JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Li Zhang,Yunfei Shi,Xinying Duan,Wanrong He,Hongyan Si,Peng Wang,Shangxing Chen,Hai Luo,Xiaoping Rao,Zongde Wang,Shengliang Liao
To develop new antifungal agents against phytopathogenic fungi, a series of citral-thiazolyl hydrazine derivatives were designed, synthesized, and characterized by FT-IR, 1H NMR, 13C NMR, and HRMS. Antifungal activity results showed that most synthetic compounds exhibited broad-spectrum antifungal activities against six phytopathogenic fungi in vitro. Notably, compounds b and c15 exhibited remarkable antifungal activity against Colletotrichum gloeosprioides, Rhizoctonia solani, Phytophthora nicotianae var. nicotianae, Diplodia pinea, Colletotrichum acutatum, and Fusarium oxysporum f. sp. niveum, which were all superior to the positive control tricyclazole. Structure–activity relationship (SAR) studies demonstrated that introducing electron-withdrawing groups such as F on the benzene ring exhibited outstanding antifungal activities against all the tested fungi. Furthermore, compound b could effectively control rice sheath blight and showed higher curative activities against R. solani than validamycin·bacillus in vivo. In addition, the in vitro cytotoxicity results indicated that compound b possessed moderate cytotoxicity activity, and all citral-thiazolyl hydrazine derivatives exhibited lower or no cytotoxicity to the LO2 and HEK293 cell lines. In addition, the acute oral toxicity test showed that compound b had moderate toxicity (level II) with an LD50 value of 310 mg/kg bw (95% confidence limit: 175–550 mg/kg bw). Finally, a preliminary action mechanism study showed that causing obvious malformation of mycelium and increasing cell membrane permeability are two of the potential mechanisms by which compound b exerts antifungal activity. The present work indicates that some of these derivatives may serve as novel potential fungicides, and compound b is expected to be the leading structure for the development of new antifungal agents.
研究领域:
植物病理学
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药物化学
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分子生物学
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DOI
高影响因子
Microbiology Spectrum
·
2022
·Vol. 10
·期 5
·
IF 9.043
Wen Wang,Xuerui Bao,Mona Bové,Petra Rigole,Xiaofeng Meng,Jianyu Su,Tom Coenye
Phytochemicals are promising antibacterials for the development of novel antibiofilm drugs, but their antibiofilm activity in physiologically relevant model systems is poorly characterized. As the host microenvironment can interfere with the activity of the phytochemicals, mimicking the complex environment found in biofilm associated infections is essential to predict the clinical potential of novel phytochemical-based antimicrobials. In the present study, we examined the antibiofilm activity of borneol, citral, and combinations of both as well as their Pickering emulsions against Staphylococcus aureus and Pseudomonas aeruginosa in an in vivo-like synthetic cystic fibrosis medium (SCFM2) model, an in vitro wound model (consisting of an artificial dermis and blood components at physiological levels), and an in vivo Galleria mellonella model. The Pickering emulsions demonstrated an enhanced biofilm inhibitory activity compared to both citral and the borneol/citral combination, reducing the minimum biofilm inhibitory concentration (MBIC) values up to 2 to 4 times against P. aeruginosa PAO1 and 2 to 8 times against S. aureus P8-AE1 in SCMF2. In addition, citral, the combination borneol/citral, and their Pickering emulsions can completely eliminate the established biofilm of S. aureus P8-AE1. The effectiveness of Pickering emulsions was also demonstrated in the wound model with a reduction of up to 4.8 log units in biofilm formation by S. aureus Mu50. Furthermore, citral and Pickering emulsions exhibited a significant degree of protection against S. aureus infection in the G. mellonella model. The present findings reveal the potential of citral- or borneol/citral-based Pickering emulsions as a type of alternative antibiofilm candidate to control pathogenicity in chronic infection.IMPORTANCE There is clearly an urgent need for novel formulations with antimicrobial and antibiofilm activity, but while there are plenty of studies investigating them using simple in vitro systems, there is a lack of studies in which (combinations of) phytochemicals are evaluated in relevant models that closely resemble the in vivo situation. Here, we examined the antibiofilm activity of borneol, citral, and their combination as well as Pickering emulsions (stabilized by solid particles) of these compounds. Activity was tested against Staphylococcus aureus and Pseudomonas aeruginosa in in vitro models mimicking cystic fibrosis sputum and wounds as well as in an in vivo Galleria mellonella model. The Pickering emulsions showed drastically increased antibiofilm activity compared to that of the compounds as such in both in vitro models and protected G. mellonella larvae from S. aureus-induced killing. Our data show that Pickering emulsions from phytochemicals are potentially useful for treating specific biofilm-related chronic infections.
