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JOURNAL OF MOLECULAR STRUCTURE · 2016 · IF 1.78

Host-guest inclusion systems of daidzein with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD): Preparation, binding behaviors and water solubility

Yinghui Deng,Yanhua Pang,Yafei Guo,Yufeng Ren,Fen Wang,Xiali Liao,Bo Yang

Daidzein is an isoflavone of naturally abundance existing in plants and foods which has attracted much attention for its significant benefits on human health. However, its application was severely limited by its poor solubilities, instability and low bioavailability. To overcome these drawbacks, inclusion complexes of daidzein with two cyclodextrin (CD) derivatives, i.e., 2-hydropropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) were prepared and characterized both in solution and solid state by 1D and 2D NMR , XRD, SEM and elemental analyses. Fluorescence spectroscopy and the Job plot were used to demonstrate a mainly 1:1 inclusion mode between daidzein and CDs. Their thermal stabilities were evaluated with TG and DSC experiments. Moreover, water solubility of daidzein was significantly improved by inclusion complexation with CDs. These results might suggest valuable approaches to developments of new pharmaceutical formulations of daidzein.

CAS / MDL: 486-66-8
研究领域: 药学 · 化学 · 材料科学
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JOURNAL OF CHEMICAL ENGINEERING OF JAPAN · 2017 ·Vol. 50 ·期 9 ·748-753 · IF 0.629

Regioselective Synthesis of β-D-Glucopyranosides and Their Analogs by Plant Seed-Derived β-Glycosidases

Zhaoyu Wang,Rongling Yang,Jizhong Wang,Yanhong Bi,Chun Zhu,Xiangjie Zhao,Linghong Nie,Wenqian Li

Regioselective enzymatic glycosylation of D-glucose and various structural alcohols for synthesizing β-D-glucopyranosides was successfully conducted. Among the β-glycosidases from seven potential plant seeds, the low-cost β-glycosidase from Prunus persica seed displayed excellent activity for salidroside preparation. Several crucial parameters, such as the solvent, buffer pH, buffer content, substrate molar ratio, enzyme dosage, and temperature were examined for yield optimization. Under the optimal conditions, the initial reaction rate and yield of salidroside were as high as 3.04 mM/h and 18.90%, respectively. Moreover, the alcohol acceptor recognition of the enzyme in synthesizing β-D-glucopyranosides was also investigated. The experimental data indicated that β-glycosidase activity and yield varied widely among all the tested alcohols due to the specific spatial structures of various acceptors.

研究领域: 生物化学 · 酶工程
✓ 已验证 DOI 高影响因子
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WORLD JOURNAL OF GASTROENTEROLOGY · 2015 · IF 2.369

β-escin reverses multidrug resistance through inhibition of the GSK3β/β-catenin pathway in cholangiocarcinoma

Gui-Li Huang,Dong-Yan Shen,Cheng-Fu Cai,Qiu-Yan Zhang,Hong-Yue Ren,Qing-Xi Chen

AIM: To develop a safe and effective agent for cholangiocarcinoma (CCA) chemotherapy. METHODS: A drug combination experiment was conducted to determine the effects of β-escin in combination with chemotherapy on CCA cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was performed to determine the effects of β-escin and common chemotherapeutics on the proliferation of human CCA cells (QBC939, Sk-ChA-1, and MZ-ChA-1). Immunocytochemistry was used to detect the expression of P-glycoprotein (P-gp) protein. Luciferase reporter assay was used to detect the activation of the Wnt/β-catenin pathway. The protein levels of P-gp, pS9-GSK3β, pT216-GSK3β, GSK3β, β-catenin, and p-β-catenin were further confirmed by western blotting. RESULTS: The drug sensitivity of QBC939 and QBC939/5-fluorouracil (5-FU) cells to 5-FU, vincristine sulfate (VCR), or mitomycin C was significantly enhanced by β-escin compared with either agent alone ( P < 0.05). In addition, the combination of β-escin (20 μmol/L) with 5-FU and VCR was synergic with a combination index < 1. Further investigation found that the mRNA and protein expression of P-gp was down-regulated by β-escin. Moreover, β-escin induced GSK3β phosphorylation at Tyr-216 and dephosphorylation at Ser-9, resulting in phosphorylation and degradation of β-catenin. Interestingly, activation of the GSK3β/β-catenin pathway induced by Wnt3a resulted in up-regulation of P-gp, which was effectively abolished by β-escin, indicating that β-escin down-regulated P-gp expression in a GSK3β-dependent manner. CONCLUSION: β-escin was a potent reverser of P-gp-dependent multidrug resistance, with said effect likely being achieved via inhibition of the GSK3β/β-catenin pathway and thus suggesting a promising strategy of developing combination drugs for CCA.

