JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
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2025
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IF 3.1
Yaxuan Yue,Jing Liu,Chen Li,Fengfeng Chen,Cheng Yang,Bingtian Zhao
Candida albicans is one of the major sources of fungal infections that can lead to life-threatening systemic infections. However, effective control of C. albicans remains a great challenge. Herein, this study aimed at investigating the antifungal effect of a combination of two natural compounds, pinosylvin (PIN) and sanguinarine (SAN), against C. albicans . In order to investigate the antifungal effect and mechanism of the combination of PIN and SAN, antimicrobial assay, time-kill assay, biofilm formation assay, cell membrane integrity assay, and reactive oxygen species (ROS) assay were performed. The results showed that the combination of PIN and SAN was more effective against C. albicans than PIN or SAN alone. PIN and SAN could jointly inhibit biofilm formation and thus attenuate C. albicans adhesion and colonization ability. PIN mainly targeting the cell membrane while SAN mainly inducing the cell to produce large amounts of ROS. Besides, PIN promoted the entry of SAN into C. albicans . Finally, the hemolysis experiment demonstrated that the combination of PIN and SAN is biocompatible. Taken together, the combination of PIN and SAN enhanced the antifungal effect against C. albicans , which has a broad application prospect in the control of C. albicans .
研究领域:
微生物学
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药理学
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医学
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PubMed
高影响因子
Advanced Science
·
2025
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IF 14.1
Wei Zhang,Xiangbing Wu,Wenming Li,Haifeng Zhang,Yijun Wang,Jing Xu,Wenhao Li,Yi Qin,Zebin Wu,Gaoran Ge,Shujun Lv,Lu Mao,Liangliang Wang,Dechun Geng
Pro-inflammatory cytokines such as TNF, IL-1, and IL-6 trigger aberrant osteoclastogenesis and result in massive bone loss. During RANKL-induced osteoclastogenesis, pyroptosis of macrophages/preosteoclasts acts as a pivotal mechanism for IL-1β release, thereby promoting osteoclast maturation and bone resorption. In the current study, it is observed that Pinosylvin (PIN), a compound extracted from European red pine, selectively inhibits LPS- and RANKL-induced release of IL-1β effectively reducing osteoclastogenesis. Notably, PIN inhibits the assembly of NLRP3 and the cleavage of GSDMD, pro-IL-1β, and pro-caspase-1, suggesting its therapeutic effects are NLRP3-targeted. Mechanistically, PIN blockes the NEK7/NLRP3 interaction, but not the NLRP3/ASC interaction, through its 3,5-dihydroxy groups by binding to NEK7, thereby inhibiting subsequent pyroptosis and osteoclastogenesis. Importantly, PIN alleviates inflammatory bone loss due to estrogen deficiency, reduces cranial bone destruction from local LPS injections, and improves survival in LPS-induced septic mice. This study uncovers the specific mechanism behind PIN's potent anti-inflammatory effects and identifies a new therapeutic target for NLRP3-driven diseases.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2022
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IF 5.895
Xiancai Li,Liyuan Yao,Binghong Xiong,Yaodan Wu,Shaohua Chen,Zhifang Xu,Sheng-Xiang Qiu
Control of Aspergillus flavus is beneficial for the agricultural economy and food safety. Stilbenes exhibit antifungal properties through an unknown mechanism. Here, six stilbenes isolated from Cajanus cajan were screened for anti-A. flavus activity. Among them, pinosylvin monomethyl ether (PME) showed the strongest anti-A. flavus activity and has a broad antifungal spectrum with negligible hemolysis within the concentration range measured. PME inhibited the spore germination of A. flavus and the accumulation of aflatoxin B1. Mechanistic studies showed that PME could bind the cell membrane phospholipids, resulting in increased permeability and decreased fluidity. Further metabolic analysis showed that PME caused the lysis of cell membranes and subsequent collapse of spores, which resulted in a cell wall autolysis-like phenotype. Structure–activity relationship analysis revealed the importance of maintaining amphiphilicity harmony by substituent groups for the antifungal activity of stilbenes. Together, natural stilbenes are promising antifungal lead compounds worthy of further exploration and research for potential application in the food, pharmaceutical, and agricultural industries.