研究领域:
微生物学
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药理学
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感染病学
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DOI
高影响因子
PHARMACEUTICAL BIOLOGY
·
2018
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IF 1.918
Huaqiao Tang,Nana Long,Min Dai,Lin Lin,Jianlong Li,Fenghui Sun,Lijuan Guo
Context: Citral is used as a potential natural treatment for various infectious diseases.Objective: To examine the effect of citral on the mRNA expression and activities of cytochrome P450 (CYP450) enzymes and establish the relationship between citral-induced liver injury and oxidative stress.Materials and methods: ICR mice were randomly divided into citral (20, 200, and 2000 mg/kglow), Tween-80, and control groups (0.9% saline), 10 mice in each group. The citral-treated groups were intragastrically administered citral for 3 d, control groups treated with 0.5% Tween-80 and 0.9% saline in the same way. Liver injury and CYP450 enzymes were analyzed by analyzing the histopathological changes and the changes of related enzymes.Results: Citral treatment (2000 mg/kg) for 3 d increased serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels, as well as glutathione, gydroxyl radicals, malonaldehyde and total superoxide dismutase contents, but decreased the content of total antioxidant capacity. In doses of 20 and 200 mg/kg groups mice, the contents of NO were decreased significantly and other changes were similar to the 2000 mg/kg group mice, but the liver damage was most severe in the 2000 mg/kg group. Citral induced the mRNA expression and activities of CYP450 1A2, 2D22, and 2E1 in the liver of mice at doses of 20 and 200 mg/kg. There were no changes in testing indexes in Tween-80 treated group mice. Due to its toxic effects, the CYP induction effect of citral negatively correlated with its dose. Although the mRNA expression of CYP450 3A11 was induced by citral, its activity was not affected by low and moderate doses of citral. CYP450 3A11 activity was significantly decreased by high-dose citral.Conclusions: Citral is hepatotoxic and induced oxidative stress in higher dose, which has a negative effect on CYP450 enzymes. These data suggest caution needs to be taken in order to avoid citral-drug interactions in human beings.
研究领域:
药理学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2026
·Vol. 23
·期 8
·e71542
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IF 2.9
Min Xiao,Haowen Huang,Dagen Wang,Lili Yao,Shengliang Liao,Jie Song,Rong Zeng,Shangxing Chen
To develop citral‐based botanical fungicides, 112 previously reported derivatives across 5 series were evaluated in vitro against Colletotrichum fructicola . SAR analysis identified the citral‐thiourea series as the most potent group, with 3‐methoxy derivative c18 showing the highest intraseries activity. Notably, intermediates d (EC 50 = 0.7474 mg/L, EC 90 = 6.0319 mg/L) and g (EC 50 = 0.1073 mg/L, EC 90 = 0.6244 mg/L) demonstrated exceptional efficacy, significantly outperforming commercial chlorothalonil (EC 50 = 1.4382 mg/L, EC 90 = 268.5969 mg/L), with intermediate g emerging as the most potent compound overall. A predictive QSAR model was successfully constructed ( R 2 = 0.8345), revealing that lower polarity, enhanced electronic stability of carbon–hydrogen bonds, higher localized solvation energy, and minimized steric hindrance favor antifungal potency. Furthermore, MTT assays confirmed that derivative g exhibits low cytotoxicity toward human liver and kidney cells, substantially lower than raw citral. This work provides a solid theoretical framework for designing highly active inhibit C. fructicola agents. A library of 112 previously reported citral derivatives is screened to identify potent botanical fungicides against Colletotrichum fructicola . A predictive QSAR model ( R 2 = 0.8345) decrypts structural pathways, elegantly balancing global transmembrane transport with localized target anchoring. Providing exceptional efficacy and low cytotoxicity, these insights offer a definitive blueprint for the next‐generation green pesticides.
