PEST MANAGEMENT SCIENCE
·
2024
·Vol. 80
·期 12
·6566-6574
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IF 3.8
Mengwei Zhang,Xingyu Ren,Yuying Li,Yaqiang Wang,Yi Li,Zhiqing Ma,Yong Wang,Juntao Feng
BACKGROUND Sclerotinia sclerotiorum , a pathogenic fungus of oilseed rape, poses a severe threat to the oilseed rapeseed industry. In this study, we evaluated the potential of the natural compound hinokitiol against S. sclerotiorum by determining its biological activity and physiological characteristics. RESULTS Our results showed that hinokitiol strongly inhibited the hyphae expansion of S. sclerotiorum , and its effective concentration of hyphae growing inhibition by 50% (EC 50 ) against 103 S. sclerotiorum strains varied from 0.36 to 3.45 μg/mL, with an average of 1.23 μg/mL. Hinokitiol possessed better protective efficacy than therapeutic effects, and it exhibited no cross-resistance between carbendazim. After treatment with hinokitiol, many vesicular protrusions developed on the mycelium with rough surface and thickened cell wall. Moreover, the cell membrane permeability and glycerol content increased, while the oxalic acid declined after hinokitiol treatment. In addition, hinokitiol induced membrane lipid peroxidation and improved the production of reactive oxygen species (ROS) in S. sclerotiorum . Importantly, real-time quantitative polymerase chain reaction showed that cell wall and ROS synthesis-related genes were significantly up-regulated after hinokitiol treatment. CONCLUSION This study revealed that hinokitiol has good biological activity against S. sclerotiorum and could be considered as an alternative bio-fungicide for the resistance management in controlling sclerotinia stem rot infected by S. sclerotiorum . These investigations provided new insights into understanding the toxic action of hinokitiol against pathogenic fungi. © 2024 Society of Chemical Industry.
研究领域:
植物保护
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微生物学
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植物病理学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2022
·Vol. 19
·期 9
·e202200580
·
IF 2.745
Zhiping Che,Yibo Liu,Luyao Chen,Puhou Xing,Xiangdong Li,Xiaobo Huang,Shengming Liu,Genqiang Chen,Xiaomin Lin,Yuee Tian
In order to explore novel natural product-based anti-oomycete and nematicidal agents, sixteen unreported 2-sulfonyloxyhinokitiol derivatives were prepared using the principle of active splicing, and structurally confirmed by proton nuclear magnetic resonance ( 1 H-NMR), carbon-13 nuclear magnetic resonance ( 13 C-NMR), high-resolution mass spectrometry (HRMS), and melting point. Moreover, we evaluated the title compounds as anti-oomycete and nematicidal agents against two serious agricultural pests of Phytophthora capsici and Meloidogyne incongnita . Among the sixteen hinokitiol esters tested: (1) Compounds 3a and 3m exhibited the most potent anti-oomycete activity compared to zoxamide against P. capsici , and the median effective concentration (EC 50 ) values of 3a , 3m , and zoxamide were 18.64, 21.11, and 23.15 mg/L, respectively; Further studies showed that the existence of seven membered ring and carbonyl group was the necessary condition for the high anti-oomycete activity of hinokitiol. (2) Compounds 3n and 3p exhibited more promising nematicidal activity than hinokitiol, and the median lethal concentration (LC 50 ) values of 3n , 3p and 1 against M. incongnita were 0.2111, 0.2079, and 0.3933 mg/L, respectively. This result will pave the way for further modification of hinokitiol to develop potential new fungicides and nematicides. Graphical
研究领域:
植物化学
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农药科学
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分子生物学
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DOI
高影响因子
JOURNAL OF NEUROTRAUMA
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2023
·
IF 4.2
Hongxing Tang,Kejun He,Kun Zhao,Chen Zheng,Weichi Wu,Weilin Jin,Lixuan Yang,Baoshu Xie
Hinokitiol (β-thujaplicin, HIK) is a natural monoterpene small molecule compound showing various biological effects including antibacterial, anti- inflammatory and anti-tumor. Ferroptosis, a new form of iron-dependent cell death, has been demonstrated as one of the pathophysiological mechanisms of traumatic brain injury (TBI). However, the effect of hinokitiol on neuronal ferroptosis after traumatic brain injury has not been reported. Here, we show that hinokitiol alleviated excessive glutamate-induced intracellular reactive oxygen species (ROS), lipid peroxidation, and Fe2+ accumulation in HT-22. Moreover, hinokitiol upregulated heme oxygenase-1 (HO-1) expression, promoted nuclear factor-erythroid factor 2-related factor 2 (Nrf2) nuclear translocation, and inhibited the activation of microglia and astrocyte after TBI. Furthermore, hinokitiol remarkably reduced brain tissue lesions, mitigated neuron loss, iron deposition and attenuated neurologic impairment in the CCI-constructed TBI model in vivo. These results suggest that hinokitiol has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. In summary, we reveal a novel role of hinokitiol in TBI, which has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. Moreover, hinokitiol through activating the Nrf2/Keap1/HO-1 signaling pathway significantly reduces the neuronal damage, suggesting that it is a potential therapeutic candidate for TBI.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
