INORGANIC CHEMISTRY
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2026
·
IF 4.7
Fei Chen,Sisi Wu,Jian Kuang,Sijia Xiang,Shenghu Wang,Siming Yuan,Kaiming Cao,Lu Yu,Wenming Yang,Liqin Tang,Yangzhong Liu
Human copper transporter 1 (hCtr1) is a transport protein essential for cellular copper uptake and homeostasis, yet excess copper influx is toxic to cells. Currently, no inhibitors of hCtr1 are available to modulate intracellular copper levels. Here, we discovered that the natural phenolic compound rosmarinic acid (RA), as a moderate-strength copper chelator, can directly interact with hCtr1 and inhibit its copper-transport function. RA binds to the N-terminal copper-binding domain of hCtr1, lowering the Cu(II)-binding affinity of hCtr1. More crucially, RA and hCtr1 form a ternary complex with Cu(II) ions (RA/Cu/hCtr1). Cellular assays indicated that RA inhibited the copper-mediated membrane interaction of the hCtr1 N-terminal copper-binding domain, a crucial step in triggering cellular copper internalization. Functional assays showed that RA significantly inhibits hCtr1-mediated copper uptake under high copper conditions, hence effectively alleviating cellular copper overload and attenuating copper-induced cytotoxicity. Notably, the moderate copper-binding affinity of RA minimizes adverse effects while modulating the cellular copper levels. This work identifies RA as a promising lead compound for modulating copper-related pathologies and provides a strategy for regulating intracellular copper homeostasis by targeting hCtr1.
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高影响因子
Foods
·
2026
·Vol. 15
·期 14
·2525
·
IF 6
Yanfei Li,Run Yang,Hongjie Xiang,Zhirong Zhang,Zhijun Zhang,Nan Hu
The sustainable isolation of nonamphiphilic phytochemicals remains a formidable challenge in biochemical engineering. In this study, a highly efficient and solvent free foam fractionation process was developed for recovering rosmarinic acid from botanical extracts. By systematically screening diverse biological surfactants, whey soy protein emerged as an exceptionally robust dual functional frother and nanoscale collector. Response surface methodology optimized the operational parameters to 850 mg/L protein concentration, pH 2.5, and a gas flow rate of 470 mL/min, yielding an outstanding target recovery of 93.08 percent alongside an enrichment ratio of 1.81. This macroscopic separation superiority was comprehensively elucidated at the molecular level through multiple spectroscopic techniques and computational modeling. Results confirmed a spontaneous static quenching complexation driven by synergistic noncovalent forces, predominantly hydrogen bonding, van der Waals interactions, π-stacking, and salt bridges. These interactions induced targeted conformational unfolding within the protein backbone, exposing hydrophobic domains that drastically elevated the thermodynamic affinity for the ascending gas–liquid interface. Furthermore, the concentrated product exhibited an antioxidant capacity enhancement exceeding 3.6 times compared to the crude extract, a result attributed to selective enrichment combined with the structural shielding effect provided by the protein macromolecule. Ultimately, this work provides critical mechanistic insights and establishes a scalable technological framework for the green purification of highly valuable botanical compounds.
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ULTRASONICS SONOCHEMISTRY
·
2026
·
IF 10.2
Qiuping Chen,Huihui Zhang,Yee Ying Lee,Yong Wang,Ying Li
This study developed a green extraction paradigm for rosemary absolute oil (RAO) as a sustainable natural antioxidant to inhibit lipid oxidation in frying oils. RAO was prepared via three methods: heat reflux extraction (HRE) with n-hexane, solvent-free oil extraction (OE) using refined soybean oil, and ultrasound-assisted solvent-free oil extraction (UOE). Under optimized UOE conditions (solid-to-liquid ratio 1:10, 400 W, 25°C, 13 min), RAO yield reached 19.09%, with total phenolic content (TPC) of 347.16 ± 2.81 mg GAE/g, significantly exceeding values from HRE and OE. UOE-RAO contained elevated concentrations of bioactive compounds: carnosic acid (CA, 89.45 ± 1.89 mg/g), ursolic acid (UA, 7.43 ± 0.02 mg/g), and carnosol (16.81 mg/g), accompanied by a pronounced CA-to-carnosol conversion. In vitro antioxidant assays (DPPH) demonstrated UOE-RAO’s potent radical scavenging activity (IC 50 : 71.26 ± 0.81 μg/mL), on par with synthetic butylated hydroxytoluene (BHT). When fortifying soybean oil with 0.1% UOE-RAO, oxidative stability during 180°C frying was markedly enhanced: total polar materials (TPM) accumulation was retarded, extending oil usability from 31 h (control) to 63 h, while acid value (AV) remained consistently lower throughout frying. Differential scanning calorimetry (DSC) further validated improved oxidative resistance, with induction times for primary (12.75 ± 3.51 → 14.14 ± 0.20 min) and secondary oxidation (40.47 ± 6.02 → 61.41 ± 3.10 min) significantly prolonged. Collectively, these findings highlight that UOE enables the production of RAO with superior antioxidant efficacy, positioning it as a green, high-performance alternative to synthetic antioxidants for lipid-rich food processing, particularly high-temperature frying applications.
