AAI or its bioactive metabolite, aristolactam I, using real-time quantitative PCR and immunoblotting in renal tissues and cells. Additionally, real-time reporter assays were conducted on kidney explants from PER2::Luc knock-in reporter mice and Per2-dLuc / Bmal1-dLuc reporter cell lines. To further elucidate the regulatory role of circadian clocks in AAI-induced nephropathy, mice with global or kidney-specific knockout of Bmal1 , as well as mice subjected to experimental jetlag, were utilized. Results Our findings revealed a sex-dependent nephrotoxicity of AAI, with males exhibiting greater vulnerability. AAI-induced nephropathy was accompanied by impaired spatial cognitive function, disruptions in free-running locomotor activity, altered renal expression of multiple core clock genes, and disturbances in the circadian rhythm of renal PER2::Luc activity. Notably, kidney-specific ablation of the core clock gene Bmal1 significantly exacerbated renal injury and inflammation, whereas disruptions to the central clock, either genetically (through conventional knockout of Bmal1 ) or environmentally (mimicking jetlag), had minimal effects on AAI nephrotoxicity. Furthermore, both AAI and its bioactive metabolite aristolactam I demonstrated the ability to disrupt circadian clocks in human osteosarcoma cells (U2OS) and mouse renal tubular epithelial cells (mRTEC). Conclusion Collectively, these findings highlight the detrimental impact of aristolochic acids on local renal circadian clocks, ultimately exacerbating kidney damage. This study provides novel insights into the molecular mechanisms underlying AAI nephrotoxicity, potentially opening avenues for therapeutic interventions aimed at modulating the renal circadian clock to treat AAN.
研究领域:
肾病学
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药理学
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分子生物学
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时间生物学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2013
·Vol. 18
·期 5
·5420-5433
·
IF 2.428
Fan Chao,Dong-En Wang,Rui Liu,Qin Tu,Jian-Jun Liu,Jinyi Wang
A series of new matrinic acid derivatives5a–ewas synthesized. The chemical structures of the synthesized compounds were confirmed by1H-NMR,13C-NMR, and electrospray ionization mass spectroscopy. The anti-tumor activities were also investigatedin vitroby evaluating the effect of synthesized compounds on the proliferation of A375, A549, HeLa, and HepG2 cells. Compound5ewas found to be the most potent against A375 and HeLa cells, with IC50values of 37 and 75.5 μg/mL, respectively. Compounds5b,5c,5g, and5halso exhibited antiproliferative activities against A549 cells, with IC50values within the 36.2–47 μg/mL range. For HepG2 cells,5eand5i, with IC50values of 78.9 and 61 μg/mL, respectively, showed higher antiproliferative activity than taxol.Keywords:matrinic acid derivative;synthesis;antiproliferative activity
研究领域:
药物化学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2021
·
IF 10.618
Lu Cao,Hongguang Liu,Wenjun Xie,Shumeng Jiao,Xueqiang Wu,Kaisong Yuan,Xia Zhou,Muzi Yang,Yanyan Guan,Huaihong Cai,Zhihui Lai,Jian Chen,Haibo Zhou
With the increasing number of reports on aristolochic acid I (AAI), more and more toxic and side effects have been discovered successively. The main recognized carcinogenic mechanism is that AAI is metabolized into aristololactam I (AAT) in the body by nitroreductases , ultimately forming AAT-DNA adducts that cause disease. However, the carcinogenic mechanism is still not well understood by currently reported indirect method, there has always been a great demand to develop a direct method for real-time monitoring such process. In this work, surface-enhanced Raman spectroscopy (SERS) was used for the first time to monitor the process of AAI under the action of reducing agent sodium borohydride and catalyst Raney nickel to form AAT. We first found the abundant intermediate product-amino derivative of AAI, which was never reported before by other methods. The AAT was then obtained by a one-step dehydration reaction from the amino derivative of AAI under such reduction conditions. The product of amino derivative of AAI and AAT were further verified by thin-layer chromatography, H nuclear magnetic resonance spectra , mass spectrometry, and ultra-high performance liquid chromatography. Furthermore, a density functional theory-supported in-depth vibrational characterization of AAI and AAT was performed. The monitoring of the AAI reduction process by SERS can be of great significance for further exploration of its pathogenic mechanism, prevention, and monitoring of “nephropathy” and other diseases caused by AAI.