研究领域: 肿瘤学 · 分子生物学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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Separation Science Plus · 2024 · IF 1.3

Determination of β-Hydroxy-β-Methylbutyrate Content in Food Raw Materials by High-Performance Liquid Chromatography

Wen-hua Zhang,Cunxian Xi,Xionghai Yi,Yaqin Zhang,Weiqi Bao,Li-juan Shao,Dun-ming Xu

An analytical method based on high-performance liquid chromatography (HPLC) method was developed for the determination of β-hydroxy-β-methylbutyrate (HMB) content in food raw materials. The quantitative detection was performed by HPLC on diode array detector mode under external standard method. The limits of quantification, calculated as 10 times the standard deviation, were 2.0 g/100 g. The average recoveries were in the range of 92.3%–101%, with relative standard deviations below 3.87%, measured at three concentration levels. This method was used to determine the purity of HMB in 10 commercially available food raw materials. The real sample analysis results showed that the content and measurement uncertainties of HMB were 77.1–81.8 g/100 g and 4.51–4.68 g/100 g respectively, which met the requirement of HMB content in the range of 77–82 g/100 g in the HMB announcement. There are no studies on the detection of HMB in food raw materials in the previous reports. The established method provided reference for the rapid quantification and purity analysis of β-hydroxy-β-methylbutyrate in food raw materials.

CAS / MDL: 135236-72-5
研究领域: 分析化学 · 食品科学
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BIOCATALYSIS AND BIOTRANSFORMATION · 2016 · IF 0.892

β-galactosidase-catalyzed synthesis of 3-O-β-D-galactopyranosyl-sn-glycerol: Optimization by response surface methodology

Wei Wei,Danping Qi,Mingming Diao,Lu Zhaoxin,Fengxia Lv,Haizhen Zhao

In this study, the synthesis of 3-O-β-D-galactopyranosyl-sn-glycerol (GG) was performed by the reverse hydrolysis of D-galactose and glycerol using β-galactosidase from Kluyveromyces lactis. Four process variables, reaction temperature (30.0–45.0 °C), reaction time (24–48 h), enzyme concentration (150.00–350.00 U/mL), and substrate molar ratio (glycerol:D-galactose, 7.5:12.5 mmol/mmol) were investigated and optimized via response surface methodology (RSM) for optimal GG synthesis. Both quadratic equations and the optimal reaction conditions were established. Results showed that the four variables, i.e., reaction temperature, reaction time, enzyme concentration, and substrate molar ratio had significant (p < 0.0001) effects on the synthesis of GG. The optimal reaction conditions were identified as 350.00 U/mL of β-galactosidase concentration and 8.65:1.00 of substrate molar concentration ratio (glycerol: D-galactose) at 39.8 °C and 48 h of reaction. Under these conditions, the GG concentration was 140.03 g/L and GG yield was 55.71%, which both were close to the predicted values (143.26 g/L and 56.73%). This finding proves the RSM to be a useful tool in optimizing process conditions for GG synthesis.