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JOURNAL OF MEMBRANE SCIENCE
·
2026
·
IF 8.8
Longping Jin,Kunmei Su,Maliang Zhang,Xi Du,Zhenhuan Li
Ineffective impurities in traditional Chinese medicine extracts can cause numerous issues, making the development of efficient and environmentally friendly purification technologies imperative. An ideal separation membrane must combine high selectivity, high permeability, and reliability under harsh environments. This study proposes a "homologous reinforcement" strategy, specifically, polyphenylene sulfide (PPS) fibers treated with sulfonation were employed as multifunctional reinforcement to fabricate the fibers reinforced PPS membrane via thermally induced phase separation (TIPS). The sulfonated PPS (SPPS) fibers exhibit the perfect interfacial compatibility with PPS matrix, significantly enhancing the mechanical strength as reinforcing skeletons while serving as effective nucleation sites during phase separation, which optimizes the composite membrane crystalline morphology and pore structure. Additionally, the tensile strength of the optimal composite membrane is enhanced by over three times compared to pure PPS membrane. In terms of separation performance, this prepared membrane achieves an effective balance between retaining five typical active components of traditional Chinese medicine and removing impurities. Furthermore, the introduction of SPPS fiber endowed the membrane with persistent hydrophilicity and negative charge, conferring the excellent anti-fouling properties and high flux recovery. More importantly, this SPPS modified composite membrane maintained outstanding structural integrity and separation stability under harsh environments such as harsh pH and organic solvents, ensuring reliable long-term operation.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2022
·
IF 3.571
Ming Meng,Haofang Wan,Yida Bao,Yu He,Chang Li,Haitong Wan
Guanxin Shutong capsule (GSC) is a traditional Chinese medicinal prescription used in the treatment of coronary heart disease (CHD) and angina pectoris in clinic. However, the chemical profile of GSC is still uncovered, which hindered the progress of pharmacological study and clinical application. Herein, high performance liquid chromatography (HPLC) together with high resolution mass spectrometry (HR-MS) techniques were employed to analyze the quality consistency and to identify chemical components in GSC. As a result, a total of 111 compounds were tentatively annotated. Quantitative analysis based on HPLC-ultraviolet detection (UV) was performed for 6 main components and fingerprints of 10 different batches of GSC were established. The developed method was validated for linearity, precision, repeatability, stability, and recovery. The quality evaluation and similarity analysis of the 10 batches were also performed. Furthermore, in vitro antioxidant activity assays demonstrated that GSC exhibited potential DPPH and hydroxyl radical scavenging capacities. Especially, salvianolic acids showed the strongest free radical scavenging capacities, which might be the main component for quality control of GSC.
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FOOD CHEMISTRY
·
2023
·
IF 8.8
Zhixin Xiao,Min Liu,Wentao Bi,David Da Yong Chen
In-depth studies of the extraction mechanism using deep eutectic solvents (DES), especially extraction through the formation of a deep eutectic system (DESys), revealed commonalities between the DES- and ionic liquids (IL)-based extraction systems. New applications of ILs and DES for extraction of nutritional natural products were presented. In this study, the extraction behavior of choline chloride (ChCl) and 1-(2-hydroxyethyl)-3-methylimidazolium chloride ([HMIm][Cl]) in DES and IL, respectively, in mechanochemical extraction of target compounds from Moringa oleifera leaves was systematically studied. The results suggested that both extraction methods were based on the formation of a DESys, either a normal DESys or an IL DESys. Considering the DESys-based one-step extraction improves the extraction efficiency and reduces the preparation time, the same idea can be used in IL for performance improvement. By formation of a new IL deep eutectic system based on hydrogen bond interaction in extraction, similar improvement was obtained.