研究领域:
微生物学
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药理学
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农业科学
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食品科学
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植物科学
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DOI
PubMed
高影响因子
Biotechnology for Biofuels and Bioproducts
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2022
·Vol. 15
·期 1
·1-12
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IF 0
Hu Yueli,Zhang Chen,Zou Lihua,Zheng Zhaojuan,Ouyang Jia
Background The conversion of lignin-derived aromatic monomers into valuable chemicals has promising potential to improve the economic competitiveness of biomass biorefineries. Pinosylvin is an attractive pharmaceutical with multiple promising biological activities. Results Herein, Escherichia coli was engineered to convert the lignin-derived standard model monomer cinnamic acid into pinosylvin by introducing two novel enzymes from the wood plant: stilbene synthase from Pinus pinea (PpSTS) and 4-Coumarate-CoA ligase from Populus trichocarpa (Ptr4CL4) . The expression of Ptr4CL4 drastically improved the production of pinosylvin (42.5 ± 1.1 mg/L), achieving values 15.7-fold higher than that of Ptr4CL5 (another 4-Coumarate-CoA ligase from Populus trichocarpa ) in the absence of cerulenin. By adjusting the expression strategy, the optimized engineered strain produced pinosylvin at 153.7 ± 2.2 mg/L with an extremely high yield of 1.20 ± 0.02 mg/mg cinnamic acid in the presence of cerulenin, which is 83.9% ± 1.17 of the theoretical yield. This is the highest reported pinosylvin yield directly from cinnamic acid to date. Conclusion Our work highlights the feasibility of microbial production of pinosylvin from cinnamic acid and paves the way for converting lignin-related aromatics to valuable chemicals.
研究领域:
生物化学
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代谢工程学
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合成生物学
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DOI
PubMed
SAR AND QSAR IN ENVIRONMENTAL RESEARCH
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2024
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IF 2.3
C. Hu,Y. Zhai,H. Lin,H. Lu,J. Zheng,C. Wen,X. Li,R.S. Ge,Y. Liu,Q. Zhu
Resveratrol is converted to various metabolites by gut microbiota. Human and rat liver 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) are critical for glucocorticoid activation, while 11β-HSD2 in the kidney does the opposite reaction. It is still uncertain whether resveratrol and its analogues selectively inhibit 11β-HSD1. In this study, the inhibitory strength, mode of action, structure–activity relationship (SAR), and docking analysis of resveratrol analogues on human, rat, and mouse 11β-HSD1 and 11β-HSD2 were performed. The inhibitory strength of these chemicals on human 11β-HSD1 was dihydropinosylvin (6.91 μM) > lunularin (45.44 μM) > pinostilbene (46.82 μM) > resveratrol (171.1 μM) > pinosylvin (193.8 μM) > others. The inhibitory strength of inhibiting rat 11β-HSD1 was pinostilbene (9.67 μM) > lunularin (17.39 μM) > dihydropinosylvin (19.83 μM) > dihydroresveratrol (23.07 μM) > dihydroxystilbene (27.84 μM) > others and dihydropinosylvin (85.09 μM) and pinostilbene (>100 μM) inhibited mouse 11β-HSD1. All chemicals did not inhibit human, rat, and mouse 11β-HSD2. It was found that dihydropinosylvin, lunularin, and pinostilbene were competitive inhibitors of human 11β-HSD1 and that pinostilbene, lunularin, dihydropinosylvin, dihydropinosylvin and dihydroxystilbene were mixed inhibitors of rat 11β-HSD1. Docking analysis showed that they bind to the steroid-binding site of human and rat 11β-HSD1. In conclusion, resveratrol and its analogues can selectively inhibit human and rat 11β-HSD1, and mouse 11β-HSD1 is insensitive to the inhibition of resveratrol analogues.
研究领域:
药理学
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生物化学
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Ming Su,Lei Ye,Yunbing Tang,Shaowei Wang,Zhiyan Hu,Huitao Li,Yiyan Wang,Xiaoheng Li,Yi Liu,Ren-Shan Ge
Resveratrol and its analogs are phytochemicals. Human 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1) synthesizes steroid hormones for normal pregnancy or promoting cancer metastasis. Whether they inhibit 3β-HSD1 remains unclear. In this study, the inhibitory potency, mode of action, structure–activity relationship, and docking parameters of resveratrol and its analogs on 3β-HSD1 and rat homolog 3β-HSD4 were analyzed. The inhibitory potency of these chemicals on human 3β-HSD1 was 4,4′-dihydroxystilbene (IC50, 3.68 μM) > pinostilbene (8.07 μM) > pinosylvin (10.60 μM) > lunularin (26.84 μM) > resveratrol (30.20 μM) > dihydroresveratrol (>100 μM) = oxyresveratrol (>100 μM) > dihydropinosylvin (ineffective at 100 μM). Resveratrol analogs and metabolites are mixed or competitive inhibitors of human 3β-HSD1. Resveratrol and 4,4′-dihydroxystilbene inhibited progesterone secretion by human JAr cells at ≥1 μM. Resveratrol (IC50, 32.09 μM) and pinosylvin (34.71 μM) significantly inhibited rat placental 3β-HSD4 activity. Docking analysis shows that resveratrol analogs and metabolites bind the steroid-binding sites of human 3β-HSD1 and rat 3β-HSD4 and interact with the catalytic residues Ser125/Thr125 and Tyr155. The negative correlation of LogP and IC50 values for human 3β-HSD1 indicates that lipophilicity of chemicals plays a critical role in the inhibitory effect of chemicals. In conclusion, 4,4′-dihydroxystilbene, pinostilbene, and pinosylvin effectively inhibit human 3β-HSD1 depending on their lipophilicity, thereby acting as potential therapeutic agents.
研究领域:
生物化学
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药理学
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分子生物学
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PubMed
高影响因子
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