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Antioxidants · 2021 ·Vol. 10 ·期 9 ·1333 · IF 6.313

Discovery of Novel Pterostilbene Derivatives That Might Treat Sepsis by Attenuating Oxidative Stress and Inflammation through Modulation of MAPKs/NF-κB Signaling Pathways

Mengyuan Fang,Tingfeng Zou,Xiaoxiao Yang,Zhen Zhang,Peichang Cao,Jihong Han,Yajun Duan,Ban-Feng Ruan,Qing-Shan Li

Sepsis remains one of the most common life-threatening illnesses that is characterized by a systemic inflammatory response syndrome (SIRS) and usually arises following severe trauma and various septic infections. It is still in urgent need of new effective therapeutic agents, and chances are great that some candidates can be identified that can attenuate oxidative stress and inflammatory responses. Pterostilbene, which exerts attractive anti-oxidative and anti-inflammatory activities, is a homologue of natural polyphenolic derivative of resveratrol. Starting from it, we have made several rounds of rational optimizations. Firstly, based on the strategy of pharmacophore combination, indanone moiety was introduced onto the pterostilbene skeleton to generate a novel series of pterostilbene derivatives (PIF_1–PIF_16) which could possess both anti-oxidative and anti-inflammatory activities for sepsis treatment. Then, all target compounds were subjected to their structure–activity relationships (SAR) screening of anti-inflammatory activity in mouse mononuclear macrophage RAW264.7 cell line, and their cytotoxicities were determined after. Finally, an optimal compound,PIF_9, was identified. It decreased the mRNA levels of lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2). We also found that the anti-inflammatory effects might be contributed by its suppression on the nuclear factor-κB (NF-κB) and MAPKs signaling pathway. Moreover,PIF_9also demonstrated potent anti-oxidative activity in RAW264.7 macrophages and the sepsis mouse model. Not surprisingly, with the benefits mentioned above, it ameliorated LPS-induced sepsis in C57BL/6J mice and reduced multi-organ toxicity. Taken together,PIF_9was identified as a potential sepsis solution, targeting inflammation and oxidative stress through modulating MAPKs/NF-κB.Keywords:antioxidants;anti-inflammatory agents;indanone;pterostilbene;sepsis

研究领域: 药理学 · 传染病学 · 分子生物学
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Foods · 2023 ·Vol. 12 ·期 12 ·2326 · IF 5.2

Synergistic Inhibitory Effect of Multiple Polyphenols from Spice on Acrolein during High-Temperature Processing

Juan Liu,Yongling Lu,Bo Si,Anqi Tong,Yang Lu,Lishuang Lv

Acrolein (ACR) is a toxic unsaturated aldehyde that is produced during food thermal processing. Here, we investigated the synergistic effect of polyphenols in binary, ternary, and quaternary combinations on ACR by the Chou–Talalay method, and then explored the synergistic effect of cardamonin (CAR), alpinetin (ALP), and pinocembrin (PIN) in fixed proportion fromAlpinia katsumadaiHayata (AKH) combined with curcumin (CUR) in the model, and roasted pork using LC–MS/MS. Our results showed that their synergistic effect depended on the intensification of their individual trapping ACR activities, which resulted in the formation of more ACR adducts. In addition, by adding 1% AKH (as the carrier of CAR, ALP, and PIN) and 0.01% CUR (vs. 6% AKH single) as spices, more than 71.5% (vs. 54.0%) of ACR was eliminated in roast pork. Our results suggested that selective complex polyphenols can synergistically remove the toxic ACR that is produced in food processing.Keywords:acrolein;cardamonin;alpinetin;pinocembrin;Alpinia katsumadaiHayata;curcumin

CAS / MDL: 153-18-4
研究领域: 食品科学 · 药理学 · 化学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SEPARATION AND PURIFICATION TECHNOLOGY · 2023 · IF 8.6

Separation of dihydrosinapyl alcohol from reductive depolymerization products of lignin by multistage extraction and crystallization

Zixin Qi,Zhaofeng Zhang,Tianyu Ren,Nan Jiang,Mengfan Wang,Shengping You,Wei Qi,Rongxin Su