INORGANIC CHEMISTRY
·
2022
·
IF 5.436
Jingwen Guan,Xiaomei Wang,Peiheng Shi,Lanhua Chen,Bin Chen,Yugang Zhang,Yemeng Chen,Yigong Xu,Zhifang Chai,Shuao Wang,Juan Diwu
Despite the critical role actinide decorporation agents play in the emergency treatment of people in nuclear accidents and other scenarios that may cause internal contamination of actinides, new ligands have seldom been reported in recent decades because the current inventory has been limited to only a handful of functional groups. Therefore, new functional groups are always being urgently sought for the introduction of advanced actinide decorporation agents. Herein, a tropolone derivative, 2-hydroxy-6-(propan-2-yl)cyclohepta-2,4,6-trien-1-one (Hinokitiol or Hino), is proposed to be a promising candidate for this purpose by virtue of its well-demonstrated high membrane permeability and high affinity for metal ions. The coordination stoichiometry of Hino with uranyl is demonstrated to be 3:1 both in an aqueous solution (pH 7.4) and in the solid state. The results of a liquid–liquid extraction experiment further show that Hino exhibits strong chelating ability and selectivity toward uranyl over biological essential metal ions (i.e., Mn2+, Zn2+, Co2+, and Ni2+) with an extraction efficiency of >90.0%. The in vivo uranyl removal efficacies of Hino in kidneys and bone of mice are demonstrated to be 67.0% and 32.3%, respectively. On the basis of the observations described above, it is highly possible that further modification of Hino will lead to a large family of multidentate agents with enhanced uranyl decorporation ability.
研究领域:
无机化学
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辐射医学
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毒理学
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配位化学
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核应急响应
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DOI
高影响因子
Microbiology Spectrum
·
2023
·
IF 3.7
Chun-Yan Le,Yu-Jian Ye,Jian Xu,Lei Li,Xi-Qing Feng,Ni-Pi Chen,Bing-Qi Zhu,Zhi-Shan Ding,Chao-Dong Qian
The increasing prevalence of antibiotic resistance causes an urgent need for alternative agents to combat drug-resistant bacterial pathogens. Plant-derived compounds are promising candidates for the treatment of infections caused by antibiotic-resistant bacteria. Hinokitiol (β-thujaplicin), a natural tropolone derivative found in the heartwood of cupressaceous plants, has been widely used in oral and skin care products as an antimicrobial agent. The aim of this work was to study the synergy potential of hinokitiol with antibiotics against Staphylococcus aureus, which is an extremely successful opportunistic pathogen capable of causing nosocomial and community-acquired infections worldwide. The MIC was determined by the broth microdilution method, and the effect of combinations was evaluated through fractional inhibitory concentration indices (FICI). The mechanism behind this synergy was also investigated by using fluorescence spectroscopy and high-performance liquid chromatography (HPLC). The MICs of hinokitiol alone against most S. aureus strains were 32 μg/mL. Selectively synergistic activities (FICIs of ≤0.5) were observed for combinations of this phytochemical with tetracyclines against all tested strains of S. aureus. Importantly, hinokitiol at 1 μg/mL completely or partially reversed tetracycline resistance in staphylococcal isolates. The increased accumulation of tetracycline inside S. aureus in the presence of hinokitiol was observed. In addition, hinokitiol promoted the uptake of ethidium bromide (EB) in bacterial cells without membrane depolarization, suggesting that it may be an efflux pump inhibitor.IMPORTANCE The disease caused by S. aureus is a public health issue due to the continuing emergence of drug-resistant strains, particularly methicillin-resistant S. aureus (MRSA). Tetracyclines, one of the old classes of antimicrobials, have been used for the treatment of infections caused by S. aureus. However, the increased resistance to tetracyclines together with their toxicity have limited their use in the clinic. Here, we demonstrated that the combination of hinokitiol and tetracyclines displayed synergistic antibacterial activity against S. aureus, including tetracycline-resistant strains and MRSA, offering a potential alternative approach for the treatment of infections caused by this bacterium.