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DOI
PubMed
高影响因子
ChemistryOpen
·
2024
·
IF 2.5
Wei Gao,Xiaoju Hua,Shengliang Liao,Zhikai Xiahou,Haikuan Yang,Lifang Hu,Yunyang Chi
Graphical Compound 3h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells.The results show that 3h induces cell-cycle arrest in the S phase. Additionally, 3h exerts a strong pro-apoptotic effect. Specifically, compound 3h reduces the phosphorylation of PI3K, AKT, and ERK, thereby inhibiting both the MAPK/ERK and PI3K/AKT signaling pathways. 2H-pyran compound 1 synthesized from 6-methylpyridine-2,4-diol and citral, has been used for Cu-catalyzed N -arylation with a range of arylboric acids to obtain arylated pyranopyridine core structure derivatives (yield up to 77 %). Among them, compound 3 h exhibited a much better inhibitory effect on HepG2 liver cancer cells compared to citral, and the IC 50 value was 5.3 μM following exposure with the newly synthesized derivatives (herein named 3 h for short in this paper), which was lower than that of the cisplatin (6.5 μM). Meanwhile, the cell-cycle arrest of HepG2 cells occurred in the S phase, and the apoptosis of HepG2 cells was significantly increased with increasing drug concentration. In addition, real-time fluorescence quantification PCR and Western blotting experiments showed that the expression of apoptotic protein BAX was increased, while the expression of anti-apoptotic protein BCL2 was inhibited in a dose-dependent fashion. The results of these experiments indicated that apoptosis was promoted in HepG2 cells via apoptotic signaling pathway activated by 3 h . Furthermore, 3 h effectively decreased the phosphorylation levels of PI3 K, ATK and ERK, resulting in the inhibitions of MAPK/ERK and PI3 K/ATK signaling pathways. Briefly, 3 h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells and may be used as anti-cancer drug in the future.
研究领域:
药理学
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
Polymers
·
2022
·Vol. 14
·期 6
·1165
·
IF 4.967
Wen-Long Ma,Chuan-Lin Mou,Shi-Hao Chen,Ya-Dong Li,Hong-Bo Deng
Citral is a typical UV-irritation and acid-sensitive active and here we develop a mild method for the encapsulation of citral in calcium alginate microcapsules, in which UV irritation or acetic acid is avoided. Monodispersed oil-in-water-in-oil (O/W/O) emulsions are generated in a capillary microfluidic device as precursors. The middle aqueous phase of O/W/O emulsions contains sodium alginate, calcium-ethylenediaminetetraacetic acid (EDTA-Ca) complex as the calcium source, and D-(+)-Gluconic acid δ-lactone (GDL) as the acidifier. Hydrolysis of GDL will decrease the pH value of the middle aqueous solution, which will trigger the calcium ions released from the EDTA-Ca complex to cross-link with alginate molecules. After the gelling process, the O/W/O emulsions will convert to alginate microcapsules with a uniform structure and monodispersed size. The preparation conditions for alginate microcapsules are optimized, including the constituent concentration in the middle aqueous phase of O/W/O emulsions and the mixing manner of GDL with the alginate-contained aqueous solution. Citral-containing alginate microcapsules are successfully prepared by this mild method and the sustained-release characteristic of citral from alginate microcapsules is analyzed. Furthermore, a typical application of citral-containing alginate microcapsules to delay the oxidation of oil is also demonstrated. The mild gelling method provides us a chance to encapsulate sensitive hydrophobic actives with alginate, which takes many potential applications in pharmaceutical, food, and cosmetic areas.Keywords:alginate microcapsules;microfluidic;GDL;citral;mild gelling method
研究领域:
材料科学
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食品科学
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药物递送
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
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2024
·
IF 5.6
Wen Wang,Tom Coenye,Jianyu Su,Sheng-Xiang Qiu
Biofilms growing on food surfaces, packaging, equipment and processing environments bring huge risks to food safety and result in economic losses. Natural components are receiving increasing interest as “green” antimicrobial agents due to their biocompatibility, broad-spectrum antimicrobial properties, and antibiofilm potential. As a traditional adjuvant in Chinese medicine, borneol has the potential to enhance citral’s antibiofilm efficacy. In this study, the antibiofilm activities of citral, borneol, and the combination citral and borneol (BC) against various foodborne bacteria were evaluated using multiple techniques. Light microscopy, crystal violet (CV) staining, and the 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylaminocarbonyl]-2H-tetrazolium hydroxide (XTT) assay were employed to monitor biofilm formation. Additionally, biofilm eradication was assessed against Staphylococcus aureus and Escherichia coli biofilms grown on polycarbonate membranes. Protein leakage was measured, and field emission scanning electron microscopy (FESEM) was used to examine cell membrane integrity. Results showed that borneol and citral acted synergistically to inhibit biofilms. Borneol, citral, alone or together inhibited biofilm formation in a concentration dependent manner, and they have the ability to inactivate or kill at least 90.7 ± 1.9 % bacteria in preformed biofilms. Both borneol and citral disrupted the membrane integrity of the bacteria, increased permeability, and ultimately led to cell death. These findings suggest that the combination citral and borneol has the potential to be developed as a food preservative or bactericidal agent for controlling foodborne bacterial contamination.
