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INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION · 2018 · IF 2.317

Influence of substrates on the in vitro kinetics of steviol glucuronidation and interaction between steviol glycosides metabolites and UGT2B7

Jun-Ming Chen,Yong-Mei Xia,Yan-Dong Zhang,Tong-Tong Zhang,Qing-Rui Peng,Yun Fang

Steviol glycosides, a natural sweetener, may perform bioactivities via steviol, their main metabolite in human digestion. The metabolising kinetics, i.e. glucuronidation kinetics and interaction between steviol glycosides or their metabolites and metabolising enzyme, are important for understanding the bioactivity and cytotoxicity. The present study investigated kinetics of steviol glucuronidation in human liver microsome and a recombinant human UDP-glucuronosyltransferases isomer, UGT2B7, along with molecular docking to analyse interaction between UGT2B7 and steviol or glucose. The active pocket of UGT2B7 is consisted of Arg352, Leu347, Lys343, Phe339, Tyr354, Lys355 and Leu353. The influence of stevioside, rebaudioside A, glucose and some chemotherapy reagents on the glucuronidation was also studied. The predicted hepatic clearence suggested that steviol could be classified as high-clearence drug. The steviol glycosides did not affect the glucuronidation of steviol notably.

CAS / MDL: 27061-78-5
研究领域: 药理学 · 生物化学
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JOURNAL OF CHEMICAL AND ENGINEERING DATA · 2018 · IF 2.196

Solid–Liquid Equilibrium of Rebaudioside A in Pure and Binary Mixed Solvents at T = (288.15 to 328.15) K

Behnaz Asadzadeh,Jialun Zhong,Weidong Yan

Solid–liquid equilibrium data of rebaudioside A (a natural sweetener) in nine pure solvents (methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, 2-methoxyethanol, 2-ethoxyethanol, 2-buthoxyethanol, and ethylene glycol) and two binary mixed solvents (methanol + ethanol and 2-methoxyethanol + ethanol) were been measured by high performance liquid chromatography at temperatures ranging from (288.15 to 328.15) K and atmospheric pressure. From the experimental data, it was found that the solubility increased with the rising temperature in all studied solvents. The obtained values for the solubility of rebaudioside A in pure and mixed binary solvents were correlated with modified Apelblat and nonrandom two-liquid models. The results showed that these models can accurately correlate the solubility data obtained in this work. Furthermore, the crystal habits of rebaudioside A in selected solvents were studied.

CAS / MDL: 109-86-4
研究领域: 食品科学 · 物理化学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2018 · IF 3.909

Investigation of inulins from the roots of Morinda officinalis for potential therapeutic application as anti-osteoporosis agent

Keming Jiang,Dong Huang,Dawei Zhang,Xinluan Wang,Huijuan Cao,Qian Zhang,Chunyan Yan

Scope In China, the root of M . officinalis has been widely used over thousands of years against a wide range of bone disease such as lumbago, limb-ache, sciatica and rheumatic arthralgia, and has tremendous medicinal value. But the bioactive constituents responsible for the osteoprotective effects in M . officinalis remain unknown. Methods and results M . officinalis polysaccharides were extracted, isolated and purified via DEAE-cellulose 52 and Sephacryl S-100HR column to obtain two saccharides (MOP70-1 and MOP70-2). The results of osteogenic activity assays revealed that MOP70-1 and MOP70-2 significantly promoted the proliferation, differentiation and mineralization of MC3T3-E1 cells. Furthermore, MOP70-2 also upregulated gene expression of runt-related transcription factor 2, osterix, osteocalcin, osteopontin, bone sialoprotein and osteoprotegerin, which implied that MOP70-2 stimulated osteoblastic differentiation by up-regulating osteogenic differentiation-related marker genes. In addition, structural analysis indicated that MOP70-2 contained (2 → 1)-linked- β -D-Fru f residues and terminated with a glucose residue. Morphological and conformational analyses indicated that MOP70-2 exhibited spherical structure of conglomeration and had no triple helix structure. Conclusion Our studies reported the osteogenic inulins obtained from root of M . officinalis for the first time. The systematical investigation including extraction, purification, biological activities and structural characterization provide a strong evidence for future therapeutic applications as anti-osteoporosis agent.