研究领域:
微生物学
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药理学
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传染病学
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产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2021
·
IF 10.479
Xueyang Jin,Ming Zhang,Jinghui Lu,Ximeng Duan,Jinyao Chen,Yue Liu,Wenqiang Chang,Hongxiang Lou
Introduction The increasing morbidity of fungal infections and the prevalence of drug resistance highlighted the discovery of novel antifungal agents and investigation of their modes of action. Iron chelators have been used to treat superficial fungal infections or potentiate the efficacy of certain antifungal drugs. Hinokitiol exhibits potent antifungal activity and iron-chelating ability. However, their relationships have not been established. Objectives This study aims to explore the selectivity of hinokitiol against fungal cells and mammalian cells and determine the role of iron-chelating for the antifungal activity of hinokitiol. Methods Iron probe FeRhonox-1 was used to determine intracellular Fe 2+ content. 5-Cyano-2,3-ditolyl tetrazolium chloride probe and Cell Counting Kit-8 were used to detect the mitochondrial respiratory activities. Quantitative real-time PCR and rescue experiments were performed to determine the effect of iron on the antifungal activity of hinokitiol. The effects of hinokitiol on fungal mitochondria were further evaluated using reactive oxygen species probes and several commercial Assay Kits. The ability of hinokitiol to induce resistance in Candida species was carried out using a serial passage method. The in vivo therapeutic effect of hinokitiol was evaluated using Galleria mellonella as an infectious model. Results Hinokitiol was effective against a panel of Candida strains with multiple azole-resistant mechanisms and persistently inhibited Candida albicans growth. Mechanism investigations revealed that hinokitiol chelated fungal intracellular iron and inhibited the respiration of fungal cells but had minor effects on mammalian cells. Hinokitiol further inhibited the activities of mitochondrial respiratory chain complexes I and II and reduced mitochondrial membrane potential, thereby decreasing intracellular ATP synthesis and increasing detrimental intracellular reductive stress. Moreover, hinokitiol exhibited low potential for inducing resistance in several Candida species and greatly improved the survival of Candida -infected Galleria mellonella . Conclusions These findings suggested the potential application of hinokitiol as an iron chelator to treat fungal infections.
研究领域:
微生物学
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药理学
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真菌学
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医学真菌学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2026
·
IF 5.8
Ting Zhang,Junhao Xiang,Na Yu,Yaoxin Tang,Jing Qu,Yiming Liu,Xiubo Li
Mastitis in dairy cows is one of the most prevalent infectious diseases in the dairy industry, leading to reduced milk production, increased production costs, and substantial economic losses. Antibiotics are commonly used to prevent and treat mastitis; however, persistent biofilm formation by Staphylococcus epidermidis (S. epidermidis) has contributed to rising antibiotic resistance and poses significant challenges for complete eradication. Therefore, the development of effective therapeutic strategies is urgently needed. This study investigated the antibacterial and anti-biofilm activities of hinokitiol, both alone and in combination with Ceftiofur sodium, against biofilm-producing S. epidermidis. The checkerboard assay revealed a significant synergistic effect between hinokitiol and Ceftiofur sodium (FICI ≤ 0.5). Importantly, hinokitiol exhibited negligible cytotoxicity toward mammalian cells and low hemolytic activity against sheep erythrocytes at therapeutic concentrations. Mechanism studies demonstrated that hinokitiol disrupted bacterial membrane permeability, as evidenced by increased NPN uptake, PI staining, and significant intracellular protein leakage. Furthermore, hinokitiol induced the accumulation of intracellular reactive oxygen species (ROS), leading to oxidative stress-mediated cell death. Transcriptomic analysis and RT-qPCR validation showed that hinokitiol significantly down-regulated the expression of key genes involved in biofilm formation (icaA, fnbA, aap), quorum sensing (agrA, luxS), and global regulation (sarA, sigB), while up-regulating the repressor icaR. These findings suggest that hinokitiol exerts its antibacterial and anti-biofilm effects by damaging the cell membrane, inducing oxidative stress, and modulating multi-target regulatory pathways, making it a promising candidate for treating S. epidermidis infections. However, this study is limited by the absence of in vivo mastitis models and pharmacokinetic data. Future research should focus on validating these findings in animal models, optimizing administration routes (e.g., intramammary formulations), and assessing clinical efficacy in field conditions to facilitate the translation of hinokitiol into a viable therapeutic option for refractory S. epidermidis mastitis.
