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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2024 ·Vol. 25 ·期 14 ·7760 · IF 4.9

Integrated Metabolomics and Transcriptomics Analyses of the Biosynthesis of Arbutin and 6′-O-Caffeoylarbutin in Vaccinium dunalianum Cell Suspension Cultures Fed with Hydroquinone

Churan Li,Boxiao Wu,Weihua Wang,Xiaoqin Yang,Yun Liu,Guolei Zhu,Sida Xie,Qian Jiang,Yong Ding,Yingjun Zhang,Ping Zhao,Lihua Zou

Arbutin and 6′-O-caffeoylarbutin (CA) fromVaccinium dunalianumWight are known for their ability to inhibit melanin synthesis. To boost the production of arbutin and CA, precursor feeding with hydroquinone (HQ) was studied inV. dunalianumsuspension cells. The effect of HQ on the biosynthesis of arbutin and CA in the suspension cells was investigated using high-performance liquid chromatography (HPLC), and possible molecular mechanisms were analyzed using metabolomics and transcriptomics analyses. HPLC analysis only showed that the addition of HQ significantly enhanced arbutin synthesis in cells, peaking at 15.52 ± 0.28 mg·g−1after 0.5 mmol·L−1HQ treatment for 12 h. Subsequently, metabolomics identified 78 differential expression metabolites (DEMs), of which arbutin and CA were significantly up-regulated metabolites. Moreover, transcriptomics found a total of 10,628 differential expression genes (DEGs). The integrated transcriptomics and metabolomics revealed that HQ significantly enhanced the expression of two arbutin synthase (AS) genes (Unigene0063512 and Unigene0063513), boosting arbutin synthesis. Additionally, it is speculated that CA was generated from arbutin and 3,4,5-tricaffeoylquinic acid catalyzed by caffeoyl transferase, with Unigene0044545, Unigene0043539, and Unigene0017356 as potentially associated genes with CA synthesis. These findings indicate that the precursor feeding strategy offers a promising approach for the mass production of arbutin and CA inV. dunalianumsuspension cells and provides new insights for CA biosynthesis inV. dunalianum.

CAS / MDL: 123-31-9
研究领域: 植物科学 · 分子生物学 · 植物化学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2025 · IF 6.2

Discovery of Arbutin as Novel Potential Antiviral Agent Against Tomato Yellow Leaf Curl Virus

Ying Xu,Tingting Zhang,Shimei Mu,Yanqun Peng,Duanpu Wu,Li Yang,Qing Li,Zengxue Wu,Jian Zhang

Tomato yellow leaf curl virus (TYLCV), a major plant virus, infects multiple plant species, severely threatening global food security. Arbutin, a natural product used in cosmetics to reduce pigmentation, also exhibits antibacterial and anti-inflammatory properties. However, its potential in plant protection remains undocumented. This study reveals arbutin’s ability to inhibit TYLCV infection. In Nicotiana benthamiana, 100 μg/mL arbutin inhibited viral gene accumulation by up to 76.8%, surpassing ningnanmycin (65.8%) and ribavirin (39.5%). Besides, microscale thermophoresis indicated that arbutin bound strongly to the TYLCV coat protein (CP). Molecular docking indicated that arbutin interacted with ARG58, VAL65, and CYS69. RT-qPCR and Western blot experiments confirmed the crucial roles of these amino acids, especially VAL65, in viral infection. Transcriptome analysis revealed that mutating VAL65 affected plant–pathogen interaction pathways and MAPK signaling in host defense mechanisms. This study unveils arbutin’s novel antiviral function, providing crucial insights for developing new biopesticides against plant viruses.

CAS / MDL: 497-76-7 36791-04-5
研究领域: 植物病理学 · 分子生物学
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FOOD HYDROCOLLOIDS · 2020 · IF 7.053

Novel bind-then-release model based on fluorescence spectroscopy analysis with molecular docking simulation: New insights to zero-order release of arbutin and coumaric acid

Hao Huang,Tarun Belwal,Xingyu Lin,Jarukitt Limwachiranon,Ligen Zou,Zisheng Luo

The present study aimed to systematically investigate the mechanisms of the zero-order release of arbutin and coumaric acid from whey protein concentrate-high methoxyl pectin (WPC-HMP) complex. The morphological analysis was applied to characterize the structure of the complexes, and fluorescence spectroscopy analysis with molecular docking simulation was used to study their binding interactions. The results indicated that porous structure of WPC-HMP with average pore diameter of 29.02 μm had no influence on the release profiles. The binding constant of coumaric acid (8.71 × 10 4  L/mol) was higher than that of arbutin (2.90 × 10 4  L/mol) at 298 K, led to the priority in binding order of coumaric acid. The main binding affinities were van der Waals forces and hydrogen bonds for arbutin, but hydrophobic interactions for coumaric acid. The binding interactions also resulted in regular conformational and structural changes of WPC. Moreover, a novel bind-then-release model for arbutin and coumaric acid was developed, revealing the final zero-order release profile is the balance between the competition effect and the diffusion effect.

