PLoS Pathogens
·
2025
·Vol. 21
·期 1
·e1012787
·
IF 4.9
Tingting Wang,Huaizhi Yang,Qiushuang Sheng,Ying Ding,Jian Zhang,Feng Chen,Jianfeng Wang,Lei Song,Xuming Deng
Hypervirulent Klebsiella pneumoniae (hvKP) poses an alarming threat in clinical settings and global public health owing to its high pathogenicity, epidemic success and rapid development of drug resistance, especially the emergence of carbapenem-resistant lineages (CR-hvKP). With the decline of the “last resort” antibiotic class and the decreasing efficacy of first-line antibiotics, innovative alternative therapeutics are urgently needed. Capsule, an essential virulence determinant, is a major cause of the enhanced pathogenicity of hvKP and represents an attractive drug target to prevent the devastating clinical outcomes caused by hvKP infection. Here, we identified isoferulic acid (IFA), a natural phenolic acid compound widely present in traditional herbal medicines, as a potent broad-spectrum K . pneumoniae capsule inhibitor that suppresses capsule polysaccharide synthesis by increasing the energy status of bacteria. In this way, IFA remarkably reduced capsule thickness and impaired hypercapsule-associated hypermucoviscosity phenotype (HMV), thereby significantly sensitizing hvKP to complement-mediated bacterial killing and accelerating host cell adhesion and phagocytosis. Consequently, IFA facilitated effective bacterial clearance and thus remarkably protected mice from lethal hvKP infection, as evidenced by limited bacterial dissemination and a significant improvement in survival rate. In conclusion, this work promotes the development of a capsule-targeted alternative therapeutic strategy for the use of the promising candidate IFA as an intervention to curb hvKP infection, particularly drug-resistant cases.
Hypervirulent Klebsiella pneumoniae (hvKP) is becoming an imminent threat to public health because of the constant emergence of drug resistance and its devastating clinical outcomes. Meanwhile, the both notorious phenotypes are integrated to create carbapenem-resistant and hypervirulent K . pneumoniae (CR-hvKP), which leads to a scarcity of effective treatments. Therefore, there is an increasing urgent need for new therapeutics other than antibiotics. The indispensable role of capsule in immune evasion and pathogenesis renders it a promising target for developing novel alternative strategies to combat hvKP infections. In this study, we identified the small natural compound isoferulic acid (IFA) as a potent broad-spectrum inhibitor of K . pneumoniae capsule. Hypercapsule-associated hypermucoviscosity (HMV), a characteristic phenotype that has been shown to play a distinct and critical role in the pathogenesis of hvKP, is significantly impaired by IFA. RNA-seq analysis revealed that IFA interferes with the biosynthesis of capsule polysaccharide through altering bacterial metabolism status. Consequently, IFA sensitizes hvKP to serum killing and impedes capsule- and HMV-mediated resistance to adherence and phagocytosis. In vivo, IFA treatment facilitates effective host clearance and thereby systemically protects mice against hvKP infection. Our research sheds light on the development of capsule-targeted drug and provides an effective lead compound that may contribute to the management of hvKP infections as an intervention.