研究领域: 药理学 · 生物化学 · 中医药学
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JOURNAL OF MOLECULAR MODELING · 2021 ·Vol. 27 ·期 9 ·1-12 · IF 1.81

Theoretical design and preparation research of molecularly imprinted polymers for steviol glycosides

Zhu Yajie,Ding Yan,Tian Dongxu,Li Yan,Zhuang Linwu,Wang Yinpeng,Xiao Wei,Zhu Jingbo

In this paper, a novel molecularly imprinted polymer (MIP) for specific adsorption of steviol glycosides was designed, and the imprinting mechanism of self-assembly system between template and monomers was clearly explored. Firstly, steviol (STE) was chosen as dummy template, and the density functional theory (DFT) at B3LYP/6–31 + G (d, p) level was used to select monomers, imprinting molar ratios, solvents, and cross-linking agents. The selectivity to five steviol glycosides was also calculated. Importantly, reduced density gradient (RDG) theory combined with atom in molecules (AIM) and infrared spectrum (IR) was applied to investigate the bonding situation and the nature of noncovalent interaction in self-assembly system. The theoretical designed results showed that the template which interacts with acrylic acid (AA) has the minimum binding energy, and the complex with the molar ratio of 1 : 4 has the most stable structure. Toluene (TL) and ethylene glycol dimethacrylate (EGDMA) were chosen as the optimal solvent and cross-linking agent, respectively. Five hydrogen bonds formed in the self-assembly system are the key forces at the adsorption sites of MIPs through the RDG and AIM analyses. The MIPs were synthesized by theoretical predictions, and the results showed that the maximum adsorption capacity towards dulcoside A is 26.17 mg/g. This work provided a theoretical direction and experimental validation for deeper researches of the MIPs for steviol glycosides. In addition, the method of RDG theory coupled with AIM and IR also could be used to analyze other imprinting formation mechanisms systematically.

研究领域: 食品科学 · 材料科学 · 理论化学
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Food & Function · 2022 ·Vol. 13 ·期 7 ·4130-4141 · IF 6.317

Pharmacokinetics, distribution and excretion of inulin-type fructan CPA after oral or intravenous administration to mice

Yao Guo,Yun-yun Shao,Yi-nan Zhao,Xiao Zhang,Zhuang-peng Chang,Yi-fan Sun,Jun-jin Liu,Jianping Gao,Rui-gang Hou

The aim of this work has been to establish and validate a simple and efficient method to detect the concentration of inulin-type fructan CPA from the roots of Codonopsis pilosula (Franch.) Nannf. in biosamples, and then apply it to evaluate the pharmacokinetics behavior, distribution character in tissue and excretion in mice. In this work, fluorescein isothiocyanate (FITC) was used to label CPA. Then FCPA was intravenously and orally administered to mice at different doses. In both i.v and p.o administration, FCPA concentration slowly declined in the circulatory system with a much longer T1/2 and MRT. After p.o administration, the area under the time curve (AUC0-∞) was dose-dependently increased. Taken together, FCPA showed poor absorption and wide tissue distribution. These pharmacokinetic results yield helpful insights into the pharmacological actions of FCPA.

CAS / MDL: 67-68-5
研究领域: 药理学 · 生物化学 · 药剂学
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MACROMOLECULAR CHEMISTRY AND PHYSICS · 2021 ·Vol. 222 ·期 17 ·2100145 · IF 2.527

Preparation of P(EGDMA-co-VPBA) Adsorbent and Its Application in the Separation of Steviol Glycosides