CAS / MDL: 497-76-7 501-98-4
研究领域: 食品科学 · 生物化学
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Materials Today Bio · 2022 · IF 10.761

Arbutin-modified microspheres prevent osteoarthritis progression by mobilizing local anti-inflammatory and antioxidant responses

Jiale Jin,Yang Liu,Chao Jiang,Yifan Shen,Guangyu Chu,Can Liu,Lejian Jiang,Guanrui Huang,Yifang Qin,Yijian Zhang,Chi Zhang,Yue Wang

Osteoarthritis (OA) is a common degenerative joint disease worldwide and currently there is no effective strategy to stop its progression. It is known that oxidative stress and inflammation can promote the development of OA, and therapeutic strategies against these conditions may alleviate OA. Arbutin (ARB), a major ingredient of the Chinese medicinal herb cowberry leaf, exerts good antioxidant and anti-inflammatory activities yet has not been studied in OA. Here we developed ARB-loaded gelatine methacryloyl-Liposome ( [email protected] ) microspheres which showed long-term release of ARB and excellent cartilage-targeting effects. The ARB-loaded microspheres effectively reduced the inflammatory response in interleukin (IL)-1β-treated arthritic chondrocytes. Moreover, the synthesized [email protected] microspheres regulated cartilage extracellular matrix (ECM) homeostasis through anti-inflammation effect via inhibiting NF-κB signaling and anti-oxidative stress effect via activating Nrf2 pathway. Intra-articular use of [email protected] can effectively reduce inflammation and oxidative stress in the articular cartilage and thus, attenuating OA progression in a mouse model. The study proposed a novel ARB-laden functional microsphere, [email protected] , and demonstrated that this compound may be used as an alternative therapeutics for treating OA.

CAS / MDL: 57-88-5 111-86-4
研究领域: 药理学 · 骨科 · 生物医学工程
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SEPARATION SCIENCE AND TECHNOLOGY · 2021 · IF 2.475

Extraction and purification of pedunculoside from the dried barks of Ilex rotunda using crystallization combined with polyamide column chromatography

Weiyue Wang,Zenghao Yan,Hongliang Yao,Peibo Li,Wei Peng,Weiwei Su,Yonggang Wang

An efficient and low-cost method was developed for the preparation of pedunculoside from the dried barks of Ilex rotunda using crystallization combined with polyamide column chromatography. The kinetics of ethanol extraction was first evaluated and then the extract was concentrated to remove ethanol. Pedunculoside was partially crystallized after ethanol removal and those left in solution were further separated by polyamide column chromatography. To optimize the operating parameters for chromatography, the static and dynamic adsorption/desorption experiments were conducted. The purity of pedunculoside in the product increased to 85.69%, with an overall yield of 66.71%. The extraction and purification method developed herein provides a reference standard and can be used as the starting material for further studies.

CAS / MDL: 64-19-7
研究领域: 植物化学 · 分离科学 · 天然产物化学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2023 · IF 6.1

Efficient Whole-Cell Biotransformation for α-Arbutin Production through the Engineering of Sucrose Phosphorylase Combined with Engineered Cell Modification

Juwei Ao,Xuewei Pan,Qiang Wang,Hengwei Zhang,Kexin Ren,An Jiang,Xian Zhang,Zhiming Rao

α-Arbutin is extensively used in cosmetic industries. The lack of highly active enzymes and the cytotoxicity of hydroquinone limit the biosynthesis of α-arbutin. In this study, a whole-cell biocatalytic approach based on enzyme engineering and engineered cell modification was identified as effective in enhancing α-arbutin production. First, a sucrose phosphorylase (SPase) mutant with higher enzyme activity was obtained by experimental screening. Next, to avoid the oxidation of hydroquinone, we established an anaerobic process to improve the robustness of the cells by knocking out lytC, sdpC, and skfA in Bacillus subtilis and overcoming the inhibitory effect of a high concentration of hydroquinone. Finally, the engineered strain was used for biotransformation in a 5 L fermenter with batch feeding for 24 h. The final yield of α-arbutin achieved was 129.6 g/L, which may provide a basis for the large-scale industrial production of α-arbutin.