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METABOLIC ENGINEERING
·
2022
·
IF 8.829
Min Shi,Ruiyan Zhu,Yi Zhang,Siwei Zhang,Tingyao Liu,Kunlun Li,Shucan Liu,Leran Wang,Yao Wang,Wei Zhou,Qiang Hua,Guoyin Kai
Phenolic acids and tanshinones are main bioactive compounds produced in Salvia miltiorrhiza widely used in treatment of cardiovascular diseases, which could be promoted by abscisic acid elicitation. However, the regulation mechanism remained to be elucidated. An ABA-inducible IIa WRKY transcription factor (TF) named SmWRKY34 exhibiting high homology with AtWRKY40 was isolated. SmWRKY34 exhibited a negative role on phenolic acids and tanshinones by directly regulating SmRAS and SmGGPPS . Moreover, ABA-responsive bZIP TF member named SmbZIP3 expressing significantly in SmWRKY34 transcriptome was screened. SmWRKY3 4 showed a negative regulatory role on SmbZIP3 . SmbZIP3 acted as a positive regulator in the biosynthesis of phenolic acids and tanshinones by targeting SmTAT and two tanshinone-promoting TFs SmERF128 and SmMYB9b . Taken together, we identify a new module WRKY34-bZIP3 involved in ABA signaling that manipulates phenolic acid and tanshinone accumulation, shedding new insights in metabolic engineering application in S. miltiorrhiza .
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INDUSTRIAL CROPS AND PRODUCTS
·
2022
·
IF 6.449
Given Chisha,Chunlu Li,Lei Xiao,Bo Wang,Yueyuan Chen,Zhifang Cui
This study aimed at efficient rosmarinic acid (RA) extraction from rosemary ( Rosmarinus officinalis L.) using natural deep eutectic solvents (NADESs). Quantum chemical calculations and molecular dynamics simulation were used to dissect the microscopic mechanisms. Three choline chloride (ChCl) based NADESs and ethanol (traditional extractant as reference) were investigated. The σ -profiles of RA and each solvent were analyzed. The infinite dilution activity coefficient ( γ ∞ ) of RA in different solvents, the total non-bonded interaction energy and the average H-bond number were calculated, to predict the RA solubility, understand the bond type and strength in each system. Among the solvents studied, ChCl/LA (lactic acid) exhibited wider complementary σ -profile with that of RA, as well as lower ln γ ∞ , higher H-bond number and predominant electrostatic-interaction. Moreover, self-diffusion coefficients revealed that RA had better compatibility with ChCl/LA. Additionally, with different solvents as extractant, ChCl/LA outperformed the others by exhibiting the highest RA extraction yield. Based on results from single factor experiments, Box-Behnken design with response surface methodology was performed for further process optimization. The regressed model obtained was reliable from the ANOVA analysis of variances. RA extraction yield was 6.10% under optimal conditions of 69 °C, 5.6 h, liquid to solid ratio 34 and water content 13.5% (w/w). The combination of simulation and experiment in this study can shed light on the exploration of natural product extraction with high efficiency using green and novel NADESs.
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Frontiers in Chemistry
·
2022
·
IF 5.545
Shen Qing,Wang Haixing,Quan Bin,Sun Xiuhua,Wu Guohua,Huang Darong,Wang Qingcheng,Luo Pei
Salvia miltiorrhiza Bunge (SMB) has unambiguous biological functions in cardiovascular diseases, thus has been processed into different medicine forms. However, universal analytical method for fast quantification of bioactive compounds in SMB and SMB derived products is still missing. In this study, a polarity switching strategy was developed and optimized, which enabled the detection of the target compound in both positive and negative ion modes in a single run. The MS2 features of each compound were characterized to select the most prominent transitions for quantitative and qualitative analysis. Afterwards, the performance of this method was validated in terms of linearity (≥0.9916), limit of detection (LOD, 0.003–0.135 ngml−1), limit of quantification (LOQ, 0.010–0.450 ngml−1), precision (48.23 ± 2.58 ngml−1 to 53.72 ± 3.11 ngml−1), recovery (RSD 2.04%–5.79%), and stability (RSD ≤7.52%). Finally, the bioactive compounds in SMB and SMB derived products were determined, among which salvianate A, salvianolic acid A, and rosmarinic acid were the main components in all samples. In conclusion, the polarity switching UPLC-MS/MS method is efficient in accurate determining the bioactive compounds, which greatly shorten the time for analysis when compared with conventional methods. It has great potential quality control of SMB and SMB derived products.