研究领域:
微生物学
·
传染病学
·
药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemistry Central Journal
·
2012
·Vol. 6
·期 1
·1-10
·
IF 3.281
Li Xican,Lin Jing,Gao Yaoxiang,Han Weijuan,Chen Dongfeng
Background As a typical Chinese herbal medicine, rhizoma Cimicifugae (RC, 升麻 in Chinese) possesses various pharmacological effects involved in antioxidant activity. However, its antioxidant activity has not been reported so far. The aim of the present study was to systematically evaluate the antioxidant ability of RC in vitro, then discuss the mechanism. Methods Firstly, five RC extracts (i.e. petroleum ether extract PERC, ethyl acetate extract EARC, absolute ethanol extract AERC, 95% ethanol extract 95ERC, and water extract WRC) were prepared and determined by various antioxidant methods, including anti-lipidperoxidation, protection against DNA damage, ·OH scavenging, ·O 2 - scavenging, DPPH· (1,1-diphenyl-2-picryl-hydrazl radical) scavenging, ABTS + · (2,2’-azino-bis (3-ethylbenzo- thiazoline-6-sulfonic acid radical ion) scavenging, Cu 2+ -chelating, and Fe 3+ reducing assays. Subsequently, we measured the chemical contents of five RC extracts, including total phenolics, total saponins, total sugars, caffeic acid, ferulic acid and isoferulic acid. Finally, we quantitatively analyzed the correlations between antioxidant levels (1/IC 50 values) and chemical contents. Results In the study, the antioxidant levels and chemical contents (including total phenolics, total saponins, total sugars, caffeic acid, ferulic acid and isoferulic acid) of five RC extracts were determined by various methods. In all antioxidant assays, five RC extracts increased the antioxidant levels in a dose-dependent manner. However, their antioxidant levels (IC 50 values) and chemical contents significantly differed from each other. Quantitative analysis of the correlation showed that total phenolic was of significant positive correlations (average R value was 0.56) with antioxidant levels; In contrast, total sugars and total saponins had no positive correlation with antioxidant (the average R values were −0.20 and −0.26, for total sugars and total saponins, respectively); Among total phenolics, three phenolic acids (caffeic acid, ferulic acid and isoferulic acid) also displayed positive correlations (the average R values were 0.51, 0.50, and 0.51, for caffeic acid, ferulic acid and isoferulic acid, respectively). Conclusions As an effective antioxidant, Rhizoma Cimicifugae can protect DNA and lipids against oxidative damage. Its antioxidant ability can be responsible for its various pharmacological effects and may be mainly attributed to the existence of total phenolics, among which caffeic acid, ferulic acid and isoferulic acid are regarded as main bioactive components. Rhizoma Cimicifugae exerts its antioxidant effect through metal-chelating, and radical-scavenging which is via donating hydrogen atom (H·) and donating electron (e).
研究领域:
中药学
·
药理学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2025
·Vol. 52
·期 3
·e70025
·
IF 2.5
Suqin Sun,Rong Fan,Li Chang,Lei Gao,Chunting Liu,Dongying Liu,Shiyu Niu
Isoferulic acid (IA), a derivative of cinnamic acid, is derived from Danshen and exhibits anticancer properties by disrupting cancer cell activities. However, its role in pancreatic cancer, the “king of cancer”, was unknown. In this study, pancreatic cancer cells were subjected to treatment with IA (6.25, 12.5, 25 μM), and nude mice injected with pancreatic cancer cells were received IA at doses of 7.5 mg/kg/day or 30 mg/kg/day by oral administration. CCK8, Annexin V-FITC/propidium iodide (PI) double staining and TUNEL assay were conducted to evaluate the cell viability and apoptosis. Hoechst staining and comet assay was employed to measure DNA damage. Mitochondrial membrane potential (MMP) analysis was carried out to explain the mitochondrial damage. EdU and wound healing assay were performed for cell proliferation and migration detection. Immunofluorescence and western blot were used to explore the mechanism. We found that IA reduced cell viability and induced apoptosis, as evidenced by an increase in Annexin V-FITC + PI − and Annexin V-FITC + PI + cell populations, brighter TUNEL and Hoechst staining, and more percentage of tail DNA. Furthermore, IA decreased MMP and changed levels of apoptosis-related proteins. The cell proliferation and migration were inhibited by IA treatment. Mechanically, IA downregulated the phosphorylation of IĸBα and inhibited p65 nuclear translocation, consequently suppressing NF-κB pathway. In general, IA suppressed the cell proliferation and migration, and caused apoptosis of pancreatic cancer cells in a mitochondria-dependent manner through blocking NF-κB signalling pathway, indicating that IA may be a potential therapeutic strategy for pancreatic cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2024
·Vol. 16
·期 13
·2148
·
IF 4.8
Xiaoqin La,Xiaoting He,Jingyi Liang,Zhaoyan Zhang,Hanqing Li,Yizhi Liu,Ting Liu,Zhuoyu Li,Changxin Wu
Excessive alcohol consumption has led to the prevalence of gastrointestinal ailments. Alleviating gastric disorders attributed to alcohol-induced thinning of the mucus layer has centered on enhancing mucin secretion as a pivotal approach. In this study, foxtail millet bran polyphenol BPIS was divided into two components with MW < 200 D and MW > 200 D by molecular interception technology. Combined with MTT, cell morphology observation, and trypan blue staining, isoferulic acid (IFA) within the MW < 200 D fraction was determined as the effective constituent to mitigate ethanol-induced damage of gastric epithelial cells. Furthermore, a Wistar rat model with similar clinical features to alcohol-induced gastric mucosal injury was established. Then, gastric morphological observation, H&E staining, and assessments of changes in gastric hexosamine content and gastric wall binding mucus levels were carried out, and the results revealed that IFA (10 mg/Kg) significantly ameliorated alcohol-induced gastric mucosal damage. Finally, we applied techniques including Co-IP, molecular docking, and fluorescence spectroscopy and found that IFA inhibited the alcohol-induced downregulation of N-acetylgalactosamintransferase 2 (GALNT2) activity related to mucus synthesis through direct interaction with GALNT2 in gastric epithelial cells, thus promoting mucin synthesis. Our study lays a foundation for whole grain dietary intervention tailored to individuals suffering from alcoholic gastric mucosal injury.