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DOI
高影响因子
Cell and Bioscience
·
2023
·Vol. 13
·期 1
·1-15
·
IF 7.5
Zhao Hongting,Zhang Meng,Zhang Jinghua,Sun Zichen,Zhang Wenxin,Dong Weichen,Cheng Chen,Yao Yongzhong,Li Kuanyu
Background Ferroptosis is a unique cell death, dependent on iron and phospholipid peroxidation, involved in massive processes of physiopathology. Tremendous attention has been caught in oncology, particularly for those therapy-resistant cancers in the mesenchymal state prone to metastasis due to their exquisite vulnerability to ferroptosis. Therefore, a therapeutical ferroptosis inducer is now underway to be exploited.Results A natural compound, hinokitiol (hino), has been considered to be an iron chelator. We have a novel finding that hino complexed with iron to form Fe(hino)3 can function as a ferroptosis inducer in vitro. The efficiency, compared with the same concentration of iron, increases nearly 1000 folds. Other iron chelators, ferroptosis inhibitors, or antioxidants can inhibit Fe(hino)3-induced ferroptosis. The complex Fe(hino)3 efficacy is further confirmed in orthotopic triple-negative breast cancer (TNBC) tumor models that Fe(hino)3 significantly boosted lipid peroxidation to induce ferroptosis and significantly reduced the sizes of TNBC cell-derived tumors. The drug’s safety was also evaluated, and no detrimental side effects were found with the tested dosage.Conclusion sWhen entering cells, the chelated iron by hinokitiol as a complex Fe(hino)3 is proposed to be redox-active to vigorously promote the production of free radicals via the Fenton reaction. Thus, Fe(hino)3 is a ferroptosis inducer and, therapeutically, exhibits anti-TNBC activity.
研究领域:
肿瘤学
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药理学
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细胞生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2026
·
IF 8.1
Wenhao Zhang,Jing Wang,Tianyi Wang,Qihao Fu,Jiawen Xu,Chaochen Li,Zheng Zhou,Chenxi Zhang,Guanhua Xu,Mingjie Xia,Zhiming Cui
Secondary neuroinflammation and oxidative stress, driven partly by maladaptive microglial activation, limit recovery after spinal cord injury (SCI). We investigated whether hinokitiol promotes neural repair and whether nuclear factor erythroid 2-related factor 2 (Nrf2) signaling mediates its effects. Male C57BL/6J mice received T10 contusive SCI and intraperitoneal vehicle or hinokitiol (20 mg/kg once daily for 7 days, starting 6 h after injury). Locomotor, electrophysiological, histological, and single-nucleus transcriptomic outcomes were evaluated. In vitro, lipopolysaccharide-challenged BV2 microglia, BV2–HT22 indirect cocultures, and pharmacological Nrf2 inhibition with ML385 were used to examine inflammatory, oxidative, and neuronal apoptosis outcomes. Hinokitiol improved locomotor and motor-evoked potential outcomes; reduced lesion cavitation, collagen deposition, neuronal loss, demyelination, and astroglial activation; and shifted microglia from inflammatory/oxidative programs toward repair-associated states. Hinokitiol reduced tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, and NADPH oxidases 2/4 in spinal cord tissue and BV2 cells. Hinokitiol-pretreated microglia reduced HT22 apoptosis in coculture. Hinokitiol decreased Kelch-like ECH-associated protein 1 and increased Nrf2 and heme oxygenase-1, whereas ML385 attenuated these effects and restored inflammatory and oxidative responses. Hinokitiol supports neural repair after SCI by reprogramming microglial inflammatory-redox states, at least partly through Nrf2 signaling. These findings justify further pharmacokinetic, sex-inclusive, and long-term safety studies.