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Antioxidants
·
2021
·Vol. 10
·期 11
·1821
·
IF 6.313
Changan Zhu,Shaofang Wu,Ting Sun,Zhiwen Zhou,Zhangjian Hu,Jingquan Yu
Fruits are excellent sources of essential vitamins and health-boosting minerals. Recently, regulation of fruit ripening by both internal and external cues for the improvement of fruit quality and shelf life has received considerable attention. Rosmarinic acid (RA) is a kind of natural plant-derived polyphenol, widely used in the drug therapy and food industry due to its distinct physiological functions. However, the role of RA in plant growth and development, especially at the postharvest period of fruits, remains largely unknown. Here, we demonstrated that postharvest RA treatment delayed the ripening in tomato fruits. Exogenous application of RA decreased ripening-associated ethylene production and inhibited the fruit color change from green to red based on the decline in lycopene accumulation. We also found that the degradation of sucrose and malic acid during ripening was significantly suppressed in RA-treated tomato fruits. The results of metabolite profiling showed that RA application promoted the accumulation of multiple amino acids in tomato fruits, such as aspartic acid, serine, tyrosine, and proline. Meanwhile, RA application also strengthened the antioxidant system by increasing both the activity of antioxidant enzymes and the contents of reduced forms of antioxidants. These findings not only unveiled a novel function of RA in fruit ripening, but also indicated an attractive strategy to manage and improve shelf life, flavor, and sensory evolution of tomato fruits.Keywords:rosmarinic acid;fruit ripening;tomato;flavor quality;ethylene;antioxidant system
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Asian Pacific Journal of Cancer Prevention
·
2021
·
IF 0
Yanjun An,Jiandong Zhao,Yourui Zhang,Wen Wu,Jiangtao Hu,Haosen Hao,Yu Qiao,Ying Tao,Liping An
Background: Rosmarinic acid (RA) is a natural phenolic compound that acts as a Fyn inhibitor by 53 homology modeling of the human Fyn structure. Therefore, the apoptosis mechanism related to NF-κB signaling pathway induced by RA in HepG2 was investigated. Methods: The cell growth, apoptosis, and proliferation of HepG2 regulated by various concentrations of RA were studied. The proteins expression of MMP-2, MMP-9, PI3K, AKT, NF-κB, and apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3 were detected. Results: RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expressions of invasion-related factors, such as matrix metalloproteinase (MMP)-2 and MMP-9. TUNEL staining revealed that RA resulted in a dose-dependent increase of HepG2 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl-2 was downregulated and that of the pro-apoptotic proteins Bax and cleaved caspase-3 was increased. In addition, we found that the phosphatidylinositol 3-kinase (PI3K)/Akt/nuclear factor kappa B (NF-κB) signaling pathway was involved in RA-mediated inhibition of HepG2 cell metastasis. Conclusion: Our study identified that RA as a drug candidate for the treatment of HCC.
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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2021
·Vol. 47
·期 5
·1-11
·
IF 4.101
Yunsheng Liu,Xiangping Xu,Han Tang,Yuchen Pan,Bing Hu,Guodong Huang
There is a growing evidence that Fyn kinase is upregulated in glioblastoma multiforme (GBM), where it plays a key role in tumor proliferation and invasion. In the present study, the antitumor effects of rosmarinic acid (RA), a Fyn inhibitor, were explored in human‑derived U251 and U343 glioma cell lines. These cells were treated with various concentrations of RA to determine its effects on proliferation, migration, invasion, apoptosis, and gene and protein expression levels. The CCK‑8 assay revealed that RA significantly suppressed cell viability of U251 and U343 cells. Furthermore, RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expression levels of invasion‑related factors, such as matrix metalloproteinase (MMP)‑2 and MMP‑9. TUNEL staining revealed that RA resulted in a dose‑dependent increase of U251 and U343 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl‑2 was downregulated and that of the pro‑apoptotic proteins Bax and cleaved caspase‑3 was increased. In addition, it was revealed that the phosphatidylinositol 3‑kinase (PI3K)/Akt/nuclear factor‑κB (NF‑κB) signaling pathway was involved in RA‑induced cytotoxicity in U251 and U343 cells. Collectively, the present study suggested RA as a drug candidate for the treatment of GBM.
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