Because of the high complexity of the product and the similar physicochemical properties between G and S counterparts, the separation of aromatic monomers is one of the greatest challenges in the lignin chemical valorization, which limits its further utilization and conversion. In this study, the preparation method of the dihydroconiferyl alcohol & dihydrosinapyl alcohol-enriched oil and high purity dihydrosinapyl alcohol from reductive catalytic fractionation products catalyzed by Pd/C was first reported. Moreover, a purification process with alkali extraction - organic solvent extraction - dichloromethane reverse extraction - crystallization in the KOH ethanol solution as the main unit operation was designed. As a result, a monomer-enriched oil in which dihydroconiferyl alcohol (G-3OH) and dihydrosinapyl alcohol (S-3OH) could totally account for more than 83% was obtained, and S-3OH with a purity of 90.2% was separated by crystallization. In addition, this purification process was scaled up to 10 times. The monomer-enriched oil with a G-3OH and S-3OH content of 87.2% was obtained. The recoveries of G-3OH and S-3OH were 81.0% and 91.5%, respectively. The purity of S-3OH was 89.4%, and the recovery was 51.6%. The integrated process realizes the effective separation of the reductive depolymerization products of lignin, which can provide technical support for its industrial production.

CAS / MDL: 7440-05-3
研究领域: 生物质化学 · 林产化工
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METABOLIC ENGINEERING · 2020 · IF 7.263

Green production of silybin and isosilybin by merging metabolic engineering approaches and enzymatic catalysis

Jiazeng Yang,Jincai Liang,Lei Shao,Lihong Liu,Ke Gao,Jun-Liang Zhang,Zhenjiao Sun,Wendong Xu,Pengcheng Lin,Rongmin Yu,Jiachen Zi

Silymarin extracted from milk thistle seeds, is used for treating hepatic diseases. Silybin and isosilybin are its main components, and synthesized from coupling of taxifolin and coniferyl alcohol . Here, the biosynthetic pathways of taxifolin and coniferyl alcohol were reconstructed in Saccharomyces cerevisiae for the first time. To alleviate substantial burden caused by a great deal of genetic manipulation, expression of the enzymes (e.g. ZWF1, TYR1 and ARO8) playing multiple roles in the relevant biosynthetic pathways was selectively optimized. The strain YT1035 overexpressing seven heterologous enzymes and five native enzymes and the strain YC1053 overexpressing seven heterologous enzymes and four native enzymes, respectively produce 336.8 mg/L taxifolin and 201.1 mg/L coniferyl alcohol. Silybin and isosilybin are synthesized from taxifolin and coniferyl alcohol under catalysis of APX1t (the truncated milk thistle peroxidase), with a yield of 62.5%. This study demonstrates an approach for producing silybin and isosilybin from glucose for the first time.

研究领域: 生物技术 · 药学 · 代谢工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2023 · IF 5.6

Active metabolites and potential mechanisms of Notopterygium incisum against obstructive sleep apnea Syndrome (OSAS): network analysis and experimental assessment

Peijun Liu,Weihua Tang,Dong Zhao,Pan Zhou,Ke Hu

Background: Notopterygium incisum K.C. Ting ex H.T. Chang, a synonym of Hansenia weberbaueriana (Fedde ex H. Wolff) Pimenov & Kljuykov, is an anti-inflammatory medicinal plant. Although abrnotopterol has been reported to be its primary active metabolite, the other metabolites and their mechanisms of action remain unclear. This study aims to investigate the potential mechanisms by which its active metabolites treat Obstructive Sleep Apnea Syndrome (OSAS) through network analysis and experimental assessment. Methods: The metabolites and potential targets of Notopterygium incisum were extracted from public databases. We searched for OSAS-related genes in the Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Cytoscape 3.9.0 was used to construct the drug-target-disease network and screen for hub genes. Human bronchial epithelial (HBE) cells were cultivated in normoxia and chronic intermittent hypoxia (CIH) medium for 24 h. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) were quantified using enzyme-linked immunosorbent assay (ELISA). Prostaglandin-endoperoxide synthase 2(PTGS2) mRNA was detected using RT-qPCR, while PTGS2 and nuclear factor-kappa B (NF-κB) proteins were identified using Western blot analysis. Co-Immunoprecipitation (CoIP) and Western blotting were utilized to evaluate the ubiquitination of PTGS2 in HBE cells. Results: Pterostilbene and notopterol, isolated from Notopterygium incisum , had potential therapeutic effects on OSAS. The PTGS2 and estrogen receptor alpha (ESR1) hub genes were associated with OSAS. The pathway enrichment analysis focuses on the NF-κB, apoptosis, and HIF-1A pathways. In response to CIH, pterostilbene and notopterol decreased IL-6, TNF-α, and PGE2 levels. The NF-κB pathway was activated by an increase in PTGS2 levels. Pterostilbene promoted proteasome-mediated ubiquitination of PTGS2 protein and reduced PTGS2 levels, inhibiting the NF-κB pathway. Conclusion: This study reveals the active metabolites of Notopterygium incisum and hub genes involved in treating OSAS, which provide a basis for the follow-up development and exploitation of the botanical drug.