研究领域:
胃肠病学
·
药理学
·
分子生物学
·
营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 14
·期 1
·14
·
IF 4.7
Haoping Liu,Hua Zhang,Mengting Geng,Dingxin Shi,Dongsheng Liu,Yanxiao Jiao,Zhiqiang Lei,You Peng
In this study, the total polyphenol content (TPC), total flavonoid content (TFC), and biological activity of yam polyphenols (including free phenolics, conjugated phenolics, and bound phenolics) were investigated during home cooking. Polyphenol components were preliminary detected in raw yam by HPLC, including 2, 4-dihydroxybenzoic acid, syringic acid, vanillic acid, 4-coumaric acid, and sinapic acid. TPC and TFC of soluble conjugated polyphenols were the main phenolic compounds in Ruichang yam. Compared with uncooked yam, cooking times of 80 min and 40 min increased the TPC and TFC of multiple types of polyphenols, while cooking reduced the TPC and TFC of AHP (acid-hydrolyzed soluble conjugated polyphenols). All yam polyphenols exhibited good α-Glucosidase inhibitory activity; α-Glucosidase inhibitory activity was significantly higher for a cooking time of 120 min. Only some types of polyphenols had lower pancreatic lipase half-inhibition concentrations than orlistat when cooked. The pancreatic lipase of FPs (free polyphenols), BHPs (alkali-hydrolyzed soluble conjugated polyphenols), and ABPs (acid-hydrolyzed insoluble bound polyphenols) was the stronges when cooking for 80 min, and the pancreatic lipase inhibitory activity of AHPs and BBPs (alkali-hydrolyzed insoluble bound polyphenols) was strongest when cooking for 40 min. Pearson’s correlation coefficient analysis revealed that the TPC was positively correlated with the TFC, the IC50value of α-Glucosidase was negatively correlated with the IC50value of pancreatic lipase, and redox activity was positively correlated with the TPC and TFC, respectively.
研究领域:
食品科学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Chemistry-X
·
2024
·
IF 6.5
Kunying Nie,Jiali Zhang,Haitao Xu,Keyun Ren,Chunlei Yu,Qi Zhang,Falan Li,Qingqing Yang
Rapid simultaneous detection of multi-component adulteration markers can improve the accuracy of identification of gutter cooking oil in edible oil, which is made possible by broad-spectrum antibody (bs-mAb). This study used capsaicinoids (CPCs) and gingerol derivatives (GDs) as adulteration markers, and two broad-spectrum haptens (bs-haptens) were designed and synthesized based on a reverse design strategy of molecular docking. Electrostatic potential (ESP) and monoclonal antibodies (mAbs) preparation verified the strategy's feasibility. To further investigate the recognition mechanism, five other reported antigens and mAbs were also used. Finally, the optimal combination (Hapten 5-OVA/1-F12) and key functional groups (f-groups) were determined. The half maximal inhibitory concentration (IC 50 ) for CPCs-GDs was between 88.13 and 499.16 ng/mL. Meanwhile, a preliminary lateral flow immunoassay (LFIA) study made practical monitoring possible. The study provided a theoretical basis for the virtual screening of bs-haptens and simultaneous immunoassay of multiple exogenous markers to monitor gutter oil rapidly and accurately.
