MOLECULES
·
2017
·Vol. 22
·期 6
·870
·
IF 2.861
Jiao-Jiao Yuan,Frank G.F. Qin,Jun-Ling Tu,Bing Li
Due to the multiple hydroxyl groups in its structure, hydroxytyrosol (HT) is very sensitive to air and light and has very strong instability and hydrophilicity that affect its biological activity. This study attempted to prepare liposomes containing water-soluble HT to improve the bioavailability and biocompatibility of the target drug. The preparation process factors (temperature, mass ratio of phospholipid (PL) and cholesterol (CH), Tween-80 volume, HT mass) were studied and response surface methodology (RSM) was applied to optimize the conditions. The results demonstrated that by using a temperature of 63 °C, mass ratio of PL and CH 4.5:1, HT mass 5 mg and Tween-80 volume of 6 mL, HT liposomes with an encapsulation efficiency (EE) of 45.08% were prepared. It was found that the particle sizes of the HT liposomes were well distributed in the range of 100–400 nm. Compared to free HT, prepared HT liposomes had better stability and a distinct slow release effect in vitro. Besides, HT liposomes presented better DPPH radical scavenging activity than free HT, which could be due to the fact that HT was encapsulated fully inside the liposomes. In addition, the encapsulation mechanism of HT was evaluated. In summary, the results indicated that HT liposome could enhance the antioxidant activity and was a promising formulation for prolonging the biological activity time of the target drug.Keywords:hydroxytyrosol;liposomes;preparation;slow release;antioxidant activity
研究领域:
药剂学
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食品科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2025
·Vol. 39
·期 6
·e70303
·
IF 2.8
Hongyu Zhang,Guoshun Lin,Yang Yang,Yifei Wang,Xiushuo Yang,Guige Hou,Zhenbo Wang,Qingguo Meng,Yun Hou
Hydroxytyrosol (HT), a primary phenolic compound in olive oil, exhibits antioxidant and antiapoptotic effects in various cell types, including cardiomyocytes and human umbilical vein endothelial cells. Contrastingly, bisphenol S (BPS) is known to induce apoptosis in myocardial and endothelial cells via oxidative stress. BPS increases reactive oxygen species (ROS) production and reduces the viability of hippocampal HT22 cells. In this study, we explored whether HT could protect neurons from BPS-induced oxidative stress and apoptosis. Our results showed that HT effectively inhibited oxidative stress responses in the brains of BPS-treated mice and significantly decreased ROS production in BPS-treated HT22 and PC12 cells. Additionally, HT reduced BPS-induced neuronal apoptosis in the cortical regions of mice as well as in HT22 and PC12 cells. Further analysis revealed that BPS activates the NF-κB signaling pathway, a key mediator of oxidative stress and neuronal apoptosis, while HT counteracted these effects. In summary, this study demonstrates the antioxidant and antiapoptotic properties of HT in BPS-exposed neurons. These findings provide compelling experimental evidence supporting the potential dietary inclusion of HT-rich compounds to alleviate oxidative stress-related neuronal damage. Summary HT showed neuroprotection in BPS-treated in mice, HT22 and PC12 cells. HT attenuates oxidative stress in BPS-treated in mice, HT22 and PC12 cells. HT inhibits NF-κB activity in BPS-treated in HT22 and PC12 cells.
研究领域:
神经生物学
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药理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2025
·
IF 4.7
Wen-Kai Liu,Xiu-Xin Ren,Lian Xu,Juan Lin
Hydroxytyrosol, a naturally occurring chemical with antioxidant and antiviral properties, is widely employed in the nutrition, pharmaceutical, and cosmetic industries. In the present study, a modularized cascade composed of Modules 1 and 2 was designed and implemented to convert l -tyrosine to hydroxytyrosol. Module 1 was a four-enzymatic cascade for converting l -tyrosine to tyrosol. Engineering Module 1 by fine-tuning the expression of the desired enzymes resulted in a robust whole-cell catalyst, BL21 (M1-13), which converted l -tyrosine to tyrosol at high substrate loading. Module 2 involved a 4-hydroxyphenylacetate 3-monooxygenase (HpaBC)-catalyzed reaction to hydroxylate tyrosol to form hydroxytyrosol. The rational design of the HpaB subunit led to a positive variant, HpaB-Mu (T292S/R474A), which was subsequently applied to Module 2 for tyrosol hydroxylation, yielding a robust whole-cell catalyst, BL21 (M2-05). The two designed modules were merged for one-pot conversion of l -tyrosine to hydroxytyrosol by adjusting the ratio and total amount of whole-cell catalyst loading, capable of converting 40 mM of l -tyrosine to 35.8 mM of hydroxytyrosol with a high space–time yield (1.38 g/L/h). The current study proved that engineering HpaB at the substrate tunnel was a feasible way to boost its activity and proposed an effective method for synthesizing hydroxytyrosol from low-cost substrates, which has great economic potential.
