JOURNAL OF CHROMATOGRAPHIC SCIENCE
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2015
·Vol. 54
·期 3
·361-366
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IF 1.363
Tian Tingting,Yang Min,Zhao Zhongxi,Luan Yuxia,Tang Xuan,Zhu Meihua,Liu Yan
In this work, a stability-indicating high-performance liquid chromatography (HPLC) method was developed and validated for the simultaneous analysis of ketoconazole (KCZ) and beauvericin (BEA) as well as their degradation products in the combination tablets. KCZ is a synthetic broad-spectrum antifungal agent with the risk of hepatoxicity. However, it was found that the combined use of KCZ and BEA in their low dose had not only maintained the antifungal activity of KCZ but also significantly reduced the liver toxicity. The method development was started from forced degradation studies including acidic, basic, oxidative, thermal and photolytic degradations in the solution mixtures of KCZ and BEA. The forced degradation study results indicate that hydrolysis and oxidation were the major degradation pathways for KCZ while BEA mainly decomposed under basic hydrolytic condition. The newly developed HPLC method was validated according to the International Conference on Harmonization (ICH) guidelines with respect to specificity, linearity, precision, accuracy, limits of detection and quantification and robustness. The method validation results indicate that the new HPLC method could be successfully applied in the simultaneous detection and quantitation of KCZ and BEA and their degradation products. For example, the accuracy and the precision of the method were determined by a recovery study at 80, 100 and 120% of the tablet dosage levels. The recovery was found to be 99.6–100.2 for both analytes with a relative standard deviation of no more than 1.2% (n = 5) at any concentration level. This new method can be used for further development of various KCZ and BEA combination drug products.
研究领域:
药学
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分析化学
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 24
·12057
·
IF 4.9
Wenkai Li,Sifan Song,Wenyong Li,Jing Chen
Treating acute lung injury (ALI) presents significant challenges due to adverse drug reactions. This study systematically explored the protective effects and mechanisms of a flavonoid-rich extract fromBombyx batryticatus(FBB), a traditional Chinese medicine, in combating ALI. Through UPLC-MS/MS analysis, we identified 163 flavonoid components in FBB for the first time, including flavonoids, flavonols, and chalcones. Unlike single-component flavonoid therapies, FBB provides synergistic regulation across multiple targets and pathways. Network pharmacology predictions, supported by experimental validation, revealed that FBB primarily suppresses the expression of inflammatory factors (IL-1β, IL-6, TNF-α) and oxidative stress markers (iNOS, COX-2) by modulating the PI3K/Akt, MAPK, and NF-κB signaling pathways. FBB inhibits pro-inflammatory responses and upregulates chemokine receptors like Ccr1 and Ccr2, along with IL-2Rb, at the transcriptional level. This suggests its potential to promote inflammation resolution and tissue repair through immune microenvironment remodeling, rather than mere immunosuppression. Additionally, FBB demonstrated significant anti-apoptotic effects both in vitro and in vivo, effectively reducing pulmonary edema and vascular permeability. Its complex composition and multi-pathway synergistic mechanisms offer broader regulatory potential and unique therapeutic advantages in treating ALI compared to single flavonoid compounds or conventional hormone drugs like dexamethasone (DEX). This study reveals a novel mechanism by which FBB, a multi-component natural drug, exerts therapeutic effects in ALI, providing a theoretical and experimental foundation for developing flavonoid-based compound preparations from traditional Chinese medicine.
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Dun Jiang,Shuai Wu,Mingtao Tan,Hong Jiang,Shanchun Yan
Insect susceptibility to entomopathogenic microorganisms under heavy metal stress, as well as its regulatory mechanism is still poorly understood. This study aims to investigate the susceptibility of gypsy moth larvae to Beauveria bassiana under cadmium (Cd) stress (at 3.248 or 44.473 mg Cd/kg fresh food), and reveal the potential molecular mechanisms underlying the Cd effect on the larval susceptibility to B. bassiana via combined transcriptome and proteome analyses. Our results showed that pre-exposure to Cd increased the susceptibility of gypsy moth larvae to B. bassiana , and there was an additive effect between Cd exposure and B. bassiana infection on the larval mortality. Under the Cd stress at low and high concentrations, 138 and 899 differentially expressed genes (DEGs), as well as 514 and 840 differentially expressed proteins (DEPs) were identified, respectively. Immunotoxic effects induced by Cd exposure at the transcription level increased in a negative dose-response manner, with no immunity-related DEGs obtained at the low Cd concentration and a high number of immunity-related DEGs down-regulated at the high Cd concentration. In contrast, a potentially suppressed or stimulated trend in the Toll and Imd signaling pathway at protein level was revealed under low or high concentration of Cd treatment. Analysis of xenobiotics biodegradation-related pathways at both transcription and translation levels revealed that the gypsy moth larvae possessed an efficient homeostasis regulatory mechanism to the low-level Cd exposure, but exhibited a reduced xenobiotics biodegradation capability to the Cd stress at high levels. Together, these findings demonstrate Cd contamination promote the microbial-based biocontrol efficacy, and unravel the molecular regulatory network of heavy metal exposures that affects susceptibility of insects to pathogenic diseases.