研究领域:
分析化学
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毒理学
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药理学
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计算化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 10
·2122
·
IF 4.6
Zhinan Wang,Xiaowei Li,Liang Zhao,Saiwa Liu,Jingjing Du,Xi Jia,Lirui Ge,Jian Xu,Kexin Cui,Yu Ga,Jinxiu Wang,Xi Xia
The emergence ofmcr-1-mediated colistin resistance has become a critical global health concern, highlighting the urgent need for innovative approaches to restore colistin’s therapeutic potential. In this study, we evaluated the antibacterial activity of four matrine-type alkaloids—namely, matrine, oxymatrine, sophocarpine, and sophoramine—againstmcr-1-positiveEscherichia coli. While these alkaloids showed limited efficacy when used alone, the combination of matrine with colistin exhibited remarkable synergistic effects, as demonstrated by checkerboard assays and time-kill curve analyses. The matrine–colistin combination caused minimal erythrocyte damage while effectively attenuating resistance development in vitro. This synergy was further corroborated in a murine infection model, where the combination significantly reduced bacterial loads in target tissues. Mechanistic studies revealed that the matrine–colistin combination enhances antimicrobial activity by disrupting bacterial membrane integrity, increasing intracellular colistin accumulation, and triggering reactive oxygen species-mediated oxidative damage. Collectively, these findings highlight the potential of matrine as a promising adjuvant to overcome colistin resistance, providing a novel therapeutic approach to address the challenge of infections cause by multidrug-resistant Gram-negative bacteria.
研究领域:
微生物学
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药理学
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感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS
·
2018
·Vol. 18
·期 10
·3358
·
IF 2.475
Xuemei Wu,Xiaoqing Bai,Yang Ma,Jie Wei,Juan Peng,Keren Shi,Huiqin Yao
In this work, binary hydrogel films based on carboxylated multi-walled carbon nanotubes/poly(N,N-diethylacrylamide) (c-MWCNTs/PDEA) were successfully polymerized and assembled on a glassy carbon (GC) electrode surface. The electroactive drug probes matrine and sophoridine in solution showed reversible thermal-, salt-, methanol- and pH-responsive switchable cyclic voltammetric (CV) behaviors at the film electrodes. The control experiments showed that the pH-responsive property of the system could be ascribed to the drug components of the solutions, whereas the thermal-, salt- and methanol-sensitive behaviors were attributed to the PDEA constituent of the films. The CV signals particularly, of matrine and sophoridine were significantly amplified by the electrocatalysis of c-MWCNTs in the films at 1.02 V and 0.91 V, respectively. Moreover, the addition of esterase, urease, ethyl butyrate, and urea to the solution also changed the pH of the system, and produced similar CV peaks as with dilution by HCl or NaOH. Based on these experiments, a 6-input/5-output logic gate system and 2-to-1 encoder were successfully constructed. The present system may lead to the development of novel types of molecular computing systems.Keywords:electrocatalysis;encoder;logic gate;matrine;sophoridine
研究领域:
材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Mi Wang,Zhenyuan Wang,Jichuan Zhang,Liguo Zhang,Wei Wang,Jingbo Zhan,Ya Liao,Chengyu Wu,Wen Yu,Jiaheng Zhang
Salicylic acid (H[Sal]) is an attractive bionic acid that is widely used in cosmetics and drugs for the treatment of skin diseases, owing to its excellent anti-acne, anti-inflammatory, antibacterial, oil-control, stratum-corneum-conditioning, and anti-photoaging abilities. However, H[Sal] is a relatively strong irritant and cannot be used on sensitive skin, and its poor water solubility limits the amounts that can be included in formulas, resulting in poor transdermal efficiency and bioavailability. In this study, we develop matrinium salicylate ([Mat][Sal]), a supramolecular ionic salt that is less cytotoxic and irritates the skin less than H[Sal], while exhibiting enhanced water-solubility, transdermal-delivery, and bioactivity properties. The anticancer, antioxidant, anti-inflammatory, and antibacterial properties of [Mat][Sal] are found to be superior or comparable to those of H[Sal]. The molecular structure of [Mat][Sal] is thoroughly investigated, including through single-crystal structure refinement, to gain an in-depth understanding of its properties. Moreover, in-vitro skin penetration experiments show that forming a salt with matrine increase the transdermal efficiency of H[Sal] while not damaging the skin barrier. The transdermal mechanisms of H[Sal] and [Mat][Sal] are studied both experimentally and using molecular dynamics simulations, which show that, compared to H[Sal], [Mat][Sal] reacts more strongly with the skin, and [Sal] − diffuses more rapidly in the skin owing to its higher water solubility and the ion-pair effect. Furthermore, [Mat][Sal] exhibits satisfactory anti-acne capabilities in a clinical-efficacy trial, highlighting its great potential for use in biomedical and cosmetics applications.
研究领域:
药理学
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化妆品科学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2024
·
IF 3.8
Xueli Liu,Yuan Luo,Yu Fan,Xiujun Cao,Jun Lu,Guoxin Song,Chunhui Deng
Aristolochic acids (AAs) naturally occurring in the herbal genus Aristolochia are associated with a high risk of kidney failure, multiple tumors and cancers. However, approaches with high selectivity and rapidity for measuring AAs in biological samples are still inadequate. Inspired by the mechanism of AAs-induced nephrotoxicity, we designed a hybrid magnetic polymer-porous agarose (denoted as MNs@SiO 2 M@DNV-A), mimicking the effect of basic and aromatic residues of organic anion transporter 1 (OAT1) for efficient enriching aristolochic acid I (AA I) and aristolochic acid II (AA II) in the plasma. The monomers of vinylbenzyl trimethylammonium chloride (VBTAC), N-vinyl-2-pyrrolidinone (NVP) and divinylbenzene (DVB) were employed to construct the polymer layer, which provided a selective adsorption for AAs by multiple interactions. The porous agarose shell contributed to remove interfering proteins in the plasma samples. A magnetic solid-phase extraction (MSPE) based on the proposed composite enhanced the selectivity toward AA I and AA II in the plasma samples. In combination of HPLC analysis, the proposed method was proved to be applicable to fast and specific quantification of AAs in blood samples, which was characterized by a good linearity, high sensitivity, acceptable recovery, excellent repeatability and satisfactory reusability.