Qiaoge Fu,Nana Chen,Guanyu Wang,Ruili Guo

The poly (ethylene glycol dimethacrylate- co -vinylphenylboronic acid) P(EGDMA- co -VPBA) adsorbents are prepared via reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization with 4-vinylphenylboronic acid (VPBA) as the functional monomer, and used for selective adsorption of steviol glycosides (SGs). The boron content and pore structure of the P(EGDMA- co -VPBA) adsorbent are adjusted by changing the polymerization conditions. The adsorption results show that the pore structure of the P(EGDMA- co -VPBA) affects the adsorption capacity to SGs, the presence of boric acid functional groups shows favorable adsorption selectivity for stevioside (STV), and the adsorption selectivity is proportional to the content of boric acid in P(EGDMA- co -VPBA) adsorbents. The adsorption performance of P(EGDMA- co -VPBA) toward SGs is the best when the ratio of monomer to cross-linker is 1:50 and the solvent is acetonitrile. In the SG solution (6.0 mg mL −1 , C STV / C RA = 1:1), the adsorption capacities and adsorption selectivity ( α STV/RA ) of P(EGDMA- co -VPBA) to SGs are 113.20 mg g –1 and 4.99, respectively. The adsorption kinetics and isotherm data obey pseudo-second-order kinetic model and Langmuir isotherm model, respectively. The boric acid copolymers with VPBA as the monomer prepared by the one-step method can become a promising material for efficient separation and purification of SGs.

CAS / MDL: 97-90-5
研究领域: 化学工程 · 食品科学
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CARBOHYDRATE POLYMERS · 2023 · IF 11.2

Simultaneous improvement of the physical and biological properties of starch films by incorporating steviol glycoside-based solid dispersion

Fan Wang,Jinling Zhan,Rongrong Ma,Yaoqi Tian

Bioactive compounds are frequently incorporated into polysaccharides (e.g., starch) to form active biodegradable films for food packaging, but some of them are water insoluble (e.g., curcumin , CUR) that will make the films have undesirable performance. Herein, CUR was successfully solubilized into the aqueous starch film solution by steviol glycoside (STE, a natural sweetener)-based solid dispersion. The mechanisms of solubilization and film formation were explored through molecular dynamic simulation and various characterization methods. The results showed that the amorphous state of CUR combined with micellar encapsulation of STE achieved the solubilization of CUR. STE and starch chains cooperated to form the film via hydrogen bonding , while CUR was uniformly and densely distributed within the film in the form of needle-like microcrystals. The as-prepared film exhibited high flexibility, great moisture barrier, and excellent UV barrier (UV transmittance : ∼0 %). Compared with the film containing CUR alone, the as-prepared film possessed higher release efficiency, antibacterial activity , and pH response sensitivity due to the assistance of STE. Hence, the introduction of STE-based solid dispersion can simultaneously improve the biological and physical properties of starch films, which provides a green, nontoxic, and facile strategy for the perfect integration of hydrophobic bioactive compounds and polysaccharide-based films.

CAS / MDL: 458-37-7
研究领域: 食品科学 · 材料科学 · 生物技术
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Antioxidants · 2021 ·Vol. 10 ·期 2 ·262 · IF 6.313

Rebaudioside A Enhances Resistance to Oxidative Stress and Extends Lifespan and Healthspan in Caenorhabditis elegans

Pan Li,Zehua Wang,Sin Man Lam,Guanghou Shui

Non-nutritive sweeteners are widely used in food and medicines to reduce energy content without compromising flavor. Herein, we report that Rebaudioside A (Reb A), a natural, non-nutritive sweetener, can extend both the lifespan and healthspan ofC. elegans. The beneficial effects of Reb A were principally mediated via reducing the level of cellular reactive oxygen species (ROS) in response to oxidative stress and attenuating neutral lipid accumulation with aging. Transcriptomics analysis presented maximum differential expression of genes along the target of rapamycin (TOR) signaling pathway, which was further confirmed by quantitative real-time PCR (qPCR); while lipidomics uncovered concomitant reductions in the levels of phosphatidic acids (PAs), phosphatidylinositols (PIs) and lysophosphatidylcholines (LPCs) in worms treated with Reb A. Our results suggest that Reb A attenuates aging by acting as effective cellular antioxidants and also in lowering the ectopic accumulation of neutral lipids.Keywords:C. elegans;non-nutritive sweetener;rebaudioside A;aging;oxidative stress resistance;TOR;lipidomics

