Biomaterials Science
·
2019
·Vol. 7
·期 5
·2152-2164
·
IF 5.251
Tianqi Yi,Jun Huang,Xuewen Chen,Haiyun Xiong,Yang Kang,Jun Wu
Nano-drug delivery systems are widely used in medical diagnoses, tumour drug delivery and other fields due to their unique advantages. Thus, the preparation of more biocompatible nanocarriers by modifying natural materials has become a research hotspot in recent years. As a type of abundant and environment-friendly natural material, puerarin has been proven to be effective in the treatment of many diseases. However, its low solubility and low oral utilization limit its use. In this study, a novel biocompatible nanomaterial was developed. Puerarin was modified with an unsaturated olefin via acryloyl chloride and the amphiphilic polymer poly-puerarin was finally obtained through free radical polymerization, which was used in the preparation of a drug delivery system. Poly-puerarin nanoparticles (PPue NPs) were prepared by nanoprecipitation and used as a platform to load paclitaxel (PPue@PTX NPs). Physicochemical characterization showed that the nanoparticle size was around 70 nm and the drug loading efficiency of PTX was up to 23.8%. The cytotoxicity test revealed that the modified puerarin derivatives, PPue, exhibited good biocompatibility even at large doses of 100 μg mL−1 and the PPue@PTX NPs still maintained the excellent anti-cancer effect of PTX. The in vitro cellular uptake assay demonstrated that the PPue@PTX NPs were rapidly uptaken by CT26 cells. In the in vivo experiments, the PPue@PTX NPs featured rapid aggregation and slow clearance and the most significant effect of inhibiting tumour growth among all the treatment groups. Therefore, our work provides a new strategy for the modification of natural drugs and PPue is expected to become a new safe and reliable nano-drug delivery platform.
研究领域:
药学
·
生物材料
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2017
·Vol. 9
·期 33
·4858-4862
·
IF 1.9
Ge Zhang,Xiu-Han Guo,Shi-Sheng Wang,Yue-Qing Li,Guang-Zhe Li,Wei-Jie Zhao
Ultrafiltration combined with liquid chromatography-mass spectrometry (UF-LC-MS) is an efficient affinity-based method to screen potential ligands of biomacromolecules from natural sources. In order to investigate the effects of constituents from Pueraria labta Ohwi on tyrosinase, a UF-LC-MS method for screening tyrosinase ligands was established. Seven constituents were screened as tyrosinase ligands with high affinity and their structures were elucidated as isoflavones and isoflavone glycosides by mass spectrum analysis, among which puerarin exhibited much stronger inhibitory activity in vitro than arbutin against tyrosinase. An in silico docking study indicates that the interaction between puerarin and tyrosinase mainly derived from hydrogen bonds and π–cation interaction.
研究领域:
药理学
·
分析化学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 3
·729
·
IF 4.412
Yan Huang,Jiehong Yang,Yu Zhao,Li Yu,Yu He,Haitong Wan,Chang Li
Natural deep eutectic solvent (NaDES) is generally considered as a greener alternative to fossil solvent, with great potential in various areas. In the present work, 25 different NaDESs were screened for the extraction of puerarin (PUE) and its two natural derivatives fromRadix Pueraria(RP). As the main isoflavone in RP, PUE has a wide range of biological activities. However, its application is restricted due to its poor solubility in water and low oral bioavailability. In this study, the extraction of PUE with NaDESs showed significant advantages compared with traditional solvents. While using L-Pro-Maa (L-proline-malic acid) under optimal conditions, the optimized yields of PUE, 3-MPR and PRX were 98.7 mg/g, 16.3 mg/g and 9.9 mg/g, respectively, which were 2.2-, 2.9- and 3.4-fold higher than that of water. Furthermore, the oral bioavailability of PUE in NaDES extracts was comparatively investigated in rats with HPLC-MS technique. Pharmacokinetic analysis revealed that the relative bioavailability of PUE in L-Pro-Maa extract is 323%. The result indicated that NaDES is not only a sustainable ionic liquid with higher extraction efficiency, but also an enhancer of oral bioavailability of specific natural products.Keywords:natural eutectic solvent;Radix Pueraria;pharmacokinetic;oral bioavailability;HPLC-MS;green solvent;puerarin;extraction
研究领域:
植物化学
·
药理学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Liu Jinming,Xu Haiman,Zhang Li,Wang Shuai,Lu Danyi,Chen Min,Wu Baojian