研究领域:
药理学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Longyu Liu,Xueqiu Liu,Xinyi Lu,Xinmiao Guo,Xi Chen,Weiping Li,Xiaobin Yu,Zhiqiang Cheng
Matrine (MT) is a kind of alkaloid extracted from Sophora and is a promising substitute for chemical nematicides and botanical pesticides. The present study utilized sodium alginate (SA), zeolite imidazole salt skeleton (ZIF), and MT as raw materials to prepare a pH-response-release nematicide through the electrostatic spray technique. Zinc metal–organic framework (ZIF-8) was initially synthesized, followed by the successful loading of MT. Subsequently, the electrostatic spray process was employed to encapsulate it in SA, resulting in the formation of MT/ZIF-8@SA microcapsules. The efficiency of encapsulation and drug loadings can reach 79.93 and 26.83%, respectively. Soybean cyst nematode (SCN) is one of the important pests that harm crops; acetic acid produced by plant roots and CO2 produced by root respiration causing a decrease in the pH of the surrounding environment, which is most attractive to the SCN when the pH is between 4.5 and 5.4. MT/ZIF-8@SA releases the loaded MT in response to acetic acid produced by roots and acidic oxides produced by root respiration. The rate of release was 37.67% higher at pH 5.25 compared with pH 8.60. The control efficiency can reach 89.08% under greenhouse conditions. The above results demonstrate that the prepared MT/ZIF-8@SA not only exhibited excellent efficacy but also demonstrated a pH-responsive release of the nematicide.
研究领域:
植物保护
·
农药科学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MUTAGENESIS
·
2025
·
IF 4.3
Hu Yushi,Lei Yuyang,Gao Zhenna,Cao Yiyi,Xi Jing,Ma Yuning,Gao Qinwen,Fu Jian,Zhang Xinyu,Luan Yang
Aristolochic acid I (AAI) is a carcinogen associated with various human cancers. However, its causal relationship with hepatocellular carcinoma remains controversial, and inconsistent results from rodent studies have suggested species-specific differences. Here we evaluated AAI genotoxicity using functional human-induced hepatocyte-like cells (hiHep cells), a model that closely mimics primary human hepatocytes in gene expression and function, thereby shedding light on its potential hepatocarcinogenic risk in humans. First, we assessed AAI genotoxicity by evaluating AAI-DNA adducts and micronucleus frequency. In hiHep cells, AAI (0.7–2.5 µM) induced up to 105 adducts per 108 nucleotides, indicating high metabolic activation of AAI. A concentration-dependent increase in micronucleus frequency indicated a significant increase in chromosomal aberrations in hiHep cells. Considering the evidence of AAI inducing oxidative stress, we assessed 8-hydroxy-2′-deoxyguanosine and reactive oxygen species levels to evaluate DNA oxidative damage. For both indicators, significantly elevated levels were observed. A mechanism involving oxidative damage was further supported by observations of mitochondrial dysfunction, including changes in mitochondrial membrane potential and mitochondrial complex activity. Ascorbate treatment decreased AAI-induced oxidative DNA damage and DNA adduct formation, providing direct cellular evidence for free radical intermediates in AAI metabolic activation—a mechanism previously hypothesized but not experimentally validated in a human-relevant hepatocyte model. Our study findings revealed the genotoxic effects of AAI on hiHep cells and implicated oxidative stress as the key mechanism. These findings strengthen the association between AAI exposure and liver disease and highlight the potential role of antioxidant therapies in mitigating AAI-associated carcinogenesis.
研究领域:
毒理学
·
肝脏生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2019
·
IF 3.858
Luwei Fang,Minglei Tian,Xuemin Yan,Wei Xiao,Kyung Ho Row
A convenient, and efficient multi-phase extraction method was used to isolate aristolochic acid from real samples. To increase the efficiency, a new dual ionic liquid-immobilized silica was used as a sorbent and the effects of the adsorption conditions were investigated. IM-BIM@Sil in a methanol/water (60:40, v/v) solution at 60 °C extracted the highest amount of aristolochic acid (16.69 mg/g) compared to the other sorbents examined. The sorbent was then applied to the multi-phase extraction of aristolochic acid. After extraction eight times, 2.4–70.9 × 10 −3 mg/g of aristolochic acid was isolated from nine real samples after several washing and elution steps. The recoveries of aristolochic acid ranged from 70.0% to 110.6% with relative standard deviations of 3.5%–9.1%, highlighting the accuracy of this method.
研究领域:
分析化学
·
药物学
·
植物化学
✓ 已验证
DOI
PubMed
高影响因子