研究领域: 药理学 · 分子生物学 · 网络分析 · 实验生物学 · 睡眠障碍
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ENVIRONMENTAL SCIENCE & TECHNOLOGY · 2024 · IF 10.8

Novel Chemical Routes for Carbon Dioxide and Methane Production from Lignin Photodegradation: The Role of Environmental Free Radicals

Yongxi Deng,Kecheng Zhu,Wenjun Jiang,Yixuan Liu,Linyang Xie,Fuhao Liu,Kangjie Yang,Yuanren Jiang,Hanzhong Jia

Sunlight irradiation significantly mediates plant litter’s carbon dynamics and volatile carbon release in semi-arid and arid ecosystems. In this process, carbon loss is controlled by lignin, but the mechanisms of production of CO2 and CH4 during lignin photolysis are ambiguous. In this study, the photomineralization of plant litter and the lignocellulosic component collectively indicate that lignin is a major source of CO2 and CH4 emissions. Characterization and free radical analysis reveal that the production of CO2 is due to the oxidation and ring-opening reaction of the coniferyl alcohol unit, with the subsequent decarboxylation of carboxylic acid as an oxidation product. This reaction involves o-quinone formation by the reactions between O2, superoxide radical (O2·–), and persistent free radicals (PFRs)-bearing lignin. Of this, O2·– contributes to 43.2% of the photogenerated CO2, as a new pathway, derived from the electron transfer from PFRs to O2. Interestingly, photoinduced demethylation of the dimethoxybenzene-type compounds as the photolysis products of lignin results in a never-before-reported CH4 formation chemical route independent of that of O2. This mechanistic insight into the role of lignin in volatile carbon production from the irradiative plant litter will contribute to a deeper understanding of carbon balance in water-limited ecosystems.

研究领域: 环境科学 · 化学 · 植物生态学 · 大气化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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METABOLIC ENGINEERING · 2026 · IF 7.3

Metal ions program flavonolignan biosynthesis and enable photo-biohybrid production

Jiazeng Yang,Yajing Fan,Howard H. Chou

Abiotic photocatalysis synthesizes major milk thistle flavonolignans. • Metal ions program flavonolignan regioselectivity and productivity in vitro. • Fe 3+ and Al 3+ direct radical coupling toward silychristin synthesis. • Photo-biohybrid process enables de novo flavonolignan production from sugar. • Metal-guided photocatalysis expands flavonolignan chemical diversity. Flavonolignans are pharmacologically important plant natural products whose production has been limited to extraction from natural sources. Their defining transformation, the oxidative coupling of flavonoid and phenylpropanoid precursors, was demonstrated to be enzyme-catalyzed. Here we show that milk thistle flavonolignans can also be assembled through an abiotic, light-driven process in vitro . Photocatalytic coupling of taxifolin and coniferyl alcohol generated the major natural flavonolignans, including silychristins, whose synthesis from native precursors has not previously been reproduced in vitro . Importantly, we identify environmental metal ions as programmable regulators of reaction outcome. Fe 3+ and Al 3+ selectively direct radical coupling toward silychristin formation, whereas Mn 2+ primarily enhances catalytic efficiency. Mechanistic analyses indicate that metal coordination of flavonoid substrates governs regioselective radical attack and molecular architecture of final products. Leveraging this principle, we establish a metal-programmable photocatalytic platform for the synthesis of both natural and new-to-nature flavonolignans. Integration of this abiotic chemistry with engineered Saccharomyces cerevisiae enabled de novo flavonolignan production directly from sugar in a one-pot photo-biohybrid process for the first time, establishing a versatile strategy for the sustainable production and diversification of flavonolignans.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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CELL · 2025 · IF 42.5