研究领域:
食品科学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Algal Research-Biomass Biofuels and Bioproducts
·
2024
·
IF 4.6
Min Li,Zhen-Fang Shang,Zhi-Jing Ni,Hui-Jun Zhao,Qian Lei,Zhao-Jun Wei
Auxenochlorella pyrenoidosa 's industrial utility is closely associated with the concentration of high-value products. This study focuses on the effects of cinnamic acid (CA) and its derivatives, which known as secondary metabolites in higher plants and effective plant growth regulators, on the growth and metabolic profiles of A. pyrenoidosa . It was discovered that CA and its derivatives significantly enhance the biomass of A. pyrenoidosa under conditions of 10 mg/L over 48 h or 100 mg/L over 120 h. Cells treated with 10 mg/L CA exhibited lower oxidative stress and maintained robust metabolic activity. Metabolic pathways, including those for carbohydrates, lipids, small peptides, and cofactors, were stimulated, leading to the accumulation of a wide array of bio-products, notably high-value products such as α-linolenic acid, cis-4,7,10,13,16,19-docosahexaenoic acid (DHA), nicotinamide adenine dinucleotide plus hydrogen (NADH), glutathione, and vitamins B2/B3. This study demonstrates that CA and its derivatives are good nutritional enhancers for cultivating A. pyrenoidosa , highlighting their potential for broad application in biotechnological industries.
研究领域:
生物技术
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2018
·Vol. 23
·期 5
·1110
·
IF 3.098
Shi Shen,Jingbo Wang,Qin Zhuo,Xi Chen,Tingting Liu,Shuang-Qing Zhang
Phenolics and flavonoids in honey are considered as the main phytonutrients which not only act as natural antioxidants, but can also be used as floral markers for honey identification. In this study, the chemical profiles of phenolics and flavonoids, antioxidant competences including total phenolic content, DPPH and ABTS assays and discrimination using chemometric analysis of various Chinese monofloral honeys from six botanical origins (acacia,Vitex, linden, rapeseed,AstragalusandCodonopsis) were examined. A reproducible and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was optimized and validated for the simultaneous determination of 38 phenolics, flavonoids and abscisic acid in honey. Formononetin, ononin, calycosin and calycosin-7-O-β-d-glucoside were identified and quantified in honeys for the first time. Principal component analysis (PCA) showed obvious differences among the honey samples in three-dimensional space accounting for 72.63% of the total variance. Hierarchical cluster analysis (HCA) also revealed that the botanical origins of honey samples correlated with their phenolic and flavonoid contents. Partial least squares-discriminant analysis (PLS-DA) classification was performed to derive a model with high prediction ability. Orthogonal partial least squares-discriminant analysis (OPLS-DA) model was employed to identify markers specific to a particular honey type. The results indicated that Chinese honeys contained various and discriminative phenolics and flavonoids, as well as antioxidant competence from different botanical origins, which was an alternative approach to honey identification and nutritional evaluation.Keywords:UPLC-MS/MS;antioxidant competence;phenolic;flavonoid;chemometrics;monofloral honey
研究领域:
植物学
·
食品科学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2011
·Vol. 16
·期 4
·3444-3455
·
IF 1.988
Haisha Yang,Yuqiong Dong,Huijing Du,Haiming Shi,Yunhua Peng,Xiaobo Li
The antioxidant activities of the chloroform, ethyl acetate andn-butanol extract fractions from propolis collected in Anhui, China were evaluated in this study. The ethyl acetate fraction contained the highest amount of total phenolics and total flavonoids, and showed the greatest 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging capacities and Ferric Reducing/Antioxidant Power (FRAP). The antioxidant activity of twenty-two compounds isolated from the ethyl acetate fraction was also evaluated using the above-mentioned three assays. The results indicated that phenolics contributed to the antioxidant activity of propolis collected in Anhui, China. Therefore, propolis collected in Anhui, China and its phenolics might be used as a natural antioxidant.Keywords:propolis;antioxidant activity;phenolics;natural antioxidants
研究领域:
植物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD PROPERTIES
·
2018
·
IF 1.845
Han Peng,Zeyuan Deng,Xuan Chen,Yong Sun,Bing Zhang,Hongyan Li