CAS / MDL: 3646-73-9
研究领域: 生物化学 · 食品科学 · 酶工程
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Nature Communications · 2022 ·Vol. 13 ·期 1 ·1-13 · IF 17.694

The mitochondrial β-oxidation enzyme HADHA restrains hepatic glucagon response by promoting β-hydroxybutyrate production

Pan An,Sun Xiao-Meng,Huang Feng-Qing,Liu Jin-Feng,Cai Yuan-Yuan,Wu Xin,Alolga Raphael N.,Li Ping,Liu Bao-Lin,Liu Qun,Qi Lian-Wen

Disordered hepatic glucagon response contributes to hyperglycemia in diabetes. The regulators involved in glucagon response are less understood. This work aims to investigate the roles of mitochondrial β-oxidation enzyme HADHA and its downstream ketone bodies in hepatic glucagon response. Here we show that glucagon challenge impairs expression of HADHA. Liver-specific HADHA overexpression reversed hepatic gluconeogenesis in mice, while HADHA knockdown augmented glucagon response. Stable isotope tracing shows that HADHA promotes ketone body production via β-oxidation. The ketone body β-hydroxybutyrate (BHB) but not acetoacetate suppresses gluconeogenesis by selectively inhibiting HDAC7 activity via interaction with Glu543 site to facilitate FOXO1 nuclear exclusion. In HFD-fed mice, HADHA overexpression improved metabolic disorders, and these effects are abrogated by knockdown of BHB-producing enzyme. In conclusion, BHB is responsible for the inhibitory effect of HADHA on hepatic glucagon response, suggesting that HADHA activation or BHB elevation by pharmacological intervention hold promise in treating diabetes.

研究领域: 内分泌学 · 代谢学 · 分子生物学 · 糖尿病研究
✓ 已验证 DOI PubMed 高影响因子
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BIOCHEMICAL PHARMACOLOGY · 2023 · IF 5.8

Enhanced binding of β-catenin and β-TrCP mediates LMPt’s anti-CSCs activity in colorectal cancer

Mengyan Wang,Xiaowei Wang,Wenxia Zhao,Yang Li,Meilian Cai,Kexin Wang,Xiaoming Xi,Cong Zhao,Huimin Zhou,Rongguang Shao,Guimin Xia,Yefan Zhang,Wuli Zhao

Cancer stem cells (CSCs), a subpopulation of tumor cells with the features of self-renewal, tumor initiation, and insensitivity to common physical and chemical agents, are the key to cancer relapses , metastasis, and resistance. Accessible CSCs inhibitory strategies are primarily based on small molecule drugs, yet toxicity limits their application. Here, we report a liposome loaded with low toxicity and high effectiveness of miriplatin, lipo-miriplatin (LMPt) with high miriplatin loading, and robust stability, exhibiting a superior inhibitory effect on CSCs and non-CSCs. LMPt predominantly inhibits the survival of oxaliplatin-resistant (OXA-resistant) cells composed of CSCs. Furthermore, LMPt directly blocks stemness features of self-renewal, tumor initiation, unlimited proliferation, metastasis, and insensitivity. In mechanistic exploration, RNA sequencing (RNA-seq) revealed that LMPt downregulates the levels of pro-stemness proteins and that the β-catenin-mediated stemness pathway is enriched. Further research shows that either in adherent cells or 3D-spheres, the β-catenin-OCT4/NANOG axis, the vital pathway to maintain stemness, is depressed by LMPt. The consecutive activation of the β-catenin pathway induced by mutant β-catenin (S33Y) and OCT4/NANOG overexpression restores LMPt’s anti-CSCs effect, elucidating the key role of the β-catenin-OCT4/NANOG axis. Further studies revealed that the strengthened binding of β-catenin and β-TrCP initiates ubiquitination and degradation of β-catenin induced by LMPt. In addition, the Apc Min/+ transgenic mouse model, in which colon tumors are spontaneously formed, demonstrates LMPt’s potent anti-non-CSCs activity in vivo.

CAS / MDL: 76-03-9
研究领域: 肿瘤学 · 药理学 · 分子生物学 · 癌症研究
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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY · 2020 ·Vol. 104 ·期 11 ·4927-4943 · IF 3.53

An unusual GH1 β-glucosidase from marine sediment with β-galactosidase and transglycosidation activities for superior galacto-oligosaccharide synthesis

Deng Pengjun,Meng Chunyu,Wu Yan,Xu Jie,Tang Xiaoqing,Zhang Xuecheng,Xiao Yazhong,Wang Xiaotang,Fang Zemin,Fang Wei

A novel β -glucosidase, BglD1 with high β -galactosidase and transglycosidation activities, was screened and cloned from the deep-sea bacterium Bacillus sp. D1. BglD1 exhibited the maximal β -glucosidase and β -galactosidase activities at 55–60 °C and pH 5.5–6.0. The enzyme maintained approximately 50% of its original activity at 35 °C and pH 6.0 after 120-h incubation. When applied to synthesize galacto-oligosaccharides (GOS), BglD1 generated 118.3 g/L GOS (33.8% (w/w)) from 350 g/L lactose, with trisaccharide Gal- β (1 → 3)-Lac and disaccharide Gal- β (1 → 4)-Gal as the main components. Furthermore, BglD1 could hydrolyze lactose in milk and produce GOS simultaneously. Using milk as the substrate, BglD1 hydrolyzed 88.5% lactose and produced 3.3 g/L GOS after incubation at 30 °C for 1 h. To improve the transglycosidation activity, a mutant BglD1:E224T was generated based on the semi-rational design. The GOS yield of BglD1:E224T was 11.5% higher than that of BglD1 when using lactose solution as the substrate. Thus, BglD1 and the mutant could be used as beneficial alternatives of the existing β -galactosidases for the production of GOS.

研究领域: 微生物学 · 酶工程 · 食品科学
✓ 已验证 DOI PubMed 高影响因子
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ENVIRONMENTAL POLLUTION · 2022 · IF 9.988

Toxic mechanism of two cyanobacterial volatiles β-cyclocitral and β-ionone on the photosynthesis in duckweed by altering gene expression

Siyi Du,Haozhe Xu,Mengdan Yang,Ning Pan,Tiefeng Zheng,Chenyi Xu,Yan Li,Zhaojiang Zuo

Volatile organic compounds (VOCs) promote cyanobacteria dominating eutrophicated waters, with aquatic plant decrease and even disappearance. To uncover the toxic mechanism of cyanobacterial VOCs on aquatic plants, we investigated the growth, photosynthetic pigment levels, photosynthetic abilities and related gene expression in duckweed treated with β-cyclocitral and β-ionone, 2 main components in the VOCs. The levels of chlorophylls and carotenoids gradually declined with raising the concentration of the 2 compounds and prolonging the treatment time. Their decline should result from the down-regulation of 8 genes associated with photosynthetic pigment biosynthesis and up-regulation of 2 genes involved in carotenoid degradation. The reduction was also found in the photosystem II (PSII) efficiency and O 2 evolution rate, which should result from the lowered photosynthetic pigment levels and down-regulation of 38 genes related with photosynthetic process. The frond numbers, total frond area and fresh weight gradually decreased with raising the 2 compound concentration, which may result from the lowered photosynthetic abilities as well as down-regulated expression of 7 genes associated with growth-promoting hormone biosynthesis and signal transduction. It can be speculated that cyanobacterial VOCs may poison aquatic plants by lowering the photosynthesis and growth through altering related gene expression.

CAS / MDL: 14901-07-6
研究领域: 水生植物学 · 分子生物学 · 环境科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF MOLECULAR LIQUIDS · 2019 · IF 4.561

Physicochemical properties and fungicidal activity of inclusion complexes of fungicide chlorothalonil with β-cyclodextrin and hydroxypropyl-β-cyclodextrin

Shuang Gao,Yanyan Liu,Jingyu Jiang,Qiuyu Ji,Ying Fu,Lixia Zhao,Chunyan Li,Fei Ye

Chlorothalonil (CHT) suffered from its poor water solubility, which limited the application of CHT and might cause environmental pollution due to the use of organic solvents. In our research, inclusion complexes of hydroxypropyl-β-cyclodextrin (HPβCD) and β-cyclodextrin (β-CD) with CHT were formed to investigate the effect of β-CD and HPβCD on the water solubility, antifungal activity and thermal stability of CHT. The structure and characteristics of the two inclusion complexes were systematically evaluated by nuclear magnetic resonance ( 1 H NMR), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and thermal gravity analysis (TGA). The results of 1 H NMR, FT-IR, SEM and XRD indicated that CHT successfully entered the cavity of β-CD and HPβCD. TGA results proved that the thermal stability of CHT was significantly improved. Molecular modelling demonstrated that cyclodextrin could effectively complex with CHT. In addition, the biological activity test showed that the complexes had better antifungal activity than original CHT. Our research can provide useful information for the more reasonable use of CHT, and cyclodextrin can be more used in agriculture to improve the characteristics of pesticides.

研究领域: 农业化学 · 药学 · 环境科学
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FASEB JOURNAL · 2019 ·Vol. 33 ·期 9 ·10019-10033 · IF 5.391

Gut microbiota mediates the protective effects of dietary β-hydroxy-β-methylbutyrate (HMB) against obesity induced by high-fat diets

Yehui Duan,Yinzhao Zhong,Hao Xiao,Changbing Zheng,Bo Song,Wenlong Wang,Qiuping Guo,Yuying Li,Hui Han,Jing Gao,Kang Xu,Tiejun Li,Yulong Yin,Fengna Li,Jie Yin,Xiangfeng Kong

Obesity increases the risk of developing insulin resistance and diabetes and is a major public health concern. Our previous study shows that dietary β-hydroxy-β-methylbutyrate (HMB) improves lipid metabolism in a pig model. However, it remains unclear whether HMB blocks obesity through gut microbiota. In this study, we found that HMB reduced body weight, alleviated the whitening of brown adipose tissue, and improved insulin resistance in mice fed a high-fat diet (HFD). High-throughput pyrosequencing of the 16S rRNA demonstrated that HMB administration significantly reversed the gut microbiota dysbiosis in HFD-fed mice, including the diversity of gut microbiota and relative abundances of Bacteroidetes and Firmicutes . Moreover, microbiota transplantation from HMB-treated mice attenuated HFD-induced lipid metabolic disorders. Furthermore, HFD-fed mice showed lower short-chain fatty acids, whereas administration of HMB increased the propionic acid production. Correlation analysis identified a significant correlation between propionic acid production and the relative Bacteroidetes abundance. Sodium propionate treatment also attenuated HFD-induced lipid metabolic disorders. Collectively, our results indicated that HMB might be used as a probiotic agent to reverse HFD-induced obesity, and the potential mechanism was associated with reprogramming gut microbiota and metabolism, especially Bacteroidetes -mediated propionic acid production. In future studies, more efforts should be made to confirm and expand the beneficial effects of HMB to human models.—Duan, Y., Zhong, Y., Xiao, H., Zheng, C., Song, B., Wang, W., Guo, Q., Li, Y., Han, H., Gao, J., Xu, K., Li, T., Yin, Y., Li, F., Yin, J., Kong, X. Gut microbiota mediates the protective effects of dietary β-hydroxy-β-methylbutyrate (HMB) against obesity induced by high-fat diets. FASEB J. 33, 10019–10033 (2019). www.fasebj.org

研究领域: 营养学 · 代谢生物学 · 微生物学
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JOURNAL OF ORGANIC CHEMISTRY · 2022 · IF 4.198

Development of β,β-Dibrominated Secondary Enamides and Their Application to the Synthesis of 5-Br Oxazoles

Jun Ma,Qijie Zou,Chunhua Wang,Guangwei Yin,Fangyi Li

Herein, we report a base promoted dibromination of enamides using CBr4 as a bromine source to provide expedient access to β,β-dibrominated secondary enamides. Preliminary synthetic application study shows that these novel products can be readily transformed to 5-Br oxazoles via Cu(I) catalyzed intramolecular cyclization in good yields.

研究领域: 有机化学 · 合成化学
✓ 已验证 DOI PubMed 高影响因子
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