CAS / MDL: 123-31-9 57-50-1
研究领域: 生物化学 · 酶工程 · 工业微生物学
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Analytical Methods · 2016 ·Vol. 8 ·期 24 ·4941-4948 · IF 1.915

A chemometrics-assisted excitation–emission matrix fluorescence method for simultaneous determination of arbutin and hydroquinone in cosmetic products

Li Zhu,Hai-Long Wu,Li-Xia Xie,Huan Fang,Shou-Xia Xiang,Yong Hu,Zhi Liu,Tong Wang,Ru-Qin Yu

A fast analytical method that combines second-order calibration based on alternating trilinear decomposition (ATLD) algorithm with excitation–emission matrix (EEM) fluorescence technique is proposed to mathematically separate the overlapped spectra and simultaneously quantify arbutin (AR) and hydroquinone (HQ) in cosmetic products. This method inherits the merit of high sensitivity of traditional fluorescence and fully realizes the “second-order advantage”. For AR and HQ, the calibration ranges are 40.00–400.00 and 20.00–200.00 ng mL−1, respectively. The limits of detection for both analytes are in the range of 1.51–4.01 ng mL−1. The proposed method could be applied to diluted samples of different cosmetic products with satisfactory results. The actual concentrations of AR in the tested cosmetic products are found to be in the allowable concentration range (7%); while, the prohibited skin whitening agent HQ is detected in lotion. The contents of AR and HQ in the tested cosmetic products obtained by the proposed method are also in accordance with those of the validated high-performance liquid chromatographic method. These satisfactory results indicate that the proposed method has the potential to accurately quantify AR and HQ in complex matrices containing uncalibrated interferents, and shows promise as a reliable tool for quality monitoring of cosmetic products.

CAS / MDL: 497-76-7 123-31-9
研究领域: 分析化学 · 化妆品科学 · 光谱学
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BIOCHEMICAL ENGINEERING JOURNAL · 2022 · IF 4.446

Preparation and characterization of a novel 3D polymer support for the immobilization of cyclodextrin glucanotransferase and efficient biocatalytic synthesis of α-arbutin

Shi-Wei Zhao,Qian Zhou,Neng-Bing Long,Rui-Feng Zhang

In macropores of a melamine sponge epoxy resin was cured in ethanol solution. The produced polymer gel could uniformly deposit on the surface of melamine in either porous or nonporous morphology. The composite sponge with porous coating can be used as a large-sized and well-mass transferred support for the immobilization of cyclodextrin glucosyltransferase (CGTase, from Thermoanaerobacter sp.) through the method of adsorption and crosslinking, and a column reactor was made for the preparation of α-arbutin in a sealed circulation way. The porosity and specific surface area were 91.6 % and 46 m 2 /g, respectively. The loading amount and the specific activity of immobilized CGTase under the optimal immobilization conditions were 42 mg/g support and 651 U/g support , respectively. 5 mg/ml maltodextrin and 10 mM hydroquinone were used as a glucosyl donor and acceptor for the biosynthesis of α-arbutin, respectively. Under optimized conditions, the α-arbutin yield reached 61 % within 24 h at 40 °C. After 10 cycles, the immobilized CGTase retained 33 % of the α-arbutin yield.

研究领域: 生物化学 · 酶工程 · 材料科学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2021 · IF 5.279

Antityrosinase Mechanism and Antimelanogenic Effect of Arbutin Esters Synthesis Catalyzed by Whole-Cell Biocatalyst

Haixia Xu,Xiaofeng Li,Xuan Xin,Lan Mo,Yucong Zou,Guanglei Zhao,Yigang Yu,Kebing Chen

Tyrosinase is a key enzyme responsible for enzymatic browning of fruits and vegetables and skin disorders due to overproduction of melanin. Arbutin is an inhibitor of tyrosinase; however, its high polarity and weak transdermal absorption capacity limit its applications. In this paper, a green solvent system was developed to successfully synthesize arbutin esters with improved liposolubilities (Clog P values = 0.27–5.03). Among the obtained esters, arbutin undecenoate (AU) showed the strongest tyrosinase-inhibiting activity (15.6%), which was 9.0 times higher than that of arbutin. An enzyme kinetics study indicated that AU was a competitive inhibitor with reversible inhibition. The esters inhibited tyrosinase by making the secondary structure of tyrosinase looser and less stable; moreover, the interactions between tyrosinase and AU driven by metal interactions and hydrogen bonds also offered a mechanism for inhibition of AU on tyrosinase. In addition, AU (100 μM) reduced the melanin content of B16 mouse melanoma cells to 61.3% of the control group.