Identifying drugs with dosing time-dependent effects (chronoeffects) and understanding the underlying mechanisms would help to improve drug treatment outcome. Here, we aimed to determine chronoeffects of the herbal medicines Puerariae radix (PR) and Coptidis rhizoma (CR), and investigate a potential role of REV-ERBα as a drug target in generating chronoeffects. The pharmacological effect of PR on hyperhomocysteinemia in mice was evaluated by measuring total homocysteine, triglyceride levels and lipid accumulation. PR dosed at ZT10 generated a stronger effect on hyperhomocysteinemia than drug dosed at ZT2. Furthermore, PR increased the expression levels of REV-ERBα target genes Bhmt, Cbs and Cth (encoding three key enzymes responsible for homocysteine catabolism), thereby alleviating hyperhomocysteinemia in mice. Moreover, CR attenuated chronic colitis in mice in a dosing time-dependent manner based on measurements of disease activity index, colon length, malondialdehyde/myeloperoxidase activities and IL-1β/IL-6 levels. ZT10 dosing generated a stronger anti-colitis effect as compared to ZT2 dosing. This was accompanied by lower production of colonic inflammatory cytokines (i.e., Nlrp3, IL-1β, IL-6, Tnf-α and Ccl2, REV-ERBα target genes) in colitis mice dosed at ZT10. The diurnal patterns of PR and CR effects were respectively consistent with those of puerarin (a main active constituent of PR, a REV-ERBα antagonist) and berberine (a main active constituent of CR, a REV-ERBα agonist). In addition, loss of Rev-erbα in mice abolished the dosing time-dependency in PR and CR effects. In conclusion, the therapeutic effects of PR and CR depend on dosing time in mice, which are probably attributed to diurnal expression of REV-ERBα as the drug target. Our findings have implications for improving therapeutic outcomes of herbal medicines with a chronotherapeutic approach.
研究领域:
药理学
·
生物节律学
·
中药
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2019
·
IF 5.839
Yun He,Shishuai Wang,Jing Li,Hongshan Liang,Xianlin Wei,Dengfeng Peng,Zhengqiang Jiang,Bin Li
The objective of this study was to investigate the interaction between tannic acid (TA) and konjac glucomannan (KGM) with different molecular weight at different pHs,temperatures and urea concentration. The different molecular weight of KGM without change in primary structure were obtained by ultrasonic treatment. Turbidity titration showed that TA/KGM complexes could form at lower pH. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) results indicated that the TA/KGM complexes assembled into large and uniform colloidal particles and would lead to precipitate with the increase of TA/KGM weight ratio. Isothermal titration calorimetry (ITC) results further revealed two-step binding behavior: the first stage corresponded to soluble complex formation, while the second stage represented aggregation between complexes. When the molecular increased, the transition of TA/KGM mass ratio between stage 1 and stage 2 changed from 3.5 to 3.0. KGM of higher molecular weight needed to bind more TA to move to the next stage. When the pH was 7 at 25 °C, the pH was 3.8 at 40 °C or urea addition, the ITC signal was completely abolished, the formation of complexes between KGM and TA was shown to be highly dependent on pH, temperature, urea concentration, suggesting the main driving force of TA-KGM complexes formation was hydrogen bond.
研究领域:
食品科学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2022
·
IF 6.056
Zhilin Zhang,Jiangping Ye,Debin Guo,Jianyong Wu,Leyi Chen,Shunjing Luo,Chengmei Liu
The edible quality of starch paste formed by direct dispersion in boiling water is crucial to the design and production of instant starch-based products. In the present study, the kudzu powder was complexed with different chain-length fatty acids to improve its instant properties. The formation of V6-type kudzu powder-fatty acid complexes was initially characterized. Then, the impact of different chain-length fatty acids on instant properties of kudzu powder was characterized by measuring agglomeration rate and viscoelasticity. The agglomeration rate was decreased from 42.31% (native kudzu powder) to 0.08% (kudzu powder-myristic acid complex). Moreover, the viscoelasticity of the kudzu powder complexed with fatty acids (except for stearic acid) was stronger than that of native kudzu powder. These improvements were related to the formation of kudzu powder-fatty acid complexes with high thermal stability existed on the surface of complexed kudzu powder and extending the time for water to enter into complexed kudzu powder. Thus, all of kudzu powder could absorb sufficient water to avoid aggregating together that was involved into the formation of kudzu paste. This research had important implication for the preparation of instant starchy products that could be directly dispersed in hot water with high edible quality.