Hovenia acerba Lindl. is a perennial tree of Rhamnaceae family. In the present study, four solvents (80% methanol, ethyl acetate, n-hexane, and water) were used to extract the compounds of Hovenia acerba Lindl. peduncles (HAP). The total contents of phenolics and tannins (TPC and TTC), as well as their antioxidant activities (DPPH, ABTS, and FRAP) of these four different extracts including 80% methanol extract (ME), ethyl acetate extract (EE), n-hexane extract (HE) and water extract (WE) were compared. The antioxidant activities of HAP showed positive correlations with TPC and TTC, indicating that phenolics maybe a major contributor to the antioxidant activities of HAP. The significant difference between antioxidant activities and TPC/TTC implied the respective contribution extent of phenolics for the antioxidant activities of four solvent extracts. Besides, a total of 117 compounds, including 7 oligosaccharides, 11 organic acids, 41 phenolics, 1 steroids, 25 terpenes, 11 fatty acids, 9 amino acids, and 12 other compounds were identified or tentatively characterized in HAP for the first time. Among them, 23 bioactive constituents, including 4 organic acids, 5 phenolic acids, and 14 flavonoids, were quantified. The comparison of characterization and quantitation of 4 extracts demonstrated that 80% methanol showed the widest range of selectivity for both HAP flavonoid aglycones and glycosides, while ethyl acetate preferred to extract the flavonoids aglycone from HAP. Secondly, water and 80% methanol were excellent solvents for the extraction of phenolic acids. And both ethyl acetate and 80% methanol perform well at the extraction of terpenes and steroids.
研究领域:
植物化学
·
药理学
·
食品科学
✓ 已验证
产品关联
DOI
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2019
·
IF 3.714
Haiying Cai,Qi Zhang,Lingzhi Shen,Jie Luo,Ruiyu Zhu,Jianwei Mao,Minjie Zhao,Chenggang Cai
The polyphenolic compounds in wines are beneficial to human health. To better understand the effect of different factors on the phenolics and antioxidant activities of wine during rice wine fermentation, 6 rice materials and 7 rice wine starters from rural areas were used to ferment Chinese rice wine. The results showed that black rice and the starter O4 were preferred for the optimum polyphenolic content and antioxidant activity, respectively. In addition, the results indicated that the polyphenolics of the rice wines were mainly derived from their plant materials and that various rice materials could result in drastically different wine quality. In contrast, the total polyphenol contents could be less significantly changed by using different starters. The antioxidant activity results of these fermented wines were consistent with the results of the total polyphenol contents. The rice wines produced using 6 different rice materials were significantly different in antioxidant activity measured by ABTS and FRAP assay . Similar to the results of the total polyphenol content and the antioxidant activity, the wine samples with different rice materials showed significantly different polyphenolic profiles compared with those of the rice wine group with different starters. These results suggested that rice materials and starters have different effects on polyphenol extraction and conversion of rice wines.
研究领域:
食品科学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2021
·
IF 3.205
Fengjie Yu,Jianing Zhang,Yunmin Tao,Chunping Du,Wenchao Yang,Wenbin Chen,Xijuan Tu
In the present study, a high-throughput homogenous liquid-liquid extraction method was developed for fast sample preparation of multiple phenolic compounds in propolis. This method was proposed based on cooling samples array in subzero temperature to induce phase separation of ACN-H 2 O extractant. Due to the high-throughput ability, optimization of extraction parameters was rapidly achieved by using a 5 × 4 × 3 samples array. In addition, multiple arrays were investigated for evaluating the analytical performance of the high-throughput method, which indicated that limits of detection and quantification were ranged from 0.04 to 0.35 µg/mL and 0.12 to 1.05 µg/mL, respectively. Recoveries and precisions in inter-day high-throughput studies were in the range of 90.55–105.50% and 2.58–4.30%, respectively. Comparing with the conventional liquid extraction method, this ecofriendly high-throughput method presented remarkable advantages in reducing sample and chemical consumption, as well as saving labor and time cost. The proposed method might provide a valuable strategy for the design of high-throughput extraction procedures.
研究领域:
分析化学
·
食品科学
✓ 已验证
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）