研究领域:
生物化学
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合成生物学
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酶工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shiming Tang,Zhilin Ouyang,Ying Huo,Daocheng Liao,Zhiteng Zhang,Ying Lin,Suiping Zheng
Hydroxytyrosol has been proven beneficial to human health. However, the process involving the conversion of L-DOPA to 3,4-dihydroxyphenylacetaldehyde (3,4-DHPAA) in hydroxytyrosol biosynthesis typically required the simultaneous use of decarboxylase and oxidative deaminase. In addition, phenylacetaldehyde reductase from Solanum lycopersicum (SlPAR) in hydroxytyrosol biosynthesis exhibits poor thermal stability. In this study, we unexpectedly discovered that L-DOPA decarboxylase from Pseudomonas putida (PpDODC) exhibits weak dual-functional activity for both decarboxylation and oxidative deamination of L-DOPA. Through a dual-function reshaping strategy, the best dual-functional mutant PpDODC/Y79F/Y324F achieved an enzyme activity of 0.95 U/mg and exhibited a 256.8-fold increase in activity compared to the wild-type. Through rational design of SlPAR, the optimal mutant SlPAR/G52D/V188I/N234W/Q286P (SlPAR-M4) maintained stability after 12 h' treatment at 40 °C. Based on these mutants, we established a simplified cascade to synthesize hydroxytyrosol from L-DOPA, achieving a hydroxytyrosol yield of 31.4 mM from 32 mM L-DOPA in a 5-hour reaction. This process achieved the highest molar conversion rate (98.2 %) currently reported for the synthesis of hydroxytyrosol from L-DOPA. This study provides a novel solution for hydroxytyrosol synthesis from a new perspective, and the mutants hold promise for widespread application in biotransformation studies of hydroxytyrosol and other structurally-similar compounds.
研究领域:
生物化学
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生物技术
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酶学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
·
IF 5.8
Bingqing Zhu,Mengyuan Xia,Zhenfeng Ding,Xiaoyi Rong,Xuefeng Mei
Hydroxytyrosol (HT) is a natural phenolic compound with potent antioxidant activity extracted from olive trees. It is generally a slightly hydrated viscous liquid at ambient conditions, and it is highly susceptible to oxygen due to the presence of catechol moiety. Although encapsulation technique provides HT in powder form, it does not improve its chemical stability. Herein, we propose an efficient solution to the high hygroscopicity and poor stability of HT. Four cocrystals were first reported, and their intermolecular interactions were analyzed in detail. After cocrystallization, the melting point is increased and the hygroscopicity is significantly decreased. HT cocrystals are thus solid at room temperature. Moreover, hydroxytyrosol cocrystals with betaine (HT-BET) and nicotinamide (HT-NIC) demonstrate superior chemical stability than pure HT, olive extract, and HT encapsulation material. Therefore, cocrystallization can be considered as a promising approach to overcome the application obstacles of HT.
研究领域:
食品科学
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药物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2015
·Vol. 39
·期 5
·566-574
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IF 0.741
Wu Zun-Qiu,Yue Gui-Zhou,Zhu Qing-Ping,Jiang You-Jun,Tang Kai-Yu,Chen Hua-Ping,Yang Ze-Shen,Huang Qian-Ming
Oleuropein was extracted from olive leaves by ultrasonic-assisted method and purified by silica gel column chromatography. The sample was identified as oleuropein by UV, infrared, mass spectroscopy and nuclear magnetic resonance spectroscopy analysis. Oleuropein and total phenolic contents over a year were determined by high-performance liquid chromatography and Folin–Ciocalteu methods. The results showed that 13.52% of pure oleuropein was found with a high purity of 96.54% and purification efficiency of 78.49%. Oleuropein and total phenolic contents of different olive varieties were quite different, but both had similar trends over the year. Five methods, including DPPH (2,2-diphenyl-1-picrylhydrazyl), ABST (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt), ferric reducing antioxidant power, total reducing power and nitrite-scavenging ability, were used to evaluate the antioxidant activities of oleuropein, and the IC 50 were 34.54 ± 0.14 μg/mL, 18.79 ± 0.82 μg/mL, 75.32 ± 1.83 μg/mL, 13.80 ± 0.68 μg/mL and 1.00 ± 0.08 mg/mL, respectively. Practical Applications This study provides information on the changes in contents including oleuropein and total phenolics in a year to help understand the relationship between content of oleuropein and various influencing factors. Currently, the metabolic pathways of oleuropein are not clear. These results provide information for the study of the metabolism of phenolic compounds in olive and promote research at the molecular level. Oleuropein occupies a large proportion of total polyphenols in olive and can be to be purified by silica gel column chromatography with high purification efficiency for industrial production and laboratory production. In addition, the comprehensive evaluation of activity in vitro shows that oleuropein is more useful than BHT (2,6-di- tert -butyl-4-methylphenol) for the application in food and human health.