研究领域: 衰老 · 分子生物学 · 遗传学 · 生物化学
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Canadian Journal of Chemistry · 2020 ·Vol. 98 ·期 11 · IF 1.171

Selective adsorption and separation of stevioside and rebaudioside A by a metal-organic framework with boronic acid

Guanyu Wang,Qiaoge Fu,Ruili Guo,Zhong Wei

The boronic acid functionalization metal-organic frameworks (MOFs), as unique boronate affinity adsorbents, have desired specific molecular affinity for the separation and enrichment of cis-diol-compounds. Herein, the boronic acid functionalized Zn-based MOF adsorbent (MOF-BA) was synthesized through a simple one-step microwave method and used for the recognition and isolation of steviol glycosides (SGs). This MOF-BA exhibits the same spherical structure and isostructure with the parent framework composed only of the primitive ligand as verified by SEM and XRD characterization. It was confirmed that changing the ratio of ligands could achieve the adjustability of the boron content in the framework. At the same time, the MOF-BA-1.0 showed a suitable pore size (4.69 nm), and the presence of boric acid functional groups showed favorable selectivity for stevioside (STV). The static adsorption results showed that adsorption performances of rebaudioside A (RA) and STV from crude sugar solution (5.0 mg mL−1, pH 8) on MOF-BA-1.0 were investigated at 303 K for 15 h. The adsorption capacities for STV and RA were 42.93 mg g−1 and 22.96 mg g−1, respectively, and the adsorption selectivity (αSTV/RA) reached 4.35. The adsorption isotherm and kinetic data of MOF-BA-1.0 for RA and STV obeyed the Langmuir isotherm model and pseudo second order kinetic model, respectively. The study demonstrated that MOF-BA-1.0 adsorbent could be used as a potential adsorbent to purify the active ingredients of stevia and obtain a high concentration of RA products.

CAS / MDL: 554-95-0
研究领域: 化学 · 材料科学 · 药学 · 分析化学
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CHINESE JOURNAL OF CHEMICAL ENGINEERING · 2024 · IF 3.7

Temperature-dependent solubility of Rebaudioside A in methanol/ethanol and ethyl acetate mixtures: Experimental measurements and thermodynamic modeling

Zhenguang Liu,Zexiang Ding,Yifeng Cao,Baojian Liu,Qiwei Yang,Zhiguo Zhang,Qilong Ren,Zongbi Bao

The equilibrium solubility of Rebaudioside A (Reb A) Form II in binary mixtures of methanol/ethanol and ethyl acetate was quantitatively determined within the temperature range of 283.15 to 328.15 K at ambient pressure. The experimental findings indicate a positive correlation between the solubility of Reb A (Form II) and both the temperature and the methanol/ethanol content in the solvent system. To describe the solubility data, six distinct models were employed: the modified Apelblat equation, the λh model, the CNIBS/R-K model, the van't Hoff-Jouyban-Acree (VJA) model, the Apelblat-Jouyban-Acree (AJA) model, and the Non-Random Two-Liquid (NRTL) model. The CNIBS/R-K model exhibited the most precise fit for solubility in methanol+ethyl acetate mixtures, reflected by an Average Relative Deviation (ARD) of 0.0011 and a Root Mean Square Deviation (RMSD) of 0.0000012. Conversely, for ethanol+ethyl acetate mixtures, the modified Apelblat equation provided a superior correlation (ARD=0.0014, RMSD=0.0000004). Furthermore, thermodynamic parameters associated with the dissolution of Reb A (Form II), including enthalpy, entropy, and the Gibbs energy change, were inferred from the data. The findings underscore that the dissolution process is predominantly endothermic across the solvent systems examined. Notably, the entropy changes appear to have a significant influence on the Gibbs free energy associated with the dissolution of Reb A (Form II), suggesting that entropic factors may play a pivotal role in the studied systems.