A de novo-originated gene drives rose scent diversification

Yajun Li,Runhui Li,Junzhong Shang,Kaige Zhao,Yaqi Sui,Zhenhua Liu,Huijun Yan,Manzhu Bao,Mei Liang,Qiao Zhao,Yao-Wu Yuan,Guogui Ning

How evolution builds genes, how these genes attain enhanced expression, and how they integrate into existing regulatory networks to drive phenotypic diversification are all fascinating questions. Here, we generated chromosome-level genome assemblies for two Rosa banksiae subspecies and re-sequenced an additional 40 rose accessions. Genomic analysis of more than 100 Rosa accessions revealed multiple evolutionary steps leading to the de novo origination of a taxon-restricted gene, SCREP, specific to the rose lineage. Extensive transcriptomic, metabolomic, and functional analyses demonstrated that the recruitment of a Miniature Inverted-repeat Transposable Element (MITE) transposon into the gene promoter led to elevated expression, that the gene SCREP orchestrates eugenol biosynthesis, and that the evolutionary dynamics of SCREP account for variation in rose scent among different species and cultivars. Our results provide insights into the mechanism of de novo gene origination, the role of transposable elements in gene expression, and the evolutionary consequences of taxon-restricted genes in phenotypic diversification.

CAS / MDL: 458-35-5 C413449
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CURRENT ISSUES IN MOLECULAR BIOLOGY · 2024 ·Vol. 46 ·期 4 ·3694-3712 · IF 2.8

Effects of Lignin-Diverted Reductant with Polyphenol Oxidases on Cellulose Degradation by Wild and Mutant Types of Lytic Polysaccharide Monooxygenase

Kai Li,Yuan Wang,Xiao Guo,Bo Wang

Establishing a multi-enzyme synergistic lignocellulosic biodegradation system using lytic polysaccharide monooxygenase (LPMO) and polyphenol oxidases is vital for efficiently utilizing plant biomass waste, ultimately benefiting the carbon cycle and promoting environmental protection. Single-residue mutations of LPMO can improve the efficiency of lignocellulosic biomass degradation. However, the activity of mutant-type LPMO in relation to lignin-diverted reducing agents has not been sufficiently explored. In this study, laccase and tyrosinase were initially investigated and their optimal conditions and impressive thermal stability were revealed, indicating their potential synergistic abilities with LPMO in lignocellulose biodegradation. When utilizing gallic acid as a reducing agent, the activities of LPMOs were increased by over 10%, which was particularly evident in mutant-type LPMOs after the addition of polyphenol oxidases. In particular, the combination of tyrosinase with either 4-hydroxy-3-methoxyphenylacetone orp-coumaric acid was shown to enhance the efficacy of LPMOs. Furthermore, the highest activity levels of wild-type LPMOs were observed with the addition of laccase and 3-methylcatechol. The similarities between wild and mutant LPMOs regarding their activities in lignin-diverted phenolic compounds and reducing agents are almost identical, suggesting that the single-residue mutation of LPMO does not have a detrimental effect on its performance. Above all, this study indicates that understanding the performance of both wild and mutant types of LPMOs in the presence of polyphenol oxidases and various reducing agents constitutes a key link in the industrialization of the multi-enzyme degradation of lignocellulose.

研究领域: 生物技术 · 生物化学 · 环境科学 · 酶学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Advanced Science · 2024 ·Vol. 11 ·期 42 ·2407543 · IF 14.3

Imaging Metabolic Flow of Water in Plants with Isotope-Traced Stimulated Raman Scattering Microscopy

Simin Bi,Jianpeng Ao,Ting Jiang,Xianmiao Zhu,Yimin Zhu,Weibing Yang,Binglian Zheng,Minbiao Ji