研究领域:
植物化学
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食品科学
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分子生物学
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产品关联
DOI
高影响因子
Industrial Chemistry & Materials
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2023
·
IF 0
Mingming Hu,Bao Han,Lin Xie,Beibei Lu,De Bai,Nuo Shi,Ya Liao,Yan Wang,Ling Liu,Shaojun Wu,Runrui Lan,Xiaomei Lei,Ci Shi,Danhua Huang,Yuanbin Li,Lin Lin,Jiaheng Zhang
In this study, an ultrasonic assisted natural deep eutectic solvent (DES) was used to extract hydroxytyrosol (HT) from olive leaves. The optimal extraction conditions of the MaPa-4 concentration, extraction time and solid–liquid ratio were obtained by single factor experiments. The formation mechanism of MaPa and its interaction with HT were analyzed by FTIR, 1H-NMR and density functional theory (DFT) calculation. Then, MaPa-4 and water extracts obtained under the optimal extraction conditions were selected for a series of efficacy tests. MaPa-4 extract demonstrated low cytotoxicity, good biocompatibility, and excellent anti-inflammatory and bacteriostatic properties. Overall, MaPa-4, as an environmentally friendly and efficient solvent, was combined with ultrasound treatment to develop an efficient, green and feasible method to extract HT from olive leaves.
Keywords: Hydroxytyrosol; Deep eutectic solvent; Single-factor experiment; Bacteriostatic; Anti-inflammatory; Antioxidant.
研究领域:
绿色化学
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植物提取
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生物医学
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DOI
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
·
2023
·Vol. 28
·期 4
·379-391
·
IF 3
Chen Chan,Tang Weikang,Chen Qinfei,Han Mengqi,Shang Qi,Liu Wenbin
Hydroxytyrosol, one of the most powerful natural antioxidants, exhibits certificated benefits for human health. In this study, a biomimetic approach to synthesize hydroxytyrosol from the hydroxylation of tyrosol was established. EDTA-Fe 2+ coordination complex served as an active center to simulate tyrosine hydroxylase. H 2 O 2 and ascorbic acid were used as oxygen donor and hydrogen donor, respectively. Hydroxy radical and singlet oxygen contributed to active species. The biomimetic system displayed analogous component, structure, and activity with TyrH. Hydroxytyrosol titer of 21.59 mM, and productivity of 9985.92 mg·L −1 ·h −1 was achieved with 100 mM tyrosol as substrate. The proposed approach provided efficient and convenient route to quickly produce high amount of hydroxytyrosol. Graphical abstract
研究领域:
生物化学
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合成生物学
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抗氧化研究
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DOI
高影响因子
MOLECULES
·
2015
·Vol. 20
·期 2
·2903-2921
·
IF 2.416
Jiao-Jiao Yuan,Cheng-Zhang Wang,Jian-Zhong Ye,Ran Tao,Yu-Si Zhang
Oleuropein (OE), the main polyphenol in olive leaf extract, is likely to decompose into hydroxytyrosol (HT) and elenolic acid under the action of light, acid, base, high temperature. In the enzymatic process, the content of OE in olive leaf extract and enzyme are key factors that affect the yield of HT. A selective enzyme was screened from among 10 enzymes with a high OE degradation rate. A single factor (pH, temperature, time, enzyme quantity) optimization process and a Box-Behnken design were studied for the enzymatic hydrolysis of 81.04% OE olive leaf extract. Additionally, enzymatic hydrolysis results with different substrates (38.6% and 81.04% OE) were compared and the DPPH antioxidant properties were also evaluated. The result showed that the performance of hydrolysis treatments was best using hemicellulase as a bio-catalyst, and the high purity of OE in olive extract was beneficial to biotransform OE into HT. The optimal enzymatic conditions for achieving a maximal yield of HT content obtained by the regression were as follows: pH 5, temperature 55 °C and enzyme quantity 55 mg. The experimental result was 11.31% ± 0.15%, and the degradation rate of OE was 98.54%. From the present investigation of the antioxidant activity determined by the DPPH method, the phenol content and radical scavenging effect were both decreased after enzymatic hydrolysis by hemicellulase. However, a high antioxidant activity of the ethyl acetate extract enzymatic hydrolysate (IC50= 41.82 μg/mL) was demonstated. The results presented in this work suggested that hemicellulase has promising and attractive properties for industrial production of HT, and indicated that HT might be a valuable biological component for use in pharmaceutical products and functional foods.Keywords:Olea europeaL.;hydroxytyrosol;oleuropein;enzymatic hydrolysis;hemicellulase