CAS / MDL: 7647-14-5
研究领域: 化学工程 · 物理化学 · 热力学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Monocyte/macrophage-mediated transport and intratumoral bacteria-responsive ZIF nanoplatform for enhanced immunotherapy against microsatellite-stable colorectal cancer

Xietao Ye,Yeyang Sun,Lin Yang,Chen Chen,Shihao Li,Shuo Dong,Xiaoying Qin,Xiaoqi Li,Congyan Liu,Jiege Huo,Yuping Liu,Yan Chen

The low infiltration and insufficient tumor recognition of cytotoxic-T-lymphocytes (CTLs) are the two primary reasons for the low objective response rate of programmed death-1 protein (PD-1) inhibitors in treating microsatellite-stable colorectal-cancer (MSS-CRC). Ginsenoside Rg1 (Rg1) and atractylenolide-I (Att) can promote CTLs infiltration and recognition of CTLs by facilitating dendritic cells (DCs) maturation and upregulating tumor MHC-I expression, respectively, and the combination of two drugs is expected to improve the efficacy of PD-1 inhibitors. However, due to their poor water solubility and limited tumor targeting, the intratumoral delivery of both drugs faces challenges. Our previously reported a tumor-apoptotic-body-membrane (Ab) modified zeolitic-imidazolate-framework (ZIF) for co-delivering Rg1 and Att (Ab@Rg1/Att-ZIF). It could be transported by monocytes/macrophages into the deep tumor regions, however, partial formulations would be degraded by intracellular lysosomes. To overcome this, we innovatively incorporated inulin into Ab@Rg1/Att-ZIF, constructing an Ab/In@Rg1/Att-ZIF delivery system. By virtue of the Ab and inulin coating on its surface, the system could be specifically phagocytosed by monocytes/macrophages while maintaining stability in the lysosomal. Furthermore, after being transported to CRC tissues, inulin of the Ab/In@Rg1/Att-ZIF is enzymatically degraded by enzymes secreted by intratumoral bacteria, releasing Rg1 and Att to promote DCs maturation and upregulate tumor MHC-I expression, respectively. Ab/In@Rg1/Att-ZIF significantly inhibits tumor growth by enhancing CTLs infiltration and recognition, synergizing with PD-1 inhibitors to achieve a tumor suppression rate of ≈80 %, which is markedly higher than the combined efficacy of Ab@Rg1/Att-ZIF. This study provides new insights for the immunotherapy of MSS-CRC and the intratumoral co-delivery of drugs.

研究领域: 免疫治疗 · 纳米医学 · 药物递送 · 肿瘤学 · 肿瘤微环境 · 癌症免疫学
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EUROPEAN JOURNAL OF PHARMACOLOGY · 2018 · IF 3.04

New application of the commercial sweetener rebaudioside a as a hepatoprotective candidate: Induction of the Nrf2 signaling pathway

Yuxin Wang,Linyao Li,Yawen Wang,Xiaokang Zhu,Mingdong Jiang,Erqun Song,Yang Song

A large population of drug candidates have failed “from bench to bed” due to unwanted toxicities. We intend to develop an alternative approach for drug discovery, that is, to seek candidates from “safe” compounds. Rebaudioside A (Reb-A) is an approved commercial sweetener from Stevia rebaudiana Bertoni. We found that Reb-A protects against carbon tetrachloride (CCl 4 )-induced oxidative injury in human liver hepatocellular carcinoma (HepG2) cells. Reb-A showed antioxidant activity on reducing cellular reactive oxygen species and malondialdehyde levels while increasing glutathione levels and superoxide dismutase and catalase activities. Reb-A treatment induced nuclear factor erythroid-derived 2-like 2 (Nrf2) activation and antioxidant response element activity, as well as the expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Further mechanistic studies indicated that c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), mitogen-active protein kinase (MAPK) and protein kinase C epsilon (PKCε) signaling was upregulated. Thus, the present in vitro study conclusively demonstrated that Reb-A is an activator of Nrf2 and is a potential candidate hepatoprotective agent. More importantly, the present study illustrated that seeking drug candidates from “safe” compounds is a promising strategy.

CAS / MDL: 56-23-5 58543-16-1
研究领域: 药理学 · 毒理学 · 细胞生物学 · 分子生物学 · 药物发现
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