研究领域:
昆虫学
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毒理学
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分子生物学
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环境科学
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PubMed
高影响因子
BIOPROCESS AND BIOSYSTEMS ENGINEERING
·
2019
·Vol. 42
·期 10
·1573-1582
·
IF 2.371
Zhou Hai-Yan,Li Yi-Zuo,Jiang Rui,Hu Hai-Feng,Wang Yuan-Shan,Liu Zhi-Qiang,Xue Ya-Ping,Zheng Yu-Guo
R -2-(4-hydroxyphenoxy)propionic acid ( R -HPPA) is a key intermediate of the enantiomerically pure phenoxypropionic acid herbicides. R -HPPA could be biosynthesized through selective introduction of a hydroxyl group (–OH) into the substrate R -2-phenoxypropionic acid ( R -PPA) at C-4 position, facilitated by microorganisms with hydroxylases. In this study, an efficient high-throughput screening method for improved R -HPPA biosynthesis through microbial hydroxylation was developed. As a hydroxylated aromatic product, R -HPPA could be oxidized by oxidant potassium dichromate to form brown-colored quinone-type compound. The concentration of R -HPPA can be quantified according to the absorbance of the colored compound at a suitable wavelength of 570 nm; and the R -HPPA biosynthetic capability of microorganism strains could also be rapidly evaluated. After optimization of the assay conditions, the high-throughput screening method was successfully used in identification of Beauveria bassiana mutants with enhanced R -HPPA biosynthesis capacity. A positive mutant C-7 with high tolerance to 20 g/L R -PPA was rapidly selected from 1920 mutants. The biomass and R -HPPA titer were 12.5- and 38.19-fold higher compared with the original strain at 20 g/L R -PPA. This high-throughput screening method developed in this work could also be a potential tool for screening strains producing other important phenolic compounds.
研究领域:
生物技术
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微生物学
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化学工程
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药学
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DOI
PubMed
高影响因子
Insect Science
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2024
·
IF 2.9
Wen-Xuan Qi,Feng Liu,Fang-Fang Liu,Hai-Yan Ren,Bang-Xian Zhang,Xiao-Qiang Yu,Xiang-Jun Rao
Antimicrobial peptides (AMPs) are critical components of innate immunity in diverse organisms, including plants, vertebrates, and insects. This study identified and characterized a novel Lepidoptera-specific AMP, named lepidoptin, from the invasive pest Spodoptera frugiperda (Lepidoptera: Noctuidae). Lepidoptin is a 116-amino acid protein containing a signal peptide and a novel β -sandwich domain that is distinct from previously reported AMPs. Temporal and spatial expression analyses revealed a significant upregulation of the lepidoptin gene in vivo and in cultured SF9 cells in response to pathogens. Molecular docking analysis identified a specific binding cavity. Enzyme-linked immunosorbent assay and binding assays confirmed that lepidoptin can bind to pathogen-associated molecular patterns, bacteria, and fungi. Recombinant lepidoptin exhibited potent antibacterial activity by inducing bacterial agglutination, inhibiting bacterial growth, increasing bacterial membrane permeability, and preventing biofilm formation. Lepidoptin also showed antifungal activity against the entomopathogenic fungus Beauveria bassiana by inhibiting spore germination, increasing fungal cell permeability, and increasing reactive oxygen species. Injection of recombinant lepidoptin into S. frugiperda larvae increased survival after B. bassiana infection, whereas knockdown of lepidoptin by RNA interference decreased larval survival. In addition, lepidoptin showed antimicrobial activity against the plant pathogen Fusarium graminearum by inhibiting spore germination and alleviating disease symptoms in wheat seedlings and cherry tomatoes. This study demonstrates the remarkable dual functionality of lepidoptin in enhancing S. frugiperda immunity and controlling plant pathogens, making it a promising candidate for biocontrol strategies in both pest management and plant disease prevention.
研究领域:
昆虫学
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微生物学
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分子生物学
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植物病理学
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害虫管理
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生物防治
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高影响因子
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