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DOI
高影响因子
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
·
2022
·
IF 5.911
Yonghui Qiao,Mengwei Zhang,Yuxuan Cao,Qianqian Mi,Shen Liang,Juntao Feng,Yong Wang
Sclerotinia rot infected by cosmopolitan fungi Sclerotinia sclerotiorum is a serious and destructive disease in carrot production, especially during their postharvest storage. Natural products with the advantages of environmentally friendly and safety have been widely concerned. This research estimated the impact of hinokitiol against S. sclerotiorum and on the quality of carrots. In vitro and in vivo tests demonstrated that hinokitiol had promising antifungal activities against both carbendazim-susceptible and -resistant isolates of S. sclerotiorum . Importantly, it effectively kept the quality and prolonged the shelf life of carrot by declining the loss of weight, ascorbic acid, carotenoid, and total phenolics content, preventing the formation of malondialdehyde, and enhancing the activities of antioxidant enzymes. Further study found that hinokitiol inhibited the formation of sclerotia by destroying the morphology and the integrality of cell membrane, reduced the pathogenicity by suppressing the synthesis of oxalic acid and exopolysaccharide, declined the activities of enzymes and the gene expression related to sclerotia development in S. sclerotiorum . These information evidenced the great potential of hinokitiol as a natural fresh-keeping agent for the management of postharvest decay infected by S. sclerotiorum .
研究领域:
植物病理学
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食品科学
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天然产物化学
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DOI
PubMed
高影响因子
CELLULOSE
·
2022
·Vol. 29
·期 4
·2731-2742
·
IF 6.123
Liu Zihan,Luo Yapei,Zhao Xiaomin,Zheng Keying,Wu Minghua,Wang Lili
Natural antibacterial agents have attracted increasing attention due to safety, ecological, and environmental protection concerns. In this study, hinokitiol-grafted-chitosan (HTCS) was prepared via the Mannich reaction and used as an antibacterial agent for the treatment of cotton fabric. The results showed that, compared with chitosan (CS) and hinokitiol (HT) alone, HTCS exhibited a lower value of minimum inhibitory concentration (MIC). Compared with the fabrics treated by CS and HT, the antibacterial rate of the treated fabric against Escherichia coli using HTCS as antibacterial agent increased by approximately 90% and 27%, the bacterial reduction rate against Staphylococcus aureus increased by about 58% and 39%. The HTCS-treated cotton fabric possessed good antibacterial properties even after 25 washing cycles. Moreover, the antibacterial cotton fabric retained original hydrophilicity, handle, and strength. Consequently, HTCS has great potential as a natural antibacterial agent for textiles.
研究领域:
纺织材料学
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生物化学
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应用微生物学
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产品关联
DOI
高影响因子
PHYTOPATHOLOGY
·
2025
·
IF 3.1
Xin Deng,Tianyu Hou,Muhammad Farrukh Nisar,Xinyu Zhang,Yingying Yang,Chuying Chen,Jinyin Chen
Citrus sour rot is normally caused by Geotrichum citri-aurantii , which not only deteriorates fruit quality but also causes huge economic losses annually. The current study delves into the underlying in vitro antifungal mechanisms of hinokitiol and assesses its efficacy in controlling sour rot development on navel oranges infected by G. citri-aurantii . Both in vitro and in vivo examinations demonstrate that hinokitiol exhibits strong antifungal activity against G. citri-aurantii , with a minimum inhibitory concentration and minimum fungicidal concentration of 25.0 mg/L, resulting in a significant reduction in citrus sour rot disease. Decreased blue fluorescence in CFW staining and cell wall components have confirmed that hinokitiol disrupts the structural organization of the G. citri-aurantii cell wall. Additionally, hinokitiol induces abnormal mycelial growth, causing more severe deformities, dried blights, plasmalemma wall separation, mitochondrial decomposition, and cell permeabilization. Furthermore, hinokitiol increases the production of H 2 O 2 , O 2 •− and MDA levels in G. citri-aurantii , resulting in permanent damage to cell membrane integrity, mitochondrial oxidative phosphorylation, and DNA function, ultimately triggering cell apoptosis. These results indicate that hinokitiol is a novel antifungal agent for controlling postharvest sour rot in citrus fruits. This study contributes new insights into the control of postharvest fungal decay and elucidates hinokitiol’s antifungal mechanism against G. citri-aurantii .
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DOI
PubMed
高影响因子
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