Water plays a vital role in the life cycle of plants, participating in various critical biochemical reactions during both non-photosynthetic and photosynthetic processes. Direct visualization of the metabolic activities of water in plants with high spatiotemporal resolution is essential to reveal the functional utilization of water. Here, stimulated Raman scattering (SRS) microscopy is applied to monitor the metabolic processes of deuterated water (D 2 O) in model plant Arabidopsis thaliana (A. thaliana) . The work shows that in plants uptaking D 2 O/water solution, proton-transfer from water to organic metabolites results in the formation of C-D bonds in newly synthesized biomolecules (lipid, protein, and polysaccharides, etc.) that allow high-resolution detection with SRS. Reversible metabolic pathways of oil-starch conversion between seed germination and seed development processes are verified. Spatial heterogeneity of metabolic activities along the vertical axis of plants (root, stem, and tip meristem), as well as the radial distributions of secondary growth on the horizontal cross-sections are quantified. Furthermore, metabolic flow of protons from plants to animals is visualized in aphids feeding on A. thaliana . Collectively, SRS microscopy has potential to trace a broad range of matter flows in plants, such as carbon storage and nutrition metabolism.

研究领域: 植物生理学 · 分子生物学 · 成像技术 · 代谢组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Horticulturae · 2026 ·Vol. 12 ·期 1 ·106 · IF 3

Genome-Wide Identification of CmPOD Genes and Partial Functional Characterization of CmPOD52 in Lignin-Related Granulation of ‘Sanhong’ Pomelo (Citrus maxima)

Yunxuan Liu,Xinjia Wang,Rong Lian,Yan Zhao,Yurong Zhou,Yuan Yu,Wenqin She,Zhixiong Guo,Heli Pan,Tengfei Pan

The granulation of pomelo (Citrus maxima) juice sacs severely compromises fruit quality and is closely associated with lignin accumulation, a process catalyzed by peroxidases (PODs). Analysis of ‘Sanhong’ pomelo juice sacs collected 175–215 days after flowering revealed that bound peroxidase (BPOD) activity paralleled changes in lignin content, suggesting a potential role for BPOD in lignin biosynthesis. A total of 71CmPODgenes were identified in the pomelo genome through integrated HMMER and BLAST analyses. Among them,CmPOD52was selected for functional characterization based on its alkaline peroxidase properties, absence of a CE domain, predicted extracellular localization, and gradually increasing expression pattern revealed by RT-qPCR. Its transient overexpression in ‘Sanhong’ pomelo juice sacs for 36 h increased BPOD activity 2.06-fold (p< 0.01) compared to the empty vector control, indicating thatCmPOD52may be a BPOD gene. The recombinant CmPOD52 protein was expressed in a prokaryotic system, purified, and used in enzymatic assays with sinapyl alcohol as the substrate. The recombinant CmPOD52 protein, assayed at 272 nm with controls (substrate-only blank and heat-inactivated protein), showed an activity of 13.67 ± 0.9 U. The experimental group showed new products, identified by mass spectrometry as sinapyl alcohol dimers, thus suggesting that the recombinant protein catalyzes the dehydrogenation and polymerization of sinapyl alcohol monomers. This study identifiedCmPOD52, a gene potentially involved in lignin polymerization in pomelo juice sacs, offering a key candidate for further in vivo validation.

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FOOD CHEMISTRY · 2020 · IF 6.306

Quantification of phenolic compounds in vegetable oils by mixed-mode solid-phase extraction isotope chemical labeling coupled with UHPLC-MS/MS

Xu Yu,Li Yu,Fei Ma,Peiwu Li

In the present work, a rapid, accurate and cost-effective method has been developed for the simultaneous quantification of phenolic compounds in oil using mixed-mode solid-phase extraction (SPE) coupled with chemical labeling UHPLC-MS/MS. Mix-mode SPE weak cation cartridges were selected to enrich and purify phenolic compounds in oil, and hydroxyl moiety was dansylation as stable-isotope internal standard. The major parameters that affected the extraction and chemical labeling efficiency were investigated, and the method was fully validated. The limit of quantifications and the limit of detections were 0.002 µg kg −1  ~ 0.10 µg kg −1 and 0.006 µg kg −1  ~ 0.30 µg kg −1 , respectively. The recoveries were 61.2% ~ 129.3% with intra-day and inter-day precision less than 12%. The results for 38 rapeseed oils revealed that 14 phenolic compounds, including canolol, phenolic acids, phenolic alcohols, tyrosol and vanillin from trace levels to relatively high content.

研究领域: 分析化学 · 食品科学
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