研究领域:
微生物学
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食品安全
·
天然产物研究
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产品关联
DOI
高影响因子
Food Quality and Safety
·
2024
·
IF 3
Fan Yanan,Xu Qixiang,Ren Keyu,Zhai Mengge,Xing Guozheng,Song Yishan,Zhu Yongheng
With the deepening of the harm of foodborne pathogens to human health and the increasing attention of people to healthy diet, novel food antimicrobial agents have been widely studied by researchers as hotspots. In this study, three different morphologies of citral-modified ZnO nanopaticles antimicrobial materials were prepared, and the citral-modified porous ZnO nanorods antimicrobial materials with the highest loading (60.35%) and the strongest inhibitory effect (MIC = 0.2 mg/mL ~ 0.1 mg/mL) were screened out through a series of characterization and bacterial inhibition experiments. This novel antimicrobial material has excellent and long-lasting antimicrobial properties. It inhibits Escherichia coli by 100% when stowed at 25°C and protected from light for 10 days, and inhibits the growth of E. coli by 58.17% after being stowed under the same conditions for 60 days. Furthermore, we tested the pH change during 24 hours of E. coli growth and pH responsiveness of the materials. The results demonstrated that under the acid-producing condition of E. coli growth, the pH-sensitive imine bond (-CH=N-) formed by the condensation of amino of functionalized ZnO nanoparticles and citral was hydrolyzed to release the citral, thus indicating that the release mechanism of citral in the antibacterial material was pH-sensitive acid release in the process. The antibacterial materials in this study have broad application prospects in the field of food production and packaging in the future. Meanwhile, this study provides a theoretical basis for guaranteeing food quality and safety.
研究领域:
食品科学
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纳米材料
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微生物学
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产品关联
DOI
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2019
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IF 3.714
Rui Cai,Miaomiao Hu,Yijun Zhang,Chen Niu,Tianli Yue,Yahong Yuan,Zhouli Wang
The aim of this study was to investigate the antifungal activity and mechanisms of citral, limonene and eugenol against Zygosaccharomyces rouxii . All the three essential oil ingredients presented strong antifungal activities against Z. rouxii . Minimum inhibitory concentrations of citral, limonene and eugenol were 0.188, 0.75 and 0.4 μL/mL, and the minimum fungicidal concentrations were 0.375, 3 and 0.8 μL/mL, respectively. Scanning electron microscopy showed that the tested essential oil compounds had destructive effects on the yeast cell surface. After treated by citral, limonene and eugenol, the relative electric conductivity and leakage of nucleic acid were increased significantly. SDS-PAGE analysis indicated that the essential oil components could result in the loss of soluble proteins and might also destroy the yeast protein or inhibit their expression. These results demonstrated that citral, limonene and eugenol exerted their antifungal action against Z. rouxii through cell membrane damage and destruction of cellular proteins. This study provided a theoretical possibility that citral, limonene and eugenol could be used as natural food preservatives for the control of Z. rouxii -related spoilage in the fruit juice industry.
研究领域:
食品科学
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微生物学
·
药理学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Rong Zeng,Xiuxiu Zou,Cong Huang,Hongyan Si,Jie Song,Ji Zhang,Hai Luo,Zongde Wang,Peng Wang,Guorong Fan,Xiaoping Rao,Shengliang Liao,Shangxing Chen
Although much progress has been made in developing botanical fungicides to combat fungal diseases in crops, there remains a great need to improve the efficiency and long-term safety of these fungicides. This study proposes a novel strategy for designing citral-thiourea derivatives that feature such desirable properties. The motivation of the work herein was to enhance the antifungal activity of citral against C. gloeosprioides by exploiting the synergistic effect that arises from combining citral and thiourea compounds, thereby producing citral-thiourea derivatives that exhibit good long-term safety. The results revealed that the generated compounds e1, e3, e6, e18, and g showed remarkable antifungal activities against C. gloeosprioides, with corresponding EC50 values reaching 0.16, 1.66, 1.37, 4.76, and 4.60 mg/L, respectively, showing that the compounds significantly outperformed both the positive control kresoxim-methyl and the commercially available fungicide carbendazim. Furthermore, compound g showed stronger protective efficacy against C. gloeosprioides than carbendazim on mango fruit at 25 mg/L. Investigating the preliminary structure–activity relationship (SAR) of the compounds also revealed that the citral-thiourea derivatives exhibited higher antifungal activities against C. gloeosprioides compared to citral and thiourea compounds. This reinforcement of antifungal activity observed in the derivatives was found to be attributable to the two characteristics of low molecular size and the presence of a fluorine atom in the meta-position of the benzene ring. Beyond this, it was determined from QSAR that two molecular descriptors (the Kier–Hall index (order 3) and Tot dipole of the molecules) were negatively related to the antifungal activity of the citral-thiourea derivatives, while one other (the maximum resonance energy of a C–H bond) was positively related to their antifungal activity. More importantly, the citral-thiourea derivatives with high antifungal activities (i.e., compounds e1, e3, e6, e14, e15, e18, and g) exhibited negligible cytotoxicity to LO2 and HEK293T cell lines. The antifungal mechanism of the generated citral-thiourea derivatives was investigated by scanning electron microscopy (SEM) and relative conductivity. The derivatives were found to affect mycelial morphology and increase fungal cell membrane permeability, thereby resulting in the destruction of fungal cell membranes. These promising results provide novel insights into the study and potential application value of citral-thiourea derivatives as high-efficiency antifungal agents against C. gloeosprioides.