研究领域:
食品科学
·
淀粉化学
✓ 已验证
产品关联
DOI
高影响因子
ULTRASONICS SONOCHEMISTRY
·
2024
·
IF 8.7
Yuheng Li,Chao Zhang,Shuyi Li,Zhenzhou Zhu,Xuehua Wang,Giancarlo Cravotto
The industrial preparation of kudzu starch (KS) significantly reduces the remaining of flavonoids like puerarin (PU) in the product, weakening its biological activity and making pre-treatments on kudzu crucial. Ultrasonic technique, widely used for modifying biomolecules, can enhance nutrient interactions like those between starch and polyphenols in foods. Thus, a puerarin-kudzu starch (PKS) complex was prepared with the introduction of ultrasonic pretreatment. The results indicated that sonication increased the binding of PU to KS from 0.399 ± 0.01 to 0.609 ± 0.05 mg/g. Particle size analysis and SEM revealed that the particles of the ultrasonic puerarin-kudzu starch complex (UPKS) were larger than those of the untreated complexes. XRD, UV–vis, and FT-IR spectroscopic analyses indicated that hydrogen bonding primarily governs the interaction between PU and KS. Additionally, incorporating PU decreased the starch structure’s orderliness, while ultrasonic treatment altered the helical configuration of straight-chain starch, leading to the formation of a new, ordered structure through the creation of new hydrogen bonds. Additionally, gels formed from UPKS exhibited higher viscosity, elasticity, and shear stress, suggesting that ultrasound significantly altered the intermolecular interactions between PKS. In conclusion, the use of ultrasound under optimal conditions has demonstrated its effectiveness in preparing PKS complexes, highlighting its significant potential to produce high value-added kudzu-based products.
研究领域:
食品科学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 3.7
Yuanfeng Wei,Xin Chen,Runxue Ding,Jingwen Zhang,Hui Chen,Junxiao Zhu,Jianjun Zhang,Peiya Shen
Different from salt, metal chelate is a novel state of drug constructed by more separate coordinate bonds to form a chelating circle. Due to their composition similarity, it is hard to distinguish them except identifying ionic bond (i.e., salt) or coordinate bond (i.e., chelate) in the single crystal structure. In this study, sodium chelate (CDCC No: 1865670) and lithium salt (CDCC No: 2161617) of puerarin (PUE) was prepared. In addition to difference in single crystal structure, it was found that they showed totally different phase solubility behaviors: lithium salt demonstrated a typical inverse proportion curve as other common salts, while sodium chelate exhibited disordered scatters. However, when incorporating the unit PUE-Na complex in solution state and complexation constant K 11 in chemical equation, the scatters in phase solubility diagram of chelate could be well fitted and the value of K 11 was dramatically higher with orders of magnitude than the dissociation constant K c ; while processing phase solubility curve of lithium salt by incorporating complex item, it could not well match the curve at all. PUE sodium chelate is more likely to be a weak electrolyte with partial dissociation, while PUE lithium salt acted as a strong electrolyte with complete dissociation. The phase solubility test would be served as a surrogate tool for differentiation of chelates from salts when single crystal was not available.
研究领域:
药学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2020
·
IF 4.006
Shanshan He,Xin Liu,Yanling Wang,Jianhua Xie,Heng Gao,Xiujiang Li,Zhibing Huang
Monascus mold produces useful bioactive compounds such as Monascus pigments, monacolin K, and ergosterol . In this study, metabolomics analysis was used to investigate the metabolic profile changes in Monascus aurantiacus Li AS3.4384 (MALA) induced by genistein at different fermentation times using UHPLC-Q-TOF-MS/MS. The addition of genistein was found to not only reduce citrinin but also suppress significant differential metabolites. A total of 21 significant differential metabolites were involved in the most significant metabolic pathways (impact >0.1). These metabolites affected the aspartic acid , glutamic acid pathway, tricarboxylic acid (TCA) cycle, pyruvate synthesis pathway, and lysine degradation pathway. Thus, the addition of genistein may change the precursor for citrinin synthesis of Monascus . These findings provide significant insight into the Monascus metabolic pathways affected by genistein and will help to improve the quality control and safety of Monascus in food and supplements.