CAS / MDL: 497-76-7
研究领域: 生物化学 · 药理学 · 皮肤科学
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POULTRY SCIENCE · 2024 · IF 3.8

Arbutin alleviates Mycoplasma gallinarum-induced damage caused by pulmonary fibrosis via the JAK2/STAT3 pathway

Ting Liu,Zhentao Cheng,Derong Song,Erpeng Zhu,Hui Li,Rutao Lin,Zhiling Wan,Shunxing Liu,Zeguang Gong,Chunlan Shan

Mycoplasma gallinarum ( MG ) can cause infectious respiratory diseases in poultry that are chronic. Arbutin (AR) possesses anti-inflammatory, bacteriostatic, antitussive, and expectorant pharmacological effects, but whether it exerts regulatory effects on MG -induced pneumonia and fibrosis remains unclear. The study results unveiled that pulmonary connective tissue hyperplasia, pulmonary capillary congestion, and inflammatory cell infiltration, as well as serum levels of cytokines (i.e., TNF-α, IL-1β, IL-6, and IL-10), were elevated after MG infection. Collagen fibers were significantly deposited in the lung tissue from MG -infected chicks. Furthermore, the expression levels of key factors in the JAK2/STAT3 and TGF-β/Smad pathways markedly increased. AR intervention significantly alleviated MG -induced pneumonic injury, and reduced collagen deposition and the expression of fibrosis markers in the lung tissue. AR reduced the degree of pulmonary fibrosis by regulating key factors of the JAK2/STAT3 signaling pathway in the MG -infected HD11 cells. Thus, AR effectively reduced the expression of inflammatory factors by regulating the JAK2/STAT3 signaling pathway, thereby improving lung inflammation and fibrosis.

CAS / MDL: 497-76-7
研究领域: 兽医学 · 药理学 · 呼吸系统疾病 · 分子生物学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 7 ·6013 · IF 5.6

Inhibitory Activities of Samples on Tyrosinases Were Affected by Enzyme Species and Sample Addition Methods

Wei Wang,Lijuan Yang,Weiwei Wang,Jianyong Zhang,Ulrich H. Engelhardt,Heyuan Jiang

The inhibition of tyrosinase (TYR) activity is an effective measure to inhibit melanin synthesis. At present, there are many methods with discrepant details that study the TYR inhibitory activity of samples. Under the same experimental conditions, this paper systematically studies whether enzyme species and sample addition methods are the key factors that determine the TYR inhibitory activity of samples. TYRs extracted from B16F10 cells, apple and mushroom, called BTYR, ATYR and MTYR, respectively, were selected to implement this study. Results showed that TYR inhibitory activities of samples were obviously affected by the above two factors. It was necessary to select the appropriate enzyme according to the problems to be explained. It was speculated that indirectly inhibitory activity reflected the comprehensive effects of samples on TYR catalytic activity and intracellular TYR synthesis pathway, while directly inhibitory activity reflected the effects of samples on TYR catalytic activity. Additionally, kojic acid could be used as a positive control for both B16F10 cells and MTYR models. The TYR inhibitory activity of β-arbutin was complicated and fickle, while that of epigallocatechin gallate (EGCG) was universal and stable, which is to say, EGCG always inhibited TYR activity in a dose-dependent manner. In conclusion, the TYR inhibitory activities of samples were affected by enzyme species and sample addition methods. Compared with the unstable β-arbutin, EGCG was more valuable for clinical research.Keywords:tyrosinase;species;sample addition methods;EGCG;kojic acid;β-arbutin

CAS / MDL: 497-76-7 9003-39-8
研究领域: 生物化学 · 药理学 · 皮肤病学
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ACS Sustainable Chemistry & Engineering · 2025 · IF 7.3

Amphiphilic Arbutin Derivatives as Renewable Bio-Lubricants with Efficient Antibacterial Activity and Low Cytotoxicity

Fukang Deng,Kangchun Li,Hao Luo,Fangxue Hang,Debao Niu,Kedi Yang,Fuchuan Huang,Kai Li

The synthetic lubrication materials have been properly developed. However, it is still faced with problems such as poor sustainability and insufficient lubrication performance. Therefore, it is of great significance to develop sustainable lubricants and reveal the key factors affecting their lubrication. On this basis, a new class of natural arbutin derivatives were prepared. The friction coefficients of 0.5 wt % 6-O–Decanoyl-Arbutin (ArC10) and 0.5 wt % 6-O–Dodecanoyl-Arbutin (ArC12) dispersions were 0.054 and 0.047, respectively, which were reduced by 65.2 and 69.7% compared with hyaluronic acid sodium salt (HA). The wear rates of 0.5 wt % ArC10 and 0.5 wt % ArC12 dispersions were reduced by 85.8 and 84.7% compared with HA, respectively. The amphiphilic arbutin derivatives could form micronano scale soft aggregation micelles in the water dispersion system, promote the self-assembly of hydration lubricating film, and effectively improve the tribological properties. In addition, the antibacterial efficiency of ArC10 and ArC12 against S. aureus was more than 99.84% and has low cytotoxicity. This work proved a new source of antibacterial biobased lubricants on a large scale.

研究领域: 生物材料学 · 摩擦学 · 纳米医学 · 再生医学 · 抗菌材料 · 生物润滑 · 分子自组装
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