研究领域:
植物保护
·
药物化学
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DOI
PubMed
高影响因子
FOOD CONTROL
·
2026
·
IF 7
Dong Yang,Huizhi Chen,Weijie Wu,Hangjun Chen,Lishu Wang,Maratab Ali,Ruilin Liu,Chaoyi Shen,Hailong Yang,Xiangjun Fang,Haiyan Gao
Citral inhibited Botrytis cinerea by disrupting fungal barriers and homeostasis. • T3O1 silica microcapsules enabled sustained citral release (65.16% over 30 days). • Citral microcapsules delayed decay and preserved blueberry quality. Botrytis cinerea is a major postharvest pathogen causing substantial quality losses in blueberries. Citral is a promising natural antifungal agent, but its high volatility, oxidation sensitivity, and poor stability limit practical application. This study investigated the antifungal mechanism of citral against B. cinerea and developed citral-loaded tetraethyl orthosilicate octyltriethoxysilane (TEOS/OTES) hybrid silica microcapsules for controlled release. Citral strongly inhibited mycelial growth, with a minimum inhibitory concentration (MIC) of 0.5 μL/mL, and caused morphological and ultrastructural damage. It disrupted cell wall and membrane integrity, induced reactive oxygen species (ROS) accumulation, impaired mitochondrial function, and suppressed ATP-related energy metabolism. The optimized T3O1 microcapsules exhibited favorable stability and sustained release, reaching 65.16 % cumulative citral release over 30 d. Compared with free citral, the microcapsules more effectively reduced blueberry decay and weight loss, maintained firmness and membrane integrity, preserved nutritional and bioactive compounds, enhanced antioxidant enzyme activities, and suppressed polyphenol oxidase activity. These findings support TEOS/OTES microencapsulation as a natural controlled-release strategy for improving citral stability and maintaining postharvest blueberry quality. Download: Download high-res image (404KB) Download: Download full-size image
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DOI
高影响因子
PHYSIOLOGICAL AND MOLECULAR PLANT PATHOLOGY
·
2021
·
IF 2.747
Ling Wei,Chuying Chen,Jinyin Chen,Liping Lin,Chunpeng Wan
The current study was conducted to evaluate the inhibitory effects of citral against various fungal pathogens viz: Botryosphaeria dothidea , Phomopsis macrospore , and Botrytis cinerea . The present study aimed to describe the antifungal mechanism of citral against B. dothidea , which is not fully elucidated yet. According to the results, citral showed potent inhibition on the hyphal growth of the three studied fungi with a minimum inhibitory concentration of 0.4 μL/mL. Citral changed the morphological characteristics of fungal hyphae of B. dothidea by resulting in the loss of cellular content and distortion of mycelia . Membrane permeability was increased by citral, as evidenced by increases in extracellular electrical conductivity and optical density (OD 260 ) and a decrease in soluble protein content in B. dothidea. A decline in the range of ergosterol levels proved that citral impaired the physiology of the cell membrane. Furthermore, the higher citral concentrations decrease the level of respiration-associated enzymes resulting in the disruption of energy metabolism. Importantly, citral also showed positive effects on fruit quality and reduced the decay rate of kiwifruit . These findings suggest that the antifungal activity of citral could be attributed to the increase in membrane permeability and the damage in the cell membrane. Citral can potentially be used as an alternative for kiwifruit storage.
研究领域:
植物病理学
·
食品科学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）