研究领域:
植物化学
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食品科学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Synthetic Biology
·
2018
·
IF 5.316
Xianglai Li,Zhenya Chen,Yifei Wu,Yajun Yan,Xinxiao Sun,Qipeng Yuan
Hydroxytyrosol (HT) is a valuable natural phenolic compound with strong antioxidant activity and various physiological and pharmaceutical functions. In this study, we established an artificial pathway for HT biosynthesis. First, efficient enzymes were selected to construct a tyrosol biosynthetic pathway. Aro10 from Saccharomyces cerevisiae was shown to be a better ketoacid decarboxylase than Kivd from Lactococcus lactis for tyrosol production. While knockout of feaB significantly decreased accumulation of the byproduct 4-hydroxyphenylacetic acid, overexpression of alcohol dehydrogenase ADH6 further improved tyrosol production. The titers of tyrosol reached 1469 ± 56 mg/L from tyrosine and 620 ± 23 mg/L from simple carbon sources, respectively. The pathway was further extended for HT production by overexpressing Escherichia coli native hydroxylase HpaBC. To enhance transamination of tyrosine to 4-hydroxyphenylpyruvate, NH4Cl was removed from the culture media. To decrease oxidation of HT, ascorbic acid was added to the cell culture. To reduce the toxicity of HT, 1-dodecanol was selected as the extractant for in situ removal of HT. These efforts led to an additive increase in HT titer to 1243 ± 165 mg/L in the feeding experiment. Assembly of the full pathway resulted in 647 ± 35 mg/L of HT from simple carbon sources. This work provides a promising alternative for sustainable production of HT, which shows scale-up potential.
研究领域:
生物工程
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代谢工程
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微生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2018
·
IF 3.47
Yin Wan,Yu-Xi Liang,Bin Zou,Gui-Ming Fu,Ming-Yong Xie
In this study, the inhibitory effect of hydroxytyrosol against xanthine oxidase (XOD) by in vivo animal model and in vitro inhibition assay was analysed. The results showed that hydroxytyrosol could reduce uric acid in rat serum, inhibit XOD activity in rat liver, and adjust the mRNA transcription of the renal uric acid transporters URAT1, GLUT9, OAT1, UAT and ABCG2 towards normal in the transcription level. Hydroxytyrosol was observed as an inhibitor of XOD activity, which’s IC 50 value of restraining XOD activity was 8.75 mM. Circular dichroism (CD) spectroscopy indicated that the secondary structures of XOD were changed after incubation with hydroxytyrosol. The docking simulation showed that hydroxytyrosol could enter into the active site of XOD and form hydrogen bonds with amino acid residues (such as ARG880, GLU1261 and THR1010). The results suggested that hydroxytyrosol could be a potential XOD inhibitor for hyperuricaemia treatment.
研究领域:
药理学
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生物化学
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Baoqian Liu,Jianfei Liu,Dongdong Huang,Dong Pei,Jianteng Wei,Duolong Di
Oleuropein is an important natural compound with many biological activities. How to get high purity oleuropein is an urgent issue to be solved. This study provided a method for separating and purifying high purity oleuropein from olive leaves using boric acid affinity resin and a novel solvent system. And the experimental kinetic and adsorption isotherm data of boric acid affinity resin were well–fitted pseudo–first–order kinetic model and Langmuir isotherm model, respectively. The dynamic desorption experiments showed that ethanol was the most efficient eluent while had the lowest oleuropein purity. However, after the novel solvent system treated only one cycle of adsorption and desorption , the purity of oleuropein increased by 5.55 folds from 12.31 ± 0.42% – 68.30 ± 2.08 %. The results can guide the separation and purification of high purity catechol natural products using boric acid affinity resin and mixed solvent systems.
研究领域:
植物化学
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天然产物分离纯化
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药用植物研究
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DOI
高影响因子
危险品化学品经营许可证（带存储）