PHYTOCHEMISTRY
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2024
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IF 3.2
Kaixuan Wang,Huihui Zeng,Yiqun Dai,Zixuan Wang,Huanying Tang,Junde Li,Xingchen Lu,Neng Jiang,Guoyong Xie,Yan Zhu,Yucheng Zhao,Minjian Qin
Furanocoumarins (FCs) are widely distributed secondary metabolites found in higher plants, including Apiaceae, Rutaceae, Moraceae, and Fabaceae. They play a crucial role in the physiological functions of plants and are well-known for their diverse pharmacological activities. As a representative plant of the Apiaceae family, Angelica sinensis is highly valued for its medicinal properties and FCs are one of the main ingredients of A. sinensis . However, the biosynthetic mechanism of FCs in A. sinensis remains poorly understood. In this study, we successfully cloned and verified three types of enzymes using genome analysis and in vitro functional verification, which complete the biosynthesis of the FCs core skeleton in A. sinensis . It includes a p -coumaroyl CoA 2′-hydroxylase ( AsC2′H ) responsible for umbelliferone formation, two UbiA prenyltransferases ( AsPT1 and AsPT2 ) that convert umbelliferone to demethylsuberosin (DMS) and osthenol, respectively, and two CYP736 subfamily cyclases ( AsDC and AsOD ) that catalyze the formation of FCs core skeleton. Interestingly, AsOD was demonstrated to be a bifunctional cyclase and could catalyze both DMS and osthenol, but had a higher affinity to osthenol. The characterization of these enzymes elucidates the molecular mechanism of FCs biosynthesis, providing new insights and technologies for understanding the diverse origins of FCs biosynthesis.
研究领域:
植物生物化学
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药理学
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分子生物学
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基因组学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Plant Science
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2024
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IF 4.1
Yang Wenjuan,Tang Sidi,Xu Rubing,Zhang Lu,Zhou Zihao,Yang Yong,Li Yanyan,Xiang Haibo
Fusarium is a soil-borne pathogen that poses a serious threat to the quality and yield of hundreds of crops worldwide, particularly tobacco production. Using metabolomics technology, we investigated natural metabolites from disease-conducting soil (DCS) and disease-suppressing soil (DSS) of tobacco rhizosphere as fungicides to control tobacco Fusarium wilt (TFW), which is mainly caused by Fusarium oxysporum. Furthermore, the antifungal mechanisms of these natural metabolites were preliminarily elucidated through various assessments, including antifungal activity determination, chemotaxis effect tests, PI staining experiments, and measurements of extracellular conductivity and protein content. Metabolomics results showed that the DCS with three different disease grades (G1, G5 and G9 groups) had significantly higher levels of 15, 14 and 233 differential rhizosphere metabolites (DRMs) and significantly lower levels of 72, 152 and 170 DRMs compared to the DSS (G0 group). According to KEGG pathway analysis, these DRMs were found to be enriched in the caffeine metabolism, biosynthesis of phenylpropanoids, galactose metabolism and tyrosine metabolism, etc. Linustatin, scopoletin and phenylpropiolic acid were picked out from these DRMs and found to have suppressive activity against F. oxysporum through correlation analysis and antifungal experiments. The three DRMs showed strong inhibitory effects on the growth and spore germination of F. oxysporum at concentrations of 0.5 mM or higher in each test period. Furthermore, F. oxysporum showed a phobotaxis effect against these three DRMs at concentrations as low as 0.25 mM. Finally, we found that the three DRMs had an inhibitory effect on F. oxysporum by destroying the integrity of the cell membrane and increasing the membrane permeability of F. oxysporum. This study firstly reports the inhibition activity of phenylpropiolic acid and linustatin on F. oxysporum, providing a practical and environmentally friendly method for biocontrol of TFW by using natural fungicides.
研究领域:
植物病理学
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代谢组学
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农业科学
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真菌学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Chunlan Tang,Zhiling Fang,Donghui Chu,Lulu Zhang,Yuqing Tang,Jinyue Zhou,Rui Fang,Jiaming Ying,Fang Wang,Yuping Zhou,Chunshuang Xu,Qinwen Wang
Alzheimer’s disease (AD) is a common and serious neurodegenerative disease in the elderly; however, the treatment of AD is still lacking of rational drugs. In this paper, the active constituents and targets of the self-developed Chinese medicine Formula 9002A in the treatment of AD were investigated from three aspects: pharmacodynamics based on cell and animal experiments, network pharmacology analysis, and pharmacokinetic analysis. A total of 124 compounds were screened in Formula 9002A, and four constituents including salidroside, gastrodin, niacinamide, and umbelliferone were screened as potential active components for the treatment of AD by network pharmacology. Among them, salidroside and gastrodin showed higher relevance with AD targets, such as ESR1 and AR. The pharmacokinetic study showed that they could be absorbed and identified in plasma; the half-life and mean residence times of salidroside and gastrodin in plasma were nearly increased 2-fold by the administration of Formula 9002A compared with those by the administration of a monomer, indicating the extended action time of active compounds in vivo . Formula 9002A exerted the efficacy in the treatment of AD mainly by regulating APP, GSK3β, ESR1, and AR targets based on the anti-β-amyloid protein deposition, anti-oxidation and anti-apoptosis pathways. Two genes enriched in Alzheimer’s disease pathway, APP and GSK3β, were further validated. The experiments also demonstrated that Formula 9002A could downregulate APP and GSK3β protein expression in the model mice brain and improved their cognitive ability. In summary, Formula 9002A has the characteristics of multiple targets and multiple pathways in the treatment of AD, and salidroside and gastrodin might be the main active constituents, which could provide a foundation for further research and application.
研究领域:
神经学
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药理学
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中医药
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网络药理学
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药代动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2023
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IF 14.5
Peng Hua,Ruifeng Liang,Yanbei Tu,Yuying Yin,Man-Kay Law,Meiwan Chen
Normalizing inflamed soils including reactive oxygen species (ROS), nitric oxide (NO), cell-free DNA, and regulating inflammation-related seeds such as macrophages, neutrophils, fibroblasts, represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis (RA) treatment. Herein, ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o-phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol ( [email protected] /oPDA-PEG, NBOP NPs). The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation, but also decrease cytokines and chemokines to prevent immune cell recruitment. Specifically, NBOP NPs responded to high level ROS and NO, and disintegrated to release notopterol in inflamed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic ones. The released notopterol could inhibit the JAK-STAT pathway of inflammatory cells to reduce the secretion of pro-inflammatory cytokines and chemokines. This strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation, achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat model. Taken together, our work offered a reference to adjust RA soils and seeds for enhanced RA treatment.
研究领域:
纳米技术
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药理学
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风湿病学
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炎症生物学
✓ 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）