研究领域:
食品科学
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Lu Jin,Xiumin Li,Xu Chen,Xinghao Chen,Ye Liu,Haonan Xu,Qiao Wang,Zhan Tang
Puerarin (PUE), an isoflavonoid isolated from Pueraria lobata (Willd) Ohwi root, is a β -adrenergic receptor inhibitor used in treating glaucoma. The concentration range of gellan gum was determined based on the formulation viscosity and gelling capacity. PVP-K30 and gellan gum were used as variables, with the viscosity of formulation: STF = 40: 21, the 4 h permeation rate of rabbit isolated sclera, and 2 h in vitro release rate as response values. The JMP software was used to optimize the results, presenting that gellan gum was the main factor influencing viscosity. The in vitro release and permeation rate were primarily influenced by PVP-K30. The optimal prescription was 0.45% gellan gum and 6.0% PVP-K30. The in vitro release and permeation characteristics of puerarin in situ gel (PUE-ISG) were investigated using PUE solution as a control. The dialysis bag method results indicated that the release of the solution group leveled off after 4 h, while the PUE-ISG group had been continuously releasing. However, the cumulative release rates of the two were no longer significantly different at 10 h. The cumulative permeation rates of the ISG and solution groups were not significantly different ( P > 0.05) in the rabbit isolated sclera. The apparent permeability Papp and steady-state flux Jss of PUE-ISG were 0.950 ± 0.059 cm/h and 9.504 ± 0.587 mg·(cm·h), respectively. A sensitive and stable HPLC-MS/MS analytical method for quantifying aqueous humor concentrations of PUE was validated. A microdialysis technique was successfully used in the aqueous humor pharmacokinetics study to sample aqueous humor from rabbit eye continuously. The results revealed that PUE-ISG significantly increased the drug concentration in the aqueous humor, with C max and AUC (0-t) 3.77 and 4.40 times higher than those of the solution group, respectively. T max was also significantly prolonged, indicating good prospects for clinical application. The developed PUE-ISG preparation has the characteristics of rapid drug release and sustained permeation, and increase the drug concentration in aqueous humor, with all inactive ingredients remaining within the maximum allowable limits recommended by the FDA guideline.
研究领域:
药剂学
·
药物代谢动力学
·
眼科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Tongkai Chen,Wei Liu,Sha Xiong,Dongli Li,Shuhuan Fang,Zhenfeng Wu,Qi Wang,Xiaojia Chen
Recent work has highlighted the potential of puerarin (PU) as a valuable compound to treat Parkinson’s disease (PD), but its undesirable water solubility and bioavailability have constrained its utility. In this study, we sought to develop nanoparticles (NPs) that could be used to encapsulate PU, thereby extending its in vivo half-life and improving its bioavailability and accumulation in the brain to treat the symptoms of PD. We prepared spherical NPs (88.36 ± 1.67 nm) from six-armed star-shaped poly(lactide-co-glycolide) (6-s-PLGA) NPs that were used to encapsulate PU (PU-NPs) with 89.52 ± 1.74% encapsulation efficiency, 42.97 ± 1.58% drug loading, and a 48 h sustained drug release. NP formation and drug loading were largely mediated by hydrophobic interactions, while changes in the external environment led these NPs to become increasingly hydrophilic, thereby leading to drug release. Relative to PU alone, PU-NPs exhibited significantly improved cellular internalization, permeation, and neuroprotective effects. Upon the basis of Förster resonance energy transfer (FRET) of NPs-administered zebrafish, we were able to determine that these NPs were rapidly absorbed into circulation whereupon they were able to access the brain. We further conducted oral PU-NPs administration to rats, revealing significant improvements in PU accumulation within the plasma and brain relative to rats administered free PU. In MPTP-mediated neurotoxicity in mice, we found that PU-NPs treatment improved disease-associated behavioral deficits and depletion of dopamine and its metabolites. These findings indicated that PU-NPs represent a potentially viable approach to enhancing PU oral absorption, thus improving its delivery to the brain wherein it can aid in the treatment of PD.
研究领域:
药剂学
·
神经科学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Xiao-Feng Li,Tingting Yuan,Haixia Xu,Xuan Xin,Guanglei Zhao,Hui Wu,Xinglong Xiao
Puerarin, an important isoflavonoid from the edible root of Pueraria lobata, shows multiple bioactivities but suffers from low bioavailability. In this study, a new whole-cell catalytic method for acylation modification of puerarin was developed. Among the 12 strains tested, Aspergillus oryzae showed the highest catalytic activity and selectively catalyzed acylation of puerarin at the 6″-hydroxyl group. The organic solvents used significantly influenced the catalytic efficiency of the cells. In the green solvent 2-methyltetrahydrofuran, the reaction showed high substrate conversion (92.5%) and regioselectivity (95.8%), with results similar to those with tetrahydrofuran (94.2% and 98.5%, respectively) under optimal conditions. The monoester products showed higher liposolubility in comparison to puerarin, and those with C3–C8 fatty acid chain lengths showed evidently improved antioxidant activity toward erythrocyte hemolysis. Considering the operational stability of the cells and efficiency of the scaled-up reactions, this method is efficient and cost effective, with promising applications in the health food industry.
研究领域:
药理学
·
生